Early Detection and Screening for Breast Cancer.

PubMed

Coleman, Cathy

2017-05-01

To review the history, current status, and future trends related to breast cancer screening. Peer-reviewed articles, web sites, and textbooks. Breast cancer remains a complex, heterogeneous disease. Serial screening with mammography is the most effective method to detect early stage disease and decrease mortality. Although politics and economics may inhibit organized mammography screening programs in many countries, the judicious use of proficient clinical and self-breast examination can also identify small tumors leading to reduced morbidity. Oncology nurses have exciting opportunities to lead, facilitate, and advocate for delivery of high-quality screening services targeting individuals and communities. A practical approach is needed to translate the complexities and controversies surrounding breast cancer screening into improved care outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

PubMed

Islam, Md Ataul; Pillay, Tahir S

2017-08-01

In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB. © 2017 John Wiley & Sons A/S.

Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention

PubMed Central

Gradíssimo, Ana

2018-01-01

INTRODUCTION Human papillomavirus (HPV)-related cancers can be averted by type-specific vaccination (primary prevention) and/or through detection and ablation of precancerous cervical lesions (secondary prevention). This review presents current challenges to cervical cancer screening programs, focusing on recent molecular advances in HPV testing and potential improvements on risk stratification. AREAS COVERED High-risk (HR)-HPV DNA detection has been progressively incorporated into cervix cancer prevention programs based on its increased sensitivity. Advances in next-generation sequencing (NGS) are being rapidly applied to HPV typing. However, current HPV DNA tests lack specificity for identification of cervical precancer (CIN3). HPV typing methods were reviewed based on published literature, with a focus on these applications for screening and risk stratification in the emerging complex clinical scenario post-vaccine introduction. In addition, the potential for NGS technologies to increase specificity is discussed in regards to reflex testing of specimens for emerging biomarkers for cervix precancer/cancer. EXPERT COMMENTARY Integrative multi-disciplinary molecular tests accurately triaging exfoliated cervical specimens will improve cervical cancer prevention programs while simplifying healthcare procedures in HPV-infected women. Hence, the concept of a “liquid-biopsy” (i.e., “molecular” Pap test) highly specific for early identification of cervical precancerous lesions is of critical importance in the years to come. PMID:28277144

Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

PubMed Central

Kingsmore, Stephen

2012-01-01

Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

Early Pregnancy Diabetes Screening and Diagnosis: Prevalence, Rates of Abnormal Test Results, and Associated Factors.

PubMed

Mission, John F; Catov, Janet; Deihl, Tiffany E; Feghali, Maisa; Scifres, Christina

2017-11-01

To evaluate the prevalence of early diabetes screening in pregnancy, rates of abnormal diabetes test results before 24 weeks of gestation, and factors associated with early diabetes screening. This was a retrospective cohort study of all singleton deliveries from 2012 to 2014 among diverse clinical practices at a large academic medical center. We assessed rates of early (less than 24 weeks of gestation) and routine (at or beyond 24 weeks of gestation) diabetes screening, with abnormal test results defined using the Carpenter-Coustan criteria, a 50-g glucose challenge test result greater than 200 mg/dL, or a hemoglobin A1C level greater than 6.5%. Univariate and multivariate analyses were used to evaluate clinical and demographic determinants of screening and diagnosis. Overall, 1,420 of 11,331 (12.5%) women underwent early screening. Increasing body mass index (BMI) category, race, public insurance, history of gestational diabetes mellitus, a family history of diabetes, and chronic hypertension were associated with early screening. Early screening rates rose with increasing BMI category, but only 268 of 551 (48.6%) of women with class III obesity underwent early screening. Among those screened early, 2.0% of normal-weight women, 4.0% of overweight women, 4.2% of class I obese women, 3.8% of class II obese women, and 9.0% of class III obese women had abnormal early test results (P<.001). Early diabetes screening is used inconsistently, and many women with risk factors do not undergo early screening. A significant proportion of women with class III obesity will test positive for gestational diabetes mellitus before 24 weeks of gestation, and studies are urgently needed to assess the effect of early diabetes screening and diagnosis on perinatal outcomes in high-risk women.

Periodic Early Childhood Hearing Screening: The EHDI Perspective

ERIC Educational Resources Information Center

Hoffman, Jeff; Houston, K. Todd; Munoz, Karen F.; Bradham, Tamala S.

2011-01-01

State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that examined 12 areas within state EHDI programs. Concerning periodic early childhood hearing screening, 47 coordinators listed 241 items and themes were identified within each SWOT…

ESI-R: Early Screening Inventory-Revised. Examiner's Manual.

ERIC Educational Resources Information Center

Meisels, Samuel J.; Marsden, Dorothea B.; Wiske, Martha Stone; Henderson, Laura W.

This document includes the Early Screening Inventory: Revised (ESI-R), a developmental screening instrument for 3- to 6-year-olds, and an examiner's manual. The inventory comprises two sample scoring sheets, one for preschool (ages 3-4) and one for kindergarten (ages 4-6), and a parent questionnaire. The inventory is intended to be individually…

Screening for autism spectrum disorder in underserved communities: Early childcare providers as reporters.

PubMed

Janvier, Yvette M; Harris, Jill F; Coffield, Caroline N; Louis, Barbara; Xie, Ming; Cidav, Zuleyha; Mandell, David S

2016-04-01

Early diagnosis of autism typically is associated with earlier access to intervention and improved outcomes. Daycares and preschools largely have been ignored as possible venues for early identification. This may be especially important for minority children in the United States who are typically diagnosed with autism later than White children, limiting their access to early specialized interventions and possibly resulting in poorer outcomes. Early childcare providers within underserved communities completed autism screening tools for a sample of low-risk young children (n = 967) in their programs. Early childcare providers returned screening tools for 90% of the children for whom parental consent had been received. A total of 14% of children screened positive for autism spectrum disorder and 3% of the sample met criteria for autism spectrum disorder. Among those who screened positive, 34% were lost to follow-up. Findings suggest that early childcare providers can effectively screen young children for autism spectrum disorder in preschool/daycare settings, thus improving access to early diagnosis and reducing potential healthcare disparities among underserved populations. © The Author(s) 2015.

Early Adoption of a Multitarget Stool DNA Test for Colorectal Cancer Screening.

PubMed

Finney Rutten, Lila J; Jacobson, Robert M; Wilson, Patrick M; Jacobson, Debra J; Fan, Chun; Kisiel, John B; Sweetser, Seth; Tulledge-Scheitel, Sidna M; St Sauver, Jennifer L

2017-05-01

To characterize early adoption of a novel multitarget stool DNA (MT-sDNA) screening test for colorectal cancer (CRC) screening and to test the hypothesis that adoption differs by demographic characteristics and prior CRC screening behavior and proceeds predictably over time. We used the Rochester Epidemiology Project research infrastructure to assess the use of the MT-sDNA screening test in adults aged 50 to 75 years living in Olmsted County, Minnesota, in 2014 and identified 27,147 individuals eligible or due for screening colonoscopy from November 1, 2014, through November 30, 2015. We used electronic Current Procedure Terminology and Health Care Common Procedure codes to evaluate early adoption of the MT-sDNA screening test in this population and to test whether early adoption varies by age, sex, race, and prior CRC screening behavior. Overall, 2193 (8.1%) and 974 (3.6%) individuals were screened by colonoscopy and MT-sDNA, respectively. Age, sex, race, and prior CRC screening behavior were significantly and independently associated with MT-sDNA screening use compared with colonoscopy use after adjustment for all other variables (P<.05 for all). The rates of adoption of MT-sDNA screening increased over time and were highest in those aged 50 to 54 years, women, whites, and those who had a history of screening. The use of the MT-sDNA screening test varied predictably by insurance coverage. The rates of colonoscopy decreased over time, whereas overall CRC screening rates remained steady. The results of the present study are generally consistent with predictions derived from prior research and the diffusion of innovation framework, pointing to increasing use of the new screening test over time and early adoption by younger patients, women, whites, and those with prior CRC screening. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Parental Reports on Touch Screen Use in Early Childhood

PubMed Central

Cristia, Alejandrina; Seidl, Amanda

2015-01-01

Touch screens are increasingly prevalent, and anecdotal evidence suggests that young children are very drawn towards them. Yet there is little data regarding how young children use them. A brief online questionnaire queried over 450 French parents of infants between the ages of 5 and 40 months on their young child’s use of touch-screen technology. Parents estimated frequency of use, and further completed several checklists. Results suggest that, among respondent families, the use of touch screens is widespread in early childhood, meaning that most children have some exposure to touch screens. Among child users, certain activities are more frequently reported to be liked than others, findings that we discuss in light of current concern for children’s employment of time and the cognitive effects of passive media exposure. Additionally, these parental reports point to clear developmental trends for certain types of interactive gestures. These results contribute to the investigation of touch screen use on early development and suggest a number of considerations that should help improve the design of applications geared towards toddlers, particularly for scientific purposes. PMID:26083848

Added Value of Early Literacy Screening in Preschool Children.

PubMed

Iyer, Sai Nandini; Dawson, M Zachary; Sawyer, Mark I; Abdullah, Neelab; Saju, Leya; Needlman, Robert D

2017-09-01

The Early Literacy Screener (ELS) is a brief screen for emergent literacy delays in 4- and 5-year-olds. Standard developmental screens may also flag these children. What is the value of adding the ELS? Parents of children aged 4 (n = 45) and 5 (n = 26) years completed the Ages and Stages Questionnaire-3 (ASQ-3), the Survey of Well-Being in Young Children (SWYC), and the ELS. Rates of positive agreement (PA), negative agreement (NA), and overall agreement (Cohen's κ) across the various screening tools were calculated. Early literacy delays were detected in 51% of those who passed the ASQ and 38% of those who passed the SWYC. For ELS versus ASQ, κ = 0.18, PA = 0.36 (95% CI = 0.23-0.51), and NA = 0.83 (95% CI = 0.66-0.92). For ELS versus SWYC, κ = 0.42, PA = 0.61 (95% CI = 0.45-0.75), and NA = 0.82 (95% CI = 0.65-0.92). The ELS adds value by flagging early literacy delays in many children who pass either the ASQ-3 or SWYC.

Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.

PubMed

Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel

2016-08-01

Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Early Adoption of a Multi-target Stool DNA Test for Colorectal Cancer Screening

PubMed Central

Finney Rutten, Lila J.; Jacobson, Robert M.; Wilson, Patrick M.; Jacobson, Debra J.; Fan, Chun; Kisiel, John B.; Sweetser, Seth R.; Tulledge-Scheitel, Sidna M.; St. Sauver, Jennifer L.

2017-01-01

Objective To characterize early adoption of a novelmulti-target stool deoxyribonucleic acid (MTsDNA) screening test for colorectal cancer (CRC) and test the hypothesis that adoption differs by demographic characteristics, prior CRC screening behavior, and proceeds predictably over time. Patients and Methods We used the Rochester Epidemiology Project infrastructure to assess MTsDNA screening test use among adults aged 50–75 years, and identified 27,147 individuals eligible/due for screening colonoscopy from November 1, 2014 through November 30, 2015, and living in Olmsted County, Minnesota in2014. We used electronic Current Procedure Terminology and Health Care Common Procedure codes to evaluate early adoption of MTsDNA screening test in this population and to test whether early adoption varies by age, sex, race, and prior screening behavior. Results Overall, 2,193 (8.1%) and 974 (3.6%) of individuals were screened by colonoscopy and MT-sDNA, respectively. Age, sex, race, and prior screening were significantly and independently associated with MT-sDNA screening use compared to colonoscopy use after adjustment for all other variables. Rates of adoption of MTsDNA screening increased over time and were highest among those aged 50–54 years, females, whites, and had a prior history of screening. MT-sDNA screening use varied predictably by insurance coverage. Rates of colonoscopy decreased over time, while overall CRC screening rates remained steady. Conclusion Our results are generally consistent with predictions derived from prior research and Diffusion of Innovation framework, pointing to increasing use of the new screening test over time, and early adoption by younger patients, females, whites and those with prior CRC screening. PMID:28473037

[Early diagnosis and early treatment for liver cancer in Qidong: survival of patients and effectiveness of screening].

PubMed

Chen, J G; Zhang, Y H; Zhu, J; Lu, J H; Wang, J B; Sun, Y; Xue, X F; Lu, L L; Chen, Y S; Wu, Y; Jiang, X P; Ding, L L; Zhang, Q N; Zhu, Y R

2017-12-23

Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B

A deep learning method for early screening of lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Kunpeng; Jiang, Huiqin; Ma, Ling; Gao, Jianbo; Yang, Xiaopeng

2018-04-01

Lung cancer is the leading cause of cancer-related deaths among men. In this paper, we propose a pulmonary nodule detection method for early screening of lung cancer based on the improved AlexNet model. In order to maintain the same image quality as the existing B/S architecture PACS system, we convert the original CT image into JPEG format image by analyzing the DICOM file firstly. Secondly, in view of the large size and complex background of CT chest images, we design the convolution neural network on basis of AlexNet model and sparse convolution structure. At last we train our models on the software named DIGITS which is provided by NVIDIA. The main contribution of this paper is to apply the convolutional neural network for the early screening of lung cancer and improve the screening accuracy by combining the AlexNet model with the sparse convolution structure. We make a series of experiments on the chest CT images using the proposed method, of which the sensitivity and specificity indicates that the method presented in this paper can effectively improve the accuracy of early screening of lung cancer and it has certain clinical significance at the same time.

Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

PubMed Central

Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A.; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D.; Morrone, Amelia

2013-01-01

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

[Validation of three screening tests used for early detection of cervical cancer].

PubMed

Rodriguez-Reyes, Esperanza Rosalba; Cerda-Flores, Ricardo M; Quiñones-Pérez, Juan M; Cortés-Gutiérrez, Elva I

2008-01-01

to evaluate the validity (sensitivity, specificity, and accuracy) of three screening methods used in the early detection of the cervical carcinoma versus the histopathology diagnosis. a selected sample of 107 women attended in the Opportune Detection of Cervicouterine Cancer Program in the Hospital de Zona 46, Instituto Mexicano del Seguro Social in Durango, during the 2003 was included. The application of Papa-nicolaou, acetic acid test, and molecular detection of human papillomavirus, and histopatholgy diagnosis were performed in all the patients at the time of the gynecological exam. The detection and tipification of the human papillomavirus was performed by polymerase chain reaction (PCR) and analysis of polymorphisms of length of restriction fragments (RFLP). Histopathology diagnosis was considered the gold standard. The evaluation of the validity was carried out by the Bayesian method for diagnosis test. the positive cases for acetic acid test, Papanicolaou, and PCR were 47, 22, and 19. The accuracy values were 0.70, 0.80 and 0.99, respectively. since the molecular method showed a greater validity in the early detection of the cervical carcinoma we considered of vital importance its implementation in suitable programs of Opportune Detection of Cervicouterino Cancer Program in Mexico. However, in order to validate this conclusion, cross-sectional studies in different region of country must be carried out.

Gastric cancer: Prevention, screening and early diagnosis

PubMed Central

Pasechnikov, Victor; Chukov, Sergej; Fedorov, Evgeny; Kikuste, Ilze; Leja, Marcis

2014-01-01

Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach. PMID:25320521

A methodological overview on molecular preimplantation genetic diagnosis and screening: a genomic future?

PubMed

Vendrell, Xavier; Bautista-Llácer, Rosa

2012-12-01

The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.

Cancer screening and early detection in the 21st century

PubMed Central

Murphy, Jeanne

2017-01-01

Objective To review the trends in and principles of cancer screening and early detection. Data Sources Journal articles, United States Preventive Services Task Force (U SPSTF) publications, professional organization position statements, evidence-based summaries Conclusion Cancer screening has contributed to decreasing the morbidity and mortality of cancer. Efforts to improve the selection of candidates for cancer screening, to understand the biological basis of carcinogenesis, and the development of new technologies for cancer screening will allow for improvements in the cancer screening over time. Implications for Nursing Practice Nurses are well-positioned to lead the implementation of cancer screening recommendations in the 21st Century through their practice, research, educational efforts and advocacy. PMID:28343835

A Guide to Screening for the Early and Periodic Screening, Diagnosis and Treatment Program (EPSDT) Under Medicaid.

ERIC Educational Resources Information Center

Frankenburg, William K.; North, A. Frederick, Jr.

The manual was designed to help public officials, physicians, nurses, and others to plan and implement an Early and Periodic Screening, Diagnosis and Treatment (EPSDT) program under Medicaid. Procedures for carrying out components of an EPSDT program are recommended. Part 1 discusses organization and administration of screening, diagnosis, and…

Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

PubMed

Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

2017-01-01

Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

Newborn screening for citrin deficiency and carnitine uptake defect using second-tier molecular tests.

PubMed

Wang, Li-Yun; Chen, Nien-I; Chen, Pin-Wen; Chiang, Shu-Chuan; Hwu, Wuh-Liang; Lee, Ni-Chung; Chien, Yin-Hsiu

2013-02-10

Tandem mass spectrometry (MS/MS) analysis is a powerful tool for newborn screening, and many rare inborn errors of metabolism are currently screened using MS/MS. However, the sensitivity of MS/MS screening for several inborn errors, including citrin deficiency (screened by citrulline level) and carnitine uptake defect (CUD, screened by free carnitine level), is not satisfactory. This study was conducted to determine whether a second-tier molecular test could improve the sensitivity of citrin deficiency and CUD detection without increasing the false-positive rate. Three mutations in the SLC25A13 gene (for citrin deficiency) and one mutation in the SLC22A5 gene (for CUD) were analyzed in newborns who demonstrated an inconclusive primary screening result (with levels between the screening and diagnostic cutoffs). The results revealed that 314 of 46 699 newborns received a second-tier test for citrin deficiency, and two patients were identified; 206 of 30 237 newborns received a second-tier testing for CUD, and one patient was identified. No patients were identified using the diagnostic cutoffs. Although the incidences for citrin deficiency (1:23 350) and CUD (1:30 000) detected by screening are still lower than the incidences calculated from the mutation carrier rates, the second-tier molecular test increases the sensitivity of newborn screening for citrin deficiency and CUD without increasing the false-positive rate. Utilizing a molecular second-tier test for citrin deficiency and carnitine transporter deficiency is feasible.

New Evidence for the Effectiveness of the Early Screening Inventory.

ERIC Educational Resources Information Center

Meisels, Samuel J.; And Others

1993-01-01

Examines the psychometric properties of the Early Screening Inventory (ESI), a developmental screening instrument designed to identify four- to six-year-olds at high risk for school failure. The ESI was found to be highly reliable and predictive, and it may be possible to increase its accuracy by combining it with the related Parent Questionnaire.…

Bacterial Chemotaxis: The Early Years of Molecular Studies

PubMed Central

Hazelbauer, Gerald L.

2014-01-01

This review focuses on the early years of molecular studies of bacterial chemotaxis and motility, beginning in the 1960s with Julius Adler's pioneering work. It describes key observations that established the field and made bacterial chemotaxis a paradigm for the molecular understanding of biological signaling. Consideration of those early years includes aspects of science seldom described in journals: the accidental findings, personal interactions, and scientific culture that often drive scientific progress. PMID:22994495

The Early Screening Profiles: A Stability Study.

ERIC Educational Resources Information Center

Smith, Douglas K.; And Others

Stability of the Early Screening Profiles (ESP), developed by P. Harrison, was examined with a sample of 23 non-handicapped preschool children (14 females and 9 males) ranging in age from 3 years 0 months to 6 years 0 months at the time of initial testing. The sample was drawn from a rural/suburban community in the midwest with a predominantly…

"To screen or not to screen": Comparing the health and economic benefits of early peanut introduction strategies in five countries.

PubMed

Shaker, M; Stukus, D; Chan, E S; Fleischer, D M; Spergel, J M; Greenhawt, M

2018-03-30

Early peanut introduction (EPI) in the first year of life is associated with reduced risk of developing peanut allergy in children with either severe eczema and/or egg allergy. However, EPI recommendations differ among countries with formal guidelines. Using simulation and Markov modeling over a 20-year horizon to attempt to explore optimal EPI strategies applied to the US population, we compared high-risk infant-specific IgE peanut screening (US/Canadian) with the Australiasian Society for Clinical Immunology and Allergy (Australia/New Zealand) (ASCIA) and the United Kingdom Department of Health (UKDOH)-published EPI approaches. Screening peanut skin testing of all children with early-onset eczema and/or egg allergy before in-office peanut introduction was dominated by a no screening approach, in terms of number of cases of peanut allergy prevented, quality-adjusted life years (QALY), and healthcare costs, although screening resulted in a slightly lower rate of allergic reactions to peanut per patient in high-risk children. Considering costs of peanut allergy in high-risk children, the per-patient cost of early introduction without screening over the model horizon was $6556.69 (95%CI, $6512.76-$6600.62), compared with a cost of $7576.32 (95%CI, $7531.38-$7621.26) for skin test screening prior to introduction. From a US societal perspective, screening prior to introduction cost $654 115 322 and resulted in 3208 additional peanut allergy diagnoses. Both screening and nonscreening approaches dominated deliberately delayed peanut introduction. A no-screening approach for EPI has superior health and economic benefits in terms of number of peanut allergy cases prevented, QALY, and total healthcare costs compared to screening and in-office peanut introduction. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Miniature and Molecularly Specific Optical Screening Technologies for Breast Cancer

DTIC Science & Technology

2007-10-01

AD_________________ Award Number: W81XWH-05-1-0363 TITLE: Minature and Molecularly Specific...Annual 3. DATES COVERED (From - To) 1 SEP 2006 - 31 AUG 2007 4. TITLE AND SUBTITLE Minature and Molecularly Specific Optical Screening Technologies...area with a hole drilled in the center of the detector. P4-1 has a 600 μm diameter fiber fitted through the hole in the center of the detector while

Risk of Breast Cancer among Young Women and Importance of Early Screening.

PubMed

Memon, Zahid Ali; Kanwal, Noureen; Sami, Munam; Larik, Parsa Azam; Farooq, Mohammad Zain

2015-01-01

Breast cancer is the most common type of cancer in women throughout the world. However, in comparison with Western women, it presents relatively early in women of Asian ethnicity. Early menarche, late menopause, use of OCP's, family history of benign or malignant breast disease, exposure to radiation and BMI in the under-weight range are well known risk factors for the development of breast cancer in premenopausal women. Early detection with the use of breast self-examination (BSE) and breast cancer screening programs can lead to a reduction in the mortality rates due to breast cancer. The aim of our study was to assess the risk factors for breast cancer among young women and to emphasize the importance of early screening among them. We conducted a cross-sectional study among women aged 18 to 25 using a self- administered questionnaire. Data was collected over a period of 6 months from June to December, 2014. A total of 300 young women selected randomly from Dow Medical College and various departments of Karachi University successfully completed the survey. Respondents were 18-25 years of age (mean age=21.5). Out of the 300 young females, 90 (30%) had at least one risk factor, 90 (30%) had two, 40 (13%) had three, 8 (2.7%) had four, 2 (0.7%) had five while one female was found to have six positive risk factors for breast cancer. Some 66 women (22%) experienced symptoms of breast cancer such as non-cyclical pain and lumps. While 222 women (74%) had never performed breast self-examination, 22 (7.3%) had had a breast examination done by a health professional while 32 (10.7%) had participated in breast screening programs. A total of 223 (74.3%) women considered breast cancer screening important for young women. The percentage of young women with risk factors for breast cancer was found to be alarmingly high. Therefore, screening for breast cancer should start at an early age especially in high risk groups. Awareness about breast self-examination should be emphasized

Investigating the incremental validity of cognitive variables in early mathematics screening.

PubMed

Clarke, Ben; Shanley, Lina; Kosty, Derek; Baker, Scott K; Cary, Mari Strand; Fien, Hank; Smolkowski, Keith

2018-03-26

The purpose of this study was to investigate the incremental validity of a set of domain general cognitive measures added to a traditional screening battery of early numeracy measures. The sample consisted of 458 kindergarten students of whom 285 were designated as severely at-risk for mathematics difficulty. Hierarchical multiple regression results indicated that Wechsler Abbreviated Scales of Intelligence (WASI) Matrix Reasoning and Vocabulary subtests, and Digit Span Forward and Backward measures explained a small, but unique portion of the variance in kindergarten students' mathematics performance on the Test of Early Mathematics Ability-Third Edition (TEMA-3) when controlling for Early Numeracy Curriculum Based Measurement (EN-CBM) screening measures (R² change = .01). Furthermore, the incremental validity of the domain general cognitive measures was relatively stronger for the severely at-risk sample. We discuss results from the study in light of instructional decision-making and note the findings do not justify adding domain general cognitive assessments to mathematics screening batteries. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Antituberculosis activity of the molecular libraries screening center network library.

PubMed

Maddry, Joseph A; Ananthan, Subramaniam; Goldman, Robert C; Hobrath, Judith V; Kwong, Cecil D; Maddox, Clinton; Rasmussen, Lynn; Reynolds, Robert C; Secrist, John A; Sosa, Melinda I; White, E Lucile; Zhang, Wei

2009-09-01

There is an urgent need for the discovery and development of new antitubercular agents that target novel biochemical pathways and treat drug-resistant forms of the disease. One approach to addressing this need is through high-throughput screening of drug-like small molecule libraries against the whole bacterium in order to identify a variety of new, active scaffolds that will stimulate additional biological research and drug discovery. Through the Molecular Libraries Screening Center Network, the NIAID Tuberculosis Antimicrobial Acquisition and Coordinating Facility tested a 215,110-compound library against Mycobacterium tuberculosis strain H37Rv. A medicinal chemistry survey of the results from the screening campaign is reported herein.

Early Numeracy: Technical Adequacy of Select Kindergarten and First Grade Screening Measures

ERIC Educational Resources Information Center

Feldmann, Gregory Michael

2012-01-01

Because of a greater need to focus on early achievement in mathematics and increased global competition in this area, emphasis is increasingly being placed upon screening and monitoring of math development in early elementary to ensure progress for all students. Although protocols for early literacy assessment exist, research of psychometrically…

Screening for Autism in Young Children with Developmental Delay: An Evaluation of the Developmental Behaviour Checklist--Early Screen

ERIC Educational Resources Information Center

Gray, K. M.; Tonge, B. J.; Sweeney, D. J.; Einfeld, S. L.

2008-01-01

The ability to identify children who require specialist assessment for the possibility of autism at as early an age as possible has become a growing area of research. A number of measures have been developed as potential screening tools for autism. The reliability and validity of one of these measures for screening for autism in young children…

Virtual screening using molecular simulations.

PubMed

Yang, Tianyi; Wu, Johnny C; Yan, Chunli; Wang, Yuanfeng; Luo, Ray; Gonzales, Michael B; Dalby, Kevin N; Ren, Pengyu

2011-06-01

Effective virtual screening relies on our ability to make accurate prediction of protein-ligand binding, which remains a great challenge. In this work, utilizing the molecular-mechanics Poisson-Boltzmann (or Generalized Born) surface area approach, we have evaluated the binding affinity of a set of 156 ligands to seven families of proteins, trypsin β, thrombin α, cyclin-dependent kinase (CDK), cAMP-dependent kinase (PKA), urokinase-type plasminogen activator, β-glucosidase A, and coagulation factor Xa. The effect of protein dielectric constant in the implicit-solvent model on the binding free energy calculation is shown to be important. The statistical correlations between the binding energy calculated from the implicit-solvent approach and experimental free energy are in the range of 0.56-0.79 across all the families. This performance is better than that of typical docking programs especially given that the latter is directly trained using known binding data whereas the molecular mechanics is based on general physical parameters. Estimation of entropic contribution remains the barrier to accurate free energy calculation. We show that the traditional rigid rotor harmonic oscillator approximation is unable to improve the binding free energy prediction. Inclusion of conformational restriction seems to be promising but requires further investigation. On the other hand, our preliminary study suggests that implicit-solvent based alchemical perturbation, which offers explicit sampling of configuration entropy, can be a viable approach to significantly improve the prediction of binding free energy. Overall, the molecular mechanics approach has the potential for medium to high-throughput computational drug discovery. Copyright © 2011 Wiley-Liss, Inc.

Dose reduction in molecular breast imaging

NASA Astrophysics Data System (ADS)

Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

2011-10-01

Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

Identifying Novel Molecular Structures for Advanced Melanoma by Ligand-Based Virtual Screening

PubMed Central

Wang, Zhao; Lu, Yan; Seibel, William; Miller, Duane D.; Li, Wei

2009-01-01

We recently discovered a new class of thiazole analogs that are highly potent against melanoma cells. To expand the structure-activity relationship study and to explore potential new molecular scaffolds, we performed extensive ligand-based virtual screening against a compound library containing 342,910 small molecules. Two different approaches of virtual screening were carried out using the structure of our lead molecule: 1) connectivity-based search using Scitegic Pipeline Pilot from Accelerys and 2) molecular shape similarity search using Schrodinger software. Using a testing compound library, both approaches can rank similar compounds very high and rank dissimilar compounds very low, thus validating our screening methods. Structures identified from these searches were analyzed, and selected compounds were tested in vitro to assess their activity against melanoma cancer cell lines. Several molecules showed good anticancer activity. While none of the identified compounds showed better activity than our lead compound, they provided important insight into structural modifications for our lead compound and also provided novel platforms on which we can optimize new classes of anticancer compounds. One of the newly synthesized analogs based on this virtual screening has improved potency and selectivity against melanoma. PMID:19445498

Creating and virtually screening databases of fluorescently-labelled compounds for the discovery of target-specific molecular probes

NASA Astrophysics Data System (ADS)

Kamstra, Rhiannon L.; Dadgar, Saedeh; Wigg, John; Chowdhury, Morshed A.; Phenix, Christopher P.; Floriano, Wely B.

2014-11-01

Our group has recently demonstrated that virtual screening is a useful technique for the identification of target-specific molecular probes. In this paper, we discuss some of our proof-of-concept results involving two biologically relevant target proteins, and report the development of a computational script to generate large databases of fluorescence-labelled compounds for computer-assisted molecular design. The virtual screening of a small library of 1,153 fluorescently-labelled compounds against two targets, and the experimental testing of selected hits reveal that this approach is efficient at identifying molecular probes, and that the screening of a labelled library is preferred over the screening of base compounds followed by conjugation of confirmed hits. The automated script for library generation explores the known reactivity of commercially available dyes, such as NHS-esters, to create large virtual databases of fluorescence-tagged small molecules that can be easily synthesized in a laboratory. A database of 14,862 compounds, each tagged with the ATTO680 fluorophore was generated with the automated script reported here. This library is available for downloading and it is suitable for virtual ligand screening aiming at the identification of target-specific fluorescent molecular probes.

Does breast screening offer a survival benefit? A retrospective comparative study of oncological outcomes of screen-detected and symptomatic early stage breast cancer cases.

PubMed

Újhelyi, M; Pukancsik, D; Kelemen, P; Kovács, E; Kenessey, I; Udvarhelyi, N; Bak, M; Kovács, T; Mátrai, Z

2016-12-01

Mammography screening reduces breast cancer mortality by up to 32%. However, some recent studies have questioned the impact of non-palpable breast cancer detection on mortality reduction. The aim of this study was to analyse the clinicopathological and long-term follow-up data of early stage screened and symptomatic breast cancer patients. The institutional prospectively led database was systematically analysed for breast cancer cases diagnosed via the mammography screening program from 2002 to 2009. As a control group, symptomatic early stage breast cancer patients were collected randomly from the same database and matched for age and follow-up period. All medical records were reviewed retrospectively. Data from 298 breast cancer patients were collected from 47,718 mammography screenings. In addition, 331 symptomatic breast cancer patients were randomly selected. The screened group presented a significantly lower median tumour size (P < 0.00001). The incidence of negative regional lymph nodes was significantly higher in the screened group (P < 0.0006). The incidence of chemotherapy was 17% higher in the symptomatic group (P = 4*10 -5 ). At the median follow-up of 65 and 80 months, the screened group did not exhibit better overall (P = 0.717) or disease-free survival (P = 0.081) compared to the symptomatic group. Our results do not suggest that mammography screening does not reduce breast cancer mortality but the mammography screening did not bring any significant improvement in patient overall or disease-free survival for the early stage breast cancer patients compared to the symptomatic group. The drawback of symptomatic early stage tumours compared to non-palpable tumours could be equalized by modern multimodality oncology treatments. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Hepatocellular Carcinoma Screening Associated with Early Tumor Detection and Improved Survival Among Patients with Cirrhosis in the US.

PubMed

Singal, Amit G; Mittal, Sahil; Yerokun, Olutola A; Ahn, Chul; Marrero, Jorge A; Yopp, Adam C; Parikh, Neehar D; Scaglione, Steve J

2017-09-01

Professional societies recommend hepatocellular carcinoma screening in patients with cirrhosis, but high-quality data evaluating its effectiveness to improve early tumor detection and survival in "real world" clinical practice are needed. We aim to characterize the association between hepatocellular carcinoma screening and early tumor detection, curative treatment, and overall survival among patients with cirrhosis. We performed a retrospective cohort study of patients diagnosed with hepatocellular carcinoma between June 2012 and May 2013 at 4 health systems in the US. Patients were categorized in the screening group if hepatocellular carcinoma was detected by imaging performed for screening purposes. Generalized linear models and multivariate Cox regression with frailty adjustment were used to compare early detection, curative treatment, and survival between screen-detected and non-screen-detected patients. Among 374 hepatocellular carcinoma patients, 42% (n = 157) were detected by screening. Screen-detected patients had a significantly higher proportion of early tumors (Barcelona Clinic Liver Cancer stage A 63.1% vs 36.4%, P <.001) and were more likely to undergo curative treatment (31% vs 13%, P = .02). Hepatocellular carcinoma screening was significantly associated with improved survival in multivariate analysis (hazards ratio 0.41; 95% confidence interval, 0.26-0.65) after adjusting for patient demographics, Child-Pugh class, and performance status. Median survival of screen-detected patients was 14.6 months, compared with 6.0 months for non-screen-detected patients, with the difference remaining significant after adjusting for lead-time bias (hazards ratio 0.59, 95% confidence interval, 0.37-0.93). Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may

The evolution of lung cancer screening.

PubMed

Wilkinson, Neal W; Loewen, Gregory M; Klippenstein, Donald L; Litwin, Alan M; Anderson, Timothy M

2003-12-01

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

Organized screening detects breast cancer at earlier stage regardless of molecular phenotype.

PubMed

Holloway, Claire M B; Jiang, Li; Whitehead, Marlo; Racz, Jennifer M; Groome, Patti A

2018-06-16

Mortality reduction attributable to organized breast screening is modest. Screening may be less effective at detecting more aggressive cancers at an earlier stage. This study was conducted to determine the relative efficacy of screening mammography to detect cancers at an earlier stage by molecular phenotype. We identified 2882 women with primary invasive breast cancer diagnosed between January 1, 2008 and December 31, 2012 and who had a mammogram through the Ontario Breast Screening Program in the 28 months before diagnosis. Five tumor phenotypes were defined by expression of estrogen (ER) and progesterone (PR) receptors and HER2/neu oncogene. We conducted univariable and multivariable analyses to describe the predictors of detection as an interval cancer. Additional analyses identified predictors of detection at stages II, III, or IV compared with stage I, by phenotype. Analyses were adjusted for the effects of age, grade, and breast density. ER negative and HER2 positive tumors were over-represented among interval cancers, and triple negative cancers were more likely than ER +/HER2 - cancers to be detected as interval cancers OR 2.5 (95% CI 2.0-3.2, p < 0.0001). Method of detection (interval vs. screen) and molecular phenotype were independently associated with stage at diagnosis (p < 0.0001), but there was no interaction between method of detection and phenotype (p = 0.44). In a screened population, triple negative and HER2 + breast cancers are diagnosed at a higher stage but this appears to be due to higher growth rates of these tumors rather than a relative inability of screening to detect them.

Colorectal cancer development and advances in screening.

PubMed

Simon, Karen

2016-01-01

Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective.

Colorectal cancer development and advances in screening

PubMed Central

Simon, Karen

2016-01-01

Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

Impact of early screening for reflux in siblings on the detection of renal damage.

PubMed

Houle, Anne-Marie; Cheikhelard, Alaa; Barrieras, Diego; Rivest, Marie-Christine; Gaudreault, Valérie

2004-07-01

To assess the impact of screening siblings after detecting significant vesico-ureteric reflux (VUR) and renal scarring, as such screening might identify patients with VUR before urinary tract infections develop, but might also detect clinically insignificant VUR. We used a previously reported screening protocol to assess the clinical characteristics of patients, including the incidence of renal scarring, and their siblings, and compared the results. In all, 123 children were screened and 44 (36%) had VUR on voiding cystography. The median (range) age at screening was 9 (1-90) months. The grades of VUR detected were < III in 61% and > or = III in 39%; VUR was bilateral in 48%. In all, 37 siblings with VUR were assessed by ultrasonography; 70% were normal, including 12 (32%) children with VUR of grade > or = III. When used, renal scintigraphy was normal in 74% of siblings, vs 18% of index patients. However, when screened after 2 years old, siblings had twice the risk of already having renal damage on renal scintigraphy (P = 0.04). Early screening (< or = 2 years) appears to be more protective for avoiding renal damage than screening older patients. Thus we propose early screening in asymptomatic siblings to detect VUR before it becomes clinically significant.

The Early Detection of Pancreatic Cancer: What Will it Take to Diagnose and Treat Curable Pancreatic Neoplasia?

PubMed Central

Lennon, Anne Marie; Wolfgang, Christopher L.; Canto, Marcia Irene; Klein, Alison P.; Herman, Joseph M.; Goggins, Michael; Fishman, Elliot K.; Kamel, Ihab; Weiss, Matthew J.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.

2014-01-01

Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific, approaches for screening for curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. PMID:24924775

Combined Screening for Early Detection of Pre-Eclampsia

PubMed Central

Park, Hee Jin; Shim, Sung Shin; Cha, Dong Hyun

2015-01-01

Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers. PMID:26247944

[Screen potential CYP450 2E1 inhibitors from Chinese herbal medicine based on support vector regression and molecular docking method].

PubMed

Chen, Xi; Lu, Fang; Jiang, Lu-di; Cai, Yi-Lian; Li, Gong-Yu; Zhang, Yan-Ling

2016-07-01

Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use. Copyright© by the Chinese Pharmaceutical Association.

MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH AND SCREENING

EPA Science Inventory

Molecular Analysis of Human Spermatozoa: Potential for Infertility Research and Screening
David Miller1, David Dix2, Robert Reid3, Susan Wykes3 and Stephen Krawetz3
1Reproductive Biology Group, University of Leeds, UK
2Reproductive Toxicology Division, U.S. Environmenta...

Early Sexual Intercourse: Prospective Associations with Adolescents Physical Activity and Screen Time

PubMed Central

Wijtzes, Anne; van de Bongardt, Daphne; van de Looij-Jansen, Petra; Bannink, Rienke; Raat, Hein

2016-01-01

Objectives To assess the prospective associations of physical activity behaviors and screen time with early sexual intercourse initiation (i.e., before 15 years) in a large sample of adolescents. Methods We used two waves of data from the Rotterdam Youth Monitor, a longitudinal study conducted in the Netherlands. The analysis sample consisted of 2,141 adolescents aged 12 to 14 years (mean age at baseline = 12.2 years, SD = 0.43). Physical activity (e.g., sports outside school), screen time (e.g., computer use), and early sexual intercourse initiation were assessed by means of self-report questionnaires. Logistic regression models were tested to assess the associations of physical activity behaviors and screen time (separately and simultaneously) with early sexual intercourse initiation, controlling for confounders (i.e., socio-demographics and substance use). Interaction effects with gender were tested to assess whether these associations differed significantly between boys and girls. Results The only physical activity behavior that was a significant predictor of early sexual intercourse initiation was sports club membership. Adolescent boys and girls who were members of a sports club) were more likely to have had early sex (OR = 2.17; 95% CI = 1.33, 3.56. Significant gender interaction effects indicated that boys who watched TV ≥2 hours/day (OR = 2.00; 95% CI = 1.08, 3.68) and girls who used the computer ≥2 hours/day (OR = 3.92; 95% CI = 1.76, 8.69) were also significantly more likely to have engaged in early sex. Conclusion These findings have implications for professionals in general pediatric healthcare, sexual health educators, policy makers, and parents, who should be aware of these possible prospective links between sports club membership, TV watching (for boys), and computer use (for girls), and early sexual intercourse initiation. However, continued research on determinants of adolescents’ early sexual initiation is needed to further contribute to

Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

PubMed

Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

2016-04-01

Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes

Is high pressure liquid chromatography an effective screening tool for characterization of molecular defects in hemoglobinopathies?

PubMed

Moorchung, Nikhil; Phillip, Joseph; Sarkar, Ravi Shankar; Prasad, Rupesh; Dutta, Vibha

2013-01-01

Hemoglobinopathies constitute entities that are generated by either abnormal hemoglobin or thalassemias. high pressure liquid chromatography (HPLC) is one of the best methods for screening and detection of various hemoglobinopathies but it has intrinsic interpretive problems. The study was designed to evaluate the different mutations seen in cases of hemoglobinopathies and compare the same with screening tests. 68 patients of hemoglobinopathies were screened by HPLC. Mutation studies in the beta globin gene was performed using the polymerase chain reaction (PCR)-based allele-specific Amplification Refractory Mutation System (ARMS). Molecular analysis for the sickle cell mutation was done by standard methods. The IVS 1/5 mutation was the commonest mutation seen and it was seen in 26 (38.23%) of the cases. This was followed by the IVS 1/1, codon 41/42, codon 8/9, del 22 mutation, codon 15 mutation and the -619 bp deletion. No mutation was seen in eight cases. There was a 100% concordance between the sickle cell trait as diagnosed by HPLC and genetic testing. Our study underlies the importance of molecular testing in all cases of hemoglobinopathies. Although HPLC is a useful screening tool, molecular testing is very useful in accurately diagnosing the mutations. Molecular testing is especially applicable in cases with an abnormal hemoglobin (HbD, HbE and HbS) because there may be a concomitant inheritance of a beta thalassemia mutation. Molecular testing is the gold standard when it comes to the diagnosis of hemoglobinopathies.

Accessing Autonomic Function Can Early Screen Metabolic Syndrome

PubMed Central

Dai, Meng; Li, Mian; Yang, Zhi; Xu, Min; Xu, Yu; Lu, Jieli; Chen, Yuhong; Liu, Jianmin; Ning, Guang; Bi, Yufang

2012-01-01

Background Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. Methodology and Principal Findings The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend <0.0001). Moreover, EZSCAN value was associated with an increase in the number of metabolic syndrome components (p for trend <0.0001). Compared with the no risk group (EZSCAN value 0–24), participants at the high risk group (EZSCAN value: 50–100) had a 2.35 fold increased risk of prevalent metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61–0.64) for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. Conclusions and Significance In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome. PMID:22916265

Classification of human pathogen bacteria for early screening using electronic nose

NASA Astrophysics Data System (ADS)

Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

2017-10-01

This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

PubMed

Green, M R; Weaver, L T; Heeley, A F; Nicholson, K; Kuzemko, J A; Barton, D E; McMahon, R; Payne, S J; Austin, S; Yates, J R

1993-04-01

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.

Molecular screening of xerophilic Aspergillus strains producing mycophenolic acid.

PubMed

Mouhamadou, Bello; Sage, Lucile; Périgon, Sophie; Séguin, Virginie; Bouchart, Valérie; Legendre, Patrick; Caillat, Mathilde; Yamouni, Hayet; Garon, David

2017-02-01

Mycophenolic acid (MPA) is the fungal secondary metabolite displaying several biological properties. Up to now, screening of fungal strains producing MPA has mainly been the result of the search of this molecule in their culture medium by chemical methods. Here we developed a molecular approach by targeting the expression level of the MpaC gene encoding the polyketide synthase, one of the key enzymes involved in the MPA synthesis. Thirty xerophilic Aspergillus strains were identified using the RNA polymerase II subunit and the β-tubulin genes. Seven Aspergillus species were evidenced. The expression level of the MpaC gene was quantified and compared to the MPA production rate. Only Aspergillus pseudoglaucus and all the eight strains of this species produced MPA. While the MpaC gene was not expressed or weakly expressed in the MPA non-producing strains, all the A. pseudoglaucus strains presented a high level of expression of this gene. The highest expression level of the MpaC gene among the MPA non-producing strains was significantly lower than the lowest expression level of this gene in the MPA producing strains. To our knowledge, this is the first study that demonstrates the effectiveness of molecular approach for the screening of MPA-producing species. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Hyper-polyhedron model applied to molecular screening of guanidines as Na/H exchange inhibitors.

PubMed

Bao, Xin-Hua; Lu, Wen-Cong; Liu, Liang; Chen, Nian-Yi

2003-05-01

To investigate structure-activity relationships of N-(3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl) guanidines in Na/H exchange inhibitory activities and probe into a new method of the computer-aided molecular screening. The hyper-polyhedron model (HPM) was proposed in our lab. The samples with probably higher activities could be determined in such a way that their representing points should be in the hyper-polyhedron region where all known samples with high activities were distributed. And the predictive ability of different methods available was tested by the cross-validation experiment. The accurate rate of molecular screening of N-(3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl) guanidines by HPM was much higher than that obtained by PCA (principal component analysis) and Fisher methods for the data set available here. Therefore, HPM could be used as a powerful tool for screening new compounds with probably higher activities.

Genetic and epigenetic markers in colorectal cancer screening: recent advances.

PubMed

Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer

2017-07-01

Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.

Screening mammography--early detection or over-diagnosis? Contribution from Australian data.

PubMed

Bell, R J

2014-12-01

The aim of this review was to examine the benefits and harms of organized screening mammography, with particular reference to data from Australia. Published literature was examined relating to the impact of screening mammography on breast cancer-specific mortality, the trends in use of adjuvant treatments for breast cancer, the effectiveness of adjuvant treatment in terms of breast cancer-specific mortality, the impact of breast cancer treatment on non-breast cancer mortality and the magnitude of the issue of over-diagnosis. Most of the recent reduction in breast cancer-specific mortality is explained by use of adjuvant therapy rather than screening mammography. The impact of screening mammography in countries where women present with early disease and have access to adjuvant treatment is modest. There is a wide range of estimates for the magnitude of over-diagnosis. All-cause mortality (rather than breast cancer-specific mortality) should be used when assessing the impact of mammographic screening as otherwise the harm of breast cancer treatment in women who are over-diagnosed will be missed. The benefits and harms of screening mammography are finely balanced. The impact of screening mammography is at best neutral but may result in overall harm. Women should be informed of the issue of over-diagnosis. It is time to review whether organized mammographic screening programs should continue.

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening

PubMed Central

2018-01-01

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a “disease screening pill” capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents. PMID:29696981

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

PubMed

Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

2018-05-07

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

Impact of transition from microscopy to molecular screening for detection of intestinal protozoa in Dutch patients.

PubMed

Svraka-Latifovic, S; Bouter, S; Naus, H; Bakker, L J; Timmerman, C P; Dorigo-Zetsma, J W

2014-11-01

Detection of intestinal protozoa by PCR methods has been described as being sensitive and specific, and as improving the diagnostic yield. Here we present the outcome of the transition from microscopy to molecular screening for detection of a select group of intestinal protozoa in faeces in our laboratory. Introduction of molecular screening for intestinal protozoa resulted in higher sensitivity, reduced hands-on-time, reduced time-to-results, leading to improved diagnostic efficiency. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

A Lens on Learning: Early Vision Screening Can Set Children on the Path to Achievement.

ERIC Educational Resources Information Center

Black, Susan

2002-01-01

Discusses student learning difficulties linked to visual disorders such as dyslexia and amblyopia, problems associated with current school vision-screening procedures, and recommendations to improve preschool and in-school vision-screening practices with an emphasis on early, regular, and comprehensive eye examinations. (PKP)

Applications of Molecular Imaging

PubMed Central

Galbán, Craig; Galbán, Stefanie; Van Dort, Marcian; Luker, Gary D.; Bhojani, Mahaveer S.; Rehemtualla, Alnawaz; Ross, Brian D.

2015-01-01

Today molecular imaging technologies play a central role in clinical oncology. The use of imaging techniques in early cancer detection, treatment response and new therapy development is steadily growing and has already significantly impacted clinical management of cancer. In this chapter we will overview three different molecular imaging technologies used for the understanding of disease biomarkers, drug development, or monitoring therapeutic outcome. They are (1) optical imaging (bioluminescence and fluorescence imaging) (2) magnetic resonance imaging (MRI), and (3) nuclear imaging (e.g, single photon emission computed tomography (SPECT) and positron emission tomography (PET)). We will review the use of molecular reporters of biological processes (e.g. apoptosis and protein kinase activity) for high throughput drug screening and new cancer therapies, diffusion MRI as a biomarker for early treatment response and PET and SPECT radioligands in oncology. PMID:21075334

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

PubMed

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-04-14

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

PubMed Central

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-01-01

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma. PMID:24744577

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

PubMed Central

2010-01-01

Background Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials. PMID:20433705

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

PubMed

Furiak, Nicolas M; Klein, Robert W; Kahle-Wrobleski, Kristin; Siemers, Eric R; Sarpong, Eric; Klein, Timothy M

2010-04-30

Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

Screening Protocol for Early Identification of Brazilian Children at Risk for Dyslexia

PubMed Central

Germano, Giseli D.; César, Alexandra B. P. de C.; Capellini, Simone A.

2017-01-01

Early identification of students at risk of dyslexia has been an educational challenge in the past years. This research had two main goals. First, we aimed to develop a screening protocol for early identification of Brazilian children at risk for dyslexia; second, we aimed to identify the predictive variables of this protocol using Principal Component Analysis. The major step involved in developing this protocol was the selection of variables, which were chosen based on the literature review and linguistic criteria. The screening protocol was composed of seven cognitive-linguistic skills: Letter naming; Phonological Awareness (which comprises the following subtests: Rhyme production, Rhyme identification, Syllabic segmentation, Production of words from a given phoneme, Phonemic Synthesis, and Phonemic analysis); Phonological Working memory, Rapid naming Speed; Silent reading; Reading of words and non-words; and Auditory Comprehension of sentences from pictures. A total of 149 children, aged from 6 years to 6 and 11, of both genders who were enrolled in the 1st grade of elementary public schools were submitted to the screening protocol. Principal Component Analysis revealed four factors, accounting for 64.45% of the variance of the Protocol variables: first factor (“pre-reading”), second factor (“decoding”), third factor (“Reading”), and fourth factor “Auditory processing.” The factors found corroborate those reported in the National and International literature and have been described as early signs of dyslexia and reading problems. PMID:29163246

Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy

PubMed Central

Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven

2018-01-01

Objective To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579

Molecular basis of cystic fibrosis in Lithuania: incomplete CFTR mutation detection by PCR-based screening protocols.

PubMed

Giannattasio, S; Bobba, A; Jurgelevicius, V; Vacca, R A; Lattanzio, P; Merafina, R S; Utkus, A; Kucinskas, V; Marra, E

2006-01-01

Mutational analysis of the cystic fibrosis transmembrane regulator (CFTR) gene was performed in 98 unrelated CF chromosomes from 49 Lithuanian CF patients through a combined approach in which the p.F508del mutation was first screened by allele-specific PCR while CFTR mutations in nonp.F508del chromosomes have been screened for by denaturing gradient gel electrophoresis analysis. A CFTR mutation was characterized in 62.2% of CF chromosomes, two of which (2.0%) have been previously shown to carry a large gene deletion CFTRdele2,3(21 kb). The most frequent Lithuanian CF mutation is p.F508del (52.0%). Seven CFTR mutations, p.N1303K (2.0%), p.R75Q (1.0%), p.G314R (1.0%), p.R553X (4.2%), p.W1282X (1.0%), and g.3944delGT (1.0%), accounted for 10.1% of Lithuanian CF chromosomes. It was not possible to characterize 35.8% of the CF Lithuanian chromosomes. Analysis of intron 8 (TG)mTn and M470V polymorphic loci did not permit the characterization of the CFTR dysfunction underlying the CF phenotype in the patients for which no CFTR mutation was identified. Thus, screening of the eight CFTR mutations identified in this study and of the large deletion CFTRdele2,3(21 kb) allows the implementation of an early molecular or confirmatory CF diagnosis for 65% of Lithuanian CF chromosomes.

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

PubMed

Immanuel, Jincy; Simmons, David

2017-10-02

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

Investigating the Incremental Validity of Cognitive Variables in Early Mathematics Screening

ERIC Educational Resources Information Center

Clarke, Ben; Shanley, Lina; Kosty, Derek; Baker, Scott K.; Cary, Mari Strand; Fien, Hank; Smolkowski, Keith

2018-01-01

The purpose of this study was to investigate the incremental validity of a set of domain general cognitive measures added to a traditional screening battery of early numeracy measures. The sample consisted of 458 kindergarten students of whom 285 were designated as severely at-risk for mathematics difficulty. Hierarchical multiple regression…

The Effects of Using Touch-Screen Devices on Students' Molecular Visualization and Representational Competence Skills

ERIC Educational Resources Information Center

McCollum, Brett M.; Regier, Lisa; Leong, Jaque; Simpson, Sarah; Sterner, Shayne

2014-01-01

The impact of touch-screen technology on spatial cognitive skills as related to molecular geometries was assessed through 102 one-on-one interviews with undergraduate students. Participants were provided with either printed 2D ball-and-stick images of molecules or manipulable projections of 3D molecular structures on an iPad. Following a brief…

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size: Positive Implications for Future Targeted Screening.

PubMed

Hur, Chin; Tramontano, Angela C; Dowling, Emily C; Brooks, Gabriel A; Jeon, Alvin; Brugge, William R; Gazelle, G Scott; Kong, Chung Yin; Pandharipande, Pari V

2016-08-01

Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies. Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated. A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy. For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors.

PubMed

Braun, Glaucia H; Jorge, Daniel M M; Ramos, Henrique P; Alves, Raquel M; da Silva, Vinicius B; Giuliatti, Silvana; Sampaio, Suley Vilela; Taft, Carlton A; Silva, Carlos H T P

2008-02-01

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson's disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening.

PubMed

Behar, Doron M; Inbar, Ori; Shteinberg, Michal; Gur, Michal; Mussaffi, Huda; Shoseyov, David; Ashkenazi, Moshe; Alkrinawi, Soliman; Bormans, Concetta; Hakim, Fahed; Mei-Zahav, Meir; Cohen-Cymberknoh, Malena; Dagan, Adi; Prais, Dario; Sarouk, Ifat; Stafler, Patrick; Bar Aluma, Bat El; Akler, Gidon; Picard, Elie; Aviram, Micha; Efrati, Ori; Livnat, Galit; Rivlin, Joseph; Bentur, Lea; Blau, Hannah; Kerem, Eitan; Singer, Amihood

2017-05-01

Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients. An Israeli nationwide genotyping of 152 CF cases, representing 176 patients lacking molecular diagnosis, was conducted. Molecular analysis included Sanger sequencing for all exons and splice sites, multiplex ligation probe amplification (MLPA), and next-generation sequencing of the poly-T/TG tracts. We identified 54 different mutations, of which only 16 overlapped the 22 mutations included in the Israeli preconception screening program. A total of 29/54 (53.7%) mutations were already listed as CF causing by the CFTR2 database, and only 4/54 (7.4%) were novel. Molecular diagnosis was reached in 78/152 (51.3%) cases. Prenatal diagnosis of 24/78 (30.8%) cases could have been achieved by including all CFTR2-causing mutations in the Israeli panel. Our data reveal an overwhelming hidden abundance of CFTR gene mutations suggesting that expanded preconception carrier screening might achieve higher preconception detection rates.

Utility of High Throughput Screening Techniques to Predict Stability of Monoclonal Antibody Formulations During Early Stage Development.

PubMed

Goldberg, Deborah S; Lewus, Rachael A; Esfandiary, Reza; Farkas, David C; Mody, Neil; Day, Katrina J; Mallik, Priyanka; Tracka, Malgorzata B; Sealey, Smita K; Samra, Hardeep S

2017-08-01

Selecting optimal formulation conditions for monoclonal antibodies for first time in human clinical trials is challenging due to short timelines and reliance on predictive assays to ensure product quality and adequate long-term stability. Accelerated stability studies are considered to be the gold standard for excipient screening, but they are relatively low throughput and time consuming. High throughput screening (HTS) techniques allow for large amounts of data to be collected quickly and easily, and can be used to screen solution conditions for early formulation development. The utility of using accelerated stability compared to HTS techniques (differential scanning light scattering and differential scanning fluorescence) for early formulation screening was evaluated along with the impact of excipients of various types on aggregation of monoclonal antibodies from multiple IgG subtypes. The excipient rank order using quantitative HTS measures was found to correlate with accelerated stability aggregation rate ranking for only 33% (by differential scanning fluorescence) to 42% (by differential scanning light scattering) of the antibodies tested, due to the high intrinsic stability and minimal impact of excipients on aggregation rates and HTS data. Also explored was a case study of employing a platform formulation instead of broader formulation screening for early formulation development. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

[Screening interview for early detection of high-functioning autism spectrum disorders].

PubMed

Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge

2015-05-01

Various different questionnaires are available for the screening of autism spectrum disorders (ASD). These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process.

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

PubMed Central

Ballester, Pedro J.; Mangold, Martina; Howard, Nigel I.; Robinson, Richard L. Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B. O.

2012-01-01

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated Ki ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification. PMID:22933186

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.

PubMed

Ballester, Pedro J; Mangold, Martina; Howard, Nigel I; Robinson, Richard L Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B O

2012-12-07

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K(i) ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors.

PubMed

Yan, Guoyi; Hou, Manzhou; Luo, Jiang; Pu, Chunlan; Hou, Xueyan; Lan, Suke; Li, Rui

2018-02-01

Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5. © 2017 John Wiley & Sons A/S.

Consortium for Molecular Characterization of Screen-Detected Lesions Created: Eight Grants Awarded | Division of Cancer Prevention

Cancer.gov

The NCI has awarded eight grants to create the Consortium for Molecular Characterization of Screen-Detected Lesions. The consortium has seven molecular characterization laboratories (MCLs) and a coordinating center, and is supported by the Division of Cancer Prevention and the Division of Cancer Biology. | 7 laboratories and a coordinating center focused on identifying

Identification of critical chemical features for Aurora kinase-B inhibitors using Hip-Hop, virtual screening and molecular docking

NASA Astrophysics Data System (ADS)

Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; John, Shalini; Lee, Keun Woo

2011-01-01

This study was performed to find the selective chemical features for Aurora kinase-B inhibitors using the potent methods like Hip-Hop, virtual screening, homology modeling, molecular dynamics and docking. The best hypothesis, Hypo1 was validated toward a wide range of test set containing the selective inhibitors of Aurora kinase-B. Homology modeling and molecular dynamics studies were carried out to perform the molecular docking studies. The best hypothesis Hypo1 was used as a 3D query to screen the chemical databases. The screened molecules from the databases were sorted based on ADME and drug like properties. The selective hit compounds were docked and the hydrogen bond interactions with the critical amino acids present in Aurora kinase-B were compared with the chemical features present in the Hypo1. Finally, we suggest that the chemical features present in the Hypo1 are vital for a molecule to inhibit the Aurora kinase-B activity.

GPs views and understanding of PSA testing, screening and early detection; survey.

PubMed

Sutton, J; Melia, J; Kirby, M; Graffy, J; Moss, S

2016-05-01

There is currently no national prostate cancer screening programme in the UK. However, patients 50 years and older are entitled to a prostate specific antigen (PSA) test, if informed on the advantages and disadvantages of testing and their risk of cancer. The Prostate Cancer Risk Management Programme (PCRMP) provides this guidance. The aim of this study was to access GPs' views and understanding of PSA testing, prostate cancer screening and early detection. A total of 708 questionnaires were returned by GPs across two English regions in 2013 and the GP questionnaire responses were quantitatively analysed. In the 699 completed questionnaires, the majority of GPs were well informed about PSA testing, screening and early detection. Only 32% used guidelines for referral, 14% knew all age-specific PSA referral levels, 71% that Black men have a higher prostate cancer risk than White men (22% correctly answered threefold increase) and 82% that family history is a risk factor. A further 78% thought electronic prompts during consultation would encourage PCRMP guideline usage and 75% had never been offered a PSA test and prostate cancer educational course, of which 73% would like to attend a course. Only 23% were aware of the latest PSA screening evidence and 94% would like an update. Participating GPs seem to be well informed but need more information and tools to help follow recommended guidance. In particular, increased awareness of PCRMP guidelines especially by automated methods, further educational courses and evidence updates would be beneficial. © 2016 John Wiley & Sons Ltd.

The Student Risk Screening Scale for Early Childhood: An Initial Validation Study

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Oakes, Wendy Peia; Menzies, Holly Mariah; Major, Rebecca; Allegra, Laurie; Powers, Lisa; Schatschneider, Chris

2015-01-01

We report findings of two exploratory validation studies of a revised instrument: the "Student Risk Screening Scale for Early Childhood" version (SRSS-EC). The SRSS-EC was modified to reflect characteristics of externalizing and internalizing behaviors manifested by preschool-age children. In Study 1, we explored the reliability of…

Development of a tiered screening strategy for a molecular-initiating event: thyroperoxidase inhibition (SOT)

EPA Science Inventory

Adverse outcome pathway (AOP) analyses illustrate that some molecular-initiating events (MIEs) for thyroid disruption, including thyroperoxidase (TPO) inhibition, are not evaluated by current ToxCast/Tox21 high-throughput screening (HTS) assays. A novel HTS assay for TPO inhibiti...

Development of an Excel-based laboratory information management system for improving workflow efficiencies in early ADME screening.

PubMed

Lu, Xinyan

2016-01-01

There is a clear requirement for enhancing laboratory information management during early absorption, distribution, metabolism and excretion (ADME) screening. The application of a commercial laboratory information management system (LIMS) is limited by complexity, insufficient flexibility, high costs and extended timelines. An improved custom in-house LIMS for ADME screening was developed using Excel. All Excel templates were generated through macros and formulae, and information flow was streamlined as much as possible. This system has been successfully applied in task generation, process control and data management, with a reduction in both labor time and human error rates. An Excel-based LIMS can provide a simple, flexible and cost/time-saving solution for improving workflow efficiencies in early ADME screening.

Molecular clock of HIV-1 envelope genes under early immune selection

DOE PAGES

Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.; ...

2016-06-01

Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

Molecular clock of HIV-1 envelope genes under early immune selection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.

Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

Incidence and molecular characterization of Glucose-6-Phosphate Dehydrogenase deficiency among neonates for newborn screening in Chaozhou, China.

PubMed

Yang, H; Wang, Q; Zheng, L; Zhan, X-F; Lin, M; Lin, F; Tong, X; Luo, Z-Y; Huang, Y; Yang, L-Y

2015-06-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in southern China. The aim of this study is to assess the extent of this disease in Chinese neonates and determine its molecular characteristics using a novel molecular screening method. A total of 2500 neonates were routinely screened for G6PD deficiency using a modified fluorescent spot test (FST). PCR-high-resolution melting (HRM) analysis was then used for the molecular assay. The overall incidence of G6PD deficiency was 2.68% in our study cohort. Frequency in male population was 3.22% (44 neonates of 1365 male neonates), and in female population was 2.03% (23 neonates of 1135 female neonates). Of the 67 newborns suspected to be G6PD deficient based on FST (44 males, 23 females), 58 of 67 (87%) were detected with gene alterations. Seven kinds of mutations [c.95A>G, c.392G>T, c.493A>G, c.871G>A, c.1360C>T, c.1376G>T, and c.1388G>A] were identified by HRM analysis. Routine newborn screening in Chaozhou, China with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation. The usage of molecular diagnosis can favor the detection of heterozygotes which can be a supplement to regular newborn screening and useful for premarital and prenatal diagnosis for G6PD deficiency. © 2014 John Wiley & Sons Ltd.

Toxoplasmosis: Seroprevalence in pregnant women, and serological and molecular screening in neonatal umbilical cord blood.

PubMed

Shieh, Mahshad; Didehdar, Mojtaba; Hajihossein, Reza; Ahmadi, Farzam; Eslamirad, Zahra

2017-10-01

Toxoplasmosis is a common zoonotic disease that can also be transmitted from the mother to the embryo, with the risk of congenital infection varying around the world. The aim of this study was to screen pregnant women and their neonates for toxoplasmosis by serologic and molecular methods and assess the impact of risk factors associated with toxoplasmosis on the rate of congenital infection. This study was conducted at a regional maternity hospital in Arak, the capital of the Markazi Province in Iran, during a period of six months. All selected pregnant women (n=261) and the corresponding cord blood samples were serologically screened for toxoplasmosis, with seropositive samples also undergoing molecular testing. Demographic data, as well as information related to the risk factors associated with the transmission of the disease, were collected from mothers and their neonates. The detection of anti-Toxoplasma antibodies and the extraction of DNA from blood samples were conducted using commercial kits. Results showed that the sera of 87 maternal blood samples (33.3%) and 40 cord blood samples (15.3%) were positive for anti-Toxoplasma antibodies (IgG and/or IgM). Molecular screening of the seropositive samples only identified one positive cord blood sample. In other words, the diagnosis of congenital toxoplasmosis was definitive in only one neonate. There was no significant association between the risk of parasite transmission and neonatal seropositivity (p >0.05). Therefore, the results showed that the prevalence of congenital toxoplasmosis in the studied area was consistent with the global rate and suggest that the implementation of newborn screening and follow-up testing could help reduce the disease risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlations between Developmental Kindergarten Screenings and Early Reading Indicators One Year Later

ERIC Educational Resources Information Center

Coughlan-Mainard, Kelly A.

2012-01-01

School districts in the U.S. are mandated to identify young children with disabilities. Developmental screeners are typically used to screen for such skill deficits. Academic tests are used in older students. A significant challenge is identifying children with potential learning disabilities early in their school career. This study identifies a…

Children's Environmental Health in the Digital Era: Understanding Early Screen Exposure as a Preventable Risk Factor for Obesity and Sleep Disorders.

PubMed

Wolf, Candice; Wolf, Seth; Weiss, Miriam; Nino, Gustavo

2018-02-23

The quantity, accessibility and focus on child-targeted programming has exponentially increased since it entered American households in the early 1900s. It may have started with the television (TV), but technology has evolved and now fits in our pockets; as of 2017, 95% of American families own a smartphone. Availability and child-tailored content has subsequently led to a decrease in the age at initial screen exposure. The negative effects that accompany the current culture of early screen exposure are extensive and need to be considered as technology continues to enter the home and inundate social interactions. Increased levels of early screen exposure have been associated with decreased cognitive abilities, decreased growth, addictive behavior, poor school performance, poor sleep patterns, and increased levels of obesity. Research on the adverse effects of early screen exposure is mounting, but further epidemiological studies are still needed to inform prevention and regulation policies.

Accessible high-throughput virtual screening molecular docking software for students and educators.

PubMed

Jacob, Reed B; Andersen, Tim; McDougal, Owen M

2012-05-01

We survey low cost high-throughput virtual screening (HTVS) computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs) that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms.

The Role of Developmental Screening Practices in Early Diagnosis of Autism Spectrum Disorders: An Analysis of All-Payer Claims Data in New Hampshire

ERIC Educational Resources Information Center

Humphreys, Betsy P.

2013-01-01

Universal developmental screening during pediatric well child care detects early delays in development and is a critical gateway to early intervention for young children at risk for Autism Spectrum Disorders (ASD). Developmental screening practices are highly variable, and few studies have examined screening utilization for children at risk for…

Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

PubMed

Moshina, Nataliia; Sebuødegård, Sofie; Hofvind, Solveig

2017-06-01

We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers. Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007-2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ 2 test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age. The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend <0.05 for all). The recall rate increased, while rate of screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend <0.05 for all). High compression pressure was associated with higher odds of interval breast cancer compared with low compression pressure (1.89; 95% CI 1.43-2.48). High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

Advancing Early Detection of Autism Spectrum Disorder by Applying an Integrated Two-Stage Screening Approach

ERIC Educational Resources Information Center

Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

2010-01-01

Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence…

Pharmacophore modeling, virtual screening and molecular docking of ATPase inhibitors of HSP70.

PubMed

Sangeetha, K; Sasikala, R P; Meena, K S

2017-10-01

Heat shock protein 70 is an effective anticancer target as it influences many signaling pathways. Hence the study investigated the important pharmacophore feature required for ATPase inhibitors of HSP70 by generating a ligand based pharmacophore model followed by virtual based screening and subsequent validation by molecular docking in Discovery studio V4.0. The most extrapolative pharmacophore model (hypotheses 8) consisted of four hydrogen bond acceptors. Further validation by external test set prediction identified 200 hits from Mini Maybridge, Drug Diverse, SCPDB compounds and Phytochemicals. Consequently, the screened compounds were refined by rule of five, ADMET and molecular docking to retain the best competitive hits. Finally Phytochemical compounds Muricatetrocin B, Diacetylphiladelphicalactone C, Eleutheroside B and 5-(3-{[1-(benzylsulfonyl)piperidin-4-yl]amino}phenyl)- 4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid were obtained as leads to inhibit the ATPase activity of HSP70 in our findings and thus can be proposed for further in vitro and in vivo evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endoscopic Management of Early Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Screening, Diagnosis, and Therapy.

PubMed

di Pietro, Massimiliano; Canto, Marcia I; Fitzgerald, Rebecca C

2018-01-01

Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a survival at 5 years lower than 15%. Population screening by endoscopy is not cost-effective, but a number of alternative imaging and cell analysis technologies are under investigation. The ideal screening test should be inexpensive, well tolerated, and applicable to primary care. Over the past 10 years, significant progress has been made in endoscopic diagnosis and treatment of dysplasia (squamous and Barrett's), and early esophageal cancer using resection and ablation technologies supported by evidence from randomized controlled trials. We review the state-of-the-art technologies for early diagnosis and minimally invasive treatment, which together could reduce the burden of disease. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed Central

Ried, Karin; Eng, Peter; Sali, Avni

2017-01-01

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 out-of 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed

Ried, Karin; Eng, Peter; Sali, Avni

2017-08-27

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 outof 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with

Screening of tyrosinase inhibitors by capillary electrophoresis with immobilized enzyme microreactor and molecular docking.

PubMed

Cheng, Mengxia; Chen, Zilin

2017-02-01

A new method for screening tyrosinase inhibitors from traditional Chinese medicines (TCMs) was successfully developed by capillary electrophoresis with reliable online immobilized enzyme microreactor (IMER). In addition, molecular docking study has been used for supporting inhibition interaction between enzyme and inhibitors. The IMER of tyrosinase was constructed at the outlet of the capillary by using glutaraldehyde as cross-linker. The parameters including enzyme reaction, separation of the substrate and product, and the performance of immobilized tyrosinase were investigated systematically. Because of using short-end injection procedure, the product and substrate were effectively separated within 2 min. The immobilized tyrosinase could remain 80% active for 30 days at 4°C. The Michaelis-Menten constant of tyrosinase was determined as 1.78 mM. Kojic acid, a known tyrosinase inhibitor, was used as a model compound for the validation of the inhibitors screening method. The half-maximal inhibitory concentration of kojic acid was 5.55 μM. The method was successfully applied for screening tyrosinase inhibitors from 15 compounds of TCM. Four compounds including quercetin, kaempferol, bavachinin, and bakuchiol were found having inhibitory potentials. The results obtained in this work were supported by molecular docking study. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brief Report: Can Metrics of Reporting Bias Enhance Early Autism Screening Measures?

ERIC Educational Resources Information Center

Taylor, Cora M.; Vehorn, Alison; Noble, Hylan; Weitlauf, Amy S.; Warren, Zachary E.

2014-01-01

The goal of the current study was to develop and pilot the utility of two simple internal response bias metrics, over-reporting and under-reporting, in terms of additive clinical value within common screening practices for early detection of autism spectrum disorder risk. Participants were caregivers and children under 36 months of age (n = 145)…

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis

PubMed Central

Niccum, David E.; Billings, Joanne L.; Dunitz, Jordan M.; Khoruts, Alexander

2018-01-01

Background Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. Methods We analyzed prospectively collected results of colonoscopies initiated at age 40 years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30–39 years performed during the same time period at the Center. Results The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. Conclusions Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population. PMID:26851188

An Overview of Inflammatory Bowel Disease: General Consideration and Genetic Screening Approach in Diagnosis of Early Onset Subsets

PubMed Central

Nemati, Shahram; Teimourian, Shahram

2017-01-01

Inflammatory bowel disease (IBD) is the consequence of an aberrant hemostasis of the immune cells at the gut mucosal border. Based on clinical manifestation, laboratory tests, radiological studies, endoscopic and histological features, this disease is divided into three main types including Crohn’s disease (CD), Ulcerative colitis (UC), and IBDunclassified (IBD-U). IBD is frequently presented in adults, but about 20% of IBD cases are diagnosed during childhood called pediatric IBD (PIBD). Some patients in the latter group emerge the first symptoms during infancy or under 5 years of age named infantile and very early onset IBD (VEO-IBD), respectively. These subtypes make a small fraction of PIBD, but they have exclusive phenotypic and genetic characteristics such that they are accompanied by severe disease course and resistance to conventional therapy. In this context, understanding the underlying molecular pathology opens a promising field for individualized and effective treatment. Here, we describe current hypotheses on IBD pathophysiology then explain the new idea about genetic screening technology as a good potential approach to identify the causal variants early in the disease manifestation, which is especially important for the fast and accurate treatment of VEO-IBD. PMID:28638582

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

PubMed Central

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy.

PubMed

Bakken, Gregory A; Bell, Andrew S; Boehm, Markus; Everett, Jeremy R; Gonzales, Rosalia; Hepworth, David; Klug-McLeod, Jacquelyn L; Lanfear, Jeremy; Loesel, Jens; Mathias, John; Wood, Terence P

2012-11-26

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns.

Molecular Imaging: Current Status and Emerging Strategies

PubMed Central

Pysz, Marybeth A.; Gambhir, Sanjiv S.; Willmann, Jürgen K.

2011-01-01

In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use PET- or SPECT-based techniques. In ongoing preclinical research novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multimodality molecular imaging. Contrast-enhanced molecular ultrasound with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and ultrasound imaging with molecularly-targeted microbubbles are attractive strategies since they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and ultrasound modalities involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with ultrasound. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:20541650

A combined disc method with resazurin agar plate assay for early phenotypic screening of KPC, MBL and OXA-48 carbapenemases among Enterobacteriaceae.

PubMed

Teethaisong, Y; Eumkeb, G; Nakouti, I; Evans, K; Hobbs, G

2016-08-01

To validate a combined disc method along with resazurin chromogenic agar for early screening and differentiation of Klebsiella pneumoniae carbapenemase, metallo-β-lactamase and OXA-48 carbapenemase-producing Enterobacteriaceae. The combined disc test comprising of meropenem alone and with EDTA, phenylboronic acid or both EDTA and phenylboronic acid, and temocillin alone were evaluated with the resazurin chromogenic agar plate assay against a total of 86 molecularly confirmed Enterobacteriaceae clinical isolates (11 metallo-β-lactamases, eight Kl. pneumoniae carbapenemases, 11 OXA-48, 32 AmpC and 15 extended-spectrum-β-lactamase producers and nine co-producers of extended-spectrum-β-lactamase and AmpC). The inhibition zone diameters were measured and interpreted at 7 h for the presence of carbapenemase. All carbapenemase producers were phenotypically distinguished by this assay with 100% sensitivity and specificity. This early phenotypic method is very simple, inexpensive, and reliable in the detection and differentiation of carbapenemase-producing Enterobacteriaceae. It could be exploited in any microbiological laboratory for diagnosis of these recalcitrant bacteria. This assay poses excellent performance in discrimination of Kl. pneumoniae carbapenemase, metallo-β-lactamase and OXA-48 carbapenemases within 7 h, which is much faster than conventional disc diffusion methods. The rapid detection could help clinicians screen patients, control infection and provide epidemiological surveillance. © 2016 The Society for Applied Microbiology.

Early Education Screening Test Battery of Basic Skills Development: Criteria for Personalizing Programs.

ERIC Educational Resources Information Center

University City School District, MO.

The development and content of the Early Education Screening Test Battery are described elsewhere (TM 000 184). This report provides norms for the Gross Motor Test (GMO), Visual-Motor Integration (VMI), four scales of the Illinois Test of Psycholinguistic Abilities (ITPA), Peabody Picture Vocabulary Test (PPVT), and the Behavior Rating Scale…

Early Tertiary mammals from North Africa reinforce the molecular Afrotheria clade

PubMed Central

Tabuce, Rodolphe; Marivaux, Laurent; Adaci, Mohammed; Bensalah, Mustapha; Hartenberger, Jean-Louis; Mahboubi, Mohammed; Mebrouk, Fateh; Tafforeau, Paul; Jaeger, Jean-Jacques

2007-01-01

The phylogenetic pattern and timing of the radiation of mammals, especially the geographical origins of major crown clades, are areas of controversy among molecular biologists, morphologists and palaeontologists. Molecular phylogeneticists have identified an Afrotheria clade, which includes several taxa as different as tenrecs (Tenrecidae), golden moles (Chrysochloridae), elephant-shrews (Macroscelididae), aardvarks (Tubulidentata) and paenungulates (elephants, sea cows and hyracoids). Molecular data also suggest a Cretaceous African origin for Afrotheria within Placentalia followed by a long period of endemic evolution on the Afro-Arabian continent after the mid-Cretaceous Gondwanan breakup (approx. 105–25 Myr ago). However, there was no morphological support for such a natural grouping so far. Here, we report new dental and postcranial evidence of Eocene stem hyrax and macroscelidid from North Africa that, for the first time, provides a congruent phylogenetic view with the molecular Afrotheria clade. These new fossils imply, however, substantial changes regarding the historical biogeography of afrotheres. Their long period of isolation in Africa, as assumed by molecular inferences, is now to be reconsidered inasmuch as Eocene paenungulates and elephant-shrews are here found to be related to some Early Tertiary Euramerican ‘hyopsodontid condylarths’ (archaic hoofed mammals). As a result, stem members of afrotherian clades are not strictly African but also include some Early Paleogene Holarctic mammals. PMID:17329227

Children’s Environmental Health in the Digital Era: Understanding Early Screen Exposure as a Preventable Risk Factor for Obesity and Sleep Disorders

PubMed Central

Wolf, Candice; Wolf, Seth; Weiss, Miriam; Nino, Gustavo

2018-01-01

The quantity, accessibility and focus on child-targeted programming has exponentially increased since it entered American households in the early 1900s. It may have started with the television (TV), but technology has evolved and now fits in our pockets; as of 2017, 95% of American families own a smartphone. Availability and child-tailored content has subsequently led to a decrease in the age at initial screen exposure. The negative effects that accompany the current culture of early screen exposure are extensive and need to be considered as technology continues to enter the home and inundate social interactions. Increased levels of early screen exposure have been associated with decreased cognitive abilities, decreased growth, addictive behavior, poor school performance, poor sleep patterns, and increased levels of obesity. Research on the adverse effects of early screen exposure is mounting, but further epidemiological studies are still needed to inform prevention and regulation policies. PMID:29473855

The cost-effectiveness of using chronic kidney disease risk scores to screen for early-stage chronic kidney disease.

PubMed

Yarnoff, Benjamin O; Hoerger, Thomas J; Simpson, Siobhan K; Leib, Alyssa; Burrows, Nilka R; Shrestha, Sundar S; Pavkov, Meda E

2017-03-13

Better treatment during early stages of chronic kidney disease (CKD) may slow progression to end-stage renal disease and decrease associated complications and medical costs. Achieving early treatment of CKD is challenging, however, because a large fraction of persons with CKD are unaware of having this disease. Screening for CKD is one important method for increasing awareness. We examined the cost-effectiveness of identifying persons for early-stage CKD screening (i.e., screening for moderate albuminuria) using published CKD risk scores. We used the CKD Health Policy Model, a micro-simulation model, to simulate the cost-effectiveness of using CKD two published risk scores by Bang et al. and Kshirsagar et al. to identify persons in the US for CKD screening with testing for albuminuria. Alternative risk score thresholds were tested (0.20, 0.15, 0.10, 0.05, and 0.02) above which persons were assigned to receive screening at alternative intervals (1-, 2-, and 5-year) for follow-up screening if the first screening was negative. We examined incremental cost-effectiveness ratios (ICERs), incremental lifetime costs divided by incremental lifetime QALYs, relative to the next higher screening threshold to assess cost-effectiveness. Cost-effective scenarios were determined as those with ICERs less than $50,000 per QALY. Among the cost-effective scenarios, the optimal scenario was determined as the one that resulted in the highest lifetime QALYs. ICERs ranged from $8,823 per QALY to $124,626 per QALY for the Bang et al. risk score and $6,342 per QALY to $405,861 per QALY for the Kshirsagar et al. risk score. The Bang et al. risk score with a threshold of 0.02 and 2-year follow-up screening was found to be optimal because it had an ICER less than $50,000 per QALY and resulted in the highest lifetime QALYs. This study indicates that using these CKD risk scores may allow clinicians to cost-effectively identify a broader population for CKD screening with testing for albuminuria

A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

PubMed

Martin, Donel M; Katalinic, Natalie; Ingram, Anna; Schweitzer, Isaac; Smith, Deidre J; Hadzi-Pavlovic, Dusan; Loo, Colleen K

2013-12-01

Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Is health screening beneficial for early detection and prognostic improvement in pancreatic cancer?

PubMed

Kim, Eun Ran; Bae, Sun Youn; Lee, Kwang Hyuk; Lee, Kyu Taek; Son, Hee Jung; Rhee, Jong Chul; Lee, Jong Kyun

2011-06-01

The aim of this study was to evaluate the usefulness of health screening for early detection and improved prognosis in pancreatic cancer. Between 1995 and 2008, 176,361 examinees visited the Health Promotion Center (HPC). Twenty patients diagnosed with pancreatic cancer were enrolled. During the same period, 40 patients were randomly selected from 2,202 patients diagnosed with pancreatic cancer at the Out Patient Clinic (OPC) for comparison. Within the HPC group, 10 patients were initially suspected of having pancreatic cancer following abnormal ultrasonographic findings, and 9 patients had suspected cases following the detection of elevated serum CA 19-9. The curative resection rate was higher in the HPC group than in the OPC group (p=0.011). The median survival was longer in the HPC group than in the OPC group (p=0.000). However, there was no significant difference in the 3-year survival rate between the two groups. Asymptomatic patients (n=6/20) in the HPC group showed better curative resection and survival rates than symptomatic patients. However, the difference was not statistically significant. Health screening is somewhat helpful for improving the curative resection rate and median survival of patients with pancreatic cancer detected by screening tests. However, the benefit of this method in improving long-term survival is limited by how early the cancer is detected.

Design of efficient molecular organic light-emitting diodes by a high-throughput virtual screening and experimental approach

NASA Astrophysics Data System (ADS)

Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Duvenaud, David; MacLaurin, Dougal; Blood-Forsythe, Martin A.; Chae, Hyun Sik; Einzinger, Markus; Ha, Dong-Gwang; Wu, Tony; Markopoulos, Georgios; Jeon, Soonok; Kang, Hosuk; Miyazaki, Hiroshi; Numata, Masaki; Kim, Sunghan; Huang, Wenliang; Hong, Seong Ik; Baldo, Marc; Adams, Ryan P.; Aspuru-Guzik, Alán

2016-10-01

Virtual screening is becoming a ground-breaking tool for molecular discovery due to the exponential growth of available computer time and constant improvement of simulation and machine learning techniques. We report an integrated organic functional material design process that incorporates theoretical insight, quantum chemistry, cheminformatics, machine learning, industrial expertise, organic synthesis, molecular characterization, device fabrication and optoelectronic testing. After exploring a search space of 1.6 million molecules and screening over 400,000 of them using time-dependent density functional theory, we identified thousands of promising novel organic light-emitting diode molecules across the visible spectrum. Our team collaboratively selected the best candidates from this set. The experimentally determined external quantum efficiencies for these synthesized candidates were as large as 22%.

Design of efficient molecular organic light-emitting diodes by a high-throughput virtual screening and experimental approach.

PubMed

Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D; Duvenaud, David; Maclaurin, Dougal; Blood-Forsythe, Martin A; Chae, Hyun Sik; Einzinger, Markus; Ha, Dong-Gwang; Wu, Tony; Markopoulos, Georgios; Jeon, Soonok; Kang, Hosuk; Miyazaki, Hiroshi; Numata, Masaki; Kim, Sunghan; Huang, Wenliang; Hong, Seong Ik; Baldo, Marc; Adams, Ryan P; Aspuru-Guzik, Alán

2016-10-01

Virtual screening is becoming a ground-breaking tool for molecular discovery due to the exponential growth of available computer time and constant improvement of simulation and machine learning techniques. We report an integrated organic functional material design process that incorporates theoretical insight, quantum chemistry, cheminformatics, machine learning, industrial expertise, organic synthesis, molecular characterization, device fabrication and optoelectronic testing. After exploring a search space of 1.6 million molecules and screening over 400,000 of them using time-dependent density functional theory, we identified thousands of promising novel organic light-emitting diode molecules across the visible spectrum. Our team collaboratively selected the best candidates from this set. The experimentally determined external quantum efficiencies for these synthesized candidates were as large as 22%.

A Pipeline To Enhance Ligand Virtual Screening: Integrating Molecular Dynamics and Fingerprints for Ligand and Proteins.

PubMed

Spyrakis, Francesca; Benedetti, Paolo; Decherchi, Sergio; Rocchia, Walter; Cavalli, Andrea; Alcaro, Stefano; Ortuso, Francesco; Baroni, Massimo; Cruciani, Gabriele

2015-10-26

The importance of taking into account protein flexibility in drug design and virtual ligand screening (VS) has been widely debated in the literature, and molecular dynamics (MD) has been recognized as one of the most powerful tools for investigating intrinsic protein dynamics. Nevertheless, deciphering the amount of information hidden in MD simulations and recognizing a significant minimal set of states to be used in virtual screening experiments can be quite complicated. Here we present an integrated MD-FLAP (molecular dynamics-fingerprints for ligand and proteins) approach, comprising a pipeline of molecular dynamics, clustering and linear discriminant analysis, for enhancing accuracy and efficacy in VS campaigns. We first extracted a limited number of representative structures from tens of nanoseconds of MD trajectories by means of the k-medoids clustering algorithm as implemented in the BiKi Life Science Suite ( http://www.bikitech.com [accessed July 21, 2015]). Then, instead of applying arbitrary selection criteria, that is, RMSD, pharmacophore properties, or enrichment performances, we allowed the linear discriminant analysis algorithm implemented in FLAP ( http://www.moldiscovery.com [accessed July 21, 2015]) to automatically choose the best performing conformational states among medoids and X-ray structures. Retrospective virtual screenings confirmed that ensemble receptor protocols outperform single rigid receptor approaches, proved that computationally generated conformations comprise the same quantity/quality of information included in X-ray structures, and pointed to the MD-FLAP approach as a valuable tool for improving VS performances.

Breast Cancer Treatment in the Era of Molecular Imaging

PubMed Central

Edelhauser, Gundula; Funovics, Martin

2008-01-01

Summary Molecular imaging employs molecularly targeted probes to visualize and often quantify distinct disease-specific markers and pathways. Modalities like intravital confocal or multiphoton microscopy, near-infrared fluorescence combined with endoscopy, surface reflectance imaging, or fluorescence-mediated tomography, and radionuclide imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are increasingly used for small animal high-throughput screening, drug development and testing, and monitoring gene therapy experiments. In the clinical treatment of breast cancer, PET and SPECT as well as magnetic resonance-based molecular imaging are already established for the staging of distant disease and intrathoracic nodal status, for patient selection regarding receptor-directed treatments, and to gain early information about treatment efficacy. In the near future, reporter gene imaging during gene therapy and further spatial and qualitative characterization of the disease can become clinically possible with radionuclide and optical methods. Ultimately, it may be expected that every level of breast cancer treatment will be affected by molecular imaging, including screening. PMID:21048912

Preventing breast cancer in LMICs via screening and/or early detection: The real and the surreal.

PubMed

Dey, Subhojit

2014-08-10

To review the present status of breast cancer (BC) screening/early detection in low- and middle-income countries (LMICs) and identify the way forward, an open focused search for articles was undertaken in PubMed, Google Scholar and Google, and using a snowball technique, further articles were obtained from the reference list of initial search results. In addition, a query was put up on ResearchGate to obtain more references and find out the general opinion of experts on the topic. Experts were also personally contacted for their opinion. Breast cancer (BC) is the most common cancer in women in the world. The rise in incidence is highest in LMICs where the incidence has often been much lower than high-income countries. In spite of more women dying of cancer than pregnancy or childbirth related causes in LMICs, most of the focus and resources are devoted to maternal health. Also, the majority of women in LMICs present at late stages to a hospital to initiate treatment. A number of trials have been conducted in various LMICs regarding the use of clinical breast examination and mammography in various combinations to understand the best ways of implementing a population level screening/early detection of BC; nevertheless, more research in this area is badly needed for different LMIC specific contexts. Notably, very few LMICs have national level programs for BC prevention via screening/early detection and even stage reduction is not on the public health agenda. This is in addition to other barriers such as lack of awareness among women regarding BC and the presence of stigma, inappropriate attitudes and lack of following proper screening behavior, such as conducting breast self-examinations. The above is mixed with the apathy and lack of awareness of policy makers regarding the fact that BC prevention is much more cost-effective and humane than BC treatment. Implementation of population level programs for screening/early detection of BC, along with use of ways to improve

Preventing breast cancer in LMICs via screening and/or early detection: The real and the surreal

PubMed Central

Dey, Subhojit

2014-01-01

To review the present status of breast cancer (BC) screening/early detection in low- and middle-income countries (LMICs) and identify the way forward, an open focused search for articles was undertaken in PubMed, Google Scholar and Google, and using a snowball technique, further articles were obtained from the reference list of initial search results. In addition, a query was put up on ResearchGate to obtain more references and find out the general opinion of experts on the topic. Experts were also personally contacted for their opinion. Breast cancer (BC) is the most common cancer in women in the world. The rise in incidence is highest in LMICs where the incidence has often been much lower than high-income countries. In spite of more women dying of cancer than pregnancy or childbirth related causes in LMICs, most of the focus and resources are devoted to maternal health. Also, the majority of women in LMICs present at late stages to a hospital to initiate treatment. A number of trials have been conducted in various LMICs regarding the use of clinical breast examination and mammography in various combinations to understand the best ways of implementing a population level screening/early detection of BC; nevertheless, more research in this area is badly needed for different LMIC specific contexts. Notably, very few LMICs have national level programs for BC prevention via screening/early detection and even stage reduction is not on the public health agenda. This is in addition to other barriers such as lack of awareness among women regarding BC and the presence of stigma, inappropriate attitudes and lack of following proper screening behavior, such as conducting breast self-examinations. The above is mixed with the apathy and lack of awareness of policy makers regarding the fact that BC prevention is much more cost-effective and humane than BC treatment. Implementation of population level programs for screening/early detection of BC, along with use of ways to improve

Breast cancer screening

MedlinePlus

Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... performed to screen women to detect early breast cancer when it is more likely to be cured. ...

Sildenafil ameliorates right ventricular early molecular derangement during left ventricular pressure overload.

PubMed

Imai, Yousuke; Kariya, Taro; Iwakiri, Masaki; Yamada, Yoshitsugu; Takimoto, Eiki

2018-01-01

Right ventricular (RV) dysfunction following left ventricular (LV) failure is associated with poor prognosis. RV remodeling is thought initiated by the increase in the afterload of RV due to secondary pulmonary hypertension (PH) to impaired LV function; however, RV molecular changes might occur in earlier stages of the disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used to treat PH through their pulmonary vasorelaxation properties, have shown direct cardiac benefits, but their impacts on the RV in LV diseases are not fully determined. Here we show that RV molecular alterations occur early in the absence of RV hemodynamic changes during LV pressure-overload and are ameliorated by PDE5 inhibition. Two-day moderate LV pressure-overload (transverse aortic constriction) neither altered RV pressure/ function nor RV weight in mice, while it induced only mild LV hypertrophy. Importantly, pathological molecular features were already induced in the RV free wall myocardium, including up-regulation of gene markers for hypertrophy and inflammation, and activation of extracellular signal-regulated kinase (ERK) and calcineurin. Concomitant PDE5 inhibition (sildenafil) prevented induction of such pathological genes and activation of ERK and calcineurin in the RV as well as in the LV. Importantly, dexamethasone also prevented these RV molecular changes, similarly to sildenafil treatment. These results suggest the contributory role of inflammation to the early pathological interventricular interaction between RV and LV. The current study provides the first evidence for the novel early molecular cross-talk between RV and LV, preceding RV hemodynamic changes in LV disease, and supports the therapeutic strategy of enhancing cGMP signaling pathway to treat heart diseases.

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

PubMed

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

[Imaging of breast tissues changes--early detection, screening and problem solving].

PubMed

Wruk, Daniela

2008-04-01

In the industrialised countries breast cancer is the cancer with the highest prevalence and causes the highest rate of cancer deaths among women. In Switzerland alone, about 5000 newly diagnosed cases occur per year. Our three main diagnostic tools in imaging diseases of the breast in the setting of screening, early detection or problem solving are mammography, ultrasound and MRI with intravenous contrast application. The most important imaging technique is mammography, which as only method has shown evidence to be suitable for screening so far. As a major accomplishing imaging tool there is sonography, which in women under 30 years of age is the first method of choice in examination of the breasts. The MRI is able to provide additional information about the perfusion of tissue changes within the breast; because of its low specificity, however, it should cautiously be applied for specific questions.

Structure and screening in molecular and metallic hydrogen at high pressure

NASA Technical Reports Server (NTRS)

Wood, D. M.; Ashcroft, N. W.

1981-01-01

A variational wavefunction is used to express the (spin restricted) Hartree-Fock energy as reciprocal lattice sums for static lattice FCC monatomic hydrogen and diatomic Pa3 molecular hydrogen. In the monatomic phase the hydrogenic orbital range closely parallels the inverse Thomas-Fermi wavevector; the corresponding energy E has a minimum of -0.929 Ryd/electron at r sub s = 1.67. For the diatomic phase E(r sub s) is similar, but the constituent energies, screening, and bond length reflect a qualitative change in the nature of the solid at r sub s = 2.8. This change is interpreted in terms of a transition from protons as structural units (at high density) to weakly interacting models (at low density). Insensitivity of the total energy to a rapid fall in the bond length suggests association with the rotational transition where the rapid molecular orientations characteristic of high pressures disappear and the molecules rotate freely at low pressure.

Exploring barriers to the delivery of cervical cancer screening and early treatment services in Malawi: some views from service providers

PubMed Central

Munthali, Alister C; Ngwira, Bagrey M; Taulo, Frank

2015-01-01

Background Cervical cancer is the most common reproductive health cancer in Malawi. In most cases, women report to health facilities when the disease is in its advanced stage. In this study, we investigate service providers’ perceptions about barriers for women to access cervical cancer screening and early treatment services in Malawi. Methods We conducted in-depth interviews with 13 district coordinators and 40 service providers of cervical cancer screening and early treatment services in 13 districts in Malawi. The study was conducted in 2012. The district coordinators helped the research team identify the health facilities which were providing cervical cancer screening and early treatment services. Results Almost all informants reported that cervical cancer was a major public health problem in their districts and that prevention efforts for this disease were being implemented. They were aware of the test and treat approach using visual inspection with acetic acid (VIA). They, however, said that the delivery of cervical cancer screening and early treatment services was compromised because of factors such as gross shortage of staff, lack of equipment and supplies, the lack of supportive supervision, and the use of male service providers. Informants added that the lack of awareness about the disease among community members, long distances to health facilities, the lack of involvement of husbands, and prevailing misperceptions about the disease (eg, that it is caused by the exposure to the VIA process) affect the uptake of these services. Conclusion While progress has been made in the provision of cervical cancer screening and early treatment services in Malawi, a number of factors affect service delivery and uptake. There is a need to continue creating awareness among community members including husbands and also addressing identified barriers such as shortage of staff and supplies in order to improve uptake of services. PMID:25848229

An infrastructure to mine molecular descriptors for ligand selection on virtual screening.

PubMed

Seus, Vinicius Rosa; Perazzo, Giovanni Xavier; Winck, Ana T; Werhli, Adriano V; Machado, Karina S

2014-01-01

The receptor-ligand interaction evaluation is one important step in rational drug design. The databases that provide the structures of the ligands are growing on a daily basis. This makes it impossible to test all the ligands for a target receptor. Hence, a ligand selection before testing the ligands is needed. One possible approach is to evaluate a set of molecular descriptors. With the aim of describing the characteristics of promising compounds for a specific receptor we introduce a data warehouse-based infrastructure to mine molecular descriptors for virtual screening (VS). We performed experiments that consider as target the receptor HIV-1 protease and different compounds for this protein. A set of 9 molecular descriptors are taken as the predictive attributes and the free energy of binding is taken as a target attribute. By applying the J48 algorithm over the data we obtain decision tree models that achieved up to 84% of accuracy. The models indicate which molecular descriptors and their respective values are relevant to influence good FEB results. Using their rules we performed ligand selection on ZINC database. Our results show important reduction in ligands selection to be applied in VS experiments; for instance, the best selection model picked only 0.21% of the total amount of drug-like ligands.

Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery.

PubMed

Roth, Bryan L; Lopez, Estela; Beischel, Scott; Westkaemper, Richard B; Evans, Jon M

2004-05-01

Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at the "receptorome" (that portion of the proteome encoding receptors). An overview of the receptorome is given and various in silico, public-domain resources are described. Newly developed tools for the in silico mining of data derived from the National Institute of Mental Health Psychoactive Drug Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail. Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies.

Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

PubMed

Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

2014-09-01

Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting.

PubMed

Chen, Hongda; Werner, Simone; Butt, Julia; Zörnig, Inka; Knebel, Phillip; Michel, Angelika; Eichmüller, Stefan B; Jäger, Dirk; Waterboer, Tim; Pawlita, Michael; Brenner, Hermann

2016-03-29

Novel blood-based screening tests are strongly desirable for early detection of colorectal cancer (CRC). We aimed to identify and evaluate autoantibodies against tumor-associated antigens as biomarkers for early detection of CRC. 380 clinically identified CRC patients and samples of participants with selected findings from a cohort of screening colonoscopy participants in 2005-2013 (N=6826) were included in this analysis. Sixty-four serum autoantibody markers were measured by multiplex bead-based serological assays. A two-step approach with selection of biomarkers in a training set, and validation of findings in a validation set, the latter exclusively including participants from the screening setting, was applied. Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage CRC and advanced adenoma. Multi-marker combinations substantially increased sensitivity at the price of a moderate loss of specificity. Anti-TP53, anti-IMPDH2, anti-MDM2 and anti-MAGEA4 were consistently included in the best-performing 4-, 5-, and 6-marker combinations. This four-marker panel yielded a sensitivity of 26% (95% CI, 13-45%) for early stage CRC at a specificity of 90% (95% CI, 83-94%) in the validation set. Notably, it also detected 20% (95% CI, 13-29%) of advanced adenomas. Taken together, the identified biomarkers could contribute to the development of a useful multi-marker blood-based test for CRC early detection.

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

NASA Astrophysics Data System (ADS)

Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

2016-06-01

Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual

Clinical Perspective of 3D Total Body Photography for Early Detection and Screening of Melanoma.

PubMed

Rayner, Jenna E; Laino, Antonia M; Nufer, Kaitlin L; Adams, Laura; Raphael, Anthony P; Menzies, Scott W; Soyer, H Peter

2018-01-01

Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very promising prognosis. The methods that have been utilized for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging), and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi-the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilizing 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimize crucial early detection.

Infant and dyadic assessment in early community-based screening for autism spectrum disorder with the PREAUT grid.

PubMed

Olliac, Bertrand; Crespin, Graciela; Laznik, Marie-Christine; Cherif Idrissi El Ganouni, Oussama; Sarradet, Jean-Louis; Bauby, Colette; Dandres, Anne-Marie; Ruiz, Emeline; Bursztejn, Claude; Xavier, Jean; Falissard, Bruno; Bodeau, Nicolas; Cohen, David; Saint-Georges, Catherine

2017-01-01

The need for early treatment of autism spectrum disorders (ASD) necessitates early screening. Very few tools have been prospectively tested with infants of less than 12 months of age. The PREAUT grid is based on dyadic assessment through interaction and shared emotion and showed good metrics for predicting ASD in very-high-risk infants with West syndrome. We assessed the ability of the PREAUT grid to predict ASD in low-risk individuals by prospectively following and screening 12,179 infants with the PREAUT grid at four (PREAUT-4) and nine (PREAUT-9) months of age. A sample of 4,835 toddlers completed the Checklist for Autism in Toddlers (CHAT) at 24 months (CHAT-24) of age. Children who were positive at one screening (N = 100) were proposed a clinical assessment (including the Children Autism Rating Scale, a Developmental Quotient, and an ICD-10-based clinical diagnosis if appropriate) in the third year of life. A randomly selected sample of 1,100 individuals who were negative at all screenings was followed by the PMI team from three to five years of age to identify prospective false negative cases. The clinical outcome was available for 45% (N = 45) of positive children and 52.6% (N = 579) of negative children. Of the 100 children who screened positive, 45 received a diagnosis at follow-up. Among those receiving a diagnosis, 22 were healthy, 10 were diagnosed with ASD, seven with intellectual disability (ID), and six had another developmental disorder. Thus, 50% of infants positive at one screening subsequently received a neurodevelopmental diagnosis. The PREAUT grid scores were significantly associated with medium and high ASD risk status on the CHAT at 24 months (odds ratio of 12.1 (95%CI: 3.0-36.8), p < 0.001, at four months and 38.1 (95%CI: 3.65-220.3), p < 0.001, at nine months). Sensitivity (Se), specificity, negative predictive values, and positive predictive values (PPVs) for PREAUT at four or nine months, and CHAT at 24 months, were similar [PREAUT-4: Se

Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

PubMed Central

Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

2012-01-01

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

Feasibility and diagnostic accuracy of early mood screening to diagnose persisting clinical depression/anxiety disorder after stroke.

PubMed

Lees, Rosalind; Stott, David J; Quinn, Terence J; Broomfield, Niall M

2014-01-01

Depression/anxiety disorders are common after stroke and have a negative impact on outcomes. Guidelines recommend that all stroke survivors are screened for these problems. However, there is no consensus on timing or method of assessment. We investigated the feasibility and accuracy of a very early screening strategy and the diagnostic accuracy this has for depression/anxiety disorders at 1 month. Screening tools were Hospital Anxiety and Depression Scale (HADS) and Depression Intensity Scale Circles (DISCs); we also assessed cognition using the Montreal Cognitive Assessment (MoCA). Screening was offered to sequential stroke admissions. At 1 month we assessed for clinical depression/anxiety disorder using Mini-International Neuropsychiatric Interview (MINI) and retested screening tools. We described test accuracy of acute depression/anxiety screening for clinical diagnosis of depression/anxiety disorder at 1 month and described temporal change in screening test scores. We assessed feasibility by describing proportions that were able, agreed to and completed the screening tests. Over 4 months, 102/146 admissions were suitable for screening following initial medical assessment, 69 (68%) agreed to screening, of whom 33 (48%) required researcher assistance to complete the screening test battery. Median time to assessment was 2 days (IQR: 1-4). Early HADS suggested n = 9 (13%) with depression; DISCs n = 25 (37%). Median acute MoCA was 21/30. At 1 month, n = 61 (88%) provided data. Repeat scores showed improvement over time; HADS (anxiety) mean difference: 2.5 (95% CI: 1.2-3.7), HADS (depression) mean difference: 1.6 (95% CI: 0.3-2.9). MINI defined n = 12 (20%) with depression and n = 6 (10%) with anxiety disorder. Comparing baseline screening to 1-month clinical diagnosis, HADS sensitivity was 0.25 (95% CI: 0.09-0.53) and specificity 0.94 (95% CI: 0.84-0.98); DISCs sensitivity was 0.92 (95% CI: 0.65-0.99) and specificity 0.78 (95% CI: 0.64-0.87). Even amongst 'medically

Early screening of an infant's visual system

NASA Astrophysics Data System (ADS)

Costa, Manuel F. M.; Jorge, Jorge M.

1999-06-01

It is of utmost importance to the development of the child's visual system that she perceives clear focused retinal images. Furthermore if the refractive problems are not corrected in due time amblyopia may occur--myopia and hyperopia can only cause important problems in the future when they are significantly large, however for the astigmatism (rather frequent in infants) and anisometropia the problems tend to be more stringent. The early evaluation of the visual status of human infants is thus of critical importance. Photorefraction is a convenient technique for this kind of subjects. Essentially a light beam is delivered into the eyes. It is refracted by the ocular media, strikes the retina, focusing or not, reflects off and is collected by a camera. The photorefraction setup we established using new technological breakthroughs on the fields of imaging devices, digital image processing and fiber optics, allows a fast noninvasive evaluation of children visual status (refractive errors, accommodation, strabismus, ...). Results of the visual screening of a group of risk' child descents of blinds or amblyopes will be presented.

Rapid screening, separation, and detection of hydroxyl radical scavengers from total flavonoids of Ginkgo biloba leaves by chromatography combined with molecular devices.

PubMed

Wang, Jing; Zheng, Meizhu; Chen, Lina; Liu, Zhiqiang; Zhang, Yuchi; Liu, Chun-Ming; Liu, Shu

2016-11-01

Hydroxyl radicals are the most reactive free radical of human body, a strong contributor to tissue damage. In this study, liquid chromatography coupled to electrospray ionization mass spectrometry was applied to screen and identify hydroxyl radical scavengers from the total flavonoids of Ginkgo biloba leaves, and high-performance counter current chromatography was used to separate and isolate the active compounds. Furthermore, molecular devices were used to determine hydroxyl radical scavenging activities of the obtained hydroxyl radical scavengers and other flavonoids from G. biloba leaves. As a result, six compounds were screened as hydroxyl radical scavengers, but only three flavonoids, namely, rutin, cosmos glycosides and apigenin-7-O-Glu-4'-O-Rha, were isolated successfully from total flavonoids by high-performance counter current chromatography. The purities of the three obtained compounds were over 90%, respectively, as determined by liquid chromatography. Molecular devices with 96-well microplates evaluation indicated that the 50% scavenging concentration values of screened compounds were lower than that of other flavonoids, they performed greater hydroxyl radical scavenging activity, and the evaluation effects were consistent with the liquid chromatography with mass spectrometry screening results. Therefore, chromatography combined with molecular devices is a feasible and an efficient method for systematic screening, identification, isolation, and evaluation of bioactive components in mixture of botanical medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Moving from Survival to Healthy Survival through Child Health Screening and Early Intervention Services Under Rashtriya Bal Swasthya Karyakram (RBSK).

PubMed

Singh, Arun K; Kumar, Rakesh; Mishra, C K; Khera, Ajay; Srivastava, Anubhav

2015-11-01

For negating the impact of early adversities on the development and ensuring a healthy, dynamic future for all children, Ministry of Health and Family Welfare in 2013 launched a programme for child health screening and early intervention services as Rashtriya Bal Swasthya Karyakram (RBSK) which aims to improve the quality of life with special focus on improving cognition and survival outcomes for "at risk" children. It has a systemic approach of prevention, early identification and management of 30 health conditions distributed under 4Ds: Defects at birth, Diseases, Deficiencies and Developmental delays including Disabilities spread over birth to 18 y of age in a holistic manner. There is a dedicated 4 member Mobile Health team for community screening and a dedicated 14 member team at District Early Intervention Center (DEIC) for comprehensive management. Existing health infrastructure and personnel are also integrated and utilized in this endeavor. Defects at birth are screened at Delivery points, home visits by accredited social health activist (ASHA), Anganwadi centers and at schools. Developmental delays are evaluated at DEIC through a multidisciplinary team with interdisciplinary approach. Five thousand four hundred eighteen dedicated Mobile Health teams have screened a total of 12.19 crore children till Dec.14. From April to Dec. 2014, 4.20 crore children were screened, of which birth to 6-y-old children were 2.13 crore while 2.07 crore were from 6 to 18 y. 17.7 lakh children were referred to tertiary centers and 6.2 lakh availed tertiary care. 50.7 lakhs were found positive for 4Ds; 1.35 lakhs were birth defects. RBSK is a step towards universal health care for free assured services.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

NASA Astrophysics Data System (ADS)

Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics.

PubMed

Lau, Wan F; Withka, Jane M; Hepworth, David; Magee, Thomas V; Du, Yuhua J; Bakken, Gregory A; Miller, Michael D; Hendsch, Zachary S; Thanabal, Venkataraman; Kolodziej, Steve A; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S; Love, Robert; Charlton, Maura E; Hughes, Samantha; van Hoorn, Willem P; Mills, James E

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Marketing EPSDT to Clients: A Self-Instructional Module for Early Periodic Screening Diagnosis Treatment.

ERIC Educational Resources Information Center

Simon, John L.; McArdle, Patricia

Early and Periodic Screening, Diagnosis and Treatment (EPSDT) is a program of preventive health services available to individuals under 21 years of age who are eligible for Medicaid benefits. As of July 1, 1973, all states operating a Medicaid program were required to provide EPSDT services to all those eligible. The purpose of this module is to…

Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting

PubMed Central

Chen, Hongda; Werner, Simone; Butt, Julia; Zörnig, Inka; Knebel, Phillip; Michel, Angelika; Eichmüller, Stefan B.; Jäger, Dirk; Waterboer, Tim; Pawlita, Michael; Brenner, Hermann

2016-01-01

Novel blood-based screening tests are strongly desirable for early detection of colorectal cancer (CRC). We aimed to identify and evaluate autoantibodies against tumor-associated antigens as biomarkers for early detection of CRC. 380 clinically identified CRC patients and samples of participants with selected findings from a cohort of screening colonoscopy participants in 2005–2013 (N=6826) were included in this analysis. Sixty-four serum autoantibody markers were measured by multiplex bead-based serological assays. A two-step approach with selection of biomarkers in a training set, and validation of findings in a validation set, the latter exclusively including participants from the screening setting, was applied. Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage CRC and advanced adenoma. Multi-marker combinations substantially increased sensitivity at the price of a moderate loss of specificity. Anti-TP53, anti-IMPDH2, anti-MDM2 and anti-MAGEA4 were consistently included in the best-performing 4-, 5-, and 6-marker combinations. This four-marker panel yielded a sensitivity of 26% (95% CI, 13–45%) for early stage CRC at a specificity of 90% (95% CI, 83–94%) in the validation set. Notably, it also detected 20% (95% CI, 13–29%) of advanced adenomas. Taken together, the identified biomarkers could contribute to the development of a useful multi-marker blood-based test for CRC early detection. PMID:26909861

Overstating the evidence for lung cancer screening: the International Early Lung Cancer Action Program (I-ELCAP) study.

PubMed

Welch, H Gilbert; Woloshin, Steven; Schwartz, Lisa M; Gordis, Leon; Gøtzsche, Peter C; Harris, Russell; Kramer, Barnett S; Ransohoff, David F

2007-11-26

Last year, the New England Journal of Medicine ran a lead article reporting that patients with lung cancer had a 10-year survival approaching 90% if detected by screening spiral computed tomography. The publication garnered considerable media attention, and some felt that its findings provided a persuasive case for the immediate initiation of lung cancer screening. We strongly disagree. In this article, we highlight 4 reasons why the publication does not make a persuasive case for screening: the study had no control group, it lacked an unbiased outcome measure, it did not consider what is already known about this topic from previous studies, and it did not address the harms of screening. We conclude with 2 fundamental principles that physicians should remember when thinking about screening: (1) survival is always prolonged by early detection, even when deaths are not delayed nor any lives saved, and (2) randomized trials are the only way to reliably determine whether screening does more good than harm.

A rotation-translation invariant molecular descriptor of partial charges and its use in ligand-based virtual screening

PubMed Central

2014-01-01

Background Measures of similarity for chemical molecules have been developed since the dawn of chemoinformatics. Molecular similarity has been measured by a variety of methods including molecular descriptor based similarity, common molecular fragments, graph matching and 3D methods such as shape matching. Similarity measures are widespread in practice and have proven to be useful in drug discovery. Because of our interest in electrostatics and high throughput ligand-based virtual screening, we sought to exploit the information contained in atomic coordinates and partial charges of a molecule. Results A new molecular descriptor based on partial charges is proposed. It uses the autocorrelation function and linear binning to encode all atoms of a molecule into two rotation-translation invariant vectors. Combined with a scoring function, the descriptor allows to rank-order a database of compounds versus a query molecule. The proposed implementation is called ACPC (AutoCorrelation of Partial Charges) and released in open source. Extensive retrospective ligand-based virtual screening experiments were performed and other methods were compared with in order to validate the method and associated protocol. Conclusions While it is a simple method, it performed remarkably well in experiments. At an average speed of 1649 molecules per second, it reached an average median area under the curve of 0.81 on 40 different targets; hence validating the proposed protocol and implementation. PMID:24887178

Evaluation of the GADD45α-GFP GreenScreen HC assay for rapid and reliable in vitro early genotoxicity screening.

PubMed

Luzy, Anne-Pascale; Orsini, Nicolas; Linget, Jean-Michel; Bouvier, Guy

2013-11-01

Twenty-two of Galderma's proprietary compounds were tested in the GADD45α-GFP 'GreenScreen HC' assay (GS), the SOS-ChromoTest and the Mini-Ames to evaluate GSs performance for early genotoxicity screening purposes. Forty more characterized compounds were also tested, including antibiotics: metronidazole, clindamycin, tetracycline, lymecycline and neomycin; and catecholamines: resorcinol mequinol, hydroquinone, one aneugen carbendazim, one corticoid dexamethasone, one peroxisome proliferator-activated receptor rosiglitazone, one pesticide carbaryl and two further proprietary molecules with in vitro genotoxicity data. With proprietary molecules, this study concluded that the GS renders the SOS-ChromoTest obsolete for in vitro screening. The GS confirmed all results of the Mini-Ames test (100% concordance). Compared with the micronucleus test, the GS showed a concordance of 82%. With known compounds, the GS ranked the potency of positive results for catecholamines in accordance with other genotoxicity tests and showed very reproducible results. It confirmed positive results for carbendazim, for tetracycline antibiotics and for carbaryl. The GS produced negative results for metronidazole, a nitroreduction-specific bacterial mutagen, for dexamethasone (a non-genotoxic apoptosis inducer), for rosiglitazone (a GADD45γ promoter inducer) and for clindamycin and neomycin (inhibitors of macromolecular synthesis in bacteria). As such, the GS appears to be a reproducible, robust, specific and sensitive test for genotoxicity screening. Copyright © 2012 John Wiley & Sons, Ltd.

Screening for Cancer

Cancer.gov

Cancer screening is checking for cancer in people who don't have symptoms. Screening tests can help doctors find and treat several types of cancer early, but cancer screening can have harms as well as benefits.

Molecular-Simulation-Driven Fragment Screening for the Discovery of New CXCL12 Inhibitors.

PubMed

Martinez-Rosell, Gerard; Harvey, Matt J; De Fabritiis, Gianni

2018-03-26

Fragment-based drug discovery (FBDD) has become a mainstream approach in drug design because it allows the reduction of the chemical space and screening libraries while identifying fragments with high protein-ligand efficiency interactions that can later be grown into drug-like leads. In this work, we leverage high-throughput molecular dynamics (MD) simulations to screen a library of 129 fragments for a total of 5.85 ms against the CXCL12 monomer, a chemokine involved in inflammation and diseases such as cancer. Our in silico binding assay was able to recover binding poses, affinities, and kinetics for the selected library and was able to predict 8 mM-affinity fragments with ligand efficiencies higher than 0.3. All of the fragment hits present a similar chemical structure, with a hydrophobic core and a positively charged group, and bind to either sY7 or H1S68 pockets, where they share pharmacophoric properties with experimentally resolved natural binders. This work presents a large-scale screening assay using an exclusive combination of thousands of short MD adaptive simulations analyzed with a Markov state model (MSM) framework.

Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases.

PubMed

George, Rani; Kovak, Karen; Cox, Summer L

2015-06-01

Cascade genetic screening is a methodology for identifying and testing close blood relatives of individuals at increased risk for heritable conditions and follows a sequential process, minimizing testing costs and the number of family members who need to be tested. It offers considerable potential for cost savings and increased awareness of heritable conditions within families. CDC-classified Tier 1 genomic applications for hereditary breast and ovarian cancer syndrome (HBOC), Lynch Syndrome (LS), and familial hypercholesterolemia (FH) are recommended for clinical use and support the use of cascade genetic screening. Most individuals are unaware of their increased risk for heritable conditions such as HBOC, LS, and FH. Consistent implementation of cascade genetic screening could significantly increase awareness and prevention of heritable conditions. Limitations to effective implementation of cascade genetic screening include: insufficient genetic risk assessment and knowledge by a majority of healthcare providers without genetics credentials; a shortage of genetic specialists, especially in rural areas; a low rate of reimbursement for comprehensive genetic counseling services; and an individual focus on prevention by clinical guidelines and insurance coverage. The family-centric approach of cascade genetic screening improves prevention and early diagnosis of heritable diseases on a population health level. Cascade genetic screening could be better supported and augmented through changes in health policy.

[The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

PubMed

Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

2014-06-01

Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

Infant and dyadic assessment in early community-based screening for autism spectrum disorder with the PREAUT grid

PubMed Central

Crespin, Graciela; Laznik, Marie-Christine; Cherif Idrissi El Ganouni, Oussama; Sarradet, Jean-Louis; Bauby, Colette; Dandres, Anne-Marie; Ruiz, Emeline; Bursztejn, Claude; Xavier, Jean; Falissard, Bruno; Bodeau, Nicolas; Cohen, David; Saint-Georges, Catherine

2017-01-01

Background The need for early treatment of autism spectrum disorders (ASD) necessitates early screening. Very few tools have been prospectively tested with infants of less than 12 months of age. The PREAUT grid is based on dyadic assessment through interaction and shared emotion and showed good metrics for predicting ASD in very-high-risk infants with West syndrome. Methods We assessed the ability of the PREAUT grid to predict ASD in low-risk individuals by prospectively following and screening 12,179 infants with the PREAUT grid at four (PREAUT-4) and nine (PREAUT-9) months of age. A sample of 4,835 toddlers completed the Checklist for Autism in Toddlers (CHAT) at 24 months (CHAT-24) of age. Children who were positive at one screening (N = 100) were proposed a clinical assessment (including the Children Autism Rating Scale, a Developmental Quotient, and an ICD-10-based clinical diagnosis if appropriate) in the third year of life. A randomly selected sample of 1,100 individuals who were negative at all screenings was followed by the PMI team from three to five years of age to identify prospective false negative cases. The clinical outcome was available for 45% (N = 45) of positive children and 52.6% (N = 579) of negative children. Results Of the 100 children who screened positive, 45 received a diagnosis at follow-up. Among those receiving a diagnosis, 22 were healthy, 10 were diagnosed with ASD, seven with intellectual disability (ID), and six had another developmental disorder. Thus, 50% of infants positive at one screening subsequently received a neurodevelopmental diagnosis. The PREAUT grid scores were significantly associated with medium and high ASD risk status on the CHAT at 24 months (odds ratio of 12.1 (95%CI: 3.0–36.8), p < 0.001, at four months and 38.1 (95%CI: 3.65–220.3), p < 0.001, at nine months). Sensitivity (Se), specificity, negative predictive values, and positive predictive values (PPVs) for PREAUT at four or nine months, and CHAT at 24

Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false-positive findings.

PubMed

Chen, Hongda; Knebel, Phillip; Brenner, Hermann

2016-07-01

Search for biomarkers for early detection of cancer is a very active area of research, but most studies are done in clinical rather than screening settings. We aimed to empirically evaluate the role of study setting for early detection marker identification and validation. A panel of 92 candidate cancer protein markers was measured in 35 clinically identified colorectal cancer patients and 35 colorectal cancer patients identified at screening colonoscopy. For each case group, we selected 38 controls without colorectal neoplasms at screening colonoscopy. Single-, two- and three-marker combinations discriminating cases and controls were identified in each setting and subsequently validated in the alternative setting. In all scenarios, a higher number of predictive biomarkers were initially detected in the clinical setting, but a substantially lower proportion of identified biomarkers could subsequently be confirmed in the screening setting. Confirmation rates were 50.0%, 84.5%, and 74.2% for one-, two-, and three-marker algorithms identified in the screening setting and were 42.9%, 18.6%, and 25.7% for algorithms identified in the clinical setting. Validation of early detection markers of cancer in a true screening setting is important to limit the number of false-positive findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Specificity and Sensitivity Ratios of the Pediatric Language Acquisition Screening Tool for Early Referral-Revised.

ERIC Educational Resources Information Center

Sherman, Tracy; Shulman, Brian B.

1999-01-01

This study examined test characteristics of the Pediatric Language Acquisition Screening Tool for Early Referral-Revised (PLASTER-R), a set of developmental questionnaires for children 3 to 60 months of age. The PLASTER-R was moderately to highly successful in identifying children within normal limits for language development. Test-retest…

Cost-effectiveness of screening and treatment for bacterial vaginosis in early pregnancy among women at low risk for preterm birth.

PubMed

Kekki, Minnamaija; Kurki, Tapio; Kotomäki, Teija; Sintonen, Harri; Paavonen, Jorma

2004-01-01

Bacterial vaginosis (BV) is an important risk factor for preterm birth. BV is detected in 10-30% of pregnant women and is often asymptomatic. Treatment of BV during pregnancy seems to reduce the risk of preterm delivery among high-risk women. We performed a cost-effectiveness analysis of screening and treatment for BV in early pregnancy among asymptomatic women at low risk for preterm delivery. A decision tree was built with two arms. For the screening (and treatment) arm the probabilities were derived from our earlier randomized trial on screening and treatment for BV, consisting of BV-positive women treated with intravaginal clindamycin cream or placebo and also of BV-negative pregnant women. The probabilities of outcomes among these women were collected from antenatal clinic records and hospital records, and for the no-screening arm mainly from the Finnish Perinatal Statistics. The outcomes considered were preterm delivery, mode of delivery, peripartum infections and postpartum complications. The unit costs associated with these outcomes were mainly based on disease-related groups (DRGs). No-screening was compared with two screening programs (one with clindamycin, the other with metronidazole treatment) and subjected to sensitivity analyses. There was no significant difference between screening and no-screening strategies in the costs and in the rate of preterm deliveries but the screening strategy produced significantly fewer peripartum infections and postpartum complications. Sensitivity analyses suggested that the screening strategy may become cost-saving if the rate of preterm deliveries exceeds 3%. Screening and treatment for BV in early pregnancy may not reduce costs compared to no-screening in a population at low risk for preterm birth but would produce, at the same cost, more health benefits in terms of fewer peripartum infections and postpartum complications. However, it may be cost-saving if the rate of preterm deliveries is higher than 3%.

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

PubMed

Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

2015-01-01

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

Raman spectroscopy-based screening of hepatitis C and associated molecular changes

NASA Astrophysics Data System (ADS)

Bilal, Maria; Bilal, M.; Saleem, M.; Khan, Saranjam; Ullah, Rahat; Fatima, Kiran; Ahmed, M.; Hayat, Abbas; Shahzada, Shaista; Ullah Khan, Ehsan

2017-09-01

This study presents the optical screening of hepatitis C and its associated molecular changes in human blood sera using a partial least-squares regression model based on their Raman spectra. In total, 152 samples were tested through enzyme-linked immunosorbent assay for confirmation. This model utilizes minor spectral variations in the Raman spectra of the positive and control groups. Regression coefficients of this model were analyzed with reference to the variations in concentration of associated molecules in these two groups. It was found that trehalose, chitin, ammonia, and cytokines are positively correlated while lipids, beta structures of proteins, and carbohydrate-binding proteins are negatively correlated with hepatitis C. The regression vector yielded by this model is utilized to predict hepatitis C in unknown samples. This model has been evaluated by a cross-validation method, which yielded a correlation coefficient of 0.91. Moreover, 30 unknown samples were screened for hepatitis C infection using this model to test its performance. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve from these predictions were found to be 93.3%, 100%, 96.7%, and 1, respectively.

Interpretation of screen factor measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, T.; Uhl, J.T.; Prud'Homme, R.K.

1983-08-01

Screen viscometer measurements give different information about polymer molecular weight and molecular weight distribution than intrinsic viscosity or relative viscosity measurements. This study shows that conventional screen viscometers measure elongation flow properties of solutions, and that for flexible polymers such as polyacrylamides, a sharp transition in conformation from a coiled to a stretched state is observed, which occurs at a Deborah number of 0.5. Conventional screen viscometers operate just above this critical Deborah number. Evidence for this transition in polymer conformation comes from measurements on a modified screen viscometer, from extensive work by Durst and Interhal on the sudden pressuremore » jumps during flow of polyacrylamide solutions through porous media, and from polymer kinetic theory modeling of molecular deformation in flow. ll references.« less

Early detection versus primary prevention in the PLCO flexible sigmoidoscopy screening trial: Which has the greatest impact on mortality?

PubMed

Doroudi, Maryam; Schoen, Robert E; Pinsky, Paul F

2017-12-15

Screening for colorectal cancer (CRC) with flexible sigmoidoscopy (FS) has been shown to reduce CRC mortality. The current study examined whether the observed mortality reduction was due primarily to the prevention of incident CRC via removal of adenomatous polyps or to the early detection of cancer and improved survival. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomized 154,900 men and women aged 55 to 74 years. Individuals underwent FS screening at baseline and at 3 or 5 years versus usual care. CRC-specific survival was analyzed using Kaplan-Meier curves and proportional hazards modeling. The authors estimated the percentage of CRC deaths averted by early detection versus primary prevention using a model that applied intervention arm survival rates to CRC cases in the usual-care arm and vice versa. A total of 1008 cases of CRC in the intervention arm and 1291 cases of CRC in the usual-care arm were observed. Through 13 years of follow-up, there was no significant difference noted between the trial arms with regard to CRC-specific survival for all CRC (68% in the intervention arm vs 65% in the usual-care arm; P =.16) or proximal CRC (68% vs 62%, respectively; P = .11) cases; however, survival in distal CRC cases was found to be higher in the intervention arm compared with the usual-care arm (77% vs 66%; P<.0001). Within each arm, symptom-detected cases had significantly worse survival compared with screen-detected cases. Overall, approximately 29% to 35% of averted CRC deaths were estimated to be due to early detection and 65% to 71% were estimated to be due to primary prevention. CRC-specific survival was similar across arms in the PLCO trial, suggesting a limited role for early detection in preventing CRC deaths. Modeling suggested that approximately two-thirds of avoided deaths were due to primary prevention. Future CRC screening guidelines should emphasize primary prevention via the identification and removal of precursor

Moving beyond Screen Time: Redefining Developmentally Appropriate Technology Use in Early Childhood Education. Policy Brief

ERIC Educational Resources Information Center

Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

2014-01-01

Conversations about what constitutes "developmentally appropriate" use of technology in early childhood education have, to date, focused largely on a single, blunt measure--screen time--that fails to capture important nuances, such as what type of media a child is accessing and whether technology use is taking place solo or with peers.…

[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience].

PubMed

Bozkowa, K; Cabalska, B; Radomyska, B; Ołtarzewski, M; Lenartowska, I

1999-01-01

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the

Cancer Screening Practices Among Physicians in the National Breast and Cervical Cancer Early Detection Program

PubMed Central

Saraiya, Mona S.; Soman, Ashwini; Roland, Katherine B.; Yabroff, K. Robin; Miller, Jackie

2011-01-01

Abstract Background The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides low-income, uninsured women with screening and diagnostic services for breast and cervical cancer. Our study was conducted to describe the demographic and practice characteristics of participating and nonparticipating physicians, as well as their beliefs, adoption of new screening technologies, and recommendations for breast and cervical cancer screening. Methods From a 2006–2007 nationally representative survey, we identified 1,111 practicing primary care physicians who provide breast and cervical cancer screenings and assessed their recommendations using clinical vignettes related to screening initiation, frequency, and cessation. Responses of physicians participating in the NBCCEDP were compared with those from nonparticipating physicians. Results Of the physicians surveyed, 15% reported participation in the NBCCEDP, 65% were not participants, and 20% were not sure or did not respond to this question. Program physicians were significantly more likely to practice in multispecialty settings, in a rural location, and in a hospital or clinic setting and had more patients who were female and insured by Medicaid or uninsured compared with nonprogram physicians. Beliefs about the effectiveness of screening tools or procedures in reducing breast or cervical cancer mortality were similar by program participation. Adoption of new technologies, including digital mammography and human papillomavirus (HPV) testing, and making guideline-consistent recommendations for screening initiation, frequency, and cessation did not differ significantly by program participation. Conclusions Although there may be differences in physician characteristics and practice settings, the beliefs and screening practices for both breast and cervical cancer are similar between program and nonprogram providers. PMID:21774673

Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

PubMed

Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

2017-01-01

Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

Health Screening

MedlinePlus

Screenings are tests that look for diseases before you have symptoms. Screening tests can find diseases early, when they're easier ... Overweight and obesity Prostate cancer in men Which tests you need depends on your age, your sex, ...

The high throughput biomedicine unit at the institute for molecular medicine Finland: high throughput screening meets precision medicine.

PubMed

Pietiainen, Vilja; Saarela, Jani; von Schantz, Carina; Turunen, Laura; Ostling, Paivi; Wennerberg, Krister

2014-05-01

The High Throughput Biomedicine (HTB) unit at the Institute for Molecular Medicine Finland FIMM was established in 2010 to serve as a national and international academic screening unit providing access to state of the art instrumentation for chemical and RNAi-based high throughput screening. The initial focus of the unit was multiwell plate based chemical screening and high content microarray-based siRNA screening. However, over the first four years of operation, the unit has moved to a more flexible service platform where both chemical and siRNA screening is performed at different scales primarily in multiwell plate-based assays with a wide range of readout possibilities with a focus on ultraminiaturization to allow for affordable screening for the academic users. In addition to high throughput screening, the equipment of the unit is also used to support miniaturized, multiplexed and high throughput applications for other types of research such as genomics, sequencing and biobanking operations. Importantly, with the translational research goals at FIMM, an increasing part of the operations at the HTB unit is being focused on high throughput systems biological platforms for functional profiling of patient cells in personalized and precision medicine projects.

UCLA's Molecular Screening Shared Resource: enhancing small molecule discovery with functional genomics and new technology.

PubMed

Damoiseaux, Robert

2014-05-01

The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of leading-edge high throughput screening (HTS) services including drug discovery, chemical and functional genomics, and novel methods for nano and environmental toxicology. The MSSR is an open access environment with investigators from UCLA as well as from the entire globe. Industrial clients are equally welcome as are non-profit entities. The MSSR is a fee-for-service entity and does not retain intellectual property. In conjunction with the Center for Environmental Implications of Nanotechnology, the MSSR is unique in its dedicated and ongoing efforts towards high throughput toxicity testing of nanomaterials. In addition, the MSSR engages in technology development eliminating bottlenecks from the HTS workflow and enabling novel assays and readouts currently not available.

A method for fast safety screening of explosives in terms of crystal packing and molecular stability.

PubMed

Hu, Xiaohua; Chen, Nana; Li, Weichen

2016-07-01

Safety prediction is crucial to the molecular design or the material design of explosives, and the predictions based on any single factor alone will cause much inaccuracy, leading to a desire for a method on multi-bases. The presented proposes an improved method for fast screening explosive safety by combining a crystal packing factor and a molecular one, that is, steric hindrance against shear slide in crystal and molecular stability, denoted by intermolecular friction symbol (IFS) and bond dissociation energy (BDE) of trigger linkage respectively. Employing this BDE-IFS combined method, we understand the impact sensitivities of 24 existing explosives, and predict those of two energetic-energetic cocrystals of the observed CL-20/BTF and the supposed HMX/TATB. As a result, a better understanding is implemented by the combined method relative to molecular stability alone, verifying its improvement of more accurate predictions and the feasibility of IFS to graphically reflect molecular stacking in crystals. Also, this work verifies that the explosive safety is strongly related with its crystal stacking, which determines steric hindrance and influences shear slide.

Molecular Self-Assembly in a Poorly Screened Environment: F4TCNQ on Graphene/BN

PubMed Central

2015-01-01

We report a scanning tunneling microscopy and noncontact atomic force microscopy study of close-packed 2D islands of tetrafluorotetracyanoquinodimethane (F4TCNQ) molecules at the surface of a graphene layer supported by boron nitride. While F4TCNQ molecules are known to form cohesive 3D solids, the intermolecular interactions that are attractive for F4TCNQ in 3D are repulsive in 2D. Our experimental observation of cohesive molecular behavior for F4TCNQ on graphene is thus unexpected. This self-assembly behavior can be explained by a novel solid formation mechanism that occurs when charged molecules are placed in a poorly screened environment. As negatively charged molecules coalesce, the local work function increases, causing electrons to flow into the coalescing molecular island and increase its cohesive binding energy. PMID:26482218

The First Molecular Phylogeny of Strepsiptera (Insecta) Reveals an Early Burst of Molecular Evolution Correlated with the Transition to Endoparasitism

PubMed Central

McMahon, Dino P.; Hayward, Alexander; Kathirithamby, Jeyaraney

2011-01-01

A comprehensive model of evolution requires an understanding of the relationship between selection at the molecular and phenotypic level. We investigate this in Strepsiptera, an order of endoparasitic insects whose evolutionary biology is poorly studied. We present the first molecular phylogeny of Strepsiptera, and use this as a framework to investigate the association between parasitism and molecular evolution. We find evidence of a significant burst in the rate of molecular evolution in the early history of Strepsiptera. The evolution of morphological traits linked to parasitism is significantly correlated with the pattern in molecular rate. The correlated burst in genotypic-phenotypic evolution precedes the main phase of strepsipteran diversification, which is characterised by the return to a low and even molecular rate, and a period of relative morphological stability. These findings suggest that the transition to endoparasitism led to relaxation of selective constraint in the strepsipteran genome. Our results indicate that a parasitic lifestyle can affect the rate of molecular evolution, although other causal life-history traits correlated with parasitism may also play an important role. PMID:21738621

Evaluation of Standardized Instruments for Use in Universal Screening of Very Early School-Age Children: Suitability, Technical Adequacy, and Usability

ERIC Educational Resources Information Center

Miles, Sandra; Fulbrook, Paul; Mainwaring-Mägi, Debra

2018-01-01

Universal screening of very early school-age children (age 4-7 years) is important for early identification of learning problems that may require enhanced learning opportunity. In this context, use of standardized instruments is critical to obtain valid, reliable, and comparable assessment outcomes. A wide variety of standardized instruments is…

Molecular evidence of keratin and melanosomes in feathers of the Early Cretaceous bird Eoconfuciusornis.

PubMed

Pan, Yanhong; Zheng, Wenxia; Moyer, Alison E; O'Connor, Jingmai K; Wang, Min; Zheng, Xiaoting; Wang, Xiaoli; Schroeter, Elena R; Zhou, Zhonghe; Schweitzer, Mary H

2016-12-06

Microbodies associated with feathers of both nonavian dinosaurs and early birds were first identified as bacteria but have been reinterpreted as melanosomes. Whereas melanosomes in modern feathers are always surrounded by and embedded in keratin, melanosomes embedded in keratin in fossils has not been demonstrated. Here we provide multiple independent molecular analyses of both microbodies and the associated matrix recovered from feathers of a new specimen of the basal bird Eoconfuciusornis from the Early Cretaceous Jehol Biota of China. Our work represents the oldest ultrastructural and immunological recognition of avian beta-keratin from an Early Cretaceous (∼130-Ma) bird. We apply immunogold to identify protein epitopes at high resolution, by localizing antibody-antigen complexes to specific fossil ultrastructures. Retention of original keratinous proteins in the matrix surrounding electron-opaque microbodies supports their assignment as melanosomes and adds to the criteria employable to distinguish melanosomes from microbial bodies. Our work sheds new light on molecular preservation within normally labile tissues preserved in fossils.

Molecular evidence of keratin and melanosomes in feathers of the Early Cretaceous bird Eoconfuciusornis

PubMed Central

Pan, Yanhong; Zheng, Wenxia; Moyer, Alison E.; O’Connor, Jingmai K.; Zheng, Xiaoting; Wang, Xiaoli; Schroeter, Elena R.; Zhou, Zhonghe; Schweitzer, Mary H.

2016-01-01

Microbodies associated with feathers of both nonavian dinosaurs and early birds were first identified as bacteria but have been reinterpreted as melanosomes. Whereas melanosomes in modern feathers are always surrounded by and embedded in keratin, melanosomes embedded in keratin in fossils has not been demonstrated. Here we provide multiple independent molecular analyses of both microbodies and the associated matrix recovered from feathers of a new specimen of the basal bird Eoconfuciusornis from the Early Cretaceous Jehol Biota of China. Our work represents the oldest ultrastructural and immunological recognition of avian beta-keratin from an Early Cretaceous (∼130-Ma) bird. We apply immunogold to identify protein epitopes at high resolution, by localizing antibody–antigen complexes to specific fossil ultrastructures. Retention of original keratinous proteins in the matrix surrounding electron-opaque microbodies supports their assignment as melanosomes and adds to the criteria employable to distinguish melanosomes from microbial bodies. Our work sheds new light on molecular preservation within normally labile tissues preserved in fossils. PMID:27872291

A screening questionnaire for voice problems after treatment of early glottic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gogh, Christine D.L. van; Verdonck-de Leeuw, Irma M.; Boon-Kamma, Brigitte A.

Purpose: After treatment for early glottic cancer, a considerable number of patients end up with voice problems interfering with daily life activities. A 5-item screening questionnaire was designed for detection of voice impairment. The purpose of this study is to assess psychometric properties of this questionnaire in clinical practice. Methods and Materials: The questionnaire was completed by 110 controls without voice complaints and 177 patients after radiotherapy or laser surgery for early glottic cancer. Results: Based on normative data of the controls, a score of 5 or less on at least 1 of the 5 questions was considered to statemore » overall voice impairment. Reliability of the questionnaire proved to be good. Voice impairment was reported in 44% of the patients treated with radiotherapy vs. 29% of the patients treated with endoscopic laser surgery. Conclusions: The questionnaire proved to be a reliable, valid, and feasible method to detect voice impairment in daily life. The questionnaire is easy to fill in, and interpretation is straightforward. It is useful for both radiation oncologists and otorhinolaryngologists in their follow-up of patients treated for early glottic cancer.« less

Molecular Docking and Screening Studies of New Natural Sortase A Inhibitors

PubMed Central

Nitulescu, Georgiana; Nicorescu, Isabela Madalina; Olaru, Octavian Tudorel; Ungurianu, Anca; Mihai, Dragos Paul; Zanfirescu, Anca; Nitulescu, George Mihai; Margina, Denisa

2017-01-01

To date, multi-drug resistant bacteria represent an increasing health threat, with a high impact on mortality, morbidity, and health costs on a global scale. The ability of bacteria to rapidly and permanently acquire new virulence factors and drug-resistance elements requires the development of new antimicrobial agents and selection of new proper targets, such as sortase A. This specific bacterial target plays an important role in the virulence of many Gram-positive pathogens, and its inhibition should produce a mild evolutionary pressure which will not favor the development of resistance. A primary screening using a fluorescence resonance energy transfer assay was used to experimentally evaluate the inhibitory activity of several compounds on sortase A. Using molecular docking and structure-activity relationship analyses, several lead inhibitors were identified, which were further tested for antimicrobial activity using the well diffusion test and minimum inhibitory concentration. The toxicity was assessed using the Daphnia magna test and used as a future screening filter. Three natural compounds were identified in this study as promising candidates for further development into therapeutically useful anti-infective agents that could be used to treat infections caused by multi-drug resistant bacterial pathogens which include sortase A in their enzymatic set. PMID:29065551

Genarris: Random generation of molecular crystal structures and fast screening with a Harris approximation

NASA Astrophysics Data System (ADS)

Li, Xiayue; Curtis, Farren S.; Rose, Timothy; Schober, Christoph; Vazquez-Mayagoitia, Alvaro; Reuter, Karsten; Oberhofer, Harald; Marom, Noa

2018-06-01

We present Genarris, a Python package that performs configuration space screening for molecular crystals of rigid molecules by random sampling with physical constraints. For fast energy evaluations, Genarris employs a Harris approximation, whereby the total density of a molecular crystal is constructed via superposition of single molecule densities. Dispersion-inclusive density functional theory is then used for the Harris density without performing a self-consistency cycle. Genarris uses machine learning for clustering, based on a relative coordinate descriptor developed specifically for molecular crystals, which is shown to be robust in identifying packing motif similarity. In addition to random structure generation, Genarris offers three workflows based on different sequences of successive clustering and selection steps: the "Rigorous" workflow is an exhaustive exploration of the potential energy landscape, the "Energy" workflow produces a set of low energy structures, and the "Diverse" workflow produces a maximally diverse set of structures. The latter is recommended for generating initial populations for genetic algorithms. Here, the implementation of Genarris is reported and its application is demonstrated for three test cases.

Trypsin inhibitor screening in traditional Chinese medicine by using an immobilized enzyme microreactor in capillary and molecular docking study.

PubMed

Cheng, Mengxia; Chen, Zilin

2017-08-01

A trypsin immobilized enzyme microreactor was successfully prepared in capillary for studying enzyme kinetics of trypsin and online screening of trypsin inhibitors from traditional Chinese medicine through capillary electrophoresis. Trypsin was immobilized on the inner wall at the inlet of the capillary treated with polydopamine. The rest of the capillary was used as a separation channel. The parameters including the separation efficiency and the activity of immobilized trypsin were comprehensively evaluated. Under the optimal conditions, online screening of trypsin inhibitors each time can be carried out within 6 min. The Michaelis-Menten constant of immobilized trypsin was calculated to be 0.50 mM, which indicated high affinity of the immobilized trypsin for the substrate. The half-maximal inhibitory concentration of known inhibitor of benzamidine hydrochloride hydrate as a model inhibitor was 13.32 mM. The proposed method was successfully applied to screen trypsin inhibitors from 15 compounds of traditional Chinese medicine. It has been found that baicalin showed inhibitory potency. Molecular docking study well supported the experimental result by exhibiting molecular interaction between enzyme and inhibitors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile].

PubMed

Terrazas, Solana; Ibáñez, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga, María Isabel; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, Paz; Van De Wyngard, Vanessa; Ferreccio, Catterina

2015-01-01

Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. To describe the experience of implementing this new molecular test and present the main results of the study. Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

First-trimester screening for early and late preeclampsia using maternal characteristics, biomarkers, and estimated placental volume.

PubMed

Sonek, Jiri; Krantz, David; Carmichael, Jon; Downing, Cathy; Jessup, Karen; Haidar, Ziad; Ho, Shannon; Hallahan, Terrence; Kliman, Harvey J; McKenna, David

2018-01-01

Preeclampsia is a major cause of perinatal morbidity and mortality. First-trimester screening has been shown to be effective in selecting patients at an increased risk for preeclampsia in some studies. We sought to evaluate the feasibility of screening for preeclampsia in the first trimester based on maternal characteristics, medical history, biomarkers, and placental volume. This is a prospective observational nonintervention cohort study in an unselected US population. Patients who presented for an ultrasound examination between 11-13+6 weeks' gestation were included. The following parameters were assessed and were used to calculate the risk of preeclampsia: maternal characteristics (demographic, anthropometric, and medical history), maternal biomarkers (mean arterial pressure, uterine artery pulsatility index, placental growth factor, pregnancy-associated plasma protein A, and maternal serum alpha-fetoprotein), and estimated placental volume. After delivery, medical records were searched for the diagnosis of preeclampsia. Detection rates for early-onset preeclampsia (<34 weeks' gestation) and later-onset preeclampsia (≥34 weeks' gestation) for 5% and 10% false-positive rates using various combinations of markers were calculated. We screened 1288 patients of whom 1068 (82.99%) were available for analysis. In all, 46 (4.3%) developed preeclampsia, with 13 (1.22%) having early-onset preeclampsia and 33 (3.09%) having late-onset preeclampsia. Using maternal characteristics, serum biomarkers, and uterine artery pulsatility index, the detection rate of early-onset preeclampsia for either 5% or 10% false-positive rate was 85%. With the same protocol, the detection rates for preeclampsia with delivery <37 weeks were 52% and 60% for 5% and 10% false-positive rates, respectively. Based on maternal characteristics, the detection rates for late-onset preeclampsia were 15% and 48% for 5% and 10%, while for preeclampsia at ≥37 weeks' gestation the detection rates were 24

Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

PubMed

Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

2015-01-01

Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study

MLViS: A Web Tool for Machine Learning-Based Virtual Screening in Early-Phase of Drug Discovery and Development

PubMed Central

Korkmaz, Selcuk; Zararsiz, Gokmen; Goksuluk, Dincer

2015-01-01

Virtual screening is an important step in early-phase of drug discovery process. Since there are thousands of compounds, this step should be both fast and effective in order to distinguish drug-like and nondrug-like molecules. Statistical machine learning methods are widely used in drug discovery studies for classification purpose. Here, we aim to develop a new tool, which can classify molecules as drug-like and nondrug-like based on various machine learning methods, including discriminant, tree-based, kernel-based, ensemble and other algorithms. To construct this tool, first, performances of twenty-three different machine learning algorithms are compared by ten different measures, then, ten best performing algorithms have been selected based on principal component and hierarchical cluster analysis results. Besides classification, this application has also ability to create heat map and dendrogram for visual inspection of the molecules through hierarchical cluster analysis. Moreover, users can connect the PubChem database to download molecular information and to create two-dimensional structures of compounds. This application is freely available through www.biosoft.hacettepe.edu.tr/MLViS/. PMID:25928885

The Brief Early Childhood Screening Assessment: Preliminary Validity in Pediatric Primary Care.

PubMed

Fallucco, Elise M; Wysocki, Tim; James, Lauren; Kozikowski, Chelsea; Williams, Andre; Gleason, Mary M

Brief, well-validated instruments are needed to facilitate screening for early childhood behavioral and emotional problems (BEPs). The objectives of this study were to empirically reduce the length of the Early Childhood Screening Assessment (ECSA) and to assess the validity and reliability of this shorter tool. Using caregiver ECSA responses for 2467 children aged 36 to 60 months seen in primary care, individual ECSA items were ranked on a scale ranging from "absolutely retain" to "absolutely delete." Items were deleted sequentially beginning with "absolutely delete" and going up the item prioritization list, resulting in 35 shorter versions of the ECSA. A separate primary care sample (n = 69) of mothers of children aged 18 to 60 months was used to determine the sensitivity and specificity of each shorter ECSA version using psychiatric diagnosis on the Diagnostic Infant and Preschool Assessment as the gold standard. The version with the optimal balance of sensitivity, specificity, and length was selected as the Brief ECSA. Associations between Brief ECSA scores and other pertinent measures were evaluated to estimate reliability and validity. A 22-item measure reflected the best combination of brevity, sensitivity and specificity. A cutoff score of 9 or higher on the 22-item Brief ECSA demonstrated acceptable sensitivity (89%) and specificity (85%) for predicting a psychiatric diagnosis. Brief ECSA scores correlated significantly and in expected directions with scores on pertinent measures and with demographic variables. The results indicate that the Brief ECSA has sound psychometric properties for identifying young children with BEPs in primary care.

[The Battelle developmental inventory screening test for early detection of developmental disorders in cerebral palsy].

PubMed

Moraleda-Barreno, E; Romero-López, M; Cayetano-Menéndez, M J

2011-12-01

Cerebral palsy is usually associated with motor, cognitive, and language deficits, and with other disorders that cause disability in daily living skills, personal independence, social interaction and academic activities. Early detection of these deficits in the clinical setting is essential to anticipate and provide the child with the necessary support for adapting to the environment in all possible areas. The main objective of this study is to demonstrate that these deficits can be detected at an early age and comprehensively through the use of a brief development scale. We studied 100 children between 4 and 70 months old, half of them with cerebral palsy and the other half without any disorder. All subjects were evaluated using the Battelle Developmental Inventory screening test. We compared the developmental quotients in both groups and between the subjects with different motor impairments, using a simple prospective ex post facto design. The test detected statistically significant differences between the clinical group and the control group at all age levels. Statistically significant differences were also found between tetraplegia and other motor disorders. There were no differences by gender. The deficit in development associated with cerebral palsy can be quantified at early ages through the use of a brief development scale, thus we propose that the systematic implementation of protocols with this screening tool would be helpful for treatment and early intervention. This would also help in anticipating and establishing the means for the multidisciplinary actions required, and could provide guidance to other health professionals, to provide adequate school, social, and family support,. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with multi-channel fluorescence endoscopy.

PubMed

Oh, Gyungseok; Yoo, Su Woong; Jung, Yebin; Ryu, Yeon-Mi; Park, Youngrong; Kim, Sang-Yeob; Kim, Ki Hean; Kim, Sungjee; Myung, Seung-Jae; Chung, Euiheon

2014-05-01

Intravital imaging has provided molecular, cellular and anatomical insight into the study of tumor. Early detection and treatment of gastrointestinal (GI) diseases can be enhanced with specific molecular markers and endoscopic imaging modalities. We present a wide-field multi-channel fluorescence endoscope to screen GI tract for colon cancer using multiple molecular probes targeting matrix metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to colonic adenoma. The average target-to-background (T/B) ratios are 2.10 ± 0.28 and 1.78 ± 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap between the two molecular probes is 67.7 ± 8.4%. The presence of false negative indicates that even more number of targeting could increase the sensitivity of overall detection given heterogeneous molecular expression in tumors. Our approach indicates potential for the screening of small or flat lesions that are precancerous.

Understanding How Postnatal Depression Screening and Early Intervention Work in the Real World - A Singaporean Perspective.

PubMed

Lee, Theresa My; Bautista, Dianne; Chen, Helen Y

2016-10-01

Postnatal depression is a major public health problem with clearly established adverse effects in child outcomes. This study examines the 4-year outcomes of a screening and early intervention programme, in relation to improvement in symptoms, functioning and health quality of life. Women were prospectively recruited up to 6 months postdelivery, using the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool. High-scorers (EPDS >13), were offered psychiatric consultation, and those with borderline scores (EPDS 10-12) were provided counselling, and offered follow-up phone counselling by the assigned case manager. Outcome measures were obtained at baseline, and at 6 months or discharge if earlier, for levels of symptoms, functioning, and health quality of life. From 2008 to 2012, 5245 women were screened, with 307 (5.9%) women with EPDS >13 receiving intervention. Of these, 70.0% had depression, 4.6% anxiety and 3.4% psychosis. In the depression subgroup, the net change was improvement of 93.4% EPDS symptom scores, 92.2% Global Assessment of Functioning (GAF) scores, and 88.3% visual analogue scale (EQ VAS) health quality of life scores. Outcome scores across diagnostic categories demonstrated median changes of 10 points on EPDS, 20 points on GAF, and 25 points on EQ VAS, reflecting 73.9%, 36.4% and 41.7% change from baseline scores. Women with psychosis showed the biggest (80.0%) relative change in GAF functioning scores from baseline to discharge but had the lowest median change in EPDS symptom scores. A screening and intervention programme rightly-sited within an obstetric setting can improve clinical outcomes because of early detection and intervention.

Molecular Self-Assembly in a Poorly Screened Environment: F 4TCNQ on Graphene/BN

DOE PAGES

Tsai, Hsin-Zon; Omrani, Arash A.; Coh, Sinisa; ...

2015-10-20

Here we report a scanning tunneling microscopy and noncontact atomic force microscopy study of close-packed 2D islands of tetrafluoro-tetracyanoquinodimethane (F 4TCNQ) molecules at the surface of a graphene layer supported by boron nitride. While F 4TCNQ molecules are known to form cohesive 3D solids, the intermolecular interactions that are attractive for F 4TCNQ in 3D are repulsive in 2D. Our experimental observation of cohesive molecular behavior for F 4TCNQ on graphene is thus unexpected. This self-assembly behavior can be explained by a novel solid formation mechanism that occurs when charged molecules are placed in a poorly screened environment. As negativelymore » charged molecules coalesce, the local work function increases, causing electrons to flow into the coalescing molecular island and increase its cohesive binding energy.« less

Showing Value in Newborn Screening: Challenges in Quantifying the Effectiveness and Cost-Effectiveness of Early Detection of Phenylketonuria and Cystic Fibrosis

PubMed Central

Grosse, Scott D.

2015-01-01

Decision makers sometimes request information on the cost savings, cost-effectiveness, or cost-benefit of public health programs. In practice, quantifying the health and economic benefits of population-level screening programs such as newborn screening (NBS) is challenging. It requires that one specify the frequencies of health outcomes and events, such as hospitalizations, for a cohort of children with a given condition under two different scenarios—with or without NBS. Such analyses also assume that everything else, including treatments, is the same between groups. Lack of comparable data for representative screened and unscreened cohorts that are exposed to the same treatments following diagnosis can result in either under- or over-statement of differences. Accordingly, the benefits of early detection may be understated or overstated. This paper illustrates these common problems through a review of past economic evaluations of screening for two historically significant conditions, phenylketonuria and cystic fibrosis. In both examples qualitative judgments about the value of prompt identification and early treatment to an affected child were more influential than specific numerical estimates of lives or costs saved. PMID:26702401

A population-based screening program for early detection of common cancers among women in India - methodology and interim results.

PubMed

Mishra, G A; Dhivar, H D; Gupta, S D; Kulkarni, S V; Shastri, S S

2015-01-01

Cancers of the uterine cervix, breast, and oral cavity accounted for 134,420, 115,251, and 24,375 cases, respectively, and were responsible for 52.8% of the total cancers among women in India in 2008. The major objectives were to create awareness regarding common cancers among women, to detect pre-cancers of the uterine cervix and oral cavity, and early cancers of the breast, uterine cervix, and oral cavity, by conducting screening with simple, low-cost technology, within the community, and to facilitate confirmation of diagnosis among the screen positives and treatment and follow-up among the diagnosed cases. This is a community-based screening program for early detection of breast, uterine cervix, and oral cancers, being implemented among the socioeconomically disadvantaged women in Mumbai, India. The process involves selection of clusters, household surveys, health education, and screening the eligible women for breast, uterine cervix, and oral cancers, by primary healthcare workers, at a temporarily set-up clinic within the community. The program is planned to cover a 125,000 disadvantaged population in five years. Twenty-one thousand and fifteen people, with 4009 eligible women, have been covered to date. The compliance for screening for breast, cervix, and oral cavity has been 85, 70, and 88% and the screen positivity rates are 3.9, 14.9, and 3.9%, respectively. Twenty-seven oral pre-cancers, 25 cervix pre-cancers, one invasive cancer of the breast, two of the cervix, and one oral cavity cancer have been diagnosed among the screened women and all of them have complied with the treatment. The program is raising awareness about the common cancers and harms of tobacco among the disadvantaged women population in Mumbai. It is also helping in detecting pre-cancers and cancers among asymptomatic women and is assisting them in receiving treatment.

Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths.

PubMed

Abouk, Rahi; Grosse, Scott D; Ailes, Elizabeth C; Oster, Matthew E

2017-12-05

In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown. To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates. Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth. State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates. Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort. Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after

Early-onset group B streptococcal disease following culture-based screening in Japan: a single center study.

PubMed

Miyata, Akane; Takahashi, Hironori; Kubo, Takahiko; Watanabe, Noriyoshi; Tsukamoto, Keiko; Ito, Yushi; Sago, Haruhiko

2012-08-01

We investigated trends in early-onset group B streptococcal disease (EOD) after the introduction of culture-based screening in Japan. A retrospective cohort study examined EOD trends in 9506 pregnancies and 10 715 neonates at our center from 2002 to 2009. EOD occurred in four neonates (4/7332: 0.55/1000 live births). The EOD incidence among infants born to women positive for GBS by screening was 0.90 cases per 1000 live births (1/1107). In contrast, the EOD incidence among infants negative by GBS screening was 0.48 cases per 1000 live births (3/6225). Thus, of the four affected neonates, three had mothers who tested negative on antepartum GBS screening. Two neonates had symptoms of infection during labor and intrapartum antibiotic agents were administered. The other two neonates received no antibiotics because deliveries were uneventful and they were negative on GBS screening. The incidence of EOD is 0.90 cases per 1000 live births among GBS-positive women and 0.48 cases per 1000 live births among GBS-negative women. The results of our study implied that EOD can develop regardless of GBS screening and intrapartum clinical course, although the method of sample collection, indications for antibiotic prophylaxis, and the antibiotics regimen should be considered. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

The importance of retesting the hearing screening as an indicator of the real early hearing disorder.

PubMed

Silva, Daniela Polo Camargo da; Lopez, Priscila Suman; Ribeiro, Georgea Espíndola; Luna, Marcos Otávio de Mesquita; Lyra, João César; Montovani, Jair Cortez

2015-01-01

Early diagnosis of hearing loss minimizes its impact on child development. We studied factors that influence the effectiveness of screening programs. To investigate the relationship between gender, weight at birth, gestational age, risk factors for hearing loss, venue for newborn hearing screening and "pass" and "fail" results in the retest. Prospective cohort study was carried out in a tertiary referral hospital. The screening was performed in 565 newborns through transient evoked otoacoustic emissions in three admission units before hospital discharge and retest in the outpatient clinic. Gender, weight at birth, gestational age, presence of risk indicators for hearing loss and venue for newborn hearing screening were considered. Full-term infants comprised 86% of the cases, preterm 14%, and risk factors for hearing loss were identified in 11%. Considering the 165 newborns retested, only the venue for screening, Intermediate Care Unit, was related to "fail" result in the retest. Gender, weight at birth, gestational age and presence of risk factors for hearing loss were not related to "pass" and/or "fail" results in the retest. The screening performed in intermediate care units increases the chance of continued "fail" result in the Transient Otoacoustic Evoked Emissions test. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Sex chromosomal abnormalities associated with equine infertility: validation of a simple molecular screening tool in the Purebred Spanish Horse.

PubMed

Anaya, G; Molina, A; Valera, M; Moreno-Millán, M; Azor, P; Peral-García, P; Demyda-Peyrás, S

2017-08-01

Chromosomal abnormalities in the sex chromosome pair (ECAX and ECAY) are widely associated with reproductive problems in horses. However, a large proportion of these abnormalities remains undiagnosed due to the lack of an affordable diagnostic tool that allows for avoiding karyotyping tests. Hereby, we developed an STR (single-tandem-repeat)-based molecular method to determine the presence of the main sex chromosomal abnormalities in horses in a fast, cheap and reliable way. The frequency of five ECAX-linked (LEX026, LEX003, TKY38, TKY270 and UCDEQ502) and two ECAY-linked (EcaYH12 and SRY) markers was characterized in 261 Purebred Spanish Horses to determine the efficiency of the methodology developed to be used as a chromosomal diagnostic tool. All the microsatellites analyzed were highly polymorphic, with a sizeable number of alleles (polymorphic information content > 0.5). Based on this variability, the methodology showed 100% sensitivity and 99.82% specificity to detect the most important sex chromosomal abnormalities reported in horses (chimerism, Turner's syndrome and sex reversal syndromes). The method was also validated with 100% efficiency in 10 individuals previously diagnosed as chromosomally aberrant. This STR screening panel is an efficient and reliable molecular-cytogenetic tool for the early detection of sex chromosomal abnormalities in equines that could be included in breeding programs to save money, effort and time of veterinary practitioners and breeders. © 2017 Stichting International Foundation for Animal Genetics.

Performance of a docking/molecular dynamics protocol for virtual screening of nutlin-class inhibitors of Mdmx.

PubMed

Bharatham, Nagakumar; Finch, Kristin E; Min, Jaeki; Mayasundari, Anand; Dyer, Michael A; Guy, R Kiplin; Bashford, Donald

2017-06-01

A virtual screening protocol involving docking and molecular dynamics has been tested against the results of fluorescence polarization assays testing the potency of a series of compounds of the nutlin class for inhibition of the interaction between p53 and Mdmx, an interaction identified as a driver of certain cancers. The protocol uses a standard docking method (AutoDock) with a cutoff based on the AutoDock score (ADscore), followed by molecular dynamics simulation with a cutoff based on root-mean-square-deviation (RMSD) from the docked pose. An analysis of the experimental and computational results shows modest performance of ADscore alone, but dramatically improved performance when RMSD is also used. Published by Elsevier Inc.

Search for β2 Adrenergic Receptor Ligands by Virtual Screening via Grid Computing and Investigation of Binding Modes by Docking and Molecular Dynamics Simulations

PubMed Central

Bai, Qifeng; Shao, Yonghua; Pan, Dabo; Zhang, Yang; Liu, Huanxiang; Yao, Xiaojun

2014-01-01

We designed a program called MolGridCal that can be used to screen small molecule database in grid computing on basis of JPPF grid environment. Based on MolGridCal program, we proposed an integrated strategy for virtual screening and binding mode investigation by combining molecular docking, molecular dynamics (MD) simulations and free energy calculations. To test the effectiveness of MolGridCal, we screened potential ligands for β2 adrenergic receptor (β2AR) from a database containing 50,000 small molecules. MolGridCal can not only send tasks to the grid server automatically, but also can distribute tasks using the screensaver function. As for the results of virtual screening, the known agonist BI-167107 of β2AR is ranked among the top 2% of the screened candidates, indicating MolGridCal program can give reasonable results. To further study the binding mode and refine the results of MolGridCal, more accurate docking and scoring methods are used to estimate the binding affinity for the top three molecules (agonist BI-167107, neutral antagonist alprenolol and inverse agonist ICI 118,551). The results indicate agonist BI-167107 has the best binding affinity. MD simulation and free energy calculation are employed to investigate the dynamic interaction mechanism between the ligands and β2AR. The results show that the agonist BI-167107 also has the lowest binding free energy. This study can provide a new way to perform virtual screening effectively through integrating molecular docking based on grid computing, MD simulations and free energy calculations. The source codes of MolGridCal are freely available at http://molgridcal.codeplex.com. PMID:25229694

Lanthony 15-Hue Desaturated Test for screening of early color vision defects in uncomplicated juvenile diabetes.

PubMed

Giusti, C

2001-01-01

To identify the most appropriate test for screening of early color vision abnormalities in uncomplicated juvenile diabetes. Enrolled in this study were 39 diabetic adolescents, characterized by optimal Early Treatment Diabetic Retinopathy Study criteria for visual acuity, transparent dioptric means and angiographically normal retinas. Color vision was examined with Standard Pseudoisochromatic Plates (Part 2, SPP2), Roth 28-Hue Test (R28), Farnsworth-Munsell 100-Hue Tests (FM100), and Lanthony 15-Hue Desaturated Test (L15). Color confusion score (CCS) and desaturation angle (DSAT) were measured on L15 only. Thirty-nine normal subjects served as a control group. Poor metabolic control was an exclusion criteria. CCS was significantly higher in the patients than in the controls (37.8 +/- 11.1 vs 0 +/- P < .001) and normal scores were found in only 4 diabetic patients. DSAT values were spread, not showing a well-defined axis of the defect. The results of FM100 were clinically reliable but affected by a longer execution time. R28 and SPP2 demonstrated a low sensitivity, as all patients scored normally with both tests. Impaired color vision is a common observation even in patients with uncomplicated juvenile diabetes. Our results indicate that L15 is the most suitable test for screening of early color vision abnormalities in these subjects.

The Spatial Predilection for Early Esophageal Squamous Cell Neoplasia: A "Hot Zone" for Endoscopic Screening and Surveillance.

PubMed

Wang, Wen-Lun; Chang, I-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Lin, Jaw-Town; Mo, Lein-Ray; Wang, Hsiu-Po; Lee, Ching-Tai

2016-04-01

Early esophageal squamous cell neoplasias (ESCNs) are easily missed with conventional white-light endoscopy. This study aimed to assess whether early ESCNs have a spatial predilection and the patterns of recurrence after endoscopic treatment. We analyzed the circumferential and longitudinal location of early ESCNs, as well as their correlations with exposure to carcinogens in a cohort of 162 subjects with 248 early ESCNs; 219 of which were identified by screening and 29 by surveillance endoscopy. The circumferential location was identified using a clock-face orientation, and the longitudinal location was identified according to the distance from the incisor. The most common circumferential and longitudinal distributions of the early ESCNs were found in the 6 to 9 o'clock quadrant (38.5%) and at 26 to 30 cm from the incisor (41.3%), respectively. A total of 163 lesions (75%) were located in the lower hemisphere arc, and 149 (68.4%) were located at 26 to 35 cm from the incisor. One hundred eleven (51%) early ESCNs were centered within the "hot zone" (i.e., lower hemisphere arc of the esophagus at 26 to 35 cm from the incisor), which comprised 20% of the esophageal area. Exposure to alcohol, betel nut, or cigarette was risk factors for the development of early ESCNs in the lower hemisphere. After complete endoscopic treatment, the mean annual incidence of metachronous tumors was 10%. In addition, 43% of the metachronous recurrent neoplasias developed within the "hot zone." Cox regression analysis revealed that the index tumor within the hot zone (hazard ratio [HR]: 3.19; 95% confidence interval [CI]: 1.17-8.68; P = 0.02) and the presence of numerous Lugol-voiding lesions in the esophageal background mucosa were independent predictors for metachronous recurrence (HR: 4.61; 95% CI: 1.36-15.56; P = 0.01). We identified a hot zone that may be used to enhance the detection of early ESCNs during endoscopic screening and surveillance, especially in areas that

Identification of Novel Potential β-N-Acetyl-D-Hexosaminidase Inhibitors by Virtual Screening, Molecular Dynamics Simulation and MM-PBSA Calculations

PubMed Central

Liu, Jianling; Liu, Mengmeng; Yao, Yao; Wang, Jinan; Li, Yan; Li, Guohui; Wang, Yonghua

2012-01-01

Chitinolytic β-N-acetyl-d-hexosaminidases, as a class of chitin hydrolysis enzyme in insects, are a potential species-specific target for developing environmentally-friendly pesticides. Until now, pesticides targeting chitinolytic β-N-acetyl-d-hexosaminidase have not been developed. This study demonstrates a combination of different theoretical methods for investigating the key structural features of this enzyme responsible for pesticide inhibition, thus allowing for the discovery of novel small molecule inhibitors. Firstly, based on the currently reported crystal structure of this protein (OfHex1.pdb), we conducted a pre-screening of a drug-like compound database with 8 × 106 compounds by using the expanded pesticide-likeness criteria, followed by docking-based screening, obtaining 5 top-ranked compounds with favorable docking conformation into OfHex1. Secondly, molecular docking and molecular dynamics simulations are performed for the five complexes and demonstrate that one main hydrophobic pocket formed by residues Trp424, Trp448 and Trp524, which is significant for stabilization of the ligand–receptor complex, and key residues Asp477 and Trp490, are respectively responsible for forming hydrogen-bonding and π–π stacking interactions with the ligands. Finally, the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analysis indicates that van der Waals interactions are the main driving force for the inhibitor binding that agrees with the fact that the binding pocket of OfHex1 is mainly composed of hydrophobic residues. These results suggest that screening the ZINC database can maximize the identification of potential OfHex1 inhibitors and the computational protocol will be valuable for screening potential inhibitors of the binding mode, which is useful for the future rational design of novel, potent OfHex1-specific pesticides. PMID:22605995

Very early screening for sleep-disordered breathing in acute coronary syndrome in patients without acute heart failure.

PubMed

Van den Broecke, Sandra; Jobard, Olivier; Montalescot, Gilles; Bruyneel, Marie; Ninane, Vincent; Arnulf, Isabelle; Similowski, Thomas; Attali, Valérie

2014-12-01

Obstructive sleep apnea (OSA) is frequently associated with acute coronary syndrome (ACS). Screening of sleep-disordered breathing (SDB) has not been previously evaluated in ACS within 72 h in intensive care settings and its management could potentially enhance patients' prognosis. This pilot study assessed the feasibility of SDB screening at the early phase of ACS. All consecutive patients admitted to the coronary care unit (CCU) for ACS without acute heart failure underwent one overnight-attended polysomnography (PSG) within 72 h after admission. A telemonitoring (TM) system was set up to remotely monitor the signals and repair faulty sensors. The 27 recordings were analyzed as respiratory polygraphy (RP) and as PSG, and the results were compared. The TM system allowed successful intervention in 48% of recordings, resulting in excellent quality PSG for 89% of cases. The prevalence of SDB [apnea-hypopnea index (AHI) ≥ 15/h] was 82% and mainly consisted of central SDB and periodic breathing, except three patients with OSA. Compared with PSG, RP underestimated AHI, probably due to the poor sleep efficiency, reduction of slow-wave sleep, and alteration of rapid eye movement sleep. An early SDB screening by remote-attended PSG is feasible in ACS patients shortly after admission to CCU. The TM enhanced the quality of PSG. A high prevalence of central SDB was noticed, for which the etiology remains unknown. Further large-scale studies are needed to determine whether central SDB is an incidental finding in early ACS and whether the presence and severity of SDB have a prognostic impact. Copyright © 2014 Elsevier B.V. All rights reserved.

Terahertz imaging for early screening of diabetic foot syndrome: A proof of concept

NASA Astrophysics Data System (ADS)

Hernandez-Cardoso, G. G.; Rojas-Landeros, S. C.; Alfaro-Gomez, M.; Hernandez-Serrano, A. I.; Salas-Gutierrez, I.; Lemus-Bedolla, E.; Castillo-Guzman, A. R.; Lopez-Lemus, H. L.; Castro-Camus, E.

2017-02-01

Most people with diabetes suffer some deterioration of the feet. Diabetic foot syndrome causes ulceration in about 15% of cases and such deterioration leads to amputation in about 2.5% of diabetic patients, diminishing their quality of life and generating extraordinary costs for patients and public health systems. Currently, there is no objective method for the detection of diabetic foot syndrome in its early stages. We propose terahertz imaging as a method for the evaluation of such deterioration. This screening method could aid the prevention and medical treatment of this condition in the future.

Formaldehyde in Absorption: Tracing Molecular Gas in Early-Type Galaxies

NASA Astrophysics Data System (ADS)

Dollhopf, Niklaus M.; Donovan Meyer, Jennifer

2016-01-01

Early-Type Galaxies (ETGs) have been long-classified as the red, ellipsoidal branch of the classic Hubble tuning fork diagram of galactic structure. In part with this classification, ETGs are thought to be molecular and atomic gas-poor with little to no recent star formation. However, recent efforts have questioned this ingrained classification. Most notably, the ATLAS3D survey of 260 ETGs within ~40 Mpc found 22% contain CO, a common tracer for molecular gas. The presence of cold molecular gas also implies the possibility for current star formation within these galaxies. Simulations do not accurately predict the recent observations and further studies are necessary to understand the mechanisms of ETGs.CO traces molecular gas starting at densities of ~102 cm-3, which makes it a good tracer of bulk molecular gas, but does little to constrain the possible locations of star formation within the cores of dense molecular gas clouds. Formaldehyde (H2CO) traces molecular gas on the order of ~104 cm-3, providing a further constraint on the location of star-forming gas, while being simple enough to possibly be abundant in gas-poor ETGs. In cold molecular clouds at or above ~104 cm-3 densities, the structure of formaldehyde enables a phenomenon in which rotational transitions have excitation temperatures driven below the temperature of the cosmic microwave background (CMB), ~2.7 K. Because the CMB radiates isotropically, formaldehyde can be observed in absorption, independent of distance, as a tracer of moderately-dense molecular clouds and star formation.This novel observation technique of formaldehyde was incorporated for observations of twelve CO-detected ETGs from the ATLAS3D sample, including NGC 4710 and PGC 8815, to investigate the presence of cold molecular gas, and possible star formation, in ETGs. We present images from the Very Large Array, used in its C-array configuration, of the J = 11,0 - 11,1 transition of formaldehyde towards these sources. We report our

Validation of periodontitis screening model using sociodemographic, systemic, and molecular information in a Korean population.

PubMed

Kim, Hyun-Duck; Sukhbaatar, Munkhzaya; Shin, Myungseop; Ahn, Yoo-Been; Yoo, Wook-Sung

2014-12-01

This study aims to evaluate and validate a periodontitis screening model that includes sociodemographic, metabolic syndrome (MetS), and molecular information, including gingival crevicular fluid (GCF), matrix metalloproteinase (MMP), and blood cytokines. The authors selected 506 participants from the Shiwha-Banwol cohort: 322 participants from the 2005 cohort for deriving the screening model and 184 participants from the 2007 cohort for its validation. Periodontitis was assessed by dentists using the community periodontal index. Interleukin (IL)-6, IL-8, and tumor necrosis factor-α in blood and MMP-8, -9, and -13 in GCF were assayed using enzyme-linked immunosorbent assay. MetS was assessed by physicians using physical examination and blood laboratory data. Information about age, sex, income, smoking, and drinking was obtained by interview. Logistic regression analysis was applied to finalize the best-fitting model and validate the model using sensitivity, specificity, and c-statistics. The derived model for periodontitis screening had a sensitivity of 0.73, specificity of 0.85, and c-statistic of 0.86 (P <0.001); those of the validated model were 0.64, 0.91, and 0.83 (P <0.001), respectively. The model that included age, sex, income, smoking, drinking, and blood and GCF biomarkers could be useful in screening for periodontitis. A future prospective study is indicated for evaluating this model's ability to predict the occurrence of periodontitis.

Breast cancer in the 21st century: from early detection to new therapies.

PubMed

Merino Bonilla, J A; Torres Tabanera, M; Ros Mendoza, L H

The analysis of the causes that have given rise to a change in tendency in the incidence and mortality rates of breast cancer in the last few decades generates important revelations regarding the role of breast screening, the regular application of adjuvant therapies and the change of risk factors. The benefits of early detection have been accompanied by certain adverse effects, even in terms of an excessive number of prophylactic mastectomies. Recently, several updates have been published on the recommendations in breast cancer screening at an international level. On the other hand, the advances in genomics have made it possible to establish a new molecular classification of breast cancer. Our aim is to present an updated overview of the epidemiological situation of breast cancer, as well as some relevant issues from the point of view of diagnosis, such as molecular classification and different strategies for both population-based and opportunistic screening. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis.

PubMed

Wang, Long; Hu, Ya-Qian; Zhao, Zhuo-Jie; Zhang, Hong-Yang; Gao, Bo; Lu, Wei-Guang; Xu, Xiao-Long; Lin, Xi-Sheng; Wang, Jin-Peng; Jie, Qiang; Luo, Zhuo-Jing; Yang, Liu

2017-12-01

Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.

Early Dysphagia Screening by Trained Nurses Reduces Pneumonia Rate in Stroke Patients: A Clinical Intervention Study.

PubMed

Palli, Christoph; Fandler, Simon; Doppelhofer, Kathrin; Niederkorn, Kurt; Enzinger, Christian; Vetta, Christian; Trampusch, Esther; Schmidt, Reinhold; Fazekas, Franz; Gattringer, Thomas

2017-09-01

Dysphagia is a common stroke symptom and leads to serious complications such as aspiration and pneumonia. Early dysphagia screening can reduce these complications. In many hospitals, dysphagia screening is performed by speech-language therapists who are often not available on weekends/holidays, which results in delayed dysphagia assessment. We trained the nurses of our neurological department to perform formal dysphagia screening in every acute stroke patient by using the Gugging Swallowing Screen. The impact of a 24/7 dysphagia screening (intervention) over swallowing assessment by speech-language therapists during regular working hours only was compared in two 5-month periods with time to dysphagia screening, pneumonia rate, and length of hospitalization as outcome variables. Overall, 384 patients (mean age, 72.3±13.7 years; median National Institutes of Health Stroke Scale score of 3) were included in the study. Both groups (pre-intervention, n=198 versus post-intervention, n=186) were comparable regarding age, sex, and stroke severity. Time to dysphagia screening was significantly reduced in the intervention group (median, 7 hours; range, 1-69 hours) compared with the control group (median, 20 hours; range, 1-183; P =0.001). Patients in the intervention group had a lower rate of pneumonia (3.8% versus 11.6%; P =0.004) and also a reduced length of hospital stay (median, 8 days; range, 2-40 versus median, 9 days; range, 1-61 days; P =0.033). 24/7 dysphagia screening can be effectively performed by nurses and leads to reduced pneumonia rates. Therefore, empowering nurses to do a formal bedside screening for swallowing dysfunction in stroke patients timely after admission is warranted whenever speech-language therapists are not available. © 2017 American Heart Association, Inc.

Consumer preferences for teledermoscopy screening to detect melanoma early.

PubMed

Spinks, Jean; Janda, Monika; Soyer, H Peter; Whitty, Jennifer A

2016-01-01

'Store and forward' teledermoscopy is a technology with potential advantages for melanoma screening. Any large-scale implementation of this technology is dependent on consumer acceptance. To investigate preferences for melanoma screening options compared with skin self-examination in adults considered to be at increased risk of developing skin cancer. A discrete choice experiment was completed by 35 consumers, all of whom had prior experience with the use of teledermoscopy, in Queensland, Australia. Participants made 12 choices between screening alternatives described by seven attributes including monetary cost. A mixed logit model was used to estimate the relative weights that consumers place on different aspects of screening, along with the marginal willingness to pay for teledermoscopy as opposed to screening at a clinic. Overall, participants preferred screening/diagnosis by a health professional rather than skin self-examination. Key drivers of screening choice were for results to be reviewed by a dermatologist; a higher detection rate; fewer non-cancerous moles being removed in relation to every skin cancer detected; and less time spent away from usual activities. On average, participants were willing to pay AUD110 to have teledermoscopy with dermatologist review available to them as a screening option. Consumers preferentially value aspects of care that are more feasible with a teledermoscopy screening model, as compared with other skin cancer screening and diagnosis options. This study adds to previous literature in the area which has relied on the use of consumer satisfaction scales to assess the acceptability of teledermoscopy. © The Author(s) 2015.

[Cost effectiveness of mass orthoptic screening in kindergarten for early detection of developmental vision disorders].

PubMed

König, H H; Barry, J C; Leidl, R; Zrenner, E

2000-04-01

Orthoptic screening in the kindergarten is one option to improve early detection of amblyopia in children aged 3 years. The purpose of this study was to analyse the cost-effectiveness of such a screening programme in Germany. Based on data from the literature and own experience gained from orthoptic screening in kindergarten a decision-analytic model was developed. According to the model, all children in kindergarten, aged 3 years, who had not been treated for amblyopia before, were subjected to an orthoptic examination. Non-cooperative children were reexamined in kindergarten after one year. Children with positive test results were examined by an ophthalmologist for diagnosis. Effects were measured by the number of newly diagnosed cases of amblyopia, non-obvious strabismus and amblyogenic refractive errors. Direct costs were estimated from a third-party payer perspective. The influence of uncertain model parameters was tested by sensitivity analysis. In the base analysis the cost per orthoptic screening test was DM 15.39. Examination by an ophthalmologist cost DM 71.20. The total cost of the screening programme in all German kindergartens was DM 6.1 million. With a 1.5% age-specific prevalence of undiagnosed cases, a sensitivity of 95% and a specificity of 98%, a total of 4,261 new cases would be detected. The cost-effectiveness ratio was DM 1,421 per case detected. Sensitivity analysis showed considerable influence of prevalence and specificity on the cost-effectiveness ratio. It was more cost-effective to re-screen non-cooperative children in kindergarten than to have them examined by an ophthalmologist straight-away. The decision-analytic model showed stable results which may serve as a basis for discussion on the implementation of orthoptic screening and for planning a field study.

Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein-Ligand Docking Method.

PubMed

Shin, Woong-Hee; Kihara, Daisuke

2018-01-01

Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.

Early Detection of Undiagnosed Hypertension Based on Occupational Screening in the Hotel and Restaurant Industry.

PubMed

Seibt, Reingard; Hunger, Bettina; Stieler, Lisa; Stoll, Regina; Kreuzfeld, Steffi

2018-01-01

Blood pressure is the most important, modifiable risk factor for cardiovascular diseases. Lifestyle factors and also workload are the main, potential risk factors for the development of hypertension. This study focused on the early detection of unknown hypertension by screening employees in the hotel and restaurant industry (HRI). 148 HRI employees without hypertension (mean age: 34 years, men: 45%) self-measured their blood pressure during rest and for 24 hours of a normal workday. Individuals with a resting blood pressure ≥ 135/85 mmHg were classified as hypertensive. A further analysis investigated whether the currently applicable thresholds for hypertension during work, leisure, and sleep were exceeded on a working day. At rest, 36% of the study participants suffered from hypertension, which increased to 70% under workload and 46% during leisure time and dropped to 8% during sleep. Normal nocturnal dipping (10-20%) occurred only in 18% of cases; 78% were extreme dippers (>20%). Occupational hypertension screening is a suitable component of preventive healthcare. Resting blood pressure measurement alone is insufficient for the early detection of risk individuals and should be supplemented by 24-hour ambulatory blood pressure monitoring under working conditions. The impact of workload on blood pressure needs to be given more attention in the guidelines.

Early Detection of Undiagnosed Hypertension Based on Occupational Screening in the Hotel and Restaurant Industry

PubMed Central

Hunger, Bettina; Stieler, Lisa; Stoll, Regina

2018-01-01

Blood pressure is the most important, modifiable risk factor for cardiovascular diseases. Lifestyle factors and also workload are the main, potential risk factors for the development of hypertension. This study focused on the early detection of unknown hypertension by screening employees in the hotel and restaurant industry (HRI). 148 HRI employees without hypertension (mean age: 34 years, men: 45%) self-measured their blood pressure during rest and for 24 hours of a normal workday. Individuals with a resting blood pressure ≥ 135/85 mmHg were classified as hypertensive. A further analysis investigated whether the currently applicable thresholds for hypertension during work, leisure, and sleep were exceeded on a working day. At rest, 36% of the study participants suffered from hypertension, which increased to 70% under workload and 46% during leisure time and dropped to 8% during sleep. Normal nocturnal dipping (10–20%) occurred only in 18% of cases; 78% were extreme dippers (>20%). Occupational hypertension screening is a suitable component of preventive healthcare. Resting blood pressure measurement alone is insufficient for the early detection of risk individuals and should be supplemented by 24-hour ambulatory blood pressure monitoring under working conditions. The impact of workload on blood pressure needs to be given more attention in the guidelines. PMID:29850550

Evidence-based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons learned from the US Armed Forces: Consensus and Future Directions

PubMed Central

Avital, Itzhak; Langan, Russell C.; Summers, Thomas A.; Steele, Scott R.; Waldman, Scott A.; Backman, Vadim; Yee, Judy; Nissan, Aviram; Young, Patrick; Womeldorph, Craig; Mancusco, Paul; Mueller, Renee; Noto, Khristian; Grundfest, Warren; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Eberhardt, John; Man, Yan Gao; Brücher, Björn LDM; Stojadinovic, Alexander

2013-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. PMID:23459409

Barriers to innovation: nurses' risk appraisal in using a new ethics screening and early intervention tool.

PubMed

Pavlish, Carol L; Hellyer, Joan Henriksen; Brown-Saltzman, Katherine; Miers, Anne G; Squire, Karina

2013-01-01

We developed and assessed feasibility of an Ethics Screening and Early Intervention Tool that identifies at-risk clinical situations and prompts early actions to mitigate conflict and moral distress. Despite intensive care unit and oncology nurses' reports of tool benefits, they noted some risk to themselves when initiating follow-up actions. The riskiest actions were discussing ethical concerns with physicians, calling for ethics consultation, and initiating patient conversations. When discussing why initiating action was risky, participants revealed themes such as "being the troublemaker" and "questioning myself." To improve patient care and teamwork, all members of the health care team need to feel safe in raising ethics-related questions.

Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents.

PubMed

Savjani, Jignasa K; Mulamkattil, Suja; Variya, Bhavesh; Patel, Snehal

2017-04-15

Drug induced gastrointestinal ulceration, renal side effects and hepatotoxicity are the main causes of numerous Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-2 (COX-2) inhibitors discovered to decrease the gastrointestinal issues, but unfortunately, most of them are associated with major cardiovascular adverse effects. Along these lines, various new strategies and frameworks were developed wherein basic alterations of the present medications were accounted for. The aim of the study was to prepare derivatives of mefenamic acid to evaluate anti-inflammatory activity with fewer adverse reactions. In this study, molecular docking investigations of outlined derivatives were done utilizing Protein Data Bank (PDB ID-4PH9). Synthesis of heterocyclic compounds was carried out utilizing Dicyclohexylcarbodiimide/4-Dimethylaminopyridine (DCC/DMAP) coupling. Acute toxicity prediction was performed using free online GUSAR (General Unrestricted Structure-Activity Relationships) software. The study indicated most of the compounds under safe category. In-vitro pharmacological assessment of heterocyclic compounds was done for COX-1 and COX-2 enzymes for the determination of selectivity. In vivo pharmacological screening for anti-inflammatory activity and ED 50 value were determined utilizing carrageenan induced rat paw edema. Gastro intestinal safety study was carried out on selected compounds and found to be devoid of any gastric ulcer toxicity. Most of the compounds indicated high scores as compared to standard during molecular modelling, analysis and displayed interactions with active amino acids of a COX-2 enzyme. The pharmacological screening uncovered that compound substituted with p-bromophenyl indicated maximum potency. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of breast cancer knowledge and attitudes on screening and early detection among an immigrant Iranian population in southern California

PubMed Central

Kobeissi, Loulou; Samari, Goleen; Telesca, Donatello; Esfandiari, Mahtash; Galal, Osman

2014-01-01

Background Few studies explore factors influencing breast cancer screening and early detection behaviors among immigrant Iranian women residing in the United States. Methods Using a cross-sectional survey, a convenience sample of 319 Iranian-American women was selected to explore the impact of breast cancer knowledge and attitude on screening. A self-administered questionnaire assessed: breast cancer screening knowledge, attitude, and mammography use (ever, previous year and future intention). Results 79 % of the women in the study reported ever-receiving at least one mammogram and 74 % received a mammogram in the past year. Personal attitude had an independent significant effect on: mammography use in the last year, ever use of mammography and future intention to screen. Knowledge and morality-induced attitude influenced screening behavior but not significantly. Conclusion Interventions targeting breast cancer screening among immigrant Iranian women in the US should focus on enhancing personal attitudes in order to influence actual screening behavior. PMID:24096382

Molecular Building Block-Based Electronic Charges for High-Throughput Screening of Metal-Organic Frameworks for Adsorption Applications.

PubMed

Argueta, Edwin; Shaji, Jeena; Gopalan, Arun; Liao, Peilin; Snurr, Randall Q; Gómez-Gualdrón, Diego A

2018-01-09

Metal-organic frameworks (MOFs) are porous crystalline materials with attractive properties for gas separation and storage. Their remarkable tunability makes it possible to create millions of MOF variations but creates the need for fast material screening to identify promising structures. Computational high-throughput screening (HTS) is a possible solution, but its usefulness is tied to accurate predictions of MOF adsorption properties. Accurate adsorption simulations often require an accurate description of electrostatic interactions, which depend on the electronic charges of the MOF atoms. HTS-compatible methods to assign charges to MOF atoms need to accurately reproduce electrostatic potentials (ESPs) and be computationally affordable, but current methods present an unsatisfactory trade-off between computational cost and accuracy. We illustrate a method to assign charges to MOF atoms based on ab initio calculations on MOF molecular building blocks. A library of building blocks with built-in charges is thus created and used by an automated MOF construction code to create hundreds of MOFs with charges "inherited" from the constituent building blocks. The molecular building block-based (MBBB) charges are similar to REPEAT charges-which are charges that reproduce ESPs obtained from ab initio calculations on crystallographic unit cells of nanoporous crystals-and thus similar predictions of adsorption loadings, heats of adsorption, and Henry's constants are obtained with either method. The presented results indicate that the MBBB method to assign charges to MOF atoms is suitable for use in computational high-throughput screening of MOFs for applications that involve adsorption of molecules such as carbon dioxide.

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

Assessment of critical minerals: Updated application of an early-warning screening methodology

USGS Publications Warehouse

McCullough, Erin A.; Nassar, Nedal

2017-01-01

Increasing reliance on non-renewable mineral resources reinforces the need for identifying potential supply constraints before they occur. The US National Science and Technology Council recently released a report that outlines a methodology for screening potentially critical minerals based on three indicators: supply risk (R), production growth (G), and market dynamics (M). This early-warning screening was initially applied to 78 minerals across the years 1996 to 2013 and identified a subset of minerals as “potentially critical” based on the geometric average of these indicators—designated as criticality potential (C). In this study, the screening methodology has been updated to include data for 2014, as well as to incorporate revisions and modifications to the data, where applicable. Overall, C declined in 2014 for the majority of minerals examined largely due to decreases in production concentration and price volatility. However, the results vary considerably across minerals, with some minerals, such as gallium, recording increases for all three indicators. In addition to assessing magnitudinal changes, this analysis also examines the significance of the change relative to historical variation for each mineral. For example, although mined nickel’s R declined modestly in 2014 in comparison to that of other minerals, it was by far the largest annual change recorded for mined nickel across all years examined and is attributable to Indonesia’s ban on the export of unprocessed minerals. Based on the 2014 results, 20 minerals with the highest C values have been identified for further study including the rare earths, gallium, germanium, rhodium, tantalum, and tungsten.

Patient and Clinician Perspectives on Shared Decision-making in Early Adopting Lung Cancer Screening Programs: a Qualitative Study.

PubMed

Wiener, Renda Soylemez; Koppelman, Elisa; Bolton, Rendelle; Lasser, Karen E; Borrelli, Belinda; Au, David H; Slatore, Christopher G; Clark, Jack A; Kathuria, Hasmeena

2018-02-21

Guidelines recommend, and Medicare requires, shared decision-making between patients and clinicians before referring individuals at high risk of lung cancer for chest CT screening. However, little is known about the extent to which shared decision-making about lung cancer screening is achieved in real-world settings. To characterize patient and clinician impressions of early experiences with communication and decision-making about lung cancer screening and perceived barriers to achieving shared decision-making. Qualitative study entailing semi-structured interviews and focus groups. We enrolled 36 clinicians who refer patients for lung cancer screening and 49 patients who had undergone lung cancer screening in the prior year. Participants were recruited from lung cancer screening programs at four hospitals (three Veterans Health Administration, one urban safety net). Using content analysis, we analyzed transcripts to characterize communication and decision-making about lung cancer screening. Our analysis focused on the recommended components of shared decision-making (information sharing, deliberation, and decision aid use) and barriers to achieving shared decision-making. Clinicians varied in the information shared with patients, and did not consistently incorporate decision aids. Clinicians believed they explained the rationale and gave some (often purposely limited) information about the trade-offs of lung cancer screening. By contrast, some patients reported receiving little information about screening or its trade-offs and did not realize the CT was intended as a screening test for lung cancer. Clinicians and patients alike did not perceive that significant deliberation typically occurred. Clinicians perceived insufficient time, competing priorities, difficulty accessing decision aids, limited patient comprehension, and anticipated patient emotions as barriers to realizing shared decision-making. Due to multiple perceived barriers, patient

Developing the Thai Siriraj Psoriatic Arthritis Screening Tool and validating the Thai Psoriasis Epidemiology Screening Tool and the Early Arthritis for Psoriatic Patients questionnaire.

PubMed

Chiowchanwisawakit, Praveena; Wattanamongkolsil, Luksame; Srinonprasert, Varalak; Petcharat, Chonachan; Siriwanarangsun, Palanan; Katchamart, Wanruchada

2016-10-01

To validate the Thai language version of the Psoriasis Epidemiology Screening Tool (PEST) and the Early Arthritis for Psoriatic Patients Questionnaire (EARP), as well as also to develop a new tool for screening psoriatic arthritis (PsA) among psoriasis (Ps) patients. This was a cross-sectional study. Ps patients visiting the psoriasis clinic at Siriraj Hospital were recruited. They completed the EARP and PEST. Full musculoskeletal history, examination, and radiography were evaluated. PsA was diagnosed by a rheumatologist's evaluation and fulfillment of the classification criteria for psoriatic arthritis. Receiver operator characteristic (ROC) curves, sensitivity, and specificity were used to evaluate the performances of the tools. The Siriraj Psoriatic Arthritis Screening Tool (SiPAT) contained questions most relevant to peripheral arthritis, axial inflammation, and enthesitis, selected from multivariate analysis. Of a total of 159 patients, the prevalence of PsA was 78.6 %. The ROC curve analyses of Thai EARP, PEST, and SiPAT were 0.90 (95 % CI 0.84, 0.96), 0.85 (0.78, 0.92), and 0.89 (0.83, 0.95), respectively. The sensitivities of SiPAT, Thai EARP, and PEST were 91.0, 83.0, and 72.0 %, respectively, while the specificities were 69.0, 79.3, and 89.7 %, respectively. All screening questionnaires showed good diagnostic performances. SiPAT could be considered as a screening tool with its desirable properties: higher sensitivity and taking less time. Thai PEST and EARP could possibly be sequentially administered for people with a positive test from SiPAT to reduce the number of false positives.

Screening of Toxic Effects of Bisphenol A and Products of Its Degradation: Zebrafish (Danio rerio) Embryo Test and Molecular Docking.

PubMed

Makarova, Katerina; Siudem, Pawel; Zawada, Katarzyna; Kurkowiak, Justyna

2016-10-01

Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.

Molecular clocks and the early evolution of metazoan nervous systems.

PubMed

Wray, Gregory A

2015-12-19

The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. © 2015 The Author(s).

The Importance of Predictive Power in Early Screening Assessments: Implications for Placement in the Response to Intervention Framework

ERIC Educational Resources Information Center

Petscher, Yaacov; Kim, Young-Suk; Foorman, Barbara R.

2011-01-01

As schools implement response to intervention to identify and serve students with learning difficulties, it is critical for educators to know how to evaluate screening measures. In the present study, "Dynamic Indicators of Basic Early Literacy Skills" Oral Reading Fluency was used to compare the differential decisions that might occur in…

Molecular modeling and identification of novel glucokinase activators through stepwise virtual screening.

PubMed

Behera, Pabitra Mohan; Behera, Deepak Kumar; Satpati, Suresh; Agnihotri, Geetanjali; Nayak, Sanghamitra; Padhi, Payodhar; Dixit, Anshuman

2015-04-01

The glucose phosphorylating enzyme glucokinase (GK) is a 50kD monomeric protein having 465 amino acids. It maintains glucose homeostasis inside cells, acts as a glucose sensor in pancreatic β-cells and as a rate controlling enzyme for hepatic glucose clearance and glycogen synthesis. It has two binding sites, one for binding d-glucose and the other for a putative allosteric activator named glucokinase activator (GKA). The GKAs interact with the same region of the GK enzyme that is commonly affected by naturally occurring mutations in humans. However, many GKAs do not bind to GK in the absence of glucose. Recently, it has been reported that GKAs are highly effective in patients with type 2 diabetes mellitus. In this milieu a molecular modeling study has been carried out on three natural variants of GK that lie in the GKA binding site and are known to cause maturity onset diabetes of young (MODY). Additionally, a 10ns molecular dynamics simulation was done on each of the modeled variant in order to explore the flexibility of this site. Subsequently, a systematic virtual screening study was done to identify compounds which can bind with high affinity at GKA binding site of mutant GK. Copyright © 2015 Elsevier Inc. All rights reserved.

Screening white spot syndrome virus (WSSV)-resistant molecular markers from Fenneropenaeus chinensis

NASA Astrophysics Data System (ADS)

Wu, Yingying; Meng, Xianhong; Kong, Jie; Luan, Sheng; Luo, Kun; Wang, Qingyin; Zheng, Yongyun

2017-02-01

White spot syndrome virus (WSSV)-resistant molecular markers were screened from the selectively bred new variety `Huanghai No. 2' of Fenneropenaeus chinensis using unlabeled-probe high-resolution melting (HRM) technique. After the artificial infection with WSSV, the first 96 dead shrimps and the last 96 surviving shrimps were collected, representing WSSV-susceptible and -resistant populations, respectively. The genotypes at well-developed 39 single nucleotide polymorphisms (SNPs) loci were obtained. As revealed in the Chi-square test, 3 SNPs, genotype A/A of contig C364-89AT, genotype A/A of C2635-527CA and genotype C/T of contig C12355-592CT, were positively correlated with disease-resistance traits. Other 2 SNPs, genotype G/G of contig C283-145AG and genotype C/C of contig C12355-592CT, were negatively correlated. Moreover, analysis with BlastX program for disease-resistant SNPs indicated that 3 contigs, Contig283, Contig364 and Contig12355, matched to the functional genes of effector caspase of Penaeus monodon, peptide transporter family 1-like protein, and 40S ribosomal protein S2 of Perca flavescens with high sequence similarity. The results will be helpful to provide theoretical and technical supports for molecular marker-assisted selective breeding of F. chinensis.

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

PubMed Central

Buchanan, Adam H; Manickam, Kandamurugu; Meyer, Michelle N; Wagner, Jennifer K; Hallquist, Miranda L G; Williams, Janet L; Rahm, Alanna Kulchak; Williams, Marc S; Chen, Zong-Ming E; Shah, Chaitali K; Garg, Tullika K; Lazzeri, Amanda L; Schwartz, Marci L B; Lindbuchler, D'Andra M; Fan, Audrey L; Leeming, Rosemary; Servano, Pedro O; Smith, Ashlee L; Vogel, Victor G; Abul-Husn, Noura S; Dewey, Frederick E; Lebo, Matthew S; Mason-Suares, Heather M; Ritchie, Marylyn D; Davis, F Daniel; Carey, David J; Feinberg, David T; Faucett, W Andrew; Ledbetter, David H; Murray, Michael F

2018-01-01

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility. PMID:29261187

What's New with Newborn Screening

ERIC Educational Resources Information Center

Exceptional Parent, 2008

2008-01-01

Newborn screening is the process of testing and screening newborns shortly after birth for certain, potentially dangerous, conditions and/or impairments--conditions that include everything from inborn errors of metabolism and other genetic disorders to hearing impairment. Early detection through newborn screening is paramount, often allowing the…

Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors.

PubMed

Wang, Quan; Birod, Kerstin; Angioni, Carlo; Grösch, Sabine; Geppert, Tim; Schneider, Petra; Rupp, Matthias; Schneider, Gisbert

2011-01-01

Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.

A Guide to Dental Care for the Early and Periodic Screening, Diagnosis, and Treatment Program (EPSDT) Under Medicaid.

ERIC Educational Resources Information Center

Lindahl, Roy L.; Young, Wesley O.

This guide has been developed to assist administrators, providers of dental care, and others involved in carrying out the dental care provisions of the EPSDT program (Early and Periodic Screening, Diagnosis, and Treatment Program). It is intended to assist in the development of programs concerned with the unique characteristics of dental diseases…

[Molecular genetic diagnostics and screening of hereditary hemochromatosis].

PubMed

Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

2006-06-01

282Y heterozygotes (p < 0.001), C282Y/H63D compound heterozygotes (p < 0.001) and wild type subjects (p < 0.001) respectively. Our observations confirm that DNA analysis significantly contributes to differential diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. DNA analysis is recommended in patients whose transferrin saturation is 45% or more on a repeated test. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with secondary iron overload, especially patients with chronic liver disorders and chronic anemia. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified.

Screening of broad spectrum natural pesticides against conserved target arginine kinase in cotton pests by molecular modeling.

PubMed

Sakthivel, Seethalakshmi; Habeeb, S K M; Raman, Chandrasekar

2018-03-12

Cotton is an economically important crop and its production is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved target across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag profiling from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One target protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum target which are highly specific to invertebrates.

Towards a systematic nationwide screening strategy for MODY.

PubMed

Shields, Beverley; Colclough, Kevin

2017-04-01

MODY is an early-onset monogenic form of diabetes. Correctly identifying MODY is of considerable importance as diagnosing the specific genetic subtype can inform the optimal treatment, with many patients being able to discontinue unnecessary insulin treatment. Diagnostic molecular genetic testing to confirm MODY is expensive, so screening strategies are required to identify the most appropriate patients for testing. In this issue of Diabetologia, Johansson and colleagues (DOI 10.1007/s00125-016-4167-1 ) describe a nationwide systematic screening approach to identify individuals with MODY in the paediatric age range. They focused testing on patients negative for both GAD and islet antigen 2 (IA-2) islet autoantibodies, thereby ruling out those with markers of type 1 diabetes, the most common form of diabetes in this age group. This commentary discusses the advantages and limitations of the approach, and the caution required when interpreting variants of uncertain pathogenicity identified from testing whole populations rather than targeting only patients with a strong MODY phenotype.

Planck early results. XXV. Thermal dust in nearby molecular clouds

NASA Astrophysics Data System (ADS)

Planck Collaboration; Abergel, A.; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Balbi, A.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Battaner, E.; Benabed, K.; Benoît, A.; Bernard, J.-P.; Bersanelli, M.; Bhatia, R.; Bock, J. J.; Bonaldi, A.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burigana, C.; Cabella, P.; Cardoso, J.-F.; Catalano, A.; Cayón, L.; Challinor, A.; Chamballu, A.; Chiang, L.-Y.; Chiang, C.; Christensen, P. R.; Clements, D. L.; Colombi, S.; Couchot, F.; Coulais, A.; Crill, B. P.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Gasperis, G.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Dickinson, C.; Dobashi, K.; Donzelli, S.; Doré, O.; Dörl, U.; Douspis, M.; Dupac, X.; Efstathiou, G.; Enßlin, T. A.; Eriksen, H. K.; Finelli, F.; Forni, O.; Frailis, M.; Franceschi, E.; Galeotta, S.; Ganga, K.; Giard, M.; Giardino, G.; Giraud-Héraud, Y.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Guillet, V.; Hansen, F. K.; Harrison, D.; Henrot-Versillé, S.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hovest, W.; Hoyland, R. J.; Huffenberger, K. M.; Jaffe, A. H.; Jones, A.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knox, L.; Kurki-Suonio, H.; Lagache, G.; Lamarre, J.-M.; Lasenby, A.; Laureijs, R. J.; Lawrence, C. R.; Leach, S.; Leonardi, R.; Leroy, C.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; MacTavish, C. J.; Maffei, B.; Mandolesi, N.; Mann, R.; Maris, M.; Marshall, D. J.; Martin, P.; Martínez-González, E.; Masi, S.; Matarrese, S.; Matthai, F.; Mazzotta, P.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Munshi, D.; Murphy, A.; Naselsky, P.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Osborne, S.; Pajot, F.; Paladini, R.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Piacentini, F.; Piat, M.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Ponthieu, N.; Poutanen, T.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savini, G.; Scott, D.; Seiffert, M. D.; Shellard, P.; Smoot, G. F.; Starck, J.-L.; Stivoli, F.; Stolyarov, V.; Sudiwala, R.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Torre, J.-P.; Tristram, M.; Tuovinen, J.; Umana, G.; Valenziano, L.; Verstraete, L.; Vielva, P.; Villa, F.; Vittorio, N.; Wade, L. A.; Wandelt, B. D.; Yvon, D.; Zacchei, A.; Zonca, A.

2011-12-01

Planck allows unbiased mapping of Galactic sub-millimetre and millimetre emission from the most diffuse regions to the densest parts of molecular clouds. We present an early analysis of the Taurus molecular complex, on line-of-sight-averaged data and without component separation. The emission spectrum measured by Planck and IRAS can be fitted pixel by pixel using a single modified blackbody. Some systematic residuals are detected at 353 GHz and 143 GHz, with amplitudes around -7% and +13%, respectively, indicating that the measured spectra are likely more complex than a simple modified blackbody. Significant positive residuals are also detected in the molecular regions and in the 217 GHz and 100 GHz bands, mainly caused by the contribution of the J = 2 → 1 and J = 1 → 0 12CO and 13CO emission lines. We derive maps of the dust temperature T, the dust spectral emissivity index β, and the dust optical depth at 250 μm τ250. The temperature map illustrates the cooling of the dust particles in thermal equilibrium with the incident radiation field, from 16 - 17 K in the diffuse regions to 13 - 14 K in the dense parts. The distribution of spectral indices is centred at 1.78, with a standard deviation of 0.08 and a systematic error of 0.07. We detect a significant T - β anti-correlation. The dust optical depth map reveals the spatial distribution of the column density of the molecular complex from the densest molecular regions to the faint diffuse regions. We use near-infrared extinction and Hi data at 21-cm to perform a quantitative analysis of the spatial variations of the measured dust optical depth at 250 μm per hydrogen atom τ250/NH. We report an increase of τ250/NH by a factor of about 2 between the atomic phase and the molecular phase, which has a strong impact on the equilibrium temperature of the dust particles. Corresponding author: A. Abergel, e-mail: alain.abergel@ias.u-psud.fr

Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

PubMed

Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

2018-01-01

The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Development and validation of a new screening questionnaire for dysphagia in early stages of Parkinson's disease.

PubMed

Simons, Janine A; Fietzek, Urban M; Waldmann, Annika; Warnecke, Tobias; Schuster, Tibor; Ceballos-Baumann, Andrés O

2014-09-01

Dysphagia in patients with Parkinson's disease (PD) significantly reduces quality of life and predicted lifetime. Current screening procedures are insufficiently evaluated. We aimed to develop and validate a patient-reported outcome questionnaire for early diagnosis of dysphagia in patients with PD. The two-phased project comprised the questionnaire, diagnostic scales construction (N = 105), and a validation study (N = 82). Data for the project were gathered from PD patients at a German Movement Disorder Center. For validation purposes, a clinical evaluation focusing on swallowing tests, tests of sensory reflexes, and fiberoptic endoscopic evaluation of swallowing (FEES) was performed that yielded a criteria sum score against which the results of the questionnaire were compared. Specificity and sensitivity were evaluated for the detection of noticeable dysphagia and for the risk of aspiration. The Munich Dysphagia Test - Parkinson's disease (MDT-PD) consists of 26 items that show high internal consistency (α = 0.91). For the validation study, 82 patients, aged 70.9 ± 8.7 (mean ± SD), with a median Hoehn & Yahr stage of 3, were assessed. 73% of patients had dysphagia with noticeable oropharyngeal symptoms (44%) or with penetration/aspiration (29%). The criteria sum score correlated positively with the screening result (r = 0.70, p < 0.001). The MDT-PD sum score classified not noticeable dysphagia vs. risk of aspiration (noticeable dysphagia) with a sensitivity of 90% (82%) and a specificity of 86% (71%), and yielded similar results in cross-validation, respectively. MDT-PD is a valid screening tool for early diagnosis of swallowing problems and aspiration risk, as well as initial graduation of dysphagia severity in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States: a systematic review of the evidence for screening in early pregnancy

PubMed Central

Chamberlain, Catherine; McNamara, Bridgette; Williams, Emily D; Yore, Daniel; Oldenburg, Brian; Oats, Jeremy; Eades, Sandra

2013-01-01

Recently proposed international guidelines for screening for gestational diabetes mellitus (GDM) recommend additional screening in early pregnancy for sub-populations at a high risk of type 2 diabetes mellitus (T2DM), such as indigenous women. However, there are criteria that should be met to ensure the benefits outweigh the risks of population-based screening. This review examines the published evidence for early screening for indigenous women as related to these criteria. Any publications were included that referred to diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States (n = 145). The risk of bias was appraised. There is sufficient evidence describing the epidemiology of diabetes in pregnancy, demonstrating that it imposes a significant disease burden on indigenous women and their infants at birth and across the lifecourse (n = 120 studies). Women with pre-existing T2DM have a higher risk than women who develop GDM during pregnancy. However, there was insufficient evidence to address the remaining five criteria, including the following: understanding current screening practice and rates (n = 7); acceptability of GDM screening (n = 0); efficacy and cost of screening for GDM (n = 3); availability of effective treatment after diagnosis (n = 6); and effective systems for follow-up after pregnancy (n = 5). Given the impact of diabetes in pregnancy, particularly undiagnosed T2DM, GDM screening in early pregnancy offers potential benefits for indigenous women. However, researchers, policy makers and clinicians must work together with communities to develop effective strategies for implementation and minimizing the potential risks. Evidence of effective strategies for primary prevention, GDM treatment and follow-up after pregnancy are urgently needed. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23315909

Molecular imaging probe development: a chemistry perspective

PubMed Central

Nolting, Donald D; Nickels, Michael L; Guo, Ning; Pham, Wellington

2012-01-01

Molecular imaging is an attractive modality that has been widely employed in many aspects of biomedical research; especially those aimed at the early detection of diseases such as cancer, inflammation and neurodegenerative disorders. The field emerged in response to a new research paradigm in healthcare that seeks to integrate detection capabilities for the prediction and prevention of diseases. This approach made a distinct impact in biomedical research as it enabled researchers to leverage the capabilities of molecular imaging probes to visualize a targeted molecular event non-invasively, repeatedly and continuously in a living system. In addition, since such probes are inherently compact, robust, and amenable to high-throughput production, these probes could potentially facilitate screening of preclinical drug discovery, therapeutic assessment and validation of disease biomarkers. They could also be useful in drug discovery and safety evaluations. In this review, major trends in the chemical synthesis and development of positron emission tomography (PET), optical and magnetic resonance imaging (MRI) probes are discussed. PMID:22943038

Anal cancer and intraepithelial neoplasia screening: A review

PubMed Central

Leeds, Ira L; Fang, Sandy H

2016-01-01

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2.

PubMed

Samal, Himanshu Bhusan; Das, Jugal Kishore; Mahapatra, Rajani Kanta; Suar, Mrutyunjay

2015-01-01

The Mur enzymes of the peptidoglycan biosynthesis pathway constitute ideal targets for the design of new classes of antimicrobial inhibitors in Gram-negative bacteria. We built a homology model of MurD of Salmonella typhimurium LT2 using MODELLER (9v12) software. 'The homology model was subjected to energy minimization by molecular dynamics (MD) simulation study with GROMACS software for a simulation time of 20 ns in water environment. The model was subjected for virtual screening study from the Zinc Database using Dockblaster software. Inhibition assay for the best inhibitor, 3-(amino methyl)-n-(4-methoxyphenyl) aniline, by flow cytometric analysis revealed the effective inhibition of peptidoglycan biosynthesis. Results from this study provide new insights for the molecular understanding and development of new antibacterial drugs against the pathogen. Copyright © 2015 Elsevier Inc. All rights reserved.

Fragment screening by SPR and advanced application to GPCRs.

PubMed

Shepherd, Claire A; Hopkins, Andrew L; Navratilova, Iva

2014-01-01

Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). Biophysical GPCR assays using SPR have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A survey of physician receptivity to molecular diagnostic testing and readiness to act on results for early-stage colon cancer patients.

PubMed

Myers, Ronald E; Wolf, Thomas; Shwae, Phillip; Hegarty, Sarah; Peiper, Stephen C; Waldman, Scott A

2016-10-03

We sought to assess physician interest in molecular prognosic testing for patients with early stage colon cancer, and identify factors associated with the likelihood of test adoption. We identified physicians who care for patients with early-stage (pN0) colon cancer patients, mailed them a survey, and analyzed survey responses to assess clinician receptivity to the use of a new molecular test (GUCY2C) that identifies patients at risk for recurrence, and clinician readiness to act on abnormal test results. Of 104 eligible potential respondents, 41 completed and returned the survey. Among responding physicians, 56 % were receptive to using the new prognostic test. Multivariable analyses showed that physicians in academic medical centers were significantly more receptive to molecular test use than those in non-academic settings. Forty-one percent of respondents were ready to act on abnormal molecular test results. Physicians who viewed current staging methods as inaccurate and were confident in their capacity to incorporate molecular testing in practice were more likely to say they would act on abnormal test results. Physician receptivity to molecular diagnostic testing for early-stage colon cancer patients is likely to be influenced by practice setting and perceptions related to delivering quality care to patients. ClinicalTrials.gov Identifier: NCT01972737.

From Cancer Screening to Treatment: Service Delivery and Referral in the National Breast and Cervical Cancer Early Detection Program

PubMed Central

Miller, Jacqueline W.; Hanson, Vivien; Johnson, Gale D.; Royalty, Janet E.; Richardson, Lisa C.

2015-01-01

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screening and diagnostic services to low-income and underserved women through a network of providers and health care organizations. Although the program serves women 40-64 years old for breast cancer screening and 21-64 years old for cervical cancer screening, the priority populations are women 50-64 years old for breast cancer and women who have never or rarely been screened for cervical cancer. From 1991 through 2011, the NBCCEDP provided screening and diagnostic services to more than 4.3 million women, diagnosing 54,276 breast cancers, 2554 cervical cancers, and 123,563 precancerous cervical lesions. A critical component of providing screening services is to ensure that all women with abnormal screening results receive appropriate and timely diagnostic evaluations. Case management is provided to assist women with overcoming barriers that would delay or prevent follow-up care. Women diagnosed with cancer receive treatment through the states' Breast and Cervical Cancer Treatment Programs (a special waiver for Medicaid) if they are eligible. The NBCCEDP has performance measures that serve as benchmarks to monitor the completeness and timeliness of care. More than 90% of the women receive complete diagnostic care and initiate treatment less than 30 days from the time of their diagnosis. Provision of effective screening and diagnostic services depends on effective program management, networks of providers throughout the community, and the use of evidence-based knowledge, procedures, and technologies. PMID:25099897

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening.

PubMed

Cohen, Paul A; Flowers, Nicola; Tong, Stephen; Hannan, Natalie; Pertile, Mark D; Hui, Lisa

2016-08-24

Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC). This is a case control study of prospectively-collected biobank samples comprising preoperative plasma from 32 women with HGSOC (16 'early cancer' (FIGO I-II) and 16 'advanced cancer' (FIGO III-IV)) and 32 benign controls. Plasma DNA from cases and controls were sequenced using a commercial NIPT platform and chromosome dosage measured. Sequencing data were blindly analyzed with two methods: (1) Subchromosomal changes were called using an open source algorithm WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR). Genomic gains or losses ≥ 15 Mb were prespecified as "screen positive" calls, and mapped to recurrent copy number variations reported in an ovarian cancer genome atlas. (2) Selected whole chromosome gains or losses were reported using the routine NIPT pipeline for fetal aneuploidy. We detected 13/32 cancer cases using the subchromosomal analysis (sensitivity 40.6 %, 95 % CI, 23.7-59.4 %), including 6/16 early and 7/16 advanced HGSOC cases. Two of 32 benign controls had subchromosomal gains ≥ 15 Mb (specificity 93.8 %, 95 % CI, 79.2-99.2 %). Twelve of the 13 true positive cancer cases exhibited specific recurrent changes reported in HGSOC tumors. The NIPT pipeline resulted in one "monosomy 18" call from the cancer group, and two "monosomy X" calls in the controls. Low coverage plasma DNA sequencing used for prenatal testing detected 40.6 % of all HGSOC, including 38 % of early stage cases. Our

Molecular diversity of early foraminifera

NASA Astrophysics Data System (ADS)

Holzmann, Maria; Pawlowski, Jan

2017-04-01

Monothalamid foraminifera are a diverse group that is characterized by single-chambered agglutinated or organic test. They occur in all marine habitats and are also present in terrestrial and freshwater environments. Monothalamids branch at the base of foraminiferal tree, as a paraphyletic group with some clades branching at the base of Globothalamea and Tubothalamea. We have currently more than 1500 sequences of monothalamids in our database that can be divided in at least 20 clades among which certain are particularly well presented by sequence numbers and/or number of different species. These are members of clade BM that contain Bathysiphon and Micrometula, clade C that contains among others xenophyophorans, saccaminids, and a large variety of organic-walled or agglutinated genera, clade E that contains the genera Psammophaga, Vellaria and Nellya and four clades that contain freshwater foraminifera. In general, the monothalamid clades comprise both agglutinated and organic-walled genera. Some common genera, such as Crithionina, Saccammina, Hippocrepina, are polyphyletic. Our results clearly show that monothalamids are highly diverse and their molecular diversity by far surpasses their morphological variety. Based on phylogenomic studies, monothalamids evolved early in the evolution of eukaryotes, as a part of the supergroup of Rhizaria, comprising also radiolarians and other amoeboid protists. The monothalamids have diverged from ancestral radiolarians, probably about 1000 million years ago, but the exact time is difficult to infer because of the uncertainties concerning a calibration of a eukaryotic phylogenomic tree.

Lung cancer: diagnosis, treatment principles, and screening.

PubMed

Latimer, Kelly M; Mott, Timothy F

2015-02-15

Lung cancer is classified histologically into small cell and non-small cell lung cancers. The most common symptoms of lung cancer are cough, dyspnea, hemoptysis, and systemic symptoms such as weight loss and anorexia. High-risk patients who present with symptoms should undergo chest radiography. If a likely alternative diagnosis is not identified, computed tomography and possibly positron emission tomography should be performed. If suspicion for lung cancer is high, a diagnostic evaluation is warranted. The diagnostic evaluation has three simultaneous steps (tissue diagnosis, staging, and functional evaluation), all of which affect treatment planning and determination of prognosis. The least invasive method possible should be used. The diagnostic evaluation and treatment of a patient with lung cancer require a team of specialists, including a pulmonologist, medical oncologist, radiation oncologist, pathologist, radiologist, and thoracic surgeon. Non-small cell lung cancer specimens are tested for various mutations, which, if present, can be treated with new targeted molecular therapies. The family physician should remain involved in the patient's care to ensure that the values and wishes of the patient and family are considered and, if necessary, to coordinate end-of-life care. Early palliative care improves quality of life and may prolong survival. Family physicians should concentrate on early recognition of lung cancer, as well as prevention by encouraging tobacco cessation at every visit. The U.S. Preventive Services Task Force recommends lung cancer screening using low-dose computed tomography in high-risk patients. However, the American Academy of Family Physicians concludes that the evidence is insufficient to recommend for or against screening. Whether to screen high-risk patients should be a shared decision between the physician and patient.

Likelihood of early detection of breast cancer in relation to false-positive risk in life-time mammographic screening: population-based cohort study.

PubMed

Otten, J D M; Fracheboud, J; den Heeten, G J; Otto, S J; Holland, R; de Koning, H J; Broeders, M J M; Verbeek, A L M

2013-10-01

Women require balanced, high-quality information when making an informed decision on screening benefits and harms before attending biennial mammographic screening. The cumulative risk of a false-positive recall and/or (small) screen-detected or interval cancer over 13 consecutive screening examinations for women aged 50 from the start of screening were estimated using data from the Nijmegen programme, the Netherlands. Women who underwent 13 successive screens in the period 1975-1976 had a 5.3% cumulative chance of a screen-detected cancer, with a 4.2% risk of at least one false-positive recall. The risk of being diagnosed with interval cancer was 3.7%. Two decades later, these estimates were 6.9%, 7.3% and 2.9%, respectively. The chance of detection of a small, favourable invasive breast cancer, anticipating a normal life-expectancy, rose from 2.3% to 3.7%. Extrapolation to digital screening mammography indicates that the proportion of false-positive results will rise to 16%. Dutch women about to participate in the screening programme can be reassured that the chance of false-positive recall in the Netherlands is relatively low. A new screening policy and improved mammography have increased the detection of an early screening carcinoma and lowering the risk of interval carcinoma.

Molecular galactose-galectin association in neuroblastoma cells: An unconventional tool for qualitative/quantitative screening.

PubMed

Pastorino, Fabio; Ponzoni, Mirco; Simone, Giuseppina

2017-05-01

Galectin decorates the cell membrane and forms an extracellular molecular association with galactoside units. Here, galactoside probes have been used to study galectin expression in neuroblastoma cells. The hypothesis behind this investigation has been that the molecular mechanisms by which glycans modulate neural metastatic cells involve a protein-carbohydrate association, galectin-galactose. Preliminary screening to validate the hypothesis has been performed with galactose moieties anchored to beads. The molecular association has been studied by FACS. In vitro experiments reveal the molecular binding preferences of the metastatic neuroblastoma cells. Ex vivo, the galactose probes discriminate healthy tissues. The unconventional assay in microfluidics used in this study displayed results analogous to the above (GI-LI-N cell capture efficiency overcomes IMR-32). At the point of equilibrium of shear and binding forces, the capture yield inside the chamber was measured to 60 ± 4.4% in GI-LI-N versus 40 ± 2.1% in IMR-32. Staining of the fished cells and subsequent conjugation with red beads bearing the galactose also have evidenced that microfluidics can be used to study and quantify the molecular association of galectin-galactose. Most importantly, a crucial insight for obtaining single-cell qualitative/quantitative glycome analysis has been achieved. Finally, the specificity of the assay performed in microfluidics is demonstrated by comparing GI-LI-N fishing efficiency in galactose and fucose environments. The residual adhesion to fucose confirmed the existence of receptors for this glycan and that its eventual unspecific binding (i.e. due to electrostatic interactions) is insignificant compared with the molecular binding. Identification and understanding of this mechanism of discrimination can be relevant for diagnostic monitoring and for producing probes tailored to interfere with galectin activities associated with the malignant phenotype. Besides, the given

EPSDT: Child Health. Child Health Information for Workers in the Medicaid Early and Periodic Screening Diagnosis and Treatment Program.

ERIC Educational Resources Information Center

Manela, Roger; And Others

One of six information booklets with accompanying training materials for the Medicaid Early and Periodic Screening Diagnosis and Treatment (EPSDT) program, this booklet describes the stages of child growth and development and some of the health problems which EPSDT clients might have. Section I describes tests commonly included in an EPSDT…

An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening.

PubMed

Chen, Haining; Li, Sijia; Hu, Yajiao; Chen, Guo; Jiang, Qinglin; Tong, Rongsheng; Zang, Zhihe; Cai, Lulu

2016-01-01

Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multipharmacophore- based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, and five compounds were tested experimentally. Thus, these results may provide valuable information for further discovery of more novel ROCK1 inhibitors.

Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial.

PubMed

Huhn, E A; Fischer, T; Göbl, C S; Todesco Bernasconi, M; Kreft, M; Kunze, M; Schoetzau, A; Dölzlmüller, E; Eppel, W; Husslein, P; Ochsenbein-Koelble, N; Zimmermann, R; Bäz, E; Prömpeler, H; Bruder, E; Hahn, S; Hoesli, I

2016-10-12

As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an 'early' oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an 'early' OGTT 75 g and/or the new biomarker, glyFn, at 12-15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24-28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on 'early' OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. NCT02035059. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

PubMed Central

Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

2016-01-01

Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

Fifty years of newborn screening.

PubMed

Wilcken, Bridget; Wiley, Veronica

2015-01-01

Newborn screening has evolved fast following recent advances in diagnosis and treatment of disease, particularly the development of multiplex testing and applications of molecular testing. Formal evidence of benefit from newborn screening has been largely lacking, due to the rarity of individual disorders. There are wide international differences in the choice of disorders screened, and ethical issues in both screening and not screening are apparent. More evidence is needed about benefit and harm of screening for specific disorders and renewed discussion about the basic aims of newborn screening must be undertaken. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

PubMed Central

Burford, B; Gentry-Maharaj, A; Graham, R; Allen, D; Pedersen, J W; Nudelman, A S; Blixt, O; Fourkala, E O; Bueti, D; Dawnay, A; Ford, J; Desai, R; David, L; Trinder, P; Acres, B; Schwientek, T; Gammerman, A; Reis, C A; Silva, L; Osório, H; Hallett, R; Wandall, H H; Mandel, U; Hollingsworth, M A; Jacobs, I; Fentiman, I; Clausen, H; Taylor-Papadimitriou, J; Menon, U; Burchell, J M

2013-01-01

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection. PMID:23652307

Non-Invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, Lee

This is the Final Progress Report for DOE-funded research project DE-PS02-08ER08-01 titled “Non-Invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens”. The project focuses on the effects of low-linear energy transfer (LET) radiation on the ocular lens. The lens is an exquisitely radiosensitive tissue with a highly-ordered molecular structure that is amenable to non-invasive optical study from the periphery. These merits point to the lens as an ideal target for laser-based molecular biodosimetry (MBD). Following exposure to different types of ionizing radiations, the lens demonstrates molecular changes (e.g., oxidation, racemization, crosslinkage, truncation, aggregation, etc.) thatmore » impact the structure and function of the long-lived proteins in the cytosol of lens fiber cells. The vast majority of proteins in the lens comprise the highly-ordered crystallins. These highly conserved lens proteins are amongst the most concentrated and stable in the body. Once synthesized, the crystallins are retained in the fiber cell cytoplasm for life. Taken together, these properties point to the lens as an ideal system for quantitative in vivo MBD assessment using quasi-elastic light scattering (QLS) analysis. In this project, we deploy a purpose-designed non-invasive infrared laser QLS instrument as a quantitative tool for longitudinal assessment of pre-cataractous molecular changes in the lenses of living mice exposed to low-dose low-LET radiation compared to non-irradiated sham controls. We hypothesize that radiation exposure will induce dose-dependent changes in the molecular structure of matrix proteins in the lens. Mechanistic assays to ascertain radiation-induced molecular changes in the lens focus on protein aggregation and gene/protein expression patterns. We anticipate that this study will contribute to our understanding of early molecular changes associated with radiation-induced tissue pathology. This study also affords

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting.

PubMed

Werner, Simone; Krause, Friedemann; Rolny, Vinzent; Strobl, Matthias; Morgenstern, David; Datz, Christian; Chen, Hongda; Brenner, Hermann

2016-04-01

In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population. We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results. AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings. Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.

Carrier screening for single gene disorders.

PubMed

Rose, Nancy C; Wick, Myra

2018-04-01

Screening for genetic disorders began in 1963 with the initiation of newborn screening for phenylketonuria. Advances in molecular technology have made both newborn screening for newborns affected with serious disorders, and carrier screening of individuals at risk for offspring with genetic disorders, more complex and more widely available. Carrier screening today can be performed secondary to family history-based screening, ethnic-based screening, and expanded carrier screening (ECS). ECS is panel-based screening, which analyzes carrier status for hundreds of genetic disorders irrespective of patient race or ethnicity. In this article, we review the historical and current aspects of carrier screening for single gene disorders, including future research directions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm.

PubMed

Tota, Joseph E; Bentley, James; Blake, Jennifer; Coutlée, François; Duggan, Máire A; Ferenczy, Alex; Franco, Eduardo L; Fung-Kee-Fung, Michael; Gotlieb, Walter; Mayrand, Marie-Hélène; McLachlin, Meg; Murphy, Joan; Ogilvie, Gina; Ratnam, Sam

2017-05-01

Since being introduced in the 1940s, cervical cytology - despite its limitations - has had unequivocal success in reducing cervical cancer burden in many countries. However, we now know that infection with human papillomavirus (HPV) is a necessary cause of cervical cancer and there is overwhelming evidence from large-scale clinical trials, feasibility studies and real-world experience that supports the introduction of molecular testing for HPV as the primary technology in cervical cancer screening (i.e., "HPV primary screening"). While questions remain about the most appropriate age groups for screening, screening interval and triage approach, these should not be considered barriers to implementation. Many countries are in various stages of adopting HPV primary screening, whereas others have not taken any major steps towards introduction of this approach. As a group of clinical experts and researchers in cervical cancer prevention from across Canada, we have jointly authored this comprehensive examination of the evidence to implement HPV primary screening. Our intention is to create a common understanding among policy makers, agencies, clinicians, researchers and other stakeholders about the evidence concerning HPV primary screening to catalyze the adoption of this improved approach to cervical cancer prevention. With the first cohort of vaccinated girls now turning 21, the age when routine screening typically begins, there is increased urgency to introduce HPV primary screening, whose performance may be less adversely affected compared with cervical cytology as a consequence of reduced lesion prevalence post-vaccination. Published by Elsevier Inc.

Molecular screening for hemotropic mycoplasmas in captive Barbary sheep (Ammotragus lervia) in southern Brazil.

PubMed

Santos, Leonilda C; Vidotto, Odilon; Morikawa, Vivien M; Santos, Nelson J R; Vieira, Thállitha S W J; Barros Filho, Ivan R; Vieira, Rafael F C; Biondo, Alexander W

2017-08-01

This study is part of an active surveillance program for monitoring animal health status in endangered species, and was conducted to screen captive Barbary sheep ( Ammotragus lervia ) for hemoplasma infection. A total of 12 blood samples were collected, DNA extracted and further tested by a pan-hemoplasma polymerase chain reaction protocol. Animals were clinically healthy and not infested by ectoparasites. Although housekeeping gene DNA was successfully amplified, all the Barbary sheep samples tested negative for Mycoplasma sp. Notwithstanding the negative results, molecular pathogen surveys on Barbary sheep and other exotic wild mammals may provide insights regarding infection of endangered species caused by captivity stress in association with exposure to new pathogens worldwide.

Screening and characterization of novel bacteriocins from lactic acid bacteria.

PubMed

Zendo, Takeshi

2013-01-01

Bacteriocins produced by lactic acid bacteria (LAB) are expected to be safe antimicrobial agents. While the best studied LAB bacteriocin, nisin A, is widely utilized as a food preservative, various novel ones are required to control undesirable bacteria more effectively. To discover novel bacteriocins at the early step of the screening process, we developed a rapid screening system that evaluates bacteriocins produced by newly isolated LAB based on their antibacterial spectra and molecular masses. By means of this system, various novel bacteriocins were identified, including a nisin variant, nisin Q, a two-peptide bacteriocin, lactococcin Q, a leaderless bacteriocin, lacticin Q, and a circular bacteriocin, lactocyclicin Q. Moreover, some LAB isolates were found to produce multiple bacteriocins. They were characterized as to their structures, mechanisms of action, and biosynthetic mechanisms. Novel LAB bacteriocins and their biosynthetic mechanisms are expected for applications such as food preservation and peptide engineering.

Molecular classification of gastric cancer.

PubMed

Röcken, Christoph

2017-03-01

Gastric cancer is among the most common cancers worldwide. Despite declining incidences, the prognosis remains dismal in Western countries and is better in Asian countries with national cancer screening programs. Complete endoscopic or surgical resection of the primary tumor with or without lymphadenectomy offers the only chance of cure in the early stage of the disease. Survival of more locally advanced gastric cancers was improved by the introduction of perioperative, adjuvant and palliative chemotherapy. However, the identification and usage of novel predictive and diagnostic targets is urgently needed. Areas covered: Recent comprehensive molecular profiling of gastric cancer proposed four molecular subtypes, i.e. Epstein-Barr virus-associated, microsatellite instable, chromosomal instable and genomically stable carcinomas. The new molecular classification will spur clinical trials exploring novel targeted therapeutics. This review summarizes recent advancements of the molecular classification, and based on that, putative pitfalls for the development of tissue-based companion diagnostics, i.e. prevalence of actionable targets and therapeutic efficacy, tumor heterogeneity and tumor evolution, impact of ethnicity on gastric cancer biology, and standards of care in the East and West. Expert commentary: The overall low prevalence of actionable targets and tumor heterogeneity are the two main obstacles of precision medicine for gastric cancer.

A novel identification approach for discovery of 5-HydroxyTriptamine 2A antagonists: combination of 2D/3D similarity screening, molecular docking and molecular dynamics.

PubMed

Kumar, Rakesh; Jade, Dhananjay; Gupta, Dinesh

2018-03-05

5-HydroxyTriptamine 2A antagonists are potential targets for treatment of various cerebrovascular and cardiovascular disorders. In this study, we have developed and performed a unique screening pipeline for filtering ZINC database compounds on the basis of similarities to known antagonists to determine novel small molecule antagonists of 5-HydroxyTriptamine 2A. The screening pipeline is based on 2D similarity, 3D dissimilarity and a combination of 2D/3D similarity. The shortlisted compounds were docked to a 5-HydroxyTriptamine 2A homology-based model, and complexes with low binding energies (287 complexes) were selected for molecular dynamics (MD) simulations in a lipid bilayer. The MD simulations of the shortlisted compounds in complex with 5-HydroxyTriptamine 2A confirmed the stability of the complexes and revealed novel interaction insights. The receptor residues S239, N343, S242, S159, Y370 and D155 predominantly participate in hydrogen bonding. π-π stacking is observed in F339, F340, F234, W151 and W336, whereas hydrophobic interactions are observed amongst V156, F339, F234, V362, V366, F340, V235, I152 and W151. The known and potential antagonists shortlisted by us have similar overlapping molecular interaction patterns. The 287 potential 5-HydroxyTriptamine 2A antagonists may be experimentally verified.

Molecular Screening Tools to Study Arabidopsis Transcription Factors

PubMed Central

Wehner, Nora; Weiste, Christoph; Dröge-Laser, Wolfgang

2011-01-01

In the model plant Arabidopsis thaliana, more than 2000 genes are estimated to encode transcription factors (TFs), which clearly emphasizes the importance of transcriptional control. Although genomic approaches have generated large TF open reading frame (ORF) collections, only a limited number of these genes is functionally characterized, yet. This review evaluates strategies and methods to identify TF functions. In particular, we focus on two recently developed TF screening platforms, which make use of publically available GATEWAY®-compatible ORF collections. (1) The Arabidopsis thaliana TF ORF over-Expression (AtTORF-Ex) library provides pooled collections of transgenic lines over-expressing HA-tagged TF genes, which are suited for screening approaches to define TF functions in stress defense and development. (2) A high-throughput microtiter plate based protoplast trans activation (PTA) system has been established to screen for TFs which are regulating a given promoter:Luciferase construct in planta. PMID:22645547

[Clinical Practice Guide for Early Detection, Diagnosis and Treatment of the Acute Intoxication Phase in Patients with Alcohol Abuse or Dependence: Part I: Screening, Early Detection and Risk Factors in Patients with Alcohol Abuse or Dependence].

PubMed

de la Espriella Guerrero, Ricardo; de la Hoz Bradford, Ana María; Gómez-Restrepo, Carlos; Zárate, Alina Uribe-Holguín; Menéndez, Miguel Cote; Barré, Michelle Cortés; Rentería, Ana María Cano; Hernández, Delia Cristina

2012-12-01

Worldwide, alcohol is the second most-used psychotropic substance and the third risk factor for early death and disability. Its noxious use is a world public health problem given its personal, labor, family, economic and social impact. 70 % of people under risk of having alcohol problems go undetected in medical practice, a fact that underlines the need for specific screening measures allowing early detection leading to timely treatment. This article presents evidence gathered by alcohol abuse and dependence screening as well as by risk factor identification and screening. It also presents evidence concerning withdrawal symptoms, delirium tremens and Wernicke's encephalopathy in order to promote early detection and timely treatment. Systematic revision of the evidence available together with an evaluation of pertinent guidelines found in literature so as to decide whether to adopt or adapt the existing recommendation for each question or to develop de novo recommendations. For de novo recommendations as well as those adapted, it was carried out an evidence synthesis, together with evidence tables and formulation of recommendations based on the evidence. Evidence was found and recommendations were made for the pertinent screening and search of risk factors, in order to perform a diagnosis and carry out a timely management of alcohol abuse, dependence and ensuing complications: withdrawal syndrome, delirium tremens and Wernicke's encephalopathy. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Early zebrafish development: It’s in the maternal genes

PubMed Central

Abrams, Elliott W.; Mullins, Mary C.

2009-01-01

Summary The earliest stages of embryonic development in all animals examined rely on maternal gene products that are generated during oogenesis and supplied to the egg. The period of maternal control of embryonic development varies among animals according to the onset of zygotic transcription and the persistence of maternal gene products. This maternal regulation has been little studied in vertebrates, due to the difficulty in manipulating maternal gene function and lack of basic molecular information. However, recent maternal-effect screens in the zebrafish have generated more than 40 unique mutants that are providing new molecular entry points to the maternal control of early vertebrate development. Here we discuss recent studies of 12 zebrafish mutant genes that illuminate the maternal molecular controls on embryonic development, including advances in the regulation of animal-vegetal polarity, egg activation, cleavage development, body plan formation, tissue morphogenesis, microRNA function and germ cell development. PMID:19608405

Awareness levels about breast cancer risk factors, early warning signs, and screening and therapeutic approaches among Iranian adult women: a large population based study using latent class analysis.

PubMed

Tazhibi, Mahdi; Feizi, Awat

2014-01-01

Breast cancer (BC) continues to be a major cause of morbidity and mortality among women throughout the world and in Iran. Lack of awareness and early detection program in developing country is a main reason for escalating the mortality. The present research was conducted to assess the Iranian women's level of knowledge about breast cancer risk factors, early warning signs, and therapeutic and screening approaches, and their correlated determinants. In a cross-sectional study, 2250 women before participating at a community based screening and public educational program in an institute of cancer research in Isfahan, Iran, in 2012 were investigated using a self-administered questionnaire about risk factors, early warning signs, and therapeutic and screening approaches of BC. Latent class regression as a comprehensive statistical method was used for evaluating the level of knowledge and its correlated determinants. Only 33.2%, 31.9%, 26.7%, and 35.8% of study participants had high awareness levels about screening approaches, risk factors, early warning signs and therapeutic modalities of breast cancer, respectively, and majority had poor to moderate knowledge levels. Most effective predictors of high level of awareness were higher educational qualifications, attending in screening and public educational programs, personal problem, and family history of BC, respectively. Results of current study indicated that the levels of awareness among study population about key elements of BC are low. These findings reenforce the continuing need for more BC education through conducting public and professional programs that are intended to raise awareness among younger, single women and those with low educational attainments and without family history.

Molecular diagnosis of putative Stargardt disease probands by exome sequencing

PubMed Central

2012-01-01

Background The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD) caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. Methods We performed whole exome sequencing (WES) of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. Results Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. Conclusions Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques. PMID:22863181

From molecular engineering to process engineering: development of high-throughput screening methods in enzyme directed evolution.

PubMed

Ye, Lidan; Yang, Chengcheng; Yu, Hongwei

2018-01-01

With increasing concerns in sustainable development, biocatalysis has been recognized as a competitive alternative to traditional chemical routes in the past decades. As nature's biocatalysts, enzymes are able to catalyze a broad range of chemical transformations, not only with mild reaction conditions but also with high activity and selectivity. However, the insufficient activity or enantioselectivity of natural enzymes toward non-natural substrates limits their industrial application, while directed evolution provides a potent solution to this problem, thanks to its independence on detailed knowledge about the relationship between sequence, structure, and mechanism/function of the enzymes. A proper high-throughput screening (HTS) method is the key to successful and efficient directed evolution. In recent years, huge varieties of HTS methods have been developed for rapid evaluation of mutant libraries, ranging from in vitro screening to in vivo selection, from indicator addition to multi-enzyme system construction, and from plate screening to computation- or machine-assisted screening. Recently, there is a tendency to integrate directed evolution with metabolic engineering in biosynthesis, using metabolites as HTS indicators, which implies that directed evolution has transformed from molecular engineering to process engineering. This paper aims to provide an overview of HTS methods categorized based on the reaction principles or types by summarizing related studies published in recent years including the work from our group, to discuss assay design strategies and typical examples of HTS methods, and to share our understanding on HTS method development for directed evolution of enzymes involved in specific catalytic reactions or metabolic pathways.

Scoliosis Screening in Schools.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Div. of Pupil Personnel Services.

The booklet outlines New York state school policy and procedures for screening students for scoliosis, lateral curvature of the spine. It is explained that screening is designed to discover spinal deformities early enough to prevent surgery. Planning aspects, including organizing a planning team for the school district, are discussed. Among…

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

PubMed

Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

2009-09-01

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

Newborn Screening for Biliary Atresia.

PubMed

Wang, Kasper S

2015-12-01

Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child's native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States. Copyright © 2015 by the American Academy of Pediatrics.

Urinary Glucose Screening for Early Detection of Asymptomatic Type 2 Diabetes in Jeonbuk Province Korean Schoolchildren.

PubMed

Kim, Min Sun; Lee, Dae Yeol

2017-06-01

This study aimed to investigate the prevalence of glucosuria and the characteristics of diabetes in schoolchildren as detected by a school urine glucose screening program implemented from 2010 to 2013 in the Jeonbuk province area of Korea. A total of 110 children without known diabetes were analyzed. They were checked with an oral glucose tolerance test (OGTT) with other laboratory tests and their clinical data were collected. A total of 707,238 schoolchildren from a school population of 1,064,999 were screened for glucosuria. In total, over a 4-year period, 545 schoolchildren (0.077%) were positive for glucosuria on the second urine test. The prevalence of glucosuria was more common among middle and high schoolchildren than among elementary schoolchildren. Among 110 students who completed the OGTT to confirm diabetes, 40 were diagnosed with diabetes mellitus (DM); 39 children, type 2 diabetes mellitus (T2DM) and 1 child, slowly progressive insulin dependent diabetes mellitus (SPIDDM). The mean annual incidence of diabetes was 5.6 per 100,000 schoolchildren and adolescents. The subjects with diabetes diagnosed through the urine screening test showed minimal or no symptoms of diabetes. The students with diabetes were more likely to be woman and obese, and they have a higher body mass index, higher cholesterol, triglyceride, insulin, C-peptide, and fasting glucosuria values than the students with normal glucose tolerance. We identified 40 new cases of diabetes in the Korean schoolchildren with asymptomatic glucosuria on urine glucose screening. This finding shows that school urine glucose screening is a feasible and simple method for early detection of asymptomatic T2DM. © 2017 The Korean Academy of Medical Sciences.

Urinary Glucose Screening for Early Detection of Asymptomatic Type 2 Diabetes in Jeonbuk Province Korean Schoolchildren

PubMed Central

2017-01-01

This study aimed to investigate the prevalence of glucosuria and the characteristics of diabetes in schoolchildren as detected by a school urine glucose screening program implemented from 2010 to 2013 in the Jeonbuk province area of Korea. A total of 110 children without known diabetes were analyzed. They were checked with an oral glucose tolerance test (OGTT) with other laboratory tests and their clinical data were collected. A total of 707,238 schoolchildren from a school population of 1,064,999 were screened for glucosuria. In total, over a 4-year period, 545 schoolchildren (0.077%) were positive for glucosuria on the second urine test. The prevalence of glucosuria was more common among middle and high schoolchildren than among elementary schoolchildren. Among 110 students who completed the OGTT to confirm diabetes, 40 were diagnosed with diabetes mellitus (DM); 39 children, type 2 diabetes mellitus (T2DM) and 1 child, slowly progressive insulin dependent diabetes mellitus (SPIDDM). The mean annual incidence of diabetes was 5.6 per 100,000 schoolchildren and adolescents. The subjects with diabetes diagnosed through the urine screening test showed minimal or no symptoms of diabetes. The students with diabetes were more likely to be woman and obese, and they have a higher body mass index, higher cholesterol, triglyceride, insulin, C-peptide, and fasting glucosuria values than the students with normal glucose tolerance. We identified 40 new cases of diabetes in the Korean schoolchildren with asymptomatic glucosuria on urine glucose screening. This finding shows that school urine glucose screening is a feasible and simple method for early detection of asymptomatic T2DM. PMID:28480657

Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening.

PubMed

Grinzaid, Karen Arnovitz; Page, Patricia Zartman; Denton, Jessica Johnson; Ginsberg, Jessica

2015-06-01

Ethnicity-based carrier screening for the Ashkenazi Jewish population has been available and encouraged by advocacy and community groups since the early 1970's. Both the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists recommend carrier screening for this population (Obstetrics and Gynecology, 114(4), 950-953, 2009; Genetics in Medicine, 10(1), 55-56, 2008). While many physicians inquire about ethnic background and offer appropriate carrier screening, studies show that a gap remains in implementing recommendations (Genetic testing and molecular biomarkers, 2011). In addition, education and outreach efforts targeting Jewish communities have had limited success in reaching this at-risk population. Despite efforts by the medical and Jewish communities, many Jews of reproductive age are not aware of screening, and remain at risk for having children with preventable diseases. Reaching this population, preferably pre-conception, and facilitating access to screening is critically important. To address this need, genetic counselors at Emory University developed JScreen, a national Jewish genetic disease screening program. The program includes a national marketing and PR campaign, online education, at-home saliva-based screening, post-test genetic counseling via telephone or secure video conferencing, and referrals for face-to-face genetic counseling as needed. Our goals are to create a successful education and screening program for this population and to develop a model that could potentially be used for other at-risk populations.

Blocking the interaction between HIV-1 integrase and human LEDGF/p75: mutational studies, virtual screening and molecular dynamics simulations.

PubMed

Reddy, Karnati Konda; Singh, Poonam; Singh, Sanjeev Kumar

2014-03-04

HIV-1 integrase (IN) mediates integration of viral cDNA into the host cell genome, an essential step in the retroviral life cycle. The human lens epithelium-derived growth factor (LEDGF/p75) is a co-factor of HIV-1 IN that plays a crucial role in viral integration. Because of its crucial role in early steps of HIV replication, the IN-LEDGF/p75 interaction represents an attractive target for anti-HIV drug discovery. In this study, the IN-LEDGF/p75 interaction was studied by in silico mutational studies and molecular dynamics simulations. The results showed that all of the key residues in the LEDGF/p75 binding pocket of IN protein are important for stabilization of the complex. Structure-based virtual screening against HIV-1 IN using the ChemBridge database was performed through three different protocols of docking simulations with varying precisions and computational intensities. Six compounds based on the docking score, binding affinity and pharmacokinetic parameters were selected and an analysis of the interactions with key amino acid residues of IN was carried out. Subsequently, molecular dynamics simulations of these compounds in the LEDGF/p75 binding site of IN were carried out in order to study the stability of complexes and their hydrogen bonding interactions. IN residues Glu170, His171, and Thr174 in chain A as well as Gln95 and Thr125 in chain B were discovered to play important roles in the binding of compounds. These findings could be helpful for blocking IN-LEDGF/p75 interaction, and provide a method for avoiding viral resistance and cross-resistance.

Development of a Robust Static Punch Experiment for Screening Unprocessed Ultra-High Molecular Weight Polyethylene (UHMWPE) Unidirectional Cross-Ply Material

DTIC Science & Technology

2014-09-01

Cross-Ply Material by David Gray, Robert Kaste , and Paul Moy ARL-TR-7090 September 2014...Screening Unprocessed Ultra-High Molecular Weight Polyethylene (UHMWPE) Unidirectional Cross-Ply Material David Gray, Robert Kaste , and Paul...ELEMENT NUMBER 6. AUTHOR(S) David Gray, Robert Kaste , and Paul Moy 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7

Screening for skin cancer.

PubMed

Helfand, M; Mahon, S M; Eden, K B; Frame, P S; Orleans, C T

2001-04-01

Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers

Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

PubMed

Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

2012-04-15

Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

Alterations in molecular pathways in the retina of early experimental glaucoma eyes

PubMed Central

Cao, Li; Wang, Lin; Cull, Grant; Zhou, An

2015-01-01

Glaucoma is a multifactorial, neurodegenerative disease. The molecular mechanisms that underlie the pathophysiological changes in glaucomatous eyes, especially at the early stage of the disease, are poorly understood. Here, we report the findings from a quantitative proteomic analysis of retinas from experimental glaucoma (EG) eyes. An early stage of EG was modeled on unilateral eyes of five nonhuman primates (NHP) by laser treatment-induced elevation of intraocular pressure (IOP). Retinal proteins were extracted from individual EG eyes and their contralateral control eyes of the same animals, respectively, and analyzed by quantitative mass spectrometry (MS). As a result, a total, 475 retinal proteins were confidently identified and quantified. Results of bioinformatic analysis of proteins that showed an increase in the EG eyes suggested changes in apoptosis, DNA damage, immune response, cytoskeleton rearrangement and cell adhesion processes. Interestingly, hemoglobin subunit alpha (HBA) and Ras related C3 botulinum toxin substrate 1 (Rac1) were among the increased proteins. Results of molecular modeling of HBA- and Rac1-associated signaling network implicated the involvement of Mitogen-Activated Protein Kinase (MAPK) pathway in the EG, through which Rac1 may exert a regulatory role on HBA. This is the first observation of this potentially novel signaling network in the NHP retina and in EG. Results of Western blot analyses for Rac1, HBA and a selected MAPK pathway protein indicated synergistic changes in all three proteins in the EG eyes. Further, results of hierarchical cluster analysis of proteomes of control eyes revealed a clear age-proteome relationship, and such relationship appeared disrupted in the EG eyes. In conclusion, our results suggested an increased presence of a potentially novel signaling network at the early stage of glaucoma, and age might be one of the determinant factors in retinal proteomic characteristics under normal conditions. PMID

Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

DTIC Science & Technology

2014-08-01

AD_________________ Award Number: W81XWH-12-1-0323 TITLE: Advanced Lung Cancer Screening: An...Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION...August 2014 2. REPORT TYPE Annual 3. DATES COVERED 1 Aug 2013 – 31 July 2014 4. TITLE AND SUBTITLE Advanced Lung Cancer Screening: An Individualized

Molecular genetics of early-onset Alzheimer's disease revisited.

PubMed

Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

2016-06-01

As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular Quantum Similarity, Chemical Reactivity and Database Screening of 3D Pharmacophores of the Protein Kinases A, B and G from Mycobacterium tuberculosis.

PubMed

Morales-Bayuelo, Alejandro

2017-06-21

Mycobacterium tuberculosis remains one of the world's most devastating pathogens. For this reason, we developed a study involving 3D pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases A, B, and G. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these compounds, with anti-tuberculosis activity. Using the Molecular Quantum Similarity field and reactivity descriptors supported in the Density Functional Theory, it was possible to measure the quantification of the steric and electrostatic effects through the Overlap and Coulomb quantitative convergence (alpha and beta) scales. In addition, an analysis of reactivity indices using global and local descriptors was developed, identifying the binding sites and selectivity on these anti-tuberculosis compounds in the active sites. Finally, the reported pharmacophores to PKn A, B and G, were used to carry out database screening, using a database with anti-tuberculosis drugs from the Kelly Chibale research group (http://www.kellychibaleresearch.uct.ac.za/), to find the compounds with affinity for the specific protein targets associated with PKn A, B and G. In this regard, this hybrid methodology (Molecular Mechanic/Quantum Chemistry) shows new insights into drug design that may be useful in the tuberculosis treatment today.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

PubMed Central

Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Saraiya, Mona; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

2013-01-01

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22418039

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

PubMed Central

Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

2013-01-01

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium cosponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22422631

Molecular screening for hemotropic mycoplasmas in captive Barbary sheep (Ammotragus lervia) in southern Brazil

PubMed Central

Santos, Leonilda C.; Vidotto, Odilon; Morikawa, Vivien M.; Santos, Nelson J. R.; Vieira, Thállitha S. W. J.; Barros Filho, Ivan R.; Vieira, Rafael F. C.; Biondo, Alexander W.

2017-01-01

Aim: This study is part of an active surveillance program for monitoring animal health status in endangered species, and was conducted to screen captive Barbary sheep (Ammotragus lervia) for hemoplasma infection. Materials and Methods: A total of 12 blood samples were collected, DNA extracted and further tested by a pan-hemoplasma polymerase chain reaction protocol. Results: Animals were clinically healthy and not infested by ectoparasites. Although housekeeping gene DNA was successfully amplified, all the Barbary sheep samples tested negative for Mycoplasma sp. Conclusion: Notwithstanding the negative results, molecular pathogen surveys on Barbary sheep and other exotic wild mammals may provide insights regarding infection of endangered species caused by captivity stress in association with exposure to new pathogens worldwide. PMID:28919684

Cervical Cancer Screening in an Early Diagnosis and Screening Center in Mersin, Turkey.

PubMed

Nayir, Tufan; Okyay, Ramazan Azim; Nazlican, Ersin; Yesilyurt, Hakki; Akbaba, Muhsin; Ilhan, Berrin; Kemik, Aytekin

2015-01-01

Cancer is a major public health problem due to the jeavy disease burden, fatality and tendency for increased incidence. Of all cancer types, cervical cancer is reported to be the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases worldwide in 2012. It features a long preclinical phase with slowly progressing precancerous lesions such as CIN 2 and 3 and adenocarcinoma in situ. Therefore, screening programs such as with Pap smear tests may play an important role in cervical cancer prevention. The purpose of this study was to present results of a Pap smear screening survey for cervical cancer targeting women living in an urban area in the province of Mersin, located in the Mediterranean region of Turkey. This community- based descriptive study included women living at Akdeniz county of Mersin province. A total of 1,032 screened women between 30 and 65 ages within the routine screening programme constituted the study population. The mean age of the participants was 43.8 ± 8.6 (min. 30, max. 65) years. The percentage of the participants who had previously undergone smears was 40.6%. Epithelial cell changes were found in 26 (2.5%) participants, with ASC-US in 18 (1.7%), ASC-H in 2 (0.2%), LSIL in 5 (0.5%) and HSIL in 1 (0.1%). The most common clinical presentation together with epithelial changes was abnormal vaginal discharge. Taking into account the presence of women who had never undergone Pap test; it should be offered at primary level of health care in the form of a community-based service to achieve reduced morbidity and mortality rates.

Combining simple patient-oriented tests with state-of-the-art molecular diagnostics for early diagnosis of cancer.

PubMed

Fitzgerald, Rebecca C

2015-06-01

Early diagnosis is an important strategy to improve outcomes from cancer. Oesophageal adenocarcinoma is an example of a cancer that presents late, with very poor outcomes, and for which the presence of the precursor lesion Barrett's oesophagus provides the opportunity to intervene at an early stage. In this review, I describe the challenges in the field and the work that we have done to devise a conceptually novel approach to early diagnosis, using a cell collection device (Cytosponge), coupled with molecular assays. This is a personal perspective in which I also describe the career pathway that led me into academic gastroenterology, and the rewards and challenges of translational research in molecular diagnostics. There are fantastic opportunities for clinicians wishing to pursue academic medicine, because it is a time when massive strides are being made in a whole number of areas; for example: imaging, sequencing technology and targeted therapies. Clinicians who can straddle the laboratory and the clinic are essential, to maximise the progress that can be made for the benefit of patients.

Simple many-body based screening mixing ansatz for improvement of G W /Bethe-Salpeter equation excitation energies of molecular systems

NASA Astrophysics Data System (ADS)

Ziaei, Vafa; Bredow, Thomas

2017-11-01

We propose a simple many-body based screening mixing strategy to considerably enhance the performance of the Bethe-Salpeter equation (BSE) approach for prediction of excitation energies of molecular systems. This strategy enables us to closely reproduce results of highly correlated equation of motion coupled cluster singles and doubles (EOM-CCSD) through optimal use of cancellation effects. We start from the Hartree-Fock (HF) reference state and take advantage of local density approximation (LDA) based random phase approximation (RPA) screening, denoted as W0-RPA@LDA with W0 as the dynamically screened interaction built upon LDA wave functions and energies. We further use this W0-RPA@LDA screening as an initial screening guess for calculation of quasiparticle energies in the framework of G0W0 @HF. The W0-RPA@LDA screening is further injected into the BSE. By applying such an approach on a set of 22 molecules for which the traditional G W /BSE approaches fail, we observe good agreement with respect to EOM-CCSD references. The reason for the observed good accuracy of this mixing ansatz (scheme A) lies in an optimal damping of HF exchange effect through the W0-RPA@LDA strong screening, leading to substantial decrease of typically overestimated HF electronic gap, and hence to better excitation energies. Further, we present a second multiscreening ansatz (scheme B), which is similar to scheme A with the exception that now the W0-RPA@HF screening is used in the BSE in order to further improve the overestimated excitation energies of carbonyl sulfide (COS) and disilane (Si2H6 ). The reason for improvement of the excitation energies in scheme B lies in the fact that W0-RPA@HF screening is less effective (and weaker than W0-RPA@LDA), which gives rise to stronger electron-hole effects in the BSE.

Quantum probability ranking principle for ligand-based virtual screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening

NASA Astrophysics Data System (ADS)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Screening of photosynthetic pigments for herbicidal activity with a new computational molecular approach.

PubMed

Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela

2013-12-01

There is an immense interest among the researchers to identify new herbicides which are effective against the herbs without affecting the environment. In this work, photosynthetic pigments are used as the ligands to predict their herbicidal activity. The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is a good target for the herbicides. Homology modeling of the target enzyme is done using Modeler 9.11 and the model is validated. Docking studies were performed with AutoDock Vina algorithm to predict the binding of the natural pigments such as β-carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin to the target. β-carotene, phycoerythrin and phycocyanin have higher binding energies indicating the herbicidal activity of the pigments. This work reports a procedure to screen herbicides with computational molecular approach. These pigments will serve as potential bioherbicides in the future.

Colorectal Cancer Screening: An Educational Intervention for Nurse Practitioners to Increase Screening Awareness and Participation
.

PubMed

Slyne, Tai C; Gautam, Ramraj; King, Valerie

2017-10-01

Colorectal cancer screening aims to detect colorectal cancer at an early stage, when treatment is more likely to be curative. Lack of participation in such screening is a major issue in primary care practices, where nurse practitioners (NPs) often provide care. This study aimed to determine whether an educational intervention for NPs would increase their awareness of, and increase patients' participation in, colorectal cancer screening. 
.

Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants.

PubMed

Almawazini, Abdulmajid M; Hanafi, Hamdi K; Madkhali, Hasan A; Majrashi, Noura B

2017-10-01

To evaluate the effectiveness of critical congenital heart disease (CCHD) screening program for early diagnosis of cardiac anomalies in newborn infants.  Methods: This is a hospital-based prospective cross-sectional study conducted in the Pediatric and Neonatology Department, King Fahad Hospital at  Albaha, Saudi Arabia, between February 2016 and February 2017. Results: We screened 2961 (95.4%) of 3103 patients in a nursery unit; 142 (4.6%) patients were not screened. The test was positive in 114 (3.9%) patients and negative in 2847 (96.1%). There were 94 (3.2%) false positives and 20 (0.7%) true positives. Critical cardiac defects were diagnosed in 7 (0.2%) patients of all screened infants, and severe pulmonary hypertension was diagnosed in 13 (0.4%) patients. True negative results were found in 2841(96%) patients, and no cardiac defect was diagnosed, whereas false negative results were seen in 6 (0.2%) patients diagnosed with ventricular septal defect. The sensitivity was 77%, and the specificity was very high at 97%, with a positive predictive value of 18%, and a negative predictive value of 99.8% (95% confidence interval 13.78-19.18, p=0.0001). Conclusion: Pulse oximetry was found to be easy, safe, sensitive, and highly specific for diagnosis of CCHD.

Screening the molecular targets of ovarian cancer based on bioinformatics analysis.

PubMed

Du, Lei; Qian, Xiaolei; Dai, Chenyang; Wang, Lihua; Huang, Ding; Wang, Shuying; Shen, Xiaowei

2015-01-01

Ovarian cancer (OC) is the most lethal gynecologic malignancy. This study aims to explore the molecular mechanisms of OC and identify potential molecular targets for OC treatment. Microarray gene expression data (GSE14407) including 12 normal ovarian surface epithelia samples and 12 OC epithelia samples were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) between 2 kinds of ovarian tissue were identified by using limma package in R language (|log2 fold change| gt;1 and false discovery rate [FDR] lt;0.05). Protein-protein interactions (PPIs) and known OC-related genes were screened from COXPRESdb and GenBank database, respectively. Furthermore, PPI network of top 10 upregulated DEGs and top 10 downregulated DEGs was constructed and visualized through Cytoscape software. Finally, for the genes involved in PPI network, functional enrichment analysis was performed by using DAVID (FDR lt;0.05). In total, 1136 DEGs were identified, including 544 downregulated and 592 upregulated DEGs. Then, PPI network was constructed, and DEGs CDKN2A, MUC1, OGN, ZIC1, SOX17, and TFAP2A interacted with known OC-related genes CDK4, EGFR/JUN, SRC, CLI1, CTNNB1, and TP53, respectively. Moreover, functions about oxygen transport and embryonic development were enriched by the genes involved in the network of downregulated DEGs. We propose that 4 DEGs (OGN, ZIC1, SOX17, and TFAP2A) and 2 functions (oxygen transport and embryonic development) might play a role in the development of OC. These 4 DEGs and known OC-related genes might serve as therapeutic targets for OC. Further studies are required to validate these predictions.

[Steps to transform a necessity into a validated and useful screening tool for early detection of developmental problems in Mexican children].

PubMed

Rizzoli-Córdoba, Antonio; Delgado-Ginebra, Ismael

A screening test is an instrument whose primary function is to identify individuals with a probable disease among an apparently healthy population, establishing risk or suspicion of a disease. Caution must be taken when using a screening tool in order to avoid unrealistic measurements, delaying an intervention for those who may benefit from it. Before introducing a screening test into clinical practice, it is necessary to certify the presence of some characteristics making its worth useful. This "certification" process is called validation. The main objective of this paper is to describe the different steps that must be taken, from the identification of a need for early detection through the generation of a validated and reliable screening tool using, as an example, the process for the modified version of the Child Development Evaluation Test (CDE or Prueba EDI) in Mexico. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Bayesian screening for active compounds in high-dimensional chemical spaces combining property descriptors and molecular fingerprints.

PubMed

Vogt, Martin; Bajorath, Jürgen

2008-01-01

Bayesian classifiers are increasingly being used to distinguish active from inactive compounds and search large databases for novel active molecules. We introduce an approach to directly combine the contributions of property descriptors and molecular fingerprints in the search for active compounds that is based on a Bayesian framework. Conventionally, property descriptors and fingerprints are used as alternative features for virtual screening methods. Following the approach introduced here, probability distributions of descriptor values and fingerprint bit settings are calculated for active and database molecules and the divergence between the resulting combined distributions is determined as a measure of biological activity. In test calculations on a large number of compound activity classes, this methodology was found to consistently perform better than similarity searching using fingerprints and multiple reference compounds or Bayesian screening calculations using probability distributions calculated only from property descriptors. These findings demonstrate that there is considerable synergy between different types of property descriptors and fingerprints in recognizing diverse structure-activity relationships, at least in the context of Bayesian modeling.

Drug screening in medical examiner casework by high-resolution mass spectrometry (UPLC-MSE-TOF).

PubMed

Rosano, Thomas G; Wood, Michelle; Ihenetu, Kenneth; Swift, Thomas A

2013-10-01

Postmortem drug findings yield important analytical evidence in medical examiner casework, and chromatography coupled with nominal mass spectrometry (MS) serves as the predominant general unknown screening approach. We report screening by ultra performance liquid chromatography (UPLC) coupled with hybrid quadrupole time-of-flight mass spectrometer (MS(E)-TOF), with comparison to previously validated nominal mass UPLC-MS and UPLC-MS-MS methods. UPLC-MS(E)-TOF screening for over 950 toxicologically relevant drugs and metabolites was performed in a full-spectrum (m/z 50-1,000) mode using an MS(E) acquisition of both molecular and fragment ion data at low (6 eV) and ramped (10-40 eV) collision energies. Mass error averaged 1.27 ppm for a large panel of reference drugs and metabolites. The limit of detection by UPLC-MS(E)-TOF ranges from 0.5 to 100 ng/mL and compares closely with UPLC-MS-MS. The influence of column recovery and matrix effect on the limit of detection was demonstrated with ion suppression by matrix components correlating closely with early and late eluting reference analytes. Drug and metabolite findings by UPLC-MS(E)-TOF were compared with UPLC-MS and UPLC-MS-MS analyses of postmortem blood in 300 medical examiner cases. Positive findings by all methods totaled 1,528, with a detection rate of 57% by UPLC-MS, 72% by UPLC-MS-MS and 80% by combined UPLC-MS and UPLC-MS-MS screening. Compared with nominal mass screening methods, UPLC-MS(E)-TOF screening resulted in a 99% detection rate and, in addition, offered the potential for the detection of nontargeted analytes via high-resolution acquisition of molecular and fragment ion data.

Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.

PubMed

Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G; Lillquist, Yolanda P; Waters, Paula J; Olpin, S; Andresen, B S; Palaty, Jan; Nelson, Judie; Vallance, Hilary

2008-01-01

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis of MCAD and presymptomatic treatment can potentially reduce morbidity and mortality. To evaluate incidence, clinical outcome, biochemical and molecular phenotype of MCAD cases detected in the first three years of newborn screening in British Columbia (BC). Medium chain length acylcarnitines, octanoylcarnitine (C8) and decanoylcarnitine (C10), were measured on newborn screening blood spot cards. Out of 121,000 live births, 17 newborns had C8 values above the screening cut-off of 0.38 umol/L. Ten newborns had elevated C8 on repeat cards and were investigated further. Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second mutation. Two novel mutations were identified (c.260T > C and c.382T > A). The estimated incidence of MCAD was approximately 1:12,000 live births. Upon frequent feeding and carnitine supplementation, none of the patients had metabolic crises or adverse outcomes. Frequency of MCAD in BC is comparable to reports from other newborn screening programs. Persistence of elevated C8 levels and C8/C10 ratios in confirmed MCAD cases suggest that these are sensitive markers for newborn screening. Early detection and treatment have successfully prevented adverse health outcomes in patients with MCAD.

Health system barriers and enablers to early access to breast cancer screening, detection, and diagnosis: a global analysis applied to the MENA region.

PubMed

Bowser, D; Marqusee, H; El Koussa, M; Atun, R

2017-11-01

To identify barriers and enablers that impact access to early screening, detection, and diagnosis of breast cancer both globally and more specifically in the Middle East and North Africa (MENA) region (with a specific focus on Egypt, Jordan, Oman, Saudi Arabia, United Arab Emirates [UAE], and Kuwait) with a specific focus on the health system. A systematic review of literature. We conducted a systematic reviewing using the PRISMA methodology. We searched PubMed, Global Index Medicus, and EMBASE for studies on 'breast cancer', 'breast neoplasm,' or 'screening, early detection, and early diagnosis' as well as key words related to the following barriers: religion, culture, health literacy, lack of knowledge/awareness/understanding, attitudes, fatalism/fear, shame/embarrassment, and physician gender from January 1, 2000 until September 1, 2016. Two independent reviewers screened both titles and abstracts. The application of inclusion and exclusion criteria yielded a final list of articles. A conceptual framework was used to guide the thematic analysis and examine health system barriers and enablers to breast cancer screening at the broader macro health system level, at the health provider level, and the individual level. The analysis was conducted globally and in the MENA region. A total of 11,936 references were identified through the initial search strategy, of which 55 were included in the final thematic analysis. The results found the following barriers and enablers to access to breast cancer screening at the health system level, the health provider level, and the individual level: health system structures such as health insurance and care coordination systems, costs, time concerns, provider characteristics including gender of the provider, quality of care issues, medical concerns, and fear. In addition, the following seven barriers and enablers were identified at the health system or provider level as significantly impacting screening for breast cancer: (1) access

Sensitive HIV-1 detection in a homogeneous solution based on an electrochemical molecular beacon coupled with a nafion-graphene composite film modified screen-printed carbon electrode.

PubMed

Li, Bo; Li, Zhengliang; Situ, Bo; Dai, Zong; Liu, Qinlan; Wang, Qian; Gu, Dayong; Zheng, Lei

2014-02-15

A novel electrochemical sensing assay for sensitive determination of HIV-1 in a homogeneous solution has been developed using an electrochemical molecular beacon combined with a nafion-graphene composite film modified screen-printed carbon electrode (nafion-graphene/SPCE). The electrochemical molecular beacon (CAs-MB), comprising a special recognition sequence for the conserved region of the HIV-1 gag gene and a pair of carminic acid molecules as a marker, can indicate the presence of the HIV-1 target by its on/off electrochemical signal behavior. It is suitable for direct, electrochemical determination of HIV-1, thereby simplifying the detection procedure and improving the signal-to-noise (S/N) ratio. To further improve the sensitivity, the nafion-graphene/SPCE was used to monitor changes in the CAs-MB, which has notable advantages, such as being ultrasensitive, inexpensive, and disposable. Under optimized conditions, the peak currents showed a linear relationship with the logarithm of target oligonucleotide concentrations ranging from 40 nM to 2.56 μM, with a detection limit of 5 nM (S/N=3). This sensing assay also displays a good stability, with a recovery of 88-106.8% and RSD<7% (n=5) in real serum samples. This work may lead to the development of an effective method for early point-of-care diagnosis of HIV-1 infection. © 2013 Elsevier B.V. All rights reserved.

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

PubMed

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

Screening: mapping medicine's temporal spaces.

PubMed

Armstrong, David

2012-02-01

This paper examines the history of population screening through an analysis of contemporary medical journals. The term was first used in the modern sense in the inter-war years to describe the school health examination which sought to identify the early signs of disease and abnormality, a strategy which was extended to new recruits during the Second World War. After the war, screening began to target those illnesses in the civilian population which had a clear temporal trajectory, especially 'chronic' illnesses. Since the 1980s, enthusiasm for population screening has declined within the medical community: opportunistic screening has seemed more appropriate for diseases with multifactorial aetiology, and those programmes which have survived have been increasingly challenged through an expanding analysis of their potential harms. In identifying the early precursors of clinical disease in apparently normal populations, however, screening heralded the emergence of a new form of clinical practice concerned with the surveillance of 'healthy' patients within the context of new temporal spaces of illness. © 2012 The Author. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

A New Screening Programme for Autism in a General Population of Swedish Toddlers

ERIC Educational Resources Information Center

Nygren, Gudrun; Sandberg, Eva; Gillstedt, Fredrik; Ekeroth, Gunnar; Arvidsson, Thomas; Gillberg, Christopher

2012-01-01

The evidence from early intervention studies of autism has emphasised the need for early diagnosis. Insight into the early presentation of autism is crucial for early recognition, and routine screening can optimise the possibility for early diagnosis. General population screening was conducted for 2.5-year-old children at child health centres in…

Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection

PubMed Central

Becker, Andrew E; Hernandez, Yasmin G; Frucht, Harold; Lucas, Aimee L

2014-01-01

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several large-volume centers have initiated such screening protocols, and consensus-based guidelines for screening high-risk groups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields. PMID:25170203

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

PubMed

Tammemagi, Martin C; Schmidt, Heidi; Martel, Simon; McWilliams, Annette; Goffin, John R; Johnston, Michael R; Nicholas, Garth; Tremblay, Alain; Bhatia, Rick; Liu, Geoffrey; Soghrati, Kam; Yasufuku, Kazuhiro; Hwang, David M; Laberge, Francis; Gingras, Michel; Pasian, Sergio; Couture, Christian; Mayo, John R; Nasute Fauerbach, Paola V; Atkar-Khattra, Sukhinder; Peacock, Stuart J; Cressman, Sonya; Ionescu, Diana; English, John C; Finley, Richard J; Yee, John; Puksa, Serge; Stewart, Lori; Tsai, Scott; Haider, Ehsan; Boylan, Colm; Cutz, Jean-Claude; Manos, Daria; Xu, Zhaolin; Goss, Glenwood D; Seely, Jean M; Amjadi, Kayvan; Sekhon, Harmanjatinder S; Burrowes, Paul; MacEachern, Paul; Urbanski, Stefan; Sin, Don D; Tan, Wan C; Leighl, Natasha B; Shepherd, Frances A; Evans, William K; Tsao, Ming-Sound; Lam, Stephen

2017-11-01

Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer

The Rising Incidence of Younger Patients With Colorectal Cancer: Questions About Screening, Biology, and Treatment.

PubMed

Connell, Louise C; Mota, José Mauricio; Braghiroli, Maria Ignez; Hoff, Paulo M

2017-04-01

Colorectal cancer (CRC) is the third leading cancer diagnosed globally and an important cause of cancer-related mortality. Of interest, while we have witnessed a declining incidence trend over the past few decades in the older population, incidence rates for adolescents and young adults have been increasing steadily. Several factors may well explain this apparent epidemic in the young, namely a lack of routine screening and emerging lifestyle issues such as obesity, lack of exercise, and dietary factors. It is known that both environmental and genetic factors can increase the likelihood of developing CRC. Although inherited susceptibility is associated with the most striking increases in risk, and must always be considered in a young patient with CRC, the majority of CRCs are in fact sporadic rather than familial. Early-onset CRC is a truly heterogeneous disease, with mounting evidence to suggest that this patient population has a distinctive molecular profile, very different to late-onset CRC cases. Currently, both younger and older patients with CRC are treated in essentially the same manner, but with a better understanding of the molecular mechanisms underlying CRC in the young, we will have the opportunity to specifically tailor screening and clinical management strategies in this unique patient population in an effort to improve outcomes. The aim of this review is to outline our current knowledge of the distinguishing features of early-onset CRC, the ongoing research efforts, and the evolving evidence in this field.

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States

PubMed Central

Miller, Marcus J.; Burrage, Lindsay C.; Gibson, James B.; Strenk, Meghan E.; Lose, Edward J.; Bick, David P.; Elsea, Sarah H.; Sutton, V. Reid; Sun, Qin; Graham, Brett H.; Craigen, William J.; Zhang, Victor Wei; Wong, Lee-Jun C.

2016-01-01

Very long chain acyl-coA dehydrogenase deficiency (VLCADD) is an autosomal recessive inborn error of fatty acid oxidation detected by newborn screening (NBS). Follow-up molecular analyses are often required to clarify VLCADD-suggestive NBS results, but to date the outcome of these studies are not well described for the general screen-positive population. In the following study, we report the molecular findings for 693 unrelated patients that sequentially received Sanger sequence analysis of ACADVL as a result of a positive NBS for VLCADD. Highlighting the variable molecular underpinnings of this disorder, we identified 94 different pathogenic ACADVL variants (40 novel), as well as 134 variants of unknown clinical significance (VUSs). Evidence for the pathogenicity of a subset of recurrent VUSs was provided using multiple in silico analyses. Surprisingly, the most frequent finding in our cohort was carrier status, 57% all individuals had a single pathogenic variant or VUS. This result was further supported by follow-up array and/or acylcarnitine analysis that failed to provide evidence of a second pathogenic allele. Notably, exon-targeted array analysis of 131 individuals screen positive for VLCADD failed to identify copy number changes in ACADVL thus suggesting this test has a low yield in the setting of NBS follow-up. While no genotype was common, the c.848T>C (p.V283A) pathogenic variant was clearly the most frequent; at least one copy was found in ∼10% of all individuals with a positive NBS. Clinical and biochemical data for seven unrelated patients homozygous for the p.V283A allele suggests that it results in a mild phenotype that responds well to standard treatment, but hypoglycemia can occur. Collectively, our data illustrate the molecular heterogeneity of VLCADD and provide novel insight into the outcomes of NBS for this disorder. PMID:26385305

Drug and bioactive molecule screening based on a bioelectrical impedance cell culture platform

PubMed Central

Ramasamy, Sakthivel; Bennet, Devasier; Kim, Sanghyo

2014-01-01

This review will present a brief discussion on the recent advancements of bioelectrical impedance cell-based biosensors, especially the electric cell-substrate impedance sensing (ECIS) system for screening of various bioactive molecules. The different technical integrations of various chip types, working principles, measurement systems, and applications for drug targeting of molecules in cells are highlighted in this paper. Screening of bioactive molecules based on electric cell-substrate impedance sensing is a trial-and-error process toward the development of therapeutically active agents for drug discovery and therapeutics. In general, bioactive molecule screening can be used to identify active molecular targets for various diseases and toxicity at the cellular level with nanoscale resolution. In the innovation and screening of new drugs or bioactive molecules, the activeness, the efficacy of the compound, and safety in biological systems are the main concerns on which determination of drug candidates is based. Further, drug discovery and screening of compounds are often performed in cell-based test systems in order to reduce costs and save time. Moreover, this system can provide more relevant results in in vivo studies, as well as high-throughput drug screening for various diseases during the early stages of drug discovery. Recently, MEMS technologies and integration with image detection techniques have been employed successfully. These new technologies and their possible ongoing transformations are addressed. Select reports are outlined, and not all the work that has been performed in the field of drug screening and development is covered. PMID:25525360

Screening for fragile X syndrome.

PubMed

Murray, J; Cuckle, H; Taylor, G; Hewison, J

1997-01-01

BACKGROUND AND AIM OF REVIEW. In 1991, the gene responsible for fragile X syndrome, a common cause of learning disability, was discovered. As a result, diagnosis of the disorder has improved and its molecular genetics are now understood. This report seems to provide the information needed to decide whether to use DNA testing to screen for the disorder. HOW THE RESEARCH WAS CONDUCTED. A literature search of electronic reference databases of published and 'grey' literature was undertaken together with hand searching of the most recent publications. RESEARCH FINDINGS. NATURAL HISTORY. Physical characteristics of fragile X syndrome include facial atypia, joint laxity and, in boys, macro-orchidism. Most affected males have moderate-to-severe learning disabilities with IQs under 50 whereas most females have borderline IQs of 70-85. Behavioural problems are similar to those seen with autism and attention-deficit disorders. Although fragile X syndrome is not curable there are a number of medical, educational, psychological and social interventions that can improve the symptoms. About 6% of those with learning disabilities tested in institutions have fragile X syndrome. Population prevalence figures are 1 in 4000 in males and 1 in 8000 in females. GENETICS. The disorder is caused by a mutation in a gene on the X chromosome which includes a trinucleotide repeat sequence. The mutation is characterized by hyper-expansion of the repeat sequence leading to down-regulation of the gene. In males an allele with repeat size in excess of 200, termed a full mutation (FM), is always associated with the affected phenotype, whereas in females only half are affected. Individuals with alleles having repeat size in the range 55-199 are unaffected but in females the sequence is heritably unstable so that it is at high risk of expansion to an FM in her offspring. This allele is known as a pre-mutation (PM) to contrast it with the FM found in the affected individual. No spontaneous expansions

Rational approach to identify newer caspase-1 inhibitors using pharmacophore based virtual screening, docking and molecular dynamic simulation studies.

PubMed

Patel, Shivani; Modi, Palmi; Chhabria, Mahesh

2018-05-01

Caspase-1 is a key endoprotease responsible for the post-translational processing of pro-inflammatory cytokines IL-1β, 18 & 33. Excessive secretion of IL-1β leads to numerous inflammatory and autoimmune diseases. Thus caspase-1 inhibition would be considered as an important therapeutic strategy for development of newer anti-inflammatory agents. Here we have employed an integrated virtual screening by combining pharmacophore mapping and docking to identify small molecules as caspase-1 inhibitors. The ligand based 3D pharmacophore model was generated having the essential structural features of (HBA, HY & RA) using a data set of 27 compounds. A validated pharmacophore hypothesis (Hypo 1) was used to screen ZINC and Minimaybridge chemical databases. The retrieved virtual hits were filtered by ADMET properties and molecular docking analysis. Subsequently, the cross-docking study was also carried out using crystal structure of caspase-1, 3, 7 and 8 to identify the key residual interaction for specific caspase-1 inhibition. Finally, the best mapped and top scored (ZINC00885612, ZINC72003647, BTB04175 and BTB04410) molecules were subjected to molecular dynamics simulation for accessing the dynamic structure of protein after ligand binding. This study identifies the most promising hits, which can be leads for the development of novel caspase-1 inhibitors as anti-inflammatory agents. Copyright © 2018 Elsevier Inc. All rights reserved.

Cosmological Simulations with Molecular Astrochemistry: Water in the Early Universe

NASA Astrophysics Data System (ADS)

Wiggins, Brandon K.; Smidt, Joseph

2018-01-01

Water is required for the rise of life as we know it throughout the universe, but its origin and the circumstances of its first appearance remain a mystery. The abundance of deuterated water in solar system bodies cannot be explained if all the water in the solar system were created in the protoplanetary disk (Cleeves et al. 2014), suggesting that as much of half of Earth’s water predates the Sun. Water has been observed as early as one sixth the current universe’s age in MG J0414+0534 (Imprellizzeri et al. 2008). It was recently shown that water could, in principle, appear in hot halos barely enriched with heavy elements such as oxygen and carbon (Bialy et al. 2015). So far, no self-consistent calculation of cosmology physics carried out in line with a large chemical reaction network has been carried out to study the first sites of water formation in the universe. We present initial results the first such series of cosmological calculations with a 26 species low metallicity molecular chemical reaction network with Enzo (Bryan et al. 2014) to understand the role of hydrodynamics and radiative feedback on molecule formation in the early universe and to shed light on the cosmological history of this life-giving substance.

Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys.

PubMed

Mei, Davide; Darra, Francesca; Barba, Carmen; Marini, Carla; Fontana, Elena; Chiti, Laura; Parrini, Elena; Dalla Bernardina, Bernardo; Guerrini, Renzo

2014-11-01

Mutations involving the cyclin-dependent kinase-like 5 (CDKL5) gene cause an early onset epileptic encephalopathy (EE) with severe neurologic impairment and a skewed 12:1 female-to-male ratio. To date, 18 mutations have been described in boys. We analyzed our cohort of boys with early onset EE to assess the diagnostic yield of our molecular approach. We studied 74 boys who presented early onset severe seizures, including infantile spasms and developmental delay, in the setting of EE, using Sanger sequencing, next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). We identified alterations involving CDKL5 in four boys (5.4%) using NGS in one and MLPA in three. Three of four mutations were indicative of somatic mosaicism. CDKL5 gene mutations accounted for 5.4% of boys with early onset EE. Somatic mosaic mutations might be even more represented than germline mutations, probably because their less deleterious effect enhances viability of the male embryo. The molecular approach used for CDKL5 screening remarkably influences the diagnostic yield in boys. Diagnosis is optimized by Sanger sequencing combined with array-based methods or MLPA; alternatively, NGS targeted resequencing designed to also detect copy number alterations, may be performed. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.

PubMed

Sun, Tengyang; Xu, Ke; Ren, Yanfan; Xie, Yue; Zhang, Xiaohui; Tian, Lu; Li, Yang

2018-03-01

Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.

Early malnutrition screening and low cost protein supplementation in elderly patients admitted to a skilled nursing facility.

PubMed

Harding, Krystal M; Dyo, Melissa; Goebel, Joy R; Gorman, Nik; Levine, Julia

2016-08-01

Malnutrition among skilled nursing facility (SNF) patients can lead to hospital readmissions and multiple complications. To evaluate the effect of an existing malnutrition screening and management program on prealbumin levels of patients in skilled nursing facilities. A retrospective design was used to evaluate baseline admission data including a prealbumin level. Patients with malnutrition received an oral protein supplement according to protocol. A comparison prealbumin level was obtained at 30days. Nearly half of the patients were severely malnourished on admission. Patients receiving the prescribed protocol had significantly increased prealbumin levels at 30days than those patients that did not receive the protocol as prescribed. A prealbumin level upon admission at a SNF could represent a reliable tool to evaluate malnutrition. Initiation of an early malnutrition screening and protein supplement program in this setting is essential to identifying and treating at-risk patients before complications occur. Copyright © 2015 Elsevier Inc. All rights reserved.

Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer

PubMed Central

Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

2014-01-01

Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer. PMID:25988156

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting.

PubMed

Chen, Hongda; Zucknick, Manuela; Werner, Simone; Knebel, Phillip; Brenner, Hermann

2015-07-15

Novel noninvasive blood-based screening tests are strongly desirable for early detection of colorectal cancer. We aimed to conduct a head-to-head comparison of the diagnostic performance of 92 plasma-based tumor-associated protein biomarkers for early detection of colorectal cancer in a true screening setting. Among all available 35 carriers of colorectal cancer and a representative sample of 54 men and women free of colorectal neoplasms recruited in a cohort of screening colonoscopy participants in 2005-2012 (N = 5,516), the plasma levels of 92 protein biomarkers were measured. ROC analyses were conducted to evaluate the diagnostic performance. A multimarker algorithm was developed through the Lasso logistic regression model and validated in an independent validation set. The .632+ bootstrap method was used to adjust for the potential overestimation of diagnostic performance. Seventeen protein markers were identified to show statistically significant differences in plasma levels between colorectal cancer cases and controls. The adjusted area under the ROC curves (AUC) of these 17 individual markers ranged from 0.55 to 0.70. An eight-marker classifier was constructed that increased the adjusted AUC to 0.77 [95% confidence interval (CI), 0.59-0.91]. When validating this algorithm in an independent validation set, the AUC was 0.76 (95% CI, 0.65-0.85), and sensitivities at cutoff levels yielding 80% and 90% specificities were 65% (95% CI, 41-80%) and 44% (95% CI, 24-72%), respectively. The identified profile of protein biomarkers could contribute to the development of a powerful multimarker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.

Water swallow screening test for patients after surgery for head and neck cancer: early identification of dysphagia, aspiration and limitations of oral intake.

PubMed

Hey, Christiane; Lange, Benjamin P; Eberle, Silvia; Zaretsky, Yevgen; Sader, Robert; Stöver, Timo; Wagenblast, Jens

2013-09-01

Patients with head and neck cancer (HNC) are at high risk for oropharyngeal dysphagia (OD) following surgical therapy. Early identification of OD can improve outcomes and reduce economic burden. This study aimed to evaluate the validity of a water screening test using increasing volumes postsurgically for patients with HNC (N=80) regarding the early identification of OD in general, and whether there is a need for further instrumental diagnostics to investigate the presence of aspiration as well as to determine the limitations of oral intake as defined by fiberoptic endoscopic evaluation of swallowing. OD in general was identified in 65%, with aspiration in 49%, silent aspiration in 21% and limitations of oral intake in 56%. Despite a good sensitivity, for aspiration of 100% and for limitations of oral intake of 97.8%, the presented water screening test did not satisfactorily predict either of these reference criteria due to its low positive likelihood ratio (aspiration=2.6; limitations of oral intake=3.1). However, it is an accurate tool for the early identification of OD in general, with a sensitivity of 96.2% and a positive likelihood ratio of 5.4 in patients after surgery for HNC.

Economic savings and costs of periodic mammographic screening in the workplace.

PubMed

Griffiths, R I; McGrath, M M; Vogel, V G

1996-03-01

This article discusses the costs and benefits of mammographic screening in the workplace. The cost of mammography itself and of diagnostic work-up are two of the largest costs involved. Therefore, the most efficient approach to providing mammography depends on the number of employees receiving mammography; and the diagnostic accuracy of mammography and underlying incidence of breast cancer in the screened population strongly influence the number of suspicious mammograms that are not associated with breast cancer. The health benefit of mammographic screening is due to reduced mortality and morbidity through early detection and more effective treatment, which may also result in economic savings if early-stage cancer is less expensive to treat. However, the total lifetime cost of treating early-stage cancer may be greater than treating late-stage cancer because of improved survival of early-stage patients. Thus, although periodic mammographic screening is not likely to result in overall economic savings, in many populations of working-age women, especially those with identifiable risk factors, screening is cost-effective because the expenditure required to save a year of life through early detection of breast cancer is low compared to other types of health services for which employers commonly pay.

A selective screening program for the early detection of mucopolysaccharidosis: Results of the FIND project - a 2-year follow-up study.

PubMed

Colón, Cristóbal; Alvarez, J Victor; Castaño, Cristina; Gutierrez-Solana, Luís G; Marquez, Ana M; O'Callaghan, María; Sánchez-Valverde, Félix; Yeste, Carmen; Couce, María-Luz

2017-05-01

The mucopolysaccharidoses (MPSs) are underdiagnosed but they are evaluated in few newborn screening programs, probably due to the many challenges remaining, such as the identification of late-onset phenotypes. Systematic screening at the onset of clinical symptoms could help to early identify patients who may benefit from specific treatments. The aim of this prospective study was to assess a novel selective screening program, the FIND project, targeting patients aged 0 to 16 years with clinical manifestations of MPS. The project was designed to increase awareness of these diseases among pediatricians and allow early diagnosis.From July 2014 to June 2016, glycosaminoglycan (GAG) levels normalized to creatinine levels were determined in urine-impregnated analytical paper submitted by pediatricians who had patients with clinical signs and/or symptoms compatible with MPS. When high GAG concentrations were detected, a new liquid urine sample was requested to confirm and identify the GAG present. When a specific form of MPS was suspected, enzyme activity was analyzed using blood-impregnated paper to determine MPS type (I, IIIB, IIIC, IVA, IVB, VI, or VII). Age-specific reference values for GAG were previously established using 145 urine samples from healthy children.GAG levels were normal in 147 (81.7%) of the 180 initial samples received. A liquid sample was requested for the other 33 cases (18.3%); GAG levels were normal in 13 of these and slightly elevated in 12, although the electrophoresis study showed no evidence of MPS. Elevated levels with corresponding low enzymatic activity were confirmed in 8 cases. The mean time from onset of clinical symptoms to detection of MPS was 22 months, and just 2 cases were detected at the beginning of the project were detected with 35 and 71 months of evolution of clinical symptoms. Our screening strategy for MPS had a sensitivity of 100%, a specificity of 85%, and a positive predictive value of 24%.The FIND project is a useful and

Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors

PubMed Central

Cunningham, Thomas J.; Colas, Alexandre

2016-01-01

ABSTRACT Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis. Differential expression analysis of this dataset indicated that treatment with 25 nM RA, but not 1 µM RA, provided physiologically relevant findings. The 25 nM RA dataset yielded a cohort of previously known caudal RA target genes including Fgf8 (repressed) and Sox2 (activated), plus novel early RA signaling targets with nearby conserved RA response elements. Importantly, validation of top-ranked genes in vivo using RA-deficient Raldh2−/− embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny. These findings provide evidence for early instructive and permissive roles of RA in controlling differentiation of NMPs to neural and mesodermal lineages. PMID:27793834

DOCKTITE-a highly versatile step-by-step workflow for covalent docking and virtual screening in the molecular operating environment.

PubMed

Scholz, Christoph; Knorr, Sabine; Hamacher, Kay; Schmidt, Boris

2015-02-23

The formation of a covalent bond with the target is essential for a number of successful drugs, yet tools for covalent docking without significant restrictions regarding warhead or receptor classes are rare and limited in use. In this work we present DOCKTITE, a highly versatile workflow for covalent docking in the Molecular Operating Environment (MOE) combining automated warhead screening, nucleophilic side chain attachment, pharmacophore-based docking, and a novel consensus scoring approach. The comprehensive validation study includes pose predictions of 35 protein/ligand complexes which resulted in a mean RMSD of 1.74 Å and a prediction rate of 71.4% with an RMSD below 2 Å, a virtual screening with an area under the curve (AUC) for the receiver operating characteristics (ROC) of 0.81, and a significant correlation between predicted and experimental binding affinities (ρ = 0.806, R(2) = 0.649, p < 0.005).

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

PubMed Central

Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

2015-01-01

Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

Pancreatic cancer early detection: Expanding higher-risk group with clinical and metabolomics parameters

PubMed Central

Urayama, Shiro

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth and fifth leading cause of cancer death for each gender in developed countries. With lack of effective treatment and screening scheme available for the general population, the mortality rate is expected to increase over the next several decades in contrast to the other major malignancies such as lung, breast, prostate and colorectal cancers. Endoscopic ultrasound, with its highest level of detection capacity of smaller pancreatic lesions, is the commonly employed and preferred clinical imaging-based PDAC detection method. Various molecular biomarkers have been investigated for characterization of the disease, but none are shown to be useful or validated for clinical utilization for early detection. As seen from studies of a small subset of familial or genetically high-risk PDAC groups, the higher yield and utility of imaging-based screening methods are demonstrated for these groups. Multiple recent studies on the unique cancer metabolism including PDAC, demonstrate the potential for utility of the metabolites as the discriminant markers for this disease. In order to generate an early PDAC detection screening strategy available for a wider population, we propose to expand the population of higher risk PDAC group with combination clinical and metabolomics parameters. PMID:25684935

A Stochastic Spiking Neural Network for Virtual Screening.

PubMed

Morro, A; Canals, V; Oliver, A; Alomar, M L; Galan-Prado, F; Ballester, P J; Rossello, J L

2018-04-01

Virtual screening (VS) has become a key computational tool in early drug design and screening performance is of high relevance due to the large volume of data that must be processed to identify molecules with the sought activity-related pattern. At the same time, the hardware implementations of spiking neural networks (SNNs) arise as an emerging computing technique that can be applied to parallelize processes that normally present a high cost in terms of computing time and power. Consequently, SNN represents an attractive alternative to perform time-consuming processing tasks, such as VS. In this brief, we present a smart stochastic spiking neural architecture that implements the ultrafast shape recognition (USR) algorithm achieving two order of magnitude of speed improvement with respect to USR software implementations. The neural system is implemented in hardware using field-programmable gate arrays allowing a highly parallelized USR implementation. The results show that, due to the high parallelization of the system, millions of compounds can be checked in reasonable times. From these results, we can state that the proposed architecture arises as a feasible methodology to efficiently enhance time-consuming data-mining processes such as 3-D molecular similarity search.

National Evaluation of US Newborn Screening System Components

ERIC Educational Resources Information Center

Therrell, Bradford L.; Hannon, W. Harry

2006-01-01

Newborn screening has existed as a state-based public health service since the early 1960s. Every state and most territorial jurisdictions have comprehensive newborn screening programs in place, but in the United States a national newborn screening policy does not exist. This results in different administrative infrastructures, screening…

Virtual screening of B-Raf kinase inhibitors: A combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy calculation studies.

PubMed

Zhang, Wen; Qiu, Kai-Xiong; Yu, Fang; Xie, Xiao-Guang; Zhang, Shu-Qun; Chen, Ya-Juan; Xie, Hui-Ding

2017-10-01

B-Raf kinase has been identified as an important target in recent cancer treatment. In order to discover structurally diverse and novel B-Raf inhibitors (BRIs), a virtual screening of BRIs against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy (ΔG bind ) calculation studies in this work. After the virtual screening, six promising hit compounds were obtained, which were then tested for inhibitory activities of A375 cell lines. In the result, five hit compounds show good biological activities (IC 50 <50μM). The present method of virtual screening can be applied to find structurally diverse inhibitors, and the obtained five structurally diverse compounds are expected to develop novel BRIs. Copyright © 2017. Published by Elsevier Ltd.

Carrier screening for cystic fibrosis.

PubMed

Dungan, Jeffrey S

2010-03-01

Cystic fibrosis is the first genetic disorder for which universal screening of preconceptional or prenatal patients became a component of standard prenatal care. The molecular genetics and mutation profile of the CFTR gene are complex, with a wide range of phenotypic consequences. Carrier screening can facilitate risk assessment for prospective parents to have an affected offspring, although there remains a small residual risk for carrying a mutation even with a negative screening result. There are ethnic differences with respect to disease incidence and effectiveness of carrier testing, which may complicate counseling. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The molecular bacterial load assay replaces solid culture for measuring early bactericidal response to antituberculosis treatment.

PubMed

Honeyborne, Isobella; Mtafya, Bariki; Phillips, Patrick P J; Hoelscher, Michael; Ntinginya, Elias N; Kohlenberg, Anke; Rachow, Andrea; Rojas-Ponce, Gabriel; McHugh, Timothy D; Heinrich, Norbert

2014-08-01

We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

[CT-Screening for Lung Cancer - what is the Evidence?

PubMed

Watermann, Iris; Reck, Martin

2018-04-01

In patients with lung cancer treatment opportunities and prognosis are correlated to the stage of disease with a chance for curative treatment in patients with early stage disease. Therefore, early detection of lung cancer is of paramount importance for improving the prognosis of lung cancer patients.The National Lung Screening Trial (NLST) has already shown that low-dose CT increases the number of identified early stage lung cancer patients and reduces lung cancer related mortality. Critically considered in terms of CT-screening are false-positive results, overdiagnosis and unessential invasive clarification. Preliminary results of relatively small European trials haven´t yet confirmed the results of the NLST-study.Until now Lung Cancer Screening by low dose CT-scan or other methods is neither approved nor available in Germany.To improve the efficacy of CT-Screening and to introduce early detection of lung cancer in standard practice, additional, complementing methods should be further evaluated. One option might be the supplementary analysis of biomarkers in liquid biopsies or exhaled breath condensates. In addition, defining the high-risk population is of great relevance to identify candidates who might benefit of early detection programs. © Georg Thieme Verlag KG Stuttgart · New York.

Autism Spectrum Disorder Early Screening Practices: A Survey of Physicians

ERIC Educational Resources Information Center

Self, Trisha L.; Parham, Douglas F.; Rajagopalan, Jagadeesh

2015-01-01

The American Academy of Pediatrics (AAP) released a policy statement in 2007 urging physicians to screen for autism spectrum disorder (ASD) at 18 and 24 months. This study sought to identify the screening practices of pediatricians and family physicians (FPs) in following the AAP guidelines for ASD. A survey was mailed to 1,500 pediatricians and…

Endometrial Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Endometrial cancer screening is currently not recommended because no standard or routine screening test has been shown to be effective. Endometrial cancer is usually found early due to symptoms and survival rates are high. Learn more in this expert-reviewed summary.

Pharmacoinformatics exploration of polyphenol oxidases leading to novel inhibitors by virtual screening and molecular dynamic simulation study.

PubMed

Hassan, Mubashir; Abbas, Qamar; Ashraf, Zaman; Moustafa, Ahmed A; Seo, Sung-Yum

2017-06-01

Polyphenol oxidases (PPOs)/tyrosinases are metal-dependent enzymes and known as important targets for melanogenesis. Although considerable attempts have been conducted to control the melanin-associated diseases by using various inhibitors. However, the exploration of the best anti-melanin inhibitor without side effect still remains a challenge in drug discovery. In present study, protein structure prediction, ligand-based pharmacophore modeling, virtual screening, molecular docking and dynamic simulation study were used to screen the strong novel inhibitor to cure melanogenesis. The 3D structures of PPO1 and PPO2 were built through homology modeling, while the 3D crystal structures of PPO3 and PPO4 were retrieved from PDB. Pharmacophore modeling was performed using LigandScout 3.1 software and top five models were selected to screen the libraries (2601 of Aurora and 727, 842 of ZINC). Top 10 hit compounds (C1-10) were short-listed having strong binding affinities for PPO1-4. Drug and synthetic accessibility (SA) scores along with absorption, distribution, metabolism, excretion and toxicity (ADMET) assessment were employed to scrutinize the best lead hit. C4 (name) hit showed the best predicted SA score (5.75), ADMET properties and drug-likeness behavior among the short-listed compounds. Furthermore, docking simulations were performed to check the binding affinity of C1-C10 compounds against target proteins (PPOs). The binding affinity values of complex between C4 and PPOs were higher than those of other complexes (-11.70, -12.1, -9.90 and -11.20kcal/mol with PPO1, PPO2, PPO3, or PPO4, respectively). From comparative docking energy and binding analyses, PPO2 may be considered as better target for melanogenesis than others. The potential binding modes of C4, C8 and C10 against PPO2 were explored using molecular dynamics simulations. The root mean square deviation and fluctuation (RMSD/RMSF) graphs results depict the significance of C4 over the other compounds

Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

PubMed Central

Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

2016-01-01

Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

Changing Trends within the Population of Children Who Are Deaf or Hard of Hearing in Flanders (Belgium): Effects of 12 Years of Universal Newborn Hearing Screening, Early Intervention, and Early Cochlear Implantation

ERIC Educational Resources Information Center

De Raeve, Leo; Lichtert, Guido

2012-01-01

The purpose of this study is to show the changing trends within the population of children who are deaf and hard of hearing in Belgium over the last 12 years. The combination of Universal Newborn Hearing Screening programs, early intervention, and cochlear implants have tremendously influenced the education and support of children who are deaf or…

Accuracy of repeated measurements of late-night salivary cortisol to screen for early-stage recurrence of Cushing's disease following pituitary surgery.

PubMed

Danet-Lamasou, Marie; Asselineau, Julien; Perez, Paul; Vivot, Alexandre; Nunes, Marie-Laure; Loiseau, Hugues; San-Galli, François; Cherifi-Gatta, Blandine; Corcuff, Jean-Benoît; Tabarin, Antoine

2015-02-01

The performance of late-night salivary cortisol (LNSC) to accurately screen for postoperative recurrence of Cushing's disease (CD) at an early stage is unknown. The aim of this study was to compare the accuracy of multiple sampling strategies to suggest the optimal number of LNSC samples needed for diagnosing post-surgical recurrences of CD at an early stage. Retrospective analysis in a single centre. Thirty-six patients in surgical remission of CD had successive measurements of LNSC, defined as 'sequences', using a locally modified RIA assay as part of long-term follow-up (69·2 ± 10·6 months). Patients underwent an extensive biochemical evaluation within 3 months before or after a sequence of saliva sampling and were classified as being in remission or in early-stage recurrence. The accuracy of three diagnostic strategies combining two, three or four LNSC results from a sequence was estimated using areas under the ROC curves (AUC), sensitivity, specificity and predictive values. Forty-four sequences of LNSC measurements were available. Fifty-two percent of sequences were performed during early-stage recurrence. The intrasequence variability of LNSC was higher during recurrence than during remission (medians of SDs: 2·1 vs 0·5 nm; P < 0·0001). AUCs from ROC curves ranged from 0·93 to 0·96 depending on the strategy. For 90% sensitivities, the best specificities (92·9% and 90·9%) were achieved by strategies taking into account three or four measurements summarized either by their mean or their maximum value. Increase in LNSC concentration is an early abnormality during post-surgical recurrence of CD. However, due to a major within-patient variability of LNSC from 1 day to another, a screening strategy using three or four samples collected on successive days may be recommended to detect early-stage recurrence of CD with a high accuracy. © 2014 John Wiley & Sons Ltd.

Diagnosis of glutathione synthetase deficiency in newborn screening.

PubMed

Simon, E; Vogel, M; Fingerhut, R; Ristoff, E; Mayatepek, E; Spiekerkötter, U

2009-12-01

Glutathione synthetase (GSS) deficiency is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with haemolytic anaemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low GSS activity in erythrocytes or cultured skin fibroblasts. Diagnosis can be confirmed by mutational analysis. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. The most important determinants for outcome and survival in patients with GSS deficiency are early diagnosis and early initiation of treatment. The case of a newborn with GSS deficiency diagnosed by tandem mass spectrometry (MS/MS)-based newborn screening is described. After onset of clinical symptoms on the 2nd day of life, expanded newborn screening revealed normal results for all disorders included in the German screening programme; however, selective MS/MS screening revealed a >10-fold elevation of 5-oxoproline in dried blood, leading to the presumptive diagnosis of GSS deficiency by the 5th day of life. Diagnosis was later confirmed by detection of markedly reduced glutathione concentration in erythrocytes and mutational analysis of the GSS gene. Presently, GSS deficiency is not included in newborn screening programmes in Europe. As outcome depends significantly on early start of treatment, routine inclusion of this disorder in newborn screening panels should be considered.

Neonatal Screening and the Clinical Outcome in Children with Sickle Cell Disease in Central India

PubMed Central

Upadhye, Dipti S.; Jain, Dipty L.; Trivedi, Yogesh L.; Nadkarni, Anita H.; Ghosh, Kanjaksha; Colah, Roshan B.

2016-01-01

Background Sickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India. Methods and Findings Pregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS -δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies. Conclusion A systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations. PMID:26785407

Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

PubMed

Kurz, Ella; Davis, Deborah

2015-04-17

Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

Inequalities in adoption of cancer screening from a diffusion of innovation perspective: identification of late adopters.

PubMed

Hahm, Myung-Il; Park, Eun-Cheol; Choi, Kui Son; Lee, Hoo-Yeon; Park, Jae-Hyun; Park, Sohee

2011-02-01

Although national-level organized cancer screening programs have reduced barriers to screening for people of low socioeconomic status, barriers to early screening remain. Our aim was to determine the diffusion pattern and identify the factors associated with early participation in stomach and breast cancer screening programs. The study population was derived from the Korean National Cancer Screening Survey, conducted in 2007. A stratified random sample of people aged 40 years and older from a nationwide population-based database was gathered in Korea (n=1,517) in 2007. Time of participation in early screening was defined as the number of years that had elapsed between the participant's 30th birthday and the age at first screening. Significant differences were observed in the probability of adopting stomach and breast cancer screening in relation to education, household income, and job level. Results from Cox's proportional hazard model indicated that higher household income was significantly associated with an increased probability of adopting stomach cancer screening earlier (p<0.05), and people with high household incomes were more likely to adopt breast cancer screening earlier than were those with incomes under US$1,500 per month (p<0.01). When considered at a significance level of 0.1, we found that the most highly educated women were more likely than the least educated to be screened early. Despite organized governmental screening programs, there are still inequalities in the early adoption of cancer screening. The results of this study also suggest that inequalities in early adoption may affect participation in regular screening. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

PubMed

Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

PubMed Central

Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

Mammography and Other Screening Tests for Breast Problems

MedlinePlus

... in eight women will develop breast cancer by age 75 years. Regular breast screening can help find cancer at an early and more curable stage. Screening also can find problems in the breasts that are not cancer. What is mammography? Mammography is the primary tool used to screen for breast cancer and ...

Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits.

PubMed

Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

2015-01-01

Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. © 2014 Society for Laboratory Automation and Screening.

Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis.

PubMed

Lefterova, Martina I; Shen, Peidong; Odegaard, Justin I; Fung, Eula; Chiang, Tsoyu; Peng, Gang; Davis, Ronald W; Wang, Wenyi; Kharrazi, Martin; Schrijver, Iris; Scharfe, Curt

2016-03-01

Newborn screening for cystic fibrosis enables early detection and management of this debilitating genetic disease. Implementing comprehensive CFTR analysis using Sanger sequencing as a component of confirmatory testing of all screen-positive newborns has remained impractical due to relatively lengthy turnaround times and high cost. Here, we describe CFseq, a highly sensitive, specific, rapid (<3 days), and cost-effective assay for comprehensive CFTR gene analysis from dried blood spots, the common newborn screening specimen. The unique design of CFseq integrates optimized dried blood spot sample processing, a novel multiplex amplification method from as little as 1 ng of genomic DNA, and multiplex next-generation sequencing of 96 samples in a single run to detect all relevant CFTR mutation types. Sequence data analysis utilizes publicly available software supplemented by an expert-curated compendium of >2000 CFTR variants. Validation studies across 190 dried blood spots demonstrated 100% sensitivity and a positive predictive value of 100% for single-nucleotide variants and insertions and deletions and complete concordance across the polymorphic poly-TG and consecutive poly-T tracts. Additionally, we accurately detected both a known exon 2,3 deletion and a previously undetected exon 22,23 deletion. CFseq is thus able to replace all existing CFTR molecular assays with a single robust, definitive assay at significant cost and time savings and could be adapted to high-throughput screening of other inherited conditions. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Feasibility of nonselective testing for hemoglobinopathies in early pregnancy in The Netherlands.

PubMed

Kaufmann, Judith O; Demirel-Güngör, Gönül; Selles, Anke; Hudig, Cisca; Steen, Gerard; Ponjee, Gabrielle; Holleboom, Cas; Freeman, Liv M; Hendiks, Joris; Wijermans, Pierre; Giordano, Piero C; Kerkhoffs, Jean-Louis

2011-12-01

To examine the feasibility of standardized hemoglobinopathy (HBP) carrier testing for pregnant women in The Netherlands in addition to the standard anemia screening. We assessed the prevalence of HBP in women at the time of the first pregnancy visit using both a prospective cohort (N = 703) and a retrospective series of women selected at random (N = 588). For the purpose of analysis, the population was divided into a high risk and a low risk group for HBP based on maternal ethnicity. Screening for HBP utilized standard screening tests for anemia, with additional high performance liquid chromatography (Variant II); molecular analysis was performed by Gap-polymerase chain reaction (Gap-PCR) and if necessary, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Family history was reported or collected from the medical records. β-Globin defects were found in 3.9% of the total population (50/1291). The frequency in the high risk population was 5.6% (37/656), compared with 1.2% (6/501) in the low risk group. In the prospective study we found 30 HBP carriers, leading to testing of 16 partners and identification of two couples at risk. One affected child was born. Mean gestational age at the screening was 11.3 weeks with a standard deviation (SD) of 5.8. We found that the prevalence of HBP carriers is high enough in our population to warrant HBP testing for the entire multiethnic population in early pregnancy at the time of anemia screening. This is feasible as most women had their booking early in their first trimester. Copyright © 2011 John Wiley & Sons, Ltd.

Stability and Change of Behavioral and Emotional Screening Scores

ERIC Educational Resources Information Center

Dever, Bridget V.; Dowdy, Erin; Raines, Tara C.; Carnazzo, Katherine

2015-01-01

Universal screening for behavioral and emotional difficulties is integral to the identification of students needing early intervention and prevention efforts. However, unanswered questions regarding the stability of screening scores impede the ability to determine optimal strategies for subsequent screening. This study examined the 2-year…

Can Touch Screen Tablets be Used to Assess Cognitive and Motor Skills in Early Years Primary School Children? A Cross-Cultural Study.

PubMed

Pitchford, Nicola J; Outhwaite, Laura A

2016-01-01

Assessment of cognitive and motor functions is fundamental for developmental and neuropsychological profiling. Assessments are usually conducted on an individual basis, with a trained examiner, using standardized paper and pencil tests, and can take up to an hour or more to complete, depending on the nature of the test. This makes traditional standardized assessments of child development largely unsuitable for use in low-income countries. Touch screen tablets afford the opportunity to assess cognitive functions in groups of participants, with untrained administrators, with precision recording of responses, thus automating the assessment process. In turn, this enables cognitive profiling to be conducted in contexts where access to qualified examiners and standardized assessments are rarely available. As such, touch screen assessments could provide a means of assessing child development in both low- and high-income countries, which would afford cross-cultural comparisons to be made with the same assessment tool. However, before touch screen tablet assessments can be used for cognitive profiling in low-to-high-income countries they need to be shown to provide reliable and valid measures of performance. We report the development of a new touch screen tablet assessment of basic cognitive and motor functions for use with early years primary school children in low- and high-income countries. Measures of spatial intelligence, visual attention, short-term memory, working memory, manual processing speed, and manual coordination are included as well as mathematical knowledge. To investigate if this new touch screen assessment tool can be used for cross-cultural comparisons we administered it to a sample of children ( N = 283) spanning standards 1-3 in a low-income country, Malawi, and a smaller sample of children ( N = 70) from first year of formal schooling from a high-income country, the UK. Split-half reliability, test-retest reliability, face validity, convergent

Screening and Biosensor-Based Approaches for Lung Cancer Detection

PubMed Central

Wang, Lulu

2017-01-01

Early diagnosis of lung cancer helps to reduce the cancer death rate significantly. Over the years, investigators worldwide have extensively investigated many screening modalities for lung cancer detection, including computerized tomography, chest X-ray, positron emission tomography, sputum cytology, magnetic resonance imaging and biopsy. However, these techniques are not suitable for patients with other pathologies. Developing a rapid and sensitive technique for early diagnosis of lung cancer is urgently needed. Biosensor-based techniques have been recently recommended as a rapid and cost-effective tool for early diagnosis of lung tumor markers. This paper reviews the recent development in screening and biosensor-based techniques for early lung cancer detection. PMID:29065541

The power metric: a new statistically robust enrichment-type metric for virtual screening applications with early recovery capability.

PubMed

Lopes, Julio Cesar Dias; Dos Santos, Fábio Mendes; Martins-José, Andrelly; Augustyns, Koen; De Winter, Hans

2017-01-01

A new metric for the evaluation of model performance in the field of virtual screening and quantitative structure-activity relationship applications is described. This metric has been termed the power metric and is defined as the fraction of the true positive rate divided by the sum of the true positive and false positive rates, for a given cutoff threshold. The performance of this metric is compared with alternative metrics such as the enrichment factor, the relative enrichment factor, the receiver operating curve enrichment factor, the correct classification rate, Matthews correlation coefficient and Cohen's kappa coefficient. The performance of this new metric is found to be quite robust with respect to variations in the applied cutoff threshold and ratio of the number of active compounds to the total number of compounds, and at the same time being sensitive to variations in model quality. It possesses the correct characteristics for its application in early-recognition virtual screening problems.

[Cost-effectiveness analysis on colorectal cancer screening program].

PubMed

Huang, Q C; Ye, D; Jiang, X Y; Li, Q L; Yao, K Y; Wang, J B; Jin, M J; Chen, K

2017-01-10

Objective: To evaluate the cost-effectiveness of colorectal cancer screening program in different age groups from the view of health economics. Methods: The screening compliance rates, detection rates in different age groups were calculated by using the data from colorectal cancer screening program in Jiashan county, Zhejiang province. The differences in indicator among age groups were analyzed with χ (2) test or trend χ (2) test. The ratios of cost to the number of case were calculated according to cost statistics. Results: The detection rates of immunochemical fecal occult blood test (iFOBT) positivity, advanced adenoma and colorectal cancer and early stage cancer increased with age, while the early diagnosis rates were negatively associated with age. After exclusion the younger counterpart, the cost-effectiveness of individuals aged >50 years could be reduced by 15 %- 30 % . Conclusion: From health economic perspective, it is beneficial to start colorectal cancer screening at age of 50 years to improve the efficiency of the screening.

The Role of an Early Head Start Mental Health Coordinator: Screening for Maternal Depression in a Comprehensive Approach to Mental Health Care

ERIC Educational Resources Information Center

Canuso, Regina

2007-01-01

Screening for maternal depression was a core component of the P.E.A.C.E., Inc., Early Head Start program's comprehensive approach to supporting the mental health needs of low-income pregnant women and families with infants and toddlers. The addition of a mental health coordinator as a full-time staff member created an opportunity to develop a…

Screening and treatment for heritable thrombophilia in pregnancy failure: inconsistencies among UK early pregnancy units.

PubMed

Norrie, Gillian; Farquharson, Roy G; Greaves, Mike

2009-01-01

The significance of heritable thrombophilia in pregnancy failure is controversial. We surveyed all UK Early Pregnancy Units and 70% responded. The majority test routinely for heritable thrombophilias; 80%, 76% and 88% undertook at least one screening test in late miscarriage, recurrent miscarriage and placental abruption, respectively. The range of thrombophilias sought is inconsistent: testing for proteins C and S deficiency and F5 R506Q (factor V Leiden) is most prevalent. Detection of heritable thrombophilia frequently leads to administration of antithrombotics in subsequent pregnancies. Thus, thrombophilia testing and use of antithrombotics are widespread in the UK despite controversies regarding the role of heritable thrombophilia in the pathogenesis of pregnancy complications, and the lack of robust evidence for the efficacy of antithrombotic therapy.

Endometrial Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Endometrial cancer screening by ultrasonography or tissue sampling is not supported by current evidence, but most cases are diagnosed at early stage. Get detailed information about potential harms of endometrial cancer screening in this summary for clinicians.

Molecular diagnosis of cystic fibrosis.

PubMed

Shrimpton, Antony E

2002-05-01

A review of the current molecular diagnosis of cystic fibrosis including an introduction to cystic fibrosis, the gene function, the phenotypic variation, who should be screened for which mutation, newborn and couple screening, quality assurance, phenotype-genotype correlation, methods and method limitations, options, statements, recommendations, useful Websites and treatments.

Transition from film to digital mammography: impact for breast cancer screening through the national breast and cervical cancer early detection program.

PubMed

van Ravesteyn, Nicolien T; van Lier, Lisanne; Schechter, Clyde B; Ekwueme, Donatus U; Royalty, Janet; Miller, Jacqueline W; Near, Aimee M; Cronin, Kathleen A; Heijnsdijk, Eveline A M; Mandelblatt, Jeanne S; de Koning, Harry J

2015-05-01

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides mammograms and diagnostic services for low-income, uninsured women aged 40-64 years. Mammography facilities within the NBCCEDP gradually shifted from plain-film to digital mammography. The purpose of this study is to assess the impact of replacing film with digital mammography on health effects (deaths averted, life-years gained [LYG]); costs (for screening and diagnostics); and number of women reached. NBCCEDP 2010 data and data representative of the program's target population were used in two established microsimulation models. Models simulated observed screening behavior including different screening intervals (annual, biennial, irregular) and starting ages (40, 50 years) for white, black, and Hispanic women. Model runs were performed in 2012. The models predicted 8.0-8.3 LYG per 1,000 film screens for black women, 5.9-7.5 for white women, and 4.0-4.5 for Hispanic women. For all race/ethnicity groups, digital mammography had more LYG than film mammography (2%-4%), but had higher costs (34%-35%). Assuming a fixed budget, 25%-26% fewer women could be served, resulting in 22%-24% fewer LYG if all mammograms were converted to digital. The loss in LYG could be reversed to an 8%-13% increase by only including biennial screening. Digital could result in slightly more LYG than film mammography. However, with a fixed budget, fewer women may be served with fewer LYG. Changes in the program, such as only including biennial screening, will increase LYG/screen and could offset the potential decrease in LYG when shifting to digital mammography. Copyright © 2015 American Journal of Preventive Medicine. All rights reserved.

Impact of Neonatal Screening and Surveillance for the TP53 R337H Mutation on Early Detection of Childhood Adrenocortical Tumors

PubMed Central

Custódio, Gislaine; Parise, Guilherme A.; Kiesel Filho, Nilton; Komechen, Heloisa; Sabbaga, Cesar C.; Rosati, Roberto; Grisa, Leila; Parise, Ivy Z.S.; Pianovski, Mara A.D.; Fiori, Carmem M.C.M.; Ledesma, Jorge A.; Barbosa, José Renato S.; Figueiredo, Francisco R.O.; Sade, Elis R.; Ibañez, Humberto; Arram, Sohaila B.I.; Stinghen, Sérvio T.; Mengarelli, Luciano R.; Figueiredo, Mirna M.O.; Carvalho, Danilo C.; Avilla, Sylvio G.A.; Woiski, Thiago D.; Poncio, Lisiane C.; Lima, Geneci F.R.; Pontarolo, Roberto; Lalli, Enzo; Zhou, Yinmei; Zambetti, Gerard P.; Ribeiro, Raul C.; Figueiredo, Bonald C.

2013-01-01

Purpose The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers. Patients and Methods Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age < 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected. Results Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P < .001); six patient cases were identified among 228 carrier relatives age < 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P < .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48). Conclusion These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable. PMID:23733769

The politics of prostate cancer screening.

PubMed

Kaffenberger, Samuel D; Penson, David F

2014-05-01

The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routine screening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages. Published by Elsevier Inc.

Insufficient sensitivity of hemoglobin A(₁C) determination in diagnosis or screening of early diabetic states.

PubMed

Fajans, Stefan S; Herman, William H; Oral, Elif A

2011-01-01

An International Expert Committee made recommendations for using the hemoglobin A(₁C) (A1C) assay as the preferred method for the diagnosis of diabetes in nonpregnant individuals. A concentration of at least 6.5% was considered as diagnostic. It is the aim of this study to compare the sensitivity of A1C with that of plasma glucose concentrations in subjects with early diabetes or impaired glucose tolerance (IGT). We chose 2 groups of subjects who had A1C not exceeding 6.4%. The first group of 89 subjects had family histories of diabetes (MODY or type 2 diabetes mellitus) and had oral glucose tolerance test (OGTT) and A1C determinations. They included 36 subjects with diabetes or IGT and 53 with normal OGTT. The second group of 58 subjects was screened for diabetes in our Diabetes Clinic by fasting plasma glucose, 2-hour plasma glucose, or OGTT and A1C; and similar comparisons were made. Subjects with diabetes or IGT, including those with fasting hyperglycemia, had A1C ranging from 5.0% to 6.4% (mean, 5.8%). The subjects with normal OGTT had A1C of 4.2% to 6.3% (mean, 5.4%), or 5.5% for the 2 groups. The A1C may be in the normal range in subjects with diabetes or IGT, including those with fasting hyperglycemia. Approximately one third of subjects with early diabetes and IGT have A1C less than 5.7%, the cut point that the American Diabetes Association recommends as indicating the onset of risk of developing diabetes in the future. The results of our study are similar to those obtained by a large Dutch epidemiologic study. If our aim is to recognize early diabetic states to apply effective prophylactic procedures to prevent or delay progression to more severe diabetes, A1C is not sufficiently sensitive or reliable for diagnosis of diabetes or IGT. A combination of A1C and plasma glucose determinations, where necessary, is recommended for diagnosis or screening of diabetes or IGT. Published by Elsevier Inc.

Screening and treatment of maternal genitourinary tract infections in early pregnancy to prevent preterm birth in rural Sylhet, Bangladesh: a cluster randomized trial.

PubMed

Lee, Anne C C; Quaiyum, Mohammad A; Mullany, Luke C; Mitra, Dipak K; Labrique, Alain; Ahmed, Parvez; Uddin, Jamal; Rafiqullah, Iftekhar; DasGupta, Sushil; Mahmud, Arif; Koumans, Emilia H; Christian, Parul; Saha, Samir; Baqui, Abdullah H

2015-12-07

Approximately half of preterm births are attributable to maternal infections, which are commonly undetected and untreated in low-income settings. Our primary aim is to determine the impact of early pregnancy screening and treatment of maternal genitourinary tract infections on the incidence of preterm live birth in Sylhet, Bangladesh. We will also assess the effect on other adverse pregnancy outcomes, including preterm birth (stillbirth and live birth), late miscarriage, maternal morbidity, and early onset neonatal sepsis. We are conducting a cluster randomized controlled trial that will enroll 10,000 pregnant women in Sylhet district in rural northeastern Bangladesh. Twenty-four clusters, each with ~4000 population (120 pregnant women/year) and served by a community health worker (CHW), are randomized to: 1) the control arm, which provides routine antenatal and postnatal home-based care, or 2) the intervention arm, which includes routine antenatal and postnatal home-based care plus screening and treatment of pregnant women between 13 and 19 weeks of gestation for abnormal vaginal flora (AVF) and urinary tract infection (UTI). CHWs conduct monthly pregnancy surveillance, make 2 antenatal and 4 postnatal home visits for all enrolled pregnant women and newborns, and refer mothers or newborns with symptoms of serious illness to the government sub-district hospital. In the intervention clusters, CHWs perform home-based screening of AVF and UTI. Self-collected vaginal swabs are plated on slides, which are Gram stained and Nugent scored. Women with AVF (Nugent score ≥4) are treated with oral clindamycin, rescreened and retreated, if needed, after 3 weeks. Urine culture is performed and UTI treated with nitrofurantoin. Repeat urine culture is performed after 1 week for test of cure. Gestational age is determined by maternal report of last menstrual period at study enrollment using prospectively completed study calendars, and in a subset by early (<20 week) ultrasound

School scoliosis screening programme-a systematic review.

PubMed

Sabirin, J; Bakri, R; Buang, S N; Abdullah, A T; Shapie, A

2010-12-01

A systematic review on the effectiveness and cost-effectiveness of school scoliosis screening programme was carried out. A total of 248 relevant titles were identified, 117 abstracts were screened and 28 articles were included in the results. There was fair level of evidence to suggest that school scoliosis screening programme is safe, contributed to early detection and reduction of surgery. There was also evidence to suggest that school-based scoliosis screening programme is cost-effective. Based on the above review, screening for scoliosis among school children is recommended only for high risk group such as girls at twelve years of age.

Screening and Assessment of Kindergarten Children with Developmental Risks.

ERIC Educational Resources Information Center

Moore, C. Rochelle; Sunal, Cynthia S.

This paper reports the implementation of teacher-made, early education screening practices and materials for identifying pre-kindergarten and kindergarten children with developmental risks. A total of 105 children were screened in the spring of 1979 using screening tests devised by the researcher, another kindergarten teacher and a special…

Application of virtual screening and molecular dynamics for the analysis of selectivity of inhibitors of HU proteins targeted to the DNA-recognition site

NASA Astrophysics Data System (ADS)

Talyzina, A. A.; Agapova, Yu. K.; Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Rakitina, T. V.

2017-11-01

DNA-Binding HU proteins are essential for the maintenance of genomic DNA supercoiling and compaction in prokaryotic cells and are promising pharmacological targets for the design of new antibacterial agents. The virtual screening for low-molecular-weight compounds capable of specifically interacting with the DNA-recognition loop of the HU protein from the mycoplasma Spiroplasma melliferum was performed. The ability of the initially selected ligands to form stable complexes with the protein target was assessed by molecular dynamics simulation. One compound, which forms an unstable complex, was eliminated by means of a combination of computational methods, resulting in a decrease in the number of compounds that will pass to the experimental test phase. This approach can be used to solve a wide range of problems related to the search for and validation of low-molecular-weight inhibitors specific for a particular protein target.

Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

PubMed

Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

2016-01-01

Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

Early Experiences Porting the NAMD and VMD Molecular Simulation and Analysis Software to GPU-Accelerated OpenPOWER Platforms

PubMed Central

Stone, John E.; Hynninen, Antti-Pekka; Phillips, James C.; Schulten, Klaus

2017-01-01

All-atom molecular dynamics simulations of biomolecules provide a powerful tool for exploring the structure and dynamics of large protein complexes within realistic cellular environments. Unfortunately, such simulations are extremely demanding in terms of their computational requirements, and they present many challenges in terms of preparation, simulation methodology, and analysis and visualization of results. We describe our early experiences porting the popular molecular dynamics simulation program NAMD and the simulation preparation, analysis, and visualization tool VMD to GPU-accelerated OpenPOWER hardware platforms. We report our experiences with compiler-provided autovectorization and compare with hand-coded vector intrinsics for the POWER8 CPU. We explore the performance benefits obtained from unique POWER8 architectural features such as 8-way SMT and its value for particular molecular modeling tasks. Finally, we evaluate the performance of several GPU-accelerated molecular modeling kernels and relate them to other hardware platforms. PMID:29202130

Cervical cancer screening of underserved women in the United States: results from the National Breast and Cervical Cancer Early Detection Program, 1997-2012.

PubMed

Tangka, Florence K L; Howard, David H; Royalty, Janet; Dalzell, Lucinda P; Miller, Jacqueline; O'Hara, Brett J; Sabatino, Susan A; Joseph, Kristy; Kenney, Kristy; Guy, Gery P; Hall, Ingrid J

2015-05-01

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screens to low-income, uninsured, and underinsured women. We describe the number and proportion of women eligible for cervical cancer screening services and the proportion of eligible women screened over the period 1997-2012. Low-income, uninsured, and underinsured women aged 18-64 years who have not had a hysterectomy are eligible for cervical cancer screening through the NBCCEDP. We estimated the number of low-income, uninsured women using data from the US Census Bureau. We adjusted our estimates for hysterectomy status using the National Health Interview Survey and the Behavioral Risk Factor Surveillance System. We used data from the NBCCEDP to describe the number of women receiving NBCCEDP-funded screening and calculated the proportion of eligible women who received screening through the NBCCEDP at the national level (by age group, race/ethnicity) and at the state level by age group. We used the Medical Expenditure Panel Survey to estimate the proportion of NBCCEDP-eligible women who were screened outside the NBCCEDP and the proportion that are not screened. We estimate that in 2010-2012, 705,970 women aged 18-64 years, 6.5 % (705,970 of 9.8 million) of the eligible population, received NBCCEDP-funded Pap tests. We estimate that 60.2 % of eligible women aged 18-64 years were screened outside the NBCCEDP and 33.3 % were not screened. The NBCCEDP provided 623,603 screens to women aged 40-64 years, an estimated 16.5 % of the eligible population, and 83,660 screens to women aged 18-39 years, representing an estimated 1.2 % of the eligible population. The estimated proportions of eligible women screened in each state ranged from 1.5 to 32.7 % and 5 % to 73.2 % among the 18-64 and 40-64 years age groups, respectively. Changes in the proportion of eligible women screened over the study period were nonsignificant. Although the program provided cervical

Investigation of Classical Organic and Ionic Liquid Cosolvents for Early-Stage Screening in Fragment-Based Inhibitor Design with Unrelated Bacterial and Human Dihydrofolate Reductases.

PubMed

Toulouse, Jacynthe L; Abraham, Sarah M J; Kadnikova, Natalia; Bastien, Dominic; Gauchot, Vincent; Schmitzer, Andreea R; Pelletier, Joelle N

Drug design by methods such as fragment screening requires effective solubilization of millimolar concentrations of small organic compounds while maintaining the properties of the biological target. We investigate four organic solvents and three 1-butyl-3-methylimidazolium (BMIm)-based ionic liquids (ILs) as cosolvents to establish conditions for screening two structurally unrelated dihydrofolate reductases (DHFRs) that are prime drug targets. Moderate concentrations (10%-15%) of cosolvents had little effect on inhibition of the microbial type II R67 DHFR and of human DHFR (hDHFR), while higher concentrations of organic cosolvents generally decreased activity of both DHFRs. In contrast, a specific IL conserved the activity of one DHFR, while severely reducing the activity of the other, and vice versa, illustrating the differing effect of ILs on distinct protein folds. Most of the cosolvents investigated preserved the fold of R67 DHFR and had little effect on binding of the cofactor NADPH, but reduced the productive affinity for its substrate. In contrast, cosolvents resulted in modest structural destabilization of hDHFR with little effect on productive affinity. We conclude that the organic cosolvents, methanol, dimethylformamide, and dimethylsulfoxide, offer the most balanced conditions for early-stage compound screening as they maintain sufficient biological activity of both DHFRs while allowing for compound dissolution in the millimolar range. However, IL cosolvents showed poor capacity to solubilize organic compounds at millimolar concentrations, mitigating their utility in early-stage screening. Nonetheless, ILs could provide an alternative to classical organic cosolvents when low concentrations of inhibitors are used, as when characterizing higher affinity inhibitors.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

PubMed Central

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-01-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients.—Sun, D., Nakao, S., Xie, F., Zandi, S., Bagheri, A., Kanavi, M. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

[Early detection of cervical cancer in Chile: time for change].

PubMed

Léniz Martelli, Javiera; Van De Wyngard, Vanessa; Lagos, Marcela; Barriga, María Isabel; Puschel Illanes, Klaus; Ferreccio Readi, Catterina

2014-08-01

Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80's changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.

Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

PubMed Central

Wan, Minghui; Liao, Dongjiang; Peng, Guilin; Xu, Xin; Yin, Weiqiang; Guo, Guixin; Jiang, Funeng; Zhong, Weide

2017-01-01

Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition. PMID:29147652

Evaluation of Young Children for Early Intervention and Early Childhood Special Education.

ERIC Educational Resources Information Center

Allen, Diana

This technical assistance document provides guidelines for child assessment and eligibility determination for early intervention and early childhood special education programs in Oregon. An overview of the assessment process explains screening, eligibility evaluation, and assessment for the Individual Family Service Plan (IFSP). Legal requirements…

Cervical Cancer Screening

MedlinePlus

... Cancer found early may be easier to treat. Cervical cancer screening is usually part of a woman's health checkup. There are two types of tests: the Pap test and the HPV test. For both, the doctor or nurse collects cells from the surface of the cervix. With the ...

Pituitary gigantism: update on molecular biology and management.

PubMed

Lodish, Maya B; Trivellin, Giampaolo; Stratakis, Constantine A

2016-02-01

To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions. Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein gene, multiple endocrine neoplasia types 1 and 4, McCune Albright syndrome, Carney complex, and the paraganglioma, pheochromocytoma, and pituitary adenoma association because of succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging. Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach, and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone.

Results of the two incidence screenings in the National Lung Screening Trial.

PubMed

Aberle, Denise R; DeMello, Sarah; Berg, Christine D; Black, William C; Brewer, Brenda; Church, Timothy R; Clingan, Kathy L; Duan, Fenghai; Fagerstrom, Richard M; Gareen, Ilana F; Gatsonis, Constantine A; Gierada, David S; Jain, Amanda; Jones, Gordon C; Mahon, Irene; Marcus, Pamela M; Rathmell, Joshua M; Sicks, JoRean

2013-09-05

The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2). We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods. At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2. Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST

Unraveling the early molecular and physiological mechanisms involved in response to phenanthrene exposure.

PubMed

Dumas, Anne-Sophie; Taconnat, Ludivine; Barbas, Evangelos; Rigaill, Guillem; Catrice, Olivier; Bernard, Delphine; Benamar, Abdelilah; Macherel, David; El Amrani, Abdelhak; Berthomé, Richard

2016-10-21

Higher plants have to cope with increasing concentrations of pollutants of both natural and anthropogenic origin. Given their capacity to concentrate and metabolize various compounds including pollutants, plants can be used to treat environmental problems - a process called phytoremediation. However, the molecular mechanisms underlying the stabilization, the extraction, the accumulation and partial or complete degradation of pollutants by plants remain poorly understood. Here, we determined the molecular events involved in the early plant response to phenanthrene, used as a model of polycyclic aromatic hydrocarbons. A transcriptomic and a metabolic analysis strongly suggest that energy availability is the crucial limiting factor leading to high and rapid transcriptional reprogramming that can ultimately lead to death. We show that the accumulation of phenanthrene in leaves inhibits electron transfer and photosynthesis within a few minutes, probably disrupting energy transformation. This kinetic analysis improved the resolution of the transcriptome in the initial plant response to phenanthrene, identifying genes that are involved in primary processes set up to sense and detoxify this pollutant but also in molecular mechanisms used by the plant to cope with such harmful stress. The identification of first events involved in plant response to phenanthrene is a key step in the selection of candidates for further functional characterization, with the prospect of engineering efficient ecological detoxification systems for polycyclic aromatic hydrocarbons.

Molecular Genetic Analysis of Ethanol Intoxication in Drosophila melanogaster.

PubMed

Heberlein, Ulrike; Wolf, Fred W; Rothenfluh, Adrian; Guarnieri, Douglas J

2004-08-01

Recently, the fruit fly Drosophila melanogaster has been introduced as a model system to study the molecular bases of a variety of ethanol-induced behaviors. It became immediately apparent that the behavioral changes elicited by acute ethanol exposure are remarkably similar in flies and mammals. Flies show signs of acute intoxication, which range from locomotor stimulation at low doses to complete sedation at higher doses and they develop tolerance upon intermittent ethanol exposure. Genetic screens for mutants with altered responsiveness to ethanol have been carried out and a few of the disrupted genes have been identified. This analysis, while still in its early stages, has already revealed some surprising molecular parallels with mammals. The availability of powerful tools for genetic manipulation in Drosophila, together with the high degree of conservation at the genomic level, make Drosophila a promising model organism to study the mechanism by which ethanol regulates behavior and the mechanisms underlying the organism's adaptation to long-term ethanol exposure.

Screening for cervical cancer in French Guiana: screening rates from 2006 to 2011.

PubMed

Douine, M; Roué, T; Lelarge, C; Adenis, A; Thomas, N; Nacher, M

2015-12-01

In French Guiana, the age-standardized incidence rate of cervical cancer is four times higher than in France and the mortality rate 5.5 times higher. A survival study revealed that stage at diagnosis was the main factor influencing the prognosis, showing that early detection is crucial to increase cervical cancer survival. The present study aimed at evaluating the cervical cancer screening rate between 2006 and 2011 by age and for a 3-year period in French Guiana. All pap smears realised in French Guiana were analysed in two laboratories allowing exhaustive review of screening data. The screening rate was estimated at about 54% from 2006 to 2011, with a statistical difference between coastal and rural area (56.3% versus 18.7%). Although the methodological difference did not allow comparisons with metropolitan France, these results could be used to evaluate the impact of organised cervical cancer screening by the French Guiana Association for Organized Screening of Cancers which has been implemented in French Guiana since 2012.

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

PubMed

Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

2018-01-01

This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

Early language screening in city and Hackney: the concurrent validity of a measure designed for use with 2 1/2-year-olds.

PubMed

Law, J

1994-01-01

This paper reports data relating to the development of a screening test for language impairment in 2 1/2-year-old children. The screening test itself has previously been described. The results of a pilot study and a larger community study are reported. In all, 34 children were included in the pilot study and 1015 in the community study. The reference test selected was the Reynell Developmental Language Scales and the cut-off adopted 1.5 standard deviations below the mean for either the expressive or the receptive scale of the test concerned. The pass mark on the screening test was ascertained using receiver operating characteristics (ROC). The validity is reported given the cut-off identified. The specificity, sensitivity and both positive and negative predictive abilities are reported for both the pilot and the subsequent study. The application of the test is discussed in the context of the current debate about early identification.

Accuracy of a Screening Tool for Early Identification of Language Impairment

ERIC Educational Resources Information Center

Uilenburg, Noëlle; Wiefferink, Karin; Verkerk, Paul; van Denderen, Margot; van Schie, Carla; Oudesluys-Murphy, Ann-Marie

2018-01-01

Purpose: A screening tool called the "VTO Language Screening Instrument" (VTO-LSI) was developed to enable more uniform and earlier detection of language impairment. This report, consisting of 2 retrospective studies, focuses on the effects of using the VTO-LSI compared to regular detection procedures. Method: Study 1 retrospectively…

Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo.

PubMed

Wishart, Thomas M; Rooney, Timothy M; Lamont, Douglas J; Wright, Ann K; Morton, A Jennifer; Jackson, Mandy; Freeman, Marc R; Gillingwater, Thomas H

2012-01-01

Degeneration of synaptic and axonal compartments of neurons is an early event contributing to the pathogenesis of many neurodegenerative diseases, but the underlying molecular mechanisms remain unclear. Here, we demonstrate the effectiveness of a novel "top-down" approach for identifying proteins and functional pathways regulating neurodegeneration in distal compartments of neurons. A series of comparative quantitative proteomic screens on synapse-enriched fractions isolated from the mouse brain following injury identified dynamic perturbations occurring within the proteome during both initiation and onset phases of degeneration. In silico analyses highlighted significant clustering of proteins contributing to functional pathways regulating synaptic transmission and neurite development. Molecular markers of degeneration were conserved in injury and disease, with comparable responses observed in synapse-enriched fractions isolated from mouse models of Huntington's disease (HD) and spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying degeneration in axonal and synaptic compartments. Our study has identified conserved molecular responses occurring within synapse-enriched fractions of the mouse brain during the early stages of neurodegeneration, focused on functional networks modulating synaptic transmission and incorporating molecular chaperones, cytoskeletal modifiers, and calcium-binding proteins. We propose that the proteins and functional pathways identified in the current study

Toddlers and Touch Screens: Potential for Early Learning?

ERIC Educational Resources Information Center

Kirkorian, Heather L.; Pempek, Tiffany A.

2013-01-01

As interactive screens (e.g., tablet computers, smartphones) continue to enter the homes of young children, it becomes increasingly important to understand the impact of these technologies on development. Some studies suggest that while traditional television and videos hold little educational value for toddlers, young children may be able to…

Newborn screening: new developments, new dilemmas.

PubMed

Kerruish, N J; Robertson, S P

2005-07-01

Scientific and technological advances are lending pressure to expand the scope of newborn screening. Whereas this has great potential for improving child health, it also challenges our current perception of such programmes. Standard newborn screening programmes are clearly justified by the fact that early detection and treatment of affected individuals avoids significant morbidity and mortality. However, proposals to expand the scope and complexity of such testing are not all supported by a similar level of evidence for unequivocal benefit. We argue that screening for genetic susceptibility to complex disorders is inherently different from standard screening and, while of potential value, must be considered separately from conventional testing.

Can you un-ring the bell? A qualitative study of how affect influences cancer screening decisions.

PubMed

Driedger, S Michelle; Annable, Gary; Brouwers, Melissa; Turner, Donna; Maier, Ryan

2017-09-13

The belief that early detection is the best protection against cancer underlies cancer screening. Emerging research now suggests harms associated with early detection may sometimes outweigh the benefits. Governments, cancer agencies, and organizations that publish screening guidelines have found it is difficult to "un-ring the bell" on the message that "early detection is your best protection" because of its widespread communication and enduring resonance. This study explores affective factors-and their interplay with relevant analytical factors-in public/laypersons' decision making about cancer screening. A total of 93 people (47 men, 46 women) attended focus groups about, respectively, prostate cancer screening and breast cancer screening in two Canadian cities. Affective factors were a major influence on many focus group participants' decision making about cancer screening, including fear of cancer and a generalized enthusiasm for prevention/screening, and they were often inspired by anecdotes about the cancer experiences of family and friends. Affect also existed alongside more analytical factors including assessments of reduced risk in the management of any cancer diagnosis if caught early, and, for men, the belief that an unreliable test is "better than nothing," and that men deserve prostate cancer screening because women have breast and cervical cancer screening. Affective factors were particularly noticeable in the sub-groups most supportive of screening and the "early detection" message: older women who felt that mammogram screening should begin at age 40 rather than 50, and older men who felt that prostate cancer screening should be expanded beyond its current unorganized, opportunistic usage. In contrast, younger participants displayed less affective attachments to "early detection" messages and had greater concerns about harms of screening and were more receptive to nuanced messages informed by evidence. Policymakers attempting to communicate more

How to improve colon cancer screening rates

PubMed Central

Alberti, Luiz Ronaldo; Garcia, Diego Paim Carvalho; Coelho, Debora Lucciola; De Lima, David Correa Alves; Petroianu, Andy

2015-01-01

Colorectal carcinoma is a common cause of death throughout the world and may be prevented by routine control, which can detect precancerous neoplasms and early cancers before they undergo malignant transformation or metastasis. Three strategies may improve colon cancer screening rates: convince the population about the importance of undergoing a screening test; achieve higher efficacy in standard screening tests and make them more available to the community and develop new more sensitive and efficacious screening methods and make them available as routine tests. In this light, the present study seeks to review these three means through which to increase colon cancer screening rates. PMID:26688708

An opto-electronic joint detection system based on DSP aiming at early cervical cancer screening

NASA Astrophysics Data System (ADS)

Wang, Weiya; Jia, Mengyu; Gao, Feng; Yang, Lihong; Qu, Pengpeng; Zou, Changping; Liu, Pengxi; Zhao, Huijuan

2015-02-01

The cervical cancer screening at a pre-cancer stage is beneficial to reduce the mortality of women. An opto-electronic joint detection system based on DSP aiming at early cervical cancer screening is introduced in this paper. In this system, three electrodes alternately discharge to the cervical tissue and three light emitting diodes in different wavelengths alternately irradiate the cervical tissue. Then the relative optical reflectance and electrical voltage attenuation curve are obtained by optical and electrical detection, respectively. The system is based on DSP to attain the portable and cheap instrument. By adopting the relative reflectance and the voltage attenuation constant, the classification algorithm based on Support Vector Machine (SVM) discriminates abnormal cervical tissue from normal. We use particle swarm optimization to optimize the two key parameters of SVM, i.e. nuclear factor and cost factor. The clinical data were collected on 313 patients to build a clinical database of tissue responses under optical and electrical stimulations with the histopathologic examination as the gold standard. The classification result shows that the opto-electronic joint detection has higher total coincidence rate than separate optical detection or separate electrical detection. The sensitivity, specificity, and total coincidence rate increase with the increasing of sample numbers in the training set. The average total coincidence rate of the system can reach 85.1% compared with the histopathologic examination.

One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

PubMed

Binns-Hall, O; Selvarajah, D; Sanger, D; Walker, J; Scott, A; Tesfaye, S

2018-04-02

To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the 'gold standard'. A total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10-g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN-check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (P<0.001). A new diagnosis of painful distal symmetrical polyneuropathy was made in 59 participants (25%), and 56.6% had moderate- or high-risk foot. Participants rated the service very highly. Combined, eye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at-risk foot. Combined large- and small-nerve-fibre assessment using non-invasive, quantitative and quick point

Breast cancer screening patterns among military beneficiaries: racial variations in screening eliminated in an equal-access model.

PubMed

Oseni, Tawakalitu O; Soballe, Peter W

2014-10-01

African American women present with more aggressive breast tumors and at later stages than white women. Many factors have been proposed to explain these findings, including socioeconomic status, cultural beliefs, and access to medical care. The purpose of this project was to determine if stage at presentation would be equivalent in a system providing equal access to care and if screening was equivalent. The Naval Medical Center San Diego (NMCSD) tumor registry from 2007 to 2012 was queried for this cross-sectional study. Eligible women included all those diagnosed and treated for breast cancer at NMCSD. Distribution of tumor stage (early vs. advanced) between racial groups was compared by age, treatment, and receptor status. A total of 624 women were eligible; 88 % were early stage (0-II) and 12 % presented with advanced stage (III or IV). Racial differences in distribution were significant among African American and Hispanic women for early versus advanced presentation (p = 0.011). No racial disparity was seen in screening patterns among women. In a military health system with equal access to care and standard screening recommendations, screening patterns did not vary with race but did vary with stage and active duty status. African American women present with breast cancer at later stages and with more hormone-receptor negative tumors, suggesting that biology rather than socioeconomic or access factors may be the most important determinant of stage at presentation of breast cancer for African American women.

Breast cancer screening controversies: who, when, why, and how?

PubMed

Chetlen, Alison; Mack, Julie; Chan, Tiffany

2016-01-01

Mammographic screening is effective in reducing mortality from breast cancer. The issue is not whether mammography is effective, but whether the false positive rate and false negative rates can be reduced. This review will discuss controversies including the reduction in breast cancer mortality, overdiagnosis, the ideal screening candidate, and the optimal imaging modality for breast cancer screening. The article will compare and contrast screening mammography, tomosynthesis, whole-breast screening ultrasound, magnetic resonance imaging, and molecular breast imaging. Though supplemental imaging modalities are being utilized to improve breast cancer diagnosis, mammography still remains the gold standard for breast cancer screening. Copyright © 2015 Elsevier Inc. All rights reserved.

Multicenter study of the COPD-6 screening device: feasible for early detection of chronic obstructive pulmonary disease in primary care?

PubMed

Kjeldgaard, Peter; Lykkegaard, Jesper; Spillemose, Heidi; Ulrik, Charlotte Suppli

2017-01-01

Early detection of COPD may reduce the future burden of the disease. We aimed to investigate whether prescreening with a COPD-6 screening device (measuring FEV 1 and FEV 6 ) facilitates early detection of COPD in primary care. In primary care, individuals at high risk of COPD (ie, age ≥35 years, relevant exposure, and at least one respiratory symptom) and no previous diagnosis of obstructive lung disease were examined with a COPD-6 screening device. In prioritized order, the criteria for proceeding to confirmatory spirometry were FEV 1 /FEV 6 <0.7, FEV 1 <80%pred, or clinical suspicion of COPD regardless of test result (medical doctor's [MD] decision). Based on spirometry, including bronchodilator (BD) reversibility test, individuals were classified as COPD (post-BD FEV 1 /FVC <0.70), asthma (ΔFEV 1 ≥0.50 L), or no obstructive lung disease. A total of 2,990 subjects (54% men, mean age 59 years, and mean 28 pack-years) were enrolled, of whom 949 (32%) proceeded from COPD-6 screening to confirmative spirometry based on the following criteria: 510 (54%) FEV 1 /FEV 6 <0.70, 382 (40%) FEV 1 <80%pred, and 57 (6%) MD decision. Following confirmative spirometry, the 949 individuals were diagnosed as having COPD (51%), asthma (3%), and no obstructive lung disease (45%). COPD was diagnosed in 487 (16%) of the enrolled subjects in whom confirmative spirometry was performed in 69% based on FEV 1 /FEV 6 <0.7 and in 29% based on FEV 1 ≤80%pred. Prescreening with the COPD-6 device showed acceptable specificity for the selection of subjects for diagnostic spirometry and is likely to be a useful alternative to current practice in primary care.

Conducting Universal Complete Mental Health Screening via Student Self-Report

ERIC Educational Resources Information Center

Moore, Stephanie A.; Widales-Benitez, Oscar; Carnazzo, Katherine W.; Kim, Eui Kyung; Moffa, Kathryn; Dowdy, Erin

2015-01-01

Universal screening is increasingly becoming part of prevention and early intervention best practice in schools. Although the number of schools engaging in universal screening has increased over the past decade, emotional and behavioral problems are often their primary focus. Problem-focused screening, however, does not address positive…

Rapid screening for human-pathogenic Mucorales using rolling circle amplification.

PubMed

Dolatabadi, S; Najafzadeh, M J; de Hoog, G S

2014-12-01

Mucormycosis has emerged as a relatively common severe mycosis in patients with haematological and allogeneic stem cell transplantation. Source of transmission is from unidentified sources in the environment. Early diagnosis of infection and its source of contamination are paramount for rapid and appropriate therapy. In this study, rolling circle amplification (RCA) is introduced as a sensitive, specific and reproducible isothermal DNA amplification technique for rapid molecular identification of six of the most virulent species (Rhizopus microsporus, R. arrhizus var. arrhizus, R. arrhizus var. delemar, Mucor irregularis, Mucor circinelloides, Lichtheimia ramosa, Lichtheimia corymbifera). DNAs of target species were successfully amplified, with no cross reactivity between species. RCA can be considered as a rapid detection method with high specificity and sensitivity, suitable for large screening. © 2014 Blackwell Verlag GmbH.

The Early Entrance Option: Academic and Social/Emotional Outcomes.

ERIC Educational Resources Information Center

Braymen, Rebecca K. F.; Piersel, Wayne C.

1987-01-01

Examines how early kindergarten entrants fare academically and socially/emotionally in their schooling. Screening procedures are used to identify children with exceptional ability and to eliminate from early entrance children likely to have adjustment difficulties. The screening battery includes measurements of academic readiness, social/emotional…

Mycoplasma/Ureaplasma infection in pregnancy: to screen or not to screen.

PubMed

Donders, Gilbert G G; Ruban, Kateryna; Bellen, Gert; Petricevic, Ljubomir

2017-07-26

Mycoplasmata have been linked to pregnancy complications and neonatal risk. While formerly a limited number of species could be discovered by cultures, molecular biology nowadays discovers both lower quantities and more diverse species, making us realize that mycoplasmata are ubiquitous in the vaginal milieu and do not always pose a danger for pregnant women. As the meaning of mycoplasmata in pregnancy is not clear to many clinicians, we summarized the current knowledge about the meaning of different kinds of mycoplasmata in pregnancy and discuss the potential benefits and disadvantages of treatment. Currently, there is no general rule to screen and treat for mycoplasmata in pregnancy. New techniques seem to indicate that Ureaplasma parvum (Up), which now can be distinguished from U. urealyticum (Uu), may pose an increased risk for preterm birth and bronchopulmonary disease in the preterm neonate. Mycoplasma hominis (Mh) is related to early miscarriages and midtrimester abortions, especially in the presence of abnormal vaginal flora. Mycoplasma genitalium (Mg) is now recognized as a sexually transmitted infection (STI) that is involved in the causation of cervicitis, pelvic inflammatory disease (PID) in non-pregnant, and preterm birth and miscarriages in pregnant women, irrespective of the presence of concurrent other STIs, like Chlamydia or gonorrhoea. Proper studies to test for efficacy and improved pregnancy outcome are scarce and inconclusive. Azythromycin is the standard treatment now, although, for Mg, this may not be sufficient. The role of clarithromycin in clinical practice still has to be established. There is a stringent need for new studies based on molecular diagnostic techniques and randomized treatment protocols with promising and safe antimicrobials.

A plant-based chemical genomics screen for the identification of flowering inducers.

PubMed

Fiers, Martijn; Hoogenboom, Jorin; Brunazzi, Alice; Wennekes, Tom; Angenent, Gerco C; Immink, Richard G H

2017-01-01

Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study. Here we describe the set-up of the screening platform and various issues and pitfalls that need to be addressed in order to perform a chemical genomics screening on Arabidopsis plantlets. We describe the choice for a molecular marker, in combination with a sensitive reporter that's active in plants and is sufficiently sensitive for detection. In this particular screen, the firefly Luciferase marker was used, fused to the regulatory sequences of the floral meristem identity gene APETALA1 (AP1) , which is an early marker for flowering. Using this screening platform almost 9000 compounds were screened, in triplicate, in 96-well plates at a concentration of 25 µM. One of the identified potential flowering inducing compounds was studied in more detail and named Flowering1 (F1). F1 turned out to be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more potent than SA in the induction of flowering. The effect could be confirmed by watering Arabidopsis plants with SA or F1, in which F1 gave a significant reduction in time to flowering in comparison to SA treatment or the control. In this study a chemical genomics screening platform was developed to discover compounds that can induce flowering in Arabidopsis. This platform was used successfully, to identify a compound that can speed-up flowering in Arabidopsis.

A new insight into mushroom tyrosinase inhibitors: docking, pharmacophore-based virtual screening, and molecular modeling studies.

PubMed

Bagherzadeh, Kowsar; Shirgahi Talari, Faezeh; Sharifi, Amirhossein; Ganjali, Mohammad Reza; Saboury, Ali Akbar; Amanlou, Massoud

2015-01-01

Tyrosinase, a widely spread enzyme in micro-organisms, animals, and plants, participates in two rate-limiting steps in melanin formation pathway which is responsible for skin protection against UV lights' harm whose functional deficiency result in serious dermatological diseases. This enzyme seems to be responsible for neuromelanin formation in human brain as well. In plants, the enzyme leads the browning pathway which is commonly observed in injured tissues that is economically very unfavorable. Among different types of tyrosinase, mushroom tyrosinase has the highest homology with the mammalian tyrosinase and the only commercial tyrosinase available. In this study, ligand-based pharmacophore drug discovery method was applied to rapidly identify mushroom tyrosinase enzyme inhibitors using virtual screening. The model pharmacophore of essential interactions was developed and refined studying already experimentally discovered potent inhibitors employing Docking analysis methodology. After pharmacophore virtual screening and binding modes prediction, 14 compounds from ZINC database were identified as potent inhibitors of mushroom tyrosinase which were classified into five groups according to their chemical structures. The inhibition behavior of the discovered compounds was further studied through Classical Molecular Dynamic Simulations and the conformational changes induced by the presence of the studied ligands were discussed and compared to those of the substrate, tyrosine. According to the obtained results, five novel leads are introduced to be further optimized or directly used as potent inhibitors of mushroom tyrosinase.

Early screening for type 2 diabetes following gestational diabetes mellitus in France: hardly any impact of the 2010 guidelines.

PubMed

Goueslard, K; Cottenet, J; Mariet, A-S; Sagot, P; Petit, J-M; Quantin, C

2017-07-01

Women who had gestational diabetes mellitus (GDM) have a high risk of type 2 diabetes mellitus (T2DM) in the years following pregnancy. Most follow-up screening studies have been conducted in limited geographical areas leading to large variability in the results. The aim of our investigation was to measure how the publication of guidelines affected early screening for T2DM after a pregnancy with GDM during the period 2007-2013, in France. We conducted a retrospective cohort study in a representative sample of 1/97th of the French population using data from the "National Health Insurance Inter-Regime Information System," which collects individual hospital and non-hospital data for healthcare consumption. The sample included 49,080 women who gave birth in 2007-2013. In the following 3 months, only 18.49% of women with GDM had an oral glucose tolerance test or a blood glucose test in 2007. This rate had not significantly increased in 2013 (p = 0.18). The proportion of women with GDM who had the recommended glycemic follow-up at 3 months (20.30 vs. 21.58%, p = 0.19) and 6 months (32.48 vs. 37.16%, p = 0.08) was not significantly different before the guidelines (2008-2009) and after the guidelines (2012-2013). At 12 months, the difference was significant (46.77 vs. 54.05%, p = 0.009). Postpartum screening has improved only slightly since the guidelines and remains largely insufficient, with less than 25% of women with GDM screened in the first 3 months. In the first year after delivery, less than 60% of women were screened for T2DM.

Evaluation of a Stratified National Breast Screening Program in the United Kingdom: An Early Model-Based Cost-Effectiveness Analysis.

PubMed

Gray, Ewan; Donten, Anna; Karssemeijer, Nico; van Gils, Carla; Evans, D Gareth; Astley, Sue; Payne, Katherine

2017-09-01

To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1, risk 2, masking [supplemental screening for women with higher breast density], and masking and risk 1) compared with the current UK NBSP and no screening. The model assumed a lifetime horizon, the health service perspective to identify costs (£, 2015), and measured consequences in quality-adjusted life-years (QALYs). Multiple data sources were used: systematic reviews of effectiveness and utility, published studies reporting costs, and cohort studies embedded in existing NBSPs. Model parameter uncertainty was assessed using probabilistic sensitivity analysis and one-way sensitivity analysis. The base-case analysis, supported by probabilistic sensitivity analysis, suggested that the risk stratified NBSPs (risk 1 and risk-2) were relatively cost-effective when compared with the current UK NBSP, with incremental cost-effectiveness ratios of £16,689 per QALY and £23,924 per QALY, respectively. Stratified NBSP including masking approaches (supplemental screening for women with higher breast density) was not a cost-effective alternative, with incremental cost-effectiveness ratios of £212,947 per QALY (masking) and £75,254 per QALY (risk 1 and masking). When compared with no screening, all stratified NBSPs could be considered cost-effective. Key drivers of cost-effectiveness were discount rate, natural history model parameters, mammographic sensitivity, and biopsy rates for recalled cases. A key assumption was that the risk model used in the stratification process was perfectly calibrated to the population. This early model-based cost-effectiveness analysis provides indicative evidence for decision makers to understand the key drivers of costs and QALYs for exemplar stratified NBSP. Copyright

Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis.

PubMed

Ben-Rebeh, Imen; Grati, Mhamed; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber

2016-01-01

Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient's early childhood is of utmost importance, allowing better educational and therapeutic management.

Ultrafast protein structure-based virtual screening with Panther

NASA Astrophysics Data System (ADS)

Niinivehmas, Sanna P.; Salokas, Kari; Lätti, Sakari; Raunio, Hannu; Pentikäinen, Olli T.

2015-10-01

Molecular docking is by far the most common method used in protein structure-based virtual screening. This paper presents Panther, a novel ultrafast multipurpose docking tool. In Panther, a simple shape-electrostatic model of the ligand-binding area of the protein is created by utilizing the protein crystal structure. The features of the possible ligands are then compared to the model by using a similarity search algorithm. On average, one ligand can be processed in a few minutes by using classical docking methods, whereas using Panther processing takes <1 s. The presented Panther protocol can be used in several applications, such as speeding up the early phases of drug discovery projects, reducing the number of failures in the clinical phase of the drug development process, and estimating the environmental toxicity of chemicals. Panther-code is available in our web pages (http://www.jyu.fi/panther) free of charge after registration.

Ultrafast protein structure-based virtual screening with Panther.

PubMed

Niinivehmas, Sanna P; Salokas, Kari; Lätti, Sakari; Raunio, Hannu; Pentikäinen, Olli T

2015-10-01

Molecular docking is by far the most common method used in protein structure-based virtual screening. This paper presents Panther, a novel ultrafast multipurpose docking tool. In Panther, a simple shape-electrostatic model of the ligand-binding area of the protein is created by utilizing the protein crystal structure. The features of the possible ligands are then compared to the model by using a similarity search algorithm. On average, one ligand can be processed in a few minutes by using classical docking methods, whereas using Panther processing takes <1 s. The presented Panther protocol can be used in several applications, such as speeding up the early phases of drug discovery projects, reducing the number of failures in the clinical phase of the drug development process, and estimating the environmental toxicity of chemicals. Panther-code is available in our web pages (http://www.jyu.fi/panther) free of charge after registration.

Molecular fragil X screening in normal populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spence, W.C.; Black, S.H.; Fallon, L.

In December, 1993, we initiated a pilot project in which DNA fragile X (fraX) testing was offered during routine prenatal or genetic counseling to all pregnant women seen at the Genetics & IVF Institute, most of whom were referred for the indication of advanced maternal age. A brochure on fragile X syndrome was sent to each patient prior to her appointment and was reviewed by a counselor or physician during the counseling session. As of June 1995, 3,345 patients were offered testing; 474 women with no identified family history of mental retardation or learning disability and 214 women with amore » positive family history accepted the test on a self-pay basis. The second population screened was 271 potential donors in our anonymous egg donor program. DNA from blood was tested by Southern blot using EcoRI/EagI and StB12.3. If an expansion was detected, CGG repeat number was determined by PCR-based analysis. Among the 474 patients with unremarkable family histories, three fraX carriers were identified (repeat sizes = 60+), whereas none were found in the 214 patients with a positive family history. Among the potential egg donors, two high borderline patients were identified (repeat sizes = between 50 and 59). Our ongoing study indicates that screening of pregnant or preconceptual populations for fraX carrier status using DNA testing is accepted by many patients and is an important addition to current medical practice. 12 refs., 1 tab.« less

Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening.

PubMed

Smith, Robert A; Andrews, Kimberly S; Brooks, Durado; Fedewa, Stacey A; Manassaram-Baptiste, Deana; Saslow, Debbie; Brawley, Otis W; Wender, Richard C

2018-05-30

Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates from the National Health Interview Survey, and select issues related to cancer screening. In this 2018 update, we also summarize the new American Cancer Society colorectal cancer screening guideline and include a clarification in the language of the 2013 lung cancer screening guideline. CA Cancer J Clin 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Clinical relevance of molecular identification of microorganisms and detection of antimicrobial resistance genes in bloodstream infections of paediatric cancer patients.

PubMed

Carlesse, Fabianne; Cappellano, Paola; Quiles, Milene Gonçalves; Menezes, Liana Carballo; Petrilli, Antonio Sérgio; Pignatari, Antonio Carlos

2016-09-01

Bloodstream infections (BSIs) are the major cause of mortality in cancer patients. Molecular techniques are used for rapid diagnosis of BSI, allowing early therapy and improving survival. We aimed to establish whether real-time quantitative polymerase chain reaction (qPCR) could improve early diagnosis and therapy in paediatric cancer patients, and describe the predominant pathogens of BSI and their antimicrobial susceptibility. Blood samples were processed by the BACTEC system and microbial identification and susceptibility tests were performed by the Phoenix system. All samples were screened by multiplex 16 s rDNA qPCR. Seventeen species were evaluated using sex-specific TaqMan probes and resistance genes blaSHV, blaTEM, blaCTX, blaKPC, blaIMP, blaSPM, blaVIM, vanA, vanB and mecA were screened by SYBR Green reactions. Therapeutic efficacy was evaluated at the time of positive blood culture and at final phenotypic identification and antimicrobial susceptibility results. We analyzed 69 episodes of BSI from 64 patients. Gram-positive bacteria were identified in 61 % of the samples, Gram-negative bacteria in 32 % and fungi in 7 %. There was 78.2 % of agreement between the phenotypic and molecular methods in final species identification. The mecA gene was detected in 81.4 % of Staphylococcus spp., and 91.6 % were concordant with the phenotypic method. Detection of vanA gene was 100 % concordant. The concordance for Gram-negative susceptibilities was 71.4 % for Enterobacteriaceae and 50 % for Pseudomonas aeruginosa. Therapy was more frequently inadequate in patients who died, and the molecular test was concordant with the phenotypic susceptibility test in 50 %. qPCR has potential indication for early identification of pathogens and antimicrobial resistance genes from BSI in paediatric cancer patients and may improve antimicrobial therapy.

Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

PubMed

Khneisser, I; Adib, S; Assaad, S; Megarbane, A; Karam, P

2015-12-01

Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon. © The Author(s) 2015.

[New possibilities screening of refractive errors among children].

PubMed

Ondrejková, M; Kyselová, P

2013-06-01

To establish early detection of refractive errors among children in Slovakia. Different screening methods have been evaluated and compared in this work. we have been working on a prospective study. Pre-school children in kindergardens in Central Slovakia were checked up between years 2009-2011. Effectiveness of various screening methods was compared within 2 groups, using test-type and Plusoptix Vision Screener. Parentęs of children positive to refractive errors were recommended to consult a paediatrician ophthalmologist. 3982 children were examined. As a result, 13-14.1% of children who have not been examinated by the specialist, were positive. 53.3% of them went to see the doctor afterwards. establishment of early refractive errors screening is an important method how to prevent strabismus and amblyopia. It is very important to improve parentęs knowledge about the risk of refractive errors and also to improve screening methods with collaboration with kindergarten teachers.