Quantification of Orbital Apex Crowding for Screening of Dysthyroid Optic Neuropathy Using Multidetector CT

BACKGROUND AND PURPOSE: DON, a serious complication of GO, is frequently difficult to diagnose clinically in its early stages because of confounding signs and symptoms of congestive orbitopathy. We evaluated the ability of square area measurements of orbital apex crowding, calculated with MDCT, to detect DON. MATERIALS AND METHODS: Fifty-six patients with GO were studied prospectively with complete neuro-ophthalmologic examination and MDCT scanning. Square measurements were taken from coronal sections 12 mm, 18 mm, and 24 mm from the interzygomatic line. The ratio between the extraocular muscle area and the orbital bone area was used as a Cl. Intracranial fat prolapse through the superior orbital fissure was recorded as present or absent. Severity of optic nerve crowding was also subjectively graded on corona! images. Orbits were divided into 2 groups (with or without clinical evidence of DON) and compared. RESULTS: Ninety-five orbits (36 with and 59 without DON) were studied. The CIs at all 3 levels and the subjective crowding score were significantly greater in orbits with DON (P<.001). No significant difference was observed regarding intracranial fat prolapse (P=.105). The area under the ROC curves was 0.91, 0.93, and 0.87 for CIs at 12, 18, and 24 mm, respectively. The best performance was at 18 mm, where a cutoff value of 57.5% corresponded to 91.7% sensitivity, 89.8% specificity, and an odds ratio of 97.2 for detecting DON. A significant correlation (P<.001) between the CIs and VF defects was observed. CONCLUSIONS: Orbital Cls based on area measurements were found to predict DON more reliably than subjective grading of orbital crowding or intracranial fat prolapse.

Plasma Pro-B-Type Natriuretic Peptide Testing as a Screening Method for Hypertrophic Cardiomyopathy

Background: Clinical multistage risk assessment associated with electrocardiogram (ECG) and NT-proBNP may be a feasible strategy to screen hypertrophic cardiomyopathy (HCM). We investigated the effectiveness of a screening based on ECG and NT-proBNP in first-degree relatives of patients with HCM. Methods and Results: A total of 106 first-degree relatives were included. All individuals were evaluated by echocardiography, ECG, NT-proBNP, and molecular screening (available for 65 individuals). From the 106 individuals, 36 (34%) had diagnosis confirmed by echocardiography. Using echocardiography as the gold standard, ECG criteria had a sensitivity of 0.71, 0.42, and 0.52 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Mean values of NT-ProBNP were higher in affected as compared with nonaffected relatives (26.1 vs. 1290.5, P < .001). The AUC of NT-proBNP was 0.98. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.92 and specificity of 0.96. Using molecular genetics as the gold standard, ECG criteria had a sensitivity of 0.67, 0.37, and 0.42 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.83 and specificity of 0.98. Conclusion: Values of NT-proBNP above 70 pg/mL can be used to effectively select high-risk first-degree relatives for HCM screening. (J Cardiac Fail 2012;18:564-568)

Screening of CO2 Laser (10.6 mu m) Parameters for Prevention of Enamel Erosion

Objective: The aim of this study was to screen CO2 laser (10.6 mu m) parameters to increase enamel resistance to a continuous-flow erosive challenge. Background data: A new clinical CO2 laser providing pulses of hundreds of microseconds, a range known to increase tooth acid-resistance, has been introduced in the market. Methods: Different laser parameters were tested in 12 groups (n = 20) with varying fluences from 0.1 to 0.9 J/cm(2), pulse durations from 80 to 400 mu s and repetition rates from 180 to 700 Hz. Non-lased samples (n = 30) served as controls. All samples were eroded by exposure to hydrochloric acid (pH 2.6) under continuous acid flow (60 mu L/min). Calcium and phosphate release into acid was monitored colorimetrically at 30 sec intervals up to 5 min and at 1 min intervals up to a total erosion time of 15 min. Scanning electron microscopic (SEM) analysis was performed in lased samples (n = 3). Data were statistically analysed by one-way ANOVA (p < 0.05) and Dunnett's post-hoc tests. Results: Calcium and phosphate release were significantly reduced by a maximum of 20% over time in samples irradiated with 0.4 J/cm(2) (200 mu s) at 450 Hz. Short-time reduction of calcium loss (<= 1.5 min) could be also achieved by irradiation with 0.7 J/cm(2) (300 mu s) at 200 and 300 Hz. Both parameters revealed surface modification. Conclusions: A set of CO2 laser parameters was found that could significantly reduce enamel mineral loss (20%) under in vitro erosive conditions. However, as all parameters also caused surface cracking, they are not recommended for clinical use.

Development of a high sensitive automatic setup for screening of microcystins in surface waters by employing a LED-based photometric detector

In this manuscript, an automatic setup for screening of microcystins in surface waters by employing photometric detection is described. Microcystins are toxins delivered by cyanobacteria within an aquatic environment, which have been considered strongly poisonous for humans. For that reason, the World Health Organization (WHO) has proposed a provisional guideline value for drinking water of 1 mu g L-1. In this work, we developed an automated equipment setup, which allows the screening of water for concentration of microcystins below 0.1 mu g V. The photometric method was based on the enzyme-linked immunosorbent assay (ELISA) and the analytical signal was monitored at 458 nm using a homemade LED-based photometer. The proposed system was employed for the detection of microcystins in rivers and lakes waters. Accuracy was assessed by processing samples using a reference method and applying the paired t-test between results. No significant difference at the 95% confidence level was observed. Other useful features including a linear response ranging from 0.05 up to 2.00 mu g L-1 (R-2 =0.999) and a detection limit of 0.03 mu g L-1 microcystins were achieved. (C) 2011 Elsevier B.V. All rights reserved.

Comparison of venous plasma glycemia and capillary glycemia for the screening of type 2 diabetes mellitus in the Japanese-Brazilian community of Mombuca (Guatapará-SP)

Abstract Background To identify the most appropriate cut-off points of fasting glycemia for the screening of diabetes mellitus type 2 (DM2) with the comparison of the properties of capillary glycemia (CG) and venous blood plasma glycemia (PG) in a population of Japanese origin from the community of Mombuca, Guatapará - SP, Brazil. Methods This was a population-based descriptive cross-sectional study conducted on a sample of 131 individuals of both genders aged 20 years or more (66.8% of the target population). CG was measured with a glucometer in a blood sample obtained from the fingertip and PG was determined by an enzymatic method (hexokinase) in venous blood plasma, after a 10-14 hour fast in both cases. Data were analyzed by the receiver operating characteristic (ROC) curve in order to identify the best cut-off point for fasting glycemia (CG and PG) for the diagnosis of DM, using the 2-hour plasma glycemia > 200 mg/dl as gold - standard. Results The ROC curve revealed that the best cut-off point for the screening of DM was 110 mg/dl for CG and 105 mg/dl for PG, values that would optimize the relation between individuals with positive and false-positive results. The area under the ROC curve was 0.814 for CG (p < 0.01) and 0.836 for PG (p < 0.01). Conclusions The cut-off points of 105 mg/dl(5.8 mmol/l) for PG and of 110 mg/dl(6.1 mmol/l) for CG appear to be the most appropriate for the screening of DM2 in the population under study, with emphasis on the fact that the value recommended for CG is 5 mg/dl higher than that for PG, in contrast to WHO recommendations.

Results obtained with a low cost software-based audiometer for hearing screening

Introduction: The implementation of hearing screening programs can be facilitated by reducing operating costs, including the cost of equipment. The Telessaúde (TS) audiometer is a low-cost, software-based, and easy-to-use piece of equipment for conducting audiometric screening. Aim: To evaluate the TS audiometer for conducting audiometric screening. Methods: A prospective randomized study was performed. Sixty subjects, divided into those who did not have (group A, n = 30) and those who had otologic complaints (group B, n = 30), underwent audiometric screening with conventional and TS audiometers in a randomized order. Pure tones at 25 dB HL were presented at frequencies of 500, 1000, 2000, and 4000 Hz. A "fail" result was considered when the individual failed to respond to at least one of the stimuli. Pure-tone audiometry was also performed on all participants. The concordance of the results of screening with both audiometers was evaluated. The sensitivity, specificity, and positive and negative predictive values of screening with the TS audiometer were calculated. Results: For group A, 100% of the ears tested passed the screening. For group B, "pass" results were obtained in 34.2% (TS) and 38.3% (conventional) of the ears tested. The agreement between procedures (TS vs. conventional) ranged from 93% to 98%. For group B, screening with the TS audiometer showed 95.5% sensitivity, 90.4% sensitivity, and positive and negative predictive values equal to 94.9% and 91.5%, respectively. Conclusions: The results of the TS audiometer were similar to those obtained with the conventional audiometer, indicating that the TS audiometer can be used for audiometric screening.

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

Abstract Background Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances. Methods/Design An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow. Discussion Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers.

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.

Reorganization of secondary and tertiary health care levels: impact on the outcomes of oral cancer screening in the São Paulo State, Brazil

This study presents the strategies for prevention and early detection of oral cancer by means of screening in the elderly population of São Paulo, the richest and the most populous state of Brazil. This research was a retrospective longitudinal study based on the analysis of secondary data. The variables - number of participating cities, coverage of screening, and number of suspicious and confirmed cases of oral cancer - were divided into two periods: 2001-2004 and 2005-2008. Data were analyzed statistically by the chi-square test at 5% significance level. The implementation of a nationwide public oral health policy in 2004 and the reorganization of the secondary and tertiary health care were evaluated as mediator factors able to interfere in the achieved outcomes. From 2001 to 2008, 2,229,273 oral examinations were performed. There was an addition of 205 participating cities by the end of the studied period (p<0.0001). The coverage of oral cancer screening increased from 4.1% to 16% (p<0.0001). There was a decrease in the number of suspicious lesions (from 9% in 2005 to 5% in 2008) (p<0.0001) and in the rate of confirmed oral cancer cases per 100,000 examinations (from 20.89 in 2001 to 10.40 in 2008) (p<0.0001). After 8 years of screening, there was a decrease in the number of suspicious lesions and confirmed cases of oral cancer in the population. The reorganization of secondary and tertiary health care levels of oral care seems to have contributed to modify these numbers, having a positive impact on the outcomes of oral cancer screening in the São Paulo State.

Performance of six diagnostic tests to screen for Chagas disease in blood banks and prevalence of Trypanosoma cruzi infection among donors with inconclusive serology screening based on the analysis of epidemiological variables

OBJECTIVE: The frequent occurrence of inconclusive serology in blood banks and the absence of a gold standard test for Chagas'disease led us to examine the efficacy of the blood culture test and five commercial tests (ELISA, IIF, HAI, c-ELISA, rec-ELISA) used in screening blood donors for Chagas disease, as well as to investigate the prevalence of Trypanosoma cruzi infection among donors with inconclusive serology screening in respect to some epidemiological variables. METHODS: To obtain estimates of interest we considered a Bayesian latent class model with inclusion of covariates from the logit link. RESULTS: A better performance was observed with some categories of epidemiological variables. In addition, all pairs of tests (excluding the blood culture test) presented as good alternatives for both screening (sensitivity > 99.96% in parallel testing) and for confirmation (specificity > 99.93% in serial testing) of Chagas disease. The prevalence of 13.30% observed in the stratum of donors with inconclusive serology, means that probably most of these are non-reactive serology. In addition, depending on the level of specific epidemiological variables, the absence of infection can be predicted with a probability of 100% in this group from the pairs of tests using parallel testing. CONCLUSION: The epidemiological variables can lead to improved test results and thus assist in the clarification of inconclusive serology screening results. Moreover, all combinations of pairs using the five commercial tests are good alternatives to confirm results.

Factors associated with failure of clinical screening among blood donors who have altered serological results in the Centro Regional de Hemoterapia de Ribeirão Preto

OBJECTIVE: This study aimed to investigate the frequency of positive results for hepatitis B and C, HIV and syphilis in blood donations at the Centro Regional de Hemoterapia de Ribeirão Preto, to describe donors with positive results according to some demographic and socioeconomic variables, to identify risk factors associated to these donors and the reasons that they were not detected during clinical screening. METHODS: A descriptive study was performed between July 1st 2005 and July 31st 2006 by interviewing 106 donors after medical consultations where they were informed of positive results for hepatitis B, hepatitis C, HIV or syphilis. RESULTS: There was a predominance of first-time donors, males, under 50-year olds, married individuals, from Ribeirão Preto, with elementary education, low economic status and of people who donated at the request of friends or relatives. Hepatitis C was the most frequently detected infection (56.6%), followed by hepatitis B (20.7%), HIV (12.3%) and syphilis(10.4%). About 40% of donors had omitted risk factors for different reasons: because they trusted the results of serological tests, did not feel comfortable about talking of risk factors or did not consider them relevant. Other justifications were the duration of the interview, the interviewer was unskilled, embarrassment and doubts about confidentiality. CONCLUSION: The results indicate the need for changes in the approach to clinical screening and a review of methods to attract and guide potential donors.

Screening bacterial metabolites for inhibitory effects against Batrachochytrium dendrobatidis using a spectrophotometric assay

Certain bacteria present on frog skin can prevent infection by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), conferring disease resistance. Previous studies have used agar-based in vitro challenge assays to screen bacteria for Bd-inhibitory activity and to identify candidates for bacterial supplementation trials. However, agar-based assays can be difficult to set up and to replicate reliably. To overcome these difficulties, we developed a semi-quantitative spectrophotometric challenge assay technique. Cell-free supernatants were prepared from filtered bacterial cultures and added to 96-well plates in replicated wells containing Bd zoospores suspended in tryptone-gelatin hydrolysate-lactose (TGhL) broth medium. Plates were then read daily on a spectrophotometer until positive controls reached maximum growth in order to determine growth curves for Bd. We tested the technique by screening skin bacteria from the Australian green-eyed tree frog Litoria serrata. Of bacteria tested, 31% showed some degree of Bd inhibition, while some may have promoted Bd growth, a previously unknown effect. Our cell-free supernatant challenge assay technique is an effective in vitro method for screening bacterial isolates for strong Bd-inhibitory activity. It contributes to the expanding field of bioaugmentation research, which could play a significant role in mitigating the effects of chytridiomycosis on amphibians around the world.

Rapid screening of potential autophagic inductor agents using mammalian cell lines

Recent progress in understanding the molecular basis of autophagy has demonstrated its importance in several areas of human health. Affordable screening techniques with higher sensitivity and specificity to identify autophagy are, however, needed to move the field forward. In fact, only laborious and/or expensive methodologies such as electron microscopy, dye-staining of autophagic vesicles, and LC3-II immunoblotting or immunoassaying are available for autophagy identification. Aiming to fulfill this technical gap, we describe here the association of three widely used assays to determine cell viability - Crystal Violet staining (CVS), 3-[4, 5-dimethylthiaolyl]-2, 5-diphenyl-tetrazolium bromide (MTT) reduction, and neutral red uptake (NRU) - to predict autophagic cell death in vitro. The conceptual framework of the method is the superior uptake of NR in cells engaging in autophagy. NRU was then weighted by the average of MTT reduction and CVS allowing the calculation of autophagic arbitrary units (AAU), a numeric variable that correlated specifically with the autophagic cell death. The proposed strategy is very useful for drug discovery, allowing the investigation of potential autophagic inductor agents through a rapid screening using mammalian cell lines B16-F10, HaCaT, HeLa, MES-SA, and MES-SA/Dx5 in a unique single microplate.

Targeting low-druggability bromodomains: fragment based screening and inhibitor design against the BAZ2B bromodomain

Bromodomains are epigenetic reader domains that have recently become popular targets. In contrast to BET bromodomains, which have proven druggable, bromodomains from other regions of the phylogenetic tree have shallower pockets. We describe successful targeting of the challenging BAZ2B bromodomain using biophysical fragment screening and structure-based optimization of high ligand-efficiency fragments into a novel series of low-micromolar inhibitors. Our results provide attractive leads for development of BAZ2B chemical probes and indicate the whole family may be tractable.