Evaluation of a stage II screening protocol for prostate cancer

In 2003, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer and third leading cause of cancer death in Canada. During PCa population screening, approximately 25% of patients with a normal digital rectal examination (DRE) and intermediate serum prostate specific antigen (PSA) level have PCa. Since all patients typically undergo biopsy, it is expected that approximately 75% of these procedures are unnecessary. The purpose of this study was to compare the degree of efficacy of clinical tests and algorithms in stage II screening for PCa while preventing unnecessary biopsies from occurring. The sample consisted of 201 consecutive men who were suspected of PCa based on the results of a DRE and serum PSA. These men were referred for venipuncture and transrectal ultrasound (TRUS). Clinical tests included TRUS, agespecific reference range PSA (Age-PSA), prostate specific antigen density (PSAD), and free-to-total prostate specific antigen ratio (%fPSA). Clinical results were evaluated individually and within algorithms. Cutoffs of 0.12 and 0.15 ng/ml/cc were employed for PSAD. Cutoffs that would provide a minimum sensitivity of 0.90 and 0.95, respectively were utilized for %fPSA. Statistical analysis included ROC curve analysis, calculated sensitivity (Sens), specificity (Spec), and positive likelihood ratio (LR), with corresponding confidence intervals (Cl). The %fPSA, at a 23% cutoff ({ Sens=0.92; CI, 0.06}, {Spec=0.4l; CI, 0.09}, {LR=1.56; CI, O.ll}), proved to be the most efficacious independent clinical test. The combination of PSAD (cutoff 0.15 ng/ml/cc) and %fPSA (cutoff 23%) ({Sens=0.93; CI, 0.06}, {Spec=0.38; CI, 0.08}, {LR=1.50; CI, 0.10}) was the most efficacious clinical algorithm. This study advocates the use of %fPSA at a cutoff of 23% when screening patients with an intermediate serum PSA and benign DRE.

THE ASSOCIATION OF SEQUENCE OF HIRING PRACTICE AND BIOPHYSICAL COMPONENTS IN SCREENING PROBATIONARY FIREFIGHTERS

Variation in hiring procedures occurs within fire service human resource departments. In this study, City 1 and City 2 applicants were required to pass their biophysical assessments prior to being hired as firefighters at the beginning and end of the screening process, respectively. City 1 applicants demonstrated significantly lower resting heart rate (RHR), resting diastolic blood pressure (RDBP), body fat% (BF) and higher z-scores for BF, trunk flexibility (TF) and overall clinical assessment (p<0.05). Regression analysis found that age and conducting the biophysical assessment at the end of the screening process explained poorer biophysical assessment results in BF% (R2=21%), BF z-score (R2=22%), TF z-score (R2=10%) and overall clinical assessment z-score (R2=7%). Each of RHR (OR=1.06, CI=1.01-1.10), RDBP (OR=1.05, CI=1.00-1.11) and BF% (OR=1.20, CI=1.07-1.37) increased the odds of being a City 2 firefighter (p<0.05). Biophysical screening at the end of the hiring process may result in the hiring of a less healthy firefighter.

Screening for adolescent idiopathic scoliosis: an information statement by the scoliosis research society international task force

Background: Routine screening of scoliosis is a controversial subject and screening efforts vary greatly around the world. METHODS: Consensus was sought among an international group of experts (seven spine surgeons and one clinical epidemiologist) using a modified Delphi approach. The consensus achieved was based on careful analysis of a recent critical review of the literature on scoliosis screening, performed using a conceptual framework of analysis focusing on five main dimensions: technical, clinical, program, cost and treatment effectiveness. FINDINGS: A consensus was obtained in all five dimensions of analysis, resulting in 10 statements and recommendations. In summary, there is scientific evidence to support the value of scoliosis screening with respect to technical efficacy, clinical, program and treatment effectiveness, but there insufficient evidence to make a statement with respect to cost effectiveness. Scoliosis screening should be aimed at identifying suspected cases of scoliosis that will be referred for diagnostic evaluation and confirmed, or ruled out, with a clinically significant scoliosis. The scoliometer is currently the best tool available for scoliosis screening and there is moderate evidence to recommend referral with values between 5 degrees and 7 degrees. There is moderate evidence that scoliosis screening allows for detection and referral of patients at an earlier stage of the clinical course, and there is low evidence suggesting that scoliosis patients detected by screening are less likely to need surgery than those who did not have screening. There is strong evidence to support treatment by bracing. INTERPRETATION: This information statement by an expert panel supports scoliosis screening in 4 of the 5 domains studied, using a framework of analysis which includes all of the World Health Organisation criteria for a valid screening procedure.

The effectiveness of scoliosis screening programs: methods for systematic review and expert panel recommendations formulation

Background: Literature on scoliosis screening is vast, however because of the observational nature of available data and methodological flaws, data interpretation is often complex, leading to incomplete and sometimes, somewhat misleading conclusions. The need to propose a set of methods for critical appraisal of the literature about scoliosis screening, a comprehensive summary and rating of the available evidence appeared essential. METHODS: To address these gaps, the study aims were: i) To propose a framework for the assessment of published studies on scoliosis screening effectiveness; ii) To suggest specific questions to be answered on screening effectiveness instead of trying to reach a global position for or against the programs; iii) To contextualize the knowledge through expert panel consultation and meaningful recommendations. The general methodological approach proceeds through the following steps: Elaboration of the conceptual framework; Formulation of the review questions; Identification of the criteria for the review; Selection of the studies; Critical assessment of the studies; Results synthesis; Formulation and grading of recommendations in response to the questions. This plan follows at best GRADE Group (Grades of Recommendation, Assessment, Development and Evaluation) requirements for systematic reviews, assessing quality of evidence and grading the strength of recommendations. CONCLUSIONS: In this article, the methods developed in support of this work are presented since they may be of some interest for similar reviews in scoliosis and orthopaedic fields.

Natural products biological screening and ligand-based virtual screening for the discovery of new antileishmanial agents

In the course of our research program to discover novel antileishmanial agents, a biological screening of natural products against Leishmania major promastigotes allowed the identification of a furoquinoline alkaloid (1) and a furanocoumarin (2) as new hits. Subsequently, an integrated ligand-based virtual screening approach was employed to search for new antileishmanial compounds using these naturally occurring molecules as templates. Fourteen out of 40 compounds selected from a database of about 800,000 compounds (extracted from ZINC, a free database for virtual screening) were experimentally confirmed to possess significant in vitro antileishmanial properties. The application of ligand-based virtual screening as a complementary approach to experimental natural product screening was a useful strategy to facilitate the identification of new promising lead candidates.

Effectiveness of high-throughput miniaturized sorbent- and solid phase microextraction techniques combined with gas chromatography–mass spectrometry analysis for a rapid screening of volatile and semi-volatile composition of wines: a comparative study

In this study the feasibility of different extraction procedures was evaluated in order to test their potential for the extraction of the volatile (VOCs) and semi-volatile constituents (SVOCs) from wines. In this sense, and before they could be analysed by gas chromatography–quadrupole first stage masss spectrometry (GC–qMS), three different high-throughput miniaturized (ad)sorptive extraction techniques, based on solid phase extraction (SPE), microextraction by packed sorbents (MEPS) and solid phase microextraction (SPME), were studied for the first time together, for the extraction step. To achieve the most complete volatile and semi-volatile signature, distinct SPE (LiChrolut EN, Poropak Q, Styrene-Divinylbenzene and Amberlite XAD-2) and MEPS (C2, C8, C18, Silica and M1 (mixed C8-SCX)) sorbent materials, and different SPME fibre coatings (PA, PDMS, PEG, DVB/CAR/PDMS, PDMS/DVB, and CAR/PDMS), were tested and compared. All the extraction techniques were followed by GC–qMS analysis, which allowed the identification of up to 103 VOCs and SVOCs, distributed by distinct chemical families: higher alcohols, esters, fatty acids, carbonyl compounds and furan compounds. Mass spectra, standard compounds and retention index were used for identification purposes. SPE technique, using LiChrolut EN as sorbent (SPELiChrolut EN), was the most efficient method allowing for the identification of 78 VOCs and SVOCs, 63 and 19 more than MEPS and SPME techniques, respectively. In MEPS technique the best results in terms of number of extractable/identified compounds and total peak areas of volatile and semi-volatile fraction, were obtained by using C8 resin whereas DVB/CAR/PDMS was revealed the most efficient SPME coating to extract VOCs and SVOCs from Bual wine. Diethyl malate (18.8 ± 3.2%) was the main component found in wine SPELiChrolut EN extracts followed by ethyl succinate (13.5 ± 5.3%), 3-methyl-1-butanol (13.2 ± 1.7%), and 2-phenylethanol (11.2 ± 9.9%), while in SPMEDVB/CAR/PDMS technique 3-methyl-1-butanol (43.3 ± 0.6%) followed by diethyl succinate (18.9 ± 1.6%), and 2-furfural (10.4 ± 0.4%), are the major compounds. The major VOCs and SVOCs isolated by MEPSC8 were 3-methyl-1-butanol (26.8 ± 0.6%, from wine total volatile fraction), diethyl succinate (24.9 ± 0.8%), and diethyl malate (16.3 ± 0.9%). Regardless of the extraction technique, the highest extraction efficiency corresponds to esters and higher alcohols and the lowest to fatty acids. Despite some drawbacks associated with the SPE procedure such as the use of organic solvents, the time-consuming and tedious sampling procedure, it was observed that SPELiChrolut EN, revealed to be the most effective technique allowing the extraction of a higher number of compounds (78) rather than the other extraction techniques studied.

Enfermagem na atenção primária em saúde no screening de adolescentes com excesso de peso

One of the Primary Health Care strategies for adolescent health is the growth and development follow-up and the early detection of overweight adolescents. Even though the School Health Program in Brazil proposes to evaluate the nutritional state of the school population in the corresponding community health units, not all cities have adhered to the Program and many nurses do not recognize overweight as a problem in their territory. The objective of the study was to identify the nurse´s participation in the screening of overweight adolescent students in their work territory. Cross sectional study conducted in eight state supported schools of the municipality of Natal/RN and in four Primary Health Units. The total student population was 27.277. A stratified sample was statistically calculated based on the student population of the four city geographical zones: 112 North , 74 West; 108 East; and 78 South, totalizing 372 adolescents. The students were selected by a probability process where eight schools were first selected, two per district, until the number per subsample in each district was reached. Four primary health nurses, responsible for the health units were included. Two instruments were used for data collection, a screening questionnaire and a semi-structured interview form for questioning of the nurses. The content of both instruments was validated. Anthropometric and health data were collected from the students and analyzed with descriptive and analytical statistics. Interview data were transcribed and submitted to content analysis. The nursing diagnosis of overweight was identified in 50 (13,5%) of the adolescents and its association with consumption of foods that have cardiovascular risk (canned foods, pasta and fried food). An association of the nursing diagnosis was identified with family history (diabetes, hypertension, obesity, and kidney disease). The nurses judged that care of overweight adolescents was important but noted difficulties because of the absence of this population in the health units, because of their work overload, and the lack of school articulation. The nurses do not have impacting actions with this population and delegate the responsibility to other professionals. It is concluded that overweight is a nutritional problem relevant to the adolescent school population in Natal/RN, with a 13,5% prevalence and that it is related to food consumption with cardiovascular risk and family health history. The nurses consider overweight as an important public health problem but do not envision ways to maintain linkage with adolescents and with the school to promote the needed care

Screening Brazilian commercial gasoline quality by hydrogen nuclear magnetic resonance spectroscopic fingerprintings and pattern-recognition multivariate chemometric analysis

The identification of gasoline adulteration by organic solvents is not an easy task, because compounds that constitute the solvents are already in gasoline composition. In this work, the combination of Hydrogen Nuclear Magnetic Resonance ((1)H NMR) spectroscopic fingerprintings with pattern-recognition multivariate Soft Independent Modeling of Class Analogy (SIMCA) chemometric analysis provides an original and alternative approach to screening Brazilian commercial gasoline quality in a Monitoring Program for Quality Control of Automotive Fuels. SIMCA was performed on spectroscopic fingerprints to classify the quality of representative commercial gasoline samples selected by Hierarchical Cluster Analysis (HCA) and collected over a 6-month period from different gas stations in the São Paulo state, Brazil. Following optimized the (1)H NMR-SIMCA algorithm, it was possible to correctly classify 92.0% of commercial gasoline samples, which is considered acceptable. The chemometric method is recommended for routine applications in Quality-Control Monitoring Programs, since its measurements are fast and can be easily automated. Also, police laboratories could employ this method for rapid screening analysis to discourage adulteration practices. (C) 2010 Elsevier B.V. All rights reserved.

Screening Brazilian Commercial Gasoline Quality by ASTM D6733 GC and Pattern-Recognition Multivariate SIMCA Chemometric Analysis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Multiple minima hypersurfaces procedures for biomimetic ligands screening

In this work the interaction of the pesticide carbaryl with two groups of biomimetic ligands, peptides and MIPs was screened by multiple minima hypersurfaces (MMH) procedures, through the AM1 semiempirical method. Data related to the properties of the molecular association of the complex biomimetic ligand-pesticide were obtained and compared with another molecular modeling algorithm named Leapfrog, as included in the Sybyl software package, and experimental results from the literature, remarking good correlation between them. All important MMH program parameters (cells number, box size, conformers) were studied and optimized with the aim of getting the minimum computation time without losing the correlation with experimental data. The data demonstrated that MMH approach can be used as a fast biomimetic ligand screening tool for MIPs. In the case of peptides the computation time was not comparable with the molecular dynamics methods conventionally used for this approach. © 2011 Springer Science+Business Media B.V.

High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al.

Pneumonia and bacteremia in a golden-headed lion tamarin (Leontopithecus chrysomelas) caused by Klebsiella pneumoniae subsp pneumoniae during a translocation program of free-ranging animals in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neonatal hearing screening in a low-risk maternity in São Paulo state

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault).