Concordance of iron indices in homozygote and heterozygote sibling pairs in hemochromatosis families: implications for family screening

Background/Aims: Concordance of iron indices between same sex siblings homozygous for the cysteine-to-tyrosine substitution at amino acid 282 (C282Y) mutation suggests that the variable phenotype in hereditary hemochromatosis is caused by genetic factors. Concordance of iron indices between same-sex heterozygous sibling pairs would provide further evidence of genetic modifiers of disease expression, and guidance for family screening strategies of subjects heterozygous for the C282Y mutation. Methods: We compared the iron indices of 35 C282Y homozygous and 35 C282Y heterozygous same-sex sibling pairs. To clarify whether concordance between siblings was due to environmental or genetic factors we compared the iron indices of 164 C282Y homozygous-normal, same-sex dizygotic twins. Results: Serum ferritin (r = 0.50, P = 0.003), hepatic iron concentration (r = 0.61, P = 0.025) and hepatic iron index (r = 0.67, P = 0.01) were highly concordant in C282Y homozygotes. Heterozygote siblings were concordant for serum ferritin (r = 0.76, P = 0.0001) and transferrin saturation (r = 0.79, P = 0.0001). Homozygote-normal same-sex dizygotic twins were concordant for serum ferritin (r = 0.62, P = 0.0001) but not for transferrin saturation. Conclusions: Concordance of iron indices exists in C282Y homozygote and heterozygote sibling pairs. Siblings of expressing C282Y heterozygotes require phenotypic assessment. These data provide evidence for modifying genes influencing disease expression in hemochromatosis. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

The value of screening in siblings of patients with abdominal aortic aneurysm

Objectives. This study aimed to determine the incidence of abdominal aortic aneurysm (AAA) in a large group of siblings of Australian AAA patients to determine if screening in this group is justified. Methods. 1254 siblings of 400 index AAA patients were identified and offered aortic ultrasound screening. An age and sex matched control group was recruited from patients having abdominal CT scans for non-vascular indications. AAA was defined by an infrarenal aortic diameter of greater than or equal to3 cm or a ratio of the infrarenal to suprarenal aortic diameter of greater than or equal to2.0. A ratio of 1.0-1.5 was considered normal, and a ratio of >1.5 to

Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: Pigmentation marker, ultrastructural and UV-survival studies

Recent population studies have demonstrated an association with the red-hair and fair-skin phenotype with variant alleles of the melanocortin-1 receptor (MC1R) which result in amino acid substitutions within the coding region leading to an altered receptor activity. In particular, Arg151Cys, Arg160Trp and Asp294His were the most commonly associated variants seen in the south-east Queensland population with at least one of these alleles found in 93% of those with red hair. In order to study the individual effects of these variants on melanocyte biology and melanocytic pigmentation, we established a series of human melanocyte strains genotyped for the MC1R receptor which included wild-type consensus, variant heterozygotes, compound heterozygotes and homozygotes for Arg151Cys, Arg160Trp, Val60Leu and Val92Met alleles. These strains ranged from darkly pigmented to amelanotic, with all strains of consensus sequence having dark pigmentation. UV sensitivity was found not to be associated with either MC1R genotype or the level of pigmentation with a range of sensitivities seen across all genotypes. Ultrastructural analysis demonstrated that while consensus strains contained stage IV melanosomes in their terminal dendrites, Arg151Cys and Arg160Trp homozygote strains contained only stage II melanosomes. This was despite being able to show expression of tyrosinase and tyrosinase-related protein-1 markers, although at reduced levels and an ability to convert exogenous 3,4-dihydroxyphenyl-alanine (DOPA) to melanin in these strains.

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients

Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.

Ocular scanning and perceptual size distortion in hemispatial neglect: effects of prism adaptation and sequential stimulus presentation

When asked to compare two lateralized shapes for horizontal size, neglect patients often indicate the left stimulus to be smaller. Gainotti and Tiacci (1971) hypothesized that this phenomenon might be related to a rightward bias in the patients' gaze. This study aimed to assess the relation between this size underestimation and oculomotor asymmetries. Eye movements were recorded while three neglect patients judged the horizontal extent of two rectangles. Two experimental manipulations were performed to increase the likelihood of symmetrical scanning of the stimulus display. The first manipulation entailed a sequential, rather than simultaneous presentation of the two rectangles. The second required adaptation to rightward displacing prisms, which is known to reduce many manifestations of neglect. All patients consistently underestimated the left rectangle, but the pattern of verbal responses and eye movements suggested different underlying causes. These include a distortion of space perception without ocular asymmetry, a failure to view the full leftward extent of the left stimulus, and a high-level response bias. Sequential presentation of the rectangles and prism adaptation reduced ocular asymmetries without affecting size underestimation. Overall, the results suggest that leftward size underestimation in neglect can arise for a number of different reasons. Incomplete leftward scanning may perhaps be sufficient to induce perceptual size distortion, but it is not a necessary prerequisite.

Synthesis of optically complex core-shell colloidal suspensions: Pathways to multiplexed biological screening

The ability to generate enormous random libraries of DNA probes via split-and-mix synthesis on solid supports is an important biotechnological application of colloids that has not been fully utilized to date. To discriminate between colloid-based DNA probes each colloidal particle must be 'encoded' so it is distinguishable from all other particles. To this end, we have used novel particle synthesis strategies to produce large numbers of optically encoded particle suitable for DNA library synthesis. Multifluorescent particles with unique and reproducible optical signatures (i.e., fluorescence and light-scattering attributes) suitable for high-throughput flow cytometry have been produced. In the spectroscopic study presented here, we investigated the optical characteristics of multi-fluorescent particles that were synthesized by coating silica 'core' particles with up to six different fluorescent dye shells alternated with non-fluorescent silica 'spacer' shells. It was observed that the diameter of the particles increased by up to 20% as a result of the addition of twelve concentric shells and that there was a significant reduction in fluorescence emission intensities from inner shells as an increasing number of shells were deposited.

A high-throughput screening method for general cytotoxicity part I Chemical toxicity

Foi desenvolvido um método destinado a fazer a triagem rápida e o escalonamento da toxicidade geral exercida por xenobióticos tendo como modelo o Saccharomyces cerevisiae. Para padronizar as condições de experimentação foi estabelecida a relação entre a absorvência a 525 nm e o número de células em suspensão por mililitro de meio de cultura e calculadas uma curva padrão e respectiva equação definidora (Y=6,8219E-08X + 0,0327) Culturas de Saccharomyces cerevisiae em meio completo para leveduras (YPD - 1% de glucose 2%, de peptona 0,5% e extracto de levedura 1%) foram expostas a diferentes concentrações de nicotina e a inibição do crescimento avaliada.

Ball Recovery in the Handball Tournament of the 2008 Beijing Olympic Games: Sequential Analysis of Positional Play as Used by the Spanish Team’s Defence

In sport there is a great need to obtain as much information as possible about the factors which affect the dynamics of play. This study uses sequential analysis and temporal patterns (T-patterns)to examine the evolution of defence (against an equal number of attackers)as used by the Spanish handball team at the Beijing 2008 Olympic Games. The aim is to help handball coaches (during their training and gathering of professional experience)to understand the importance of the structure of defensive systems. This can be achieved through observational processes that reveal the evolution and adaptation of these defensive systems according to different variables: the match score, the response of the opposing team and progress through the tournament.

A eficácia do exame telerradiográfico de tórax como técnica de "screening" em população hospitalar

É analisada a eficácia da telerradiografía de tórax como técnica de "screening" em população hospitalar. Utilizando-se uma técnica prospectiva não concorrente, é evidenciado que pouco benefício traz ao paciente a chapa de tórax AP na internação, na primeira consulta ou no pré-operatório em geral. Para sete em cada 100 pacientes foi diagnosticado importante patologia assintomática. Nenhum paciente entre 0 e 19 anos teve anormalidade evidenciada pela chapa. Recomenda-se, para esta faixa, a eliminação do exame, e para pacientes acima de 20 anos a introdução da abreugrafia, ao invés da telerradiografia de tórax.

Diagnostic performance of visual screening tests in the elderly

This study aimed to determine and evaluate the diagnostic accuracy of visual screening tests for detecting vision loss in elderly. This study is defined as study of diagnostic performance. The diagnostic accuracy of 5 visual tests -near convergence point, near accommodation point, stereopsis, contrast sensibility and amsler grid—was evaluated by means of the ROC method (receiver operating characteristics curves), sensitivity, specificity, positive and negative likelihood ratios (LR+/LR−). Visual acuity was used as the reference standard. A sample of 44 elderly aged 76.7 years (±9.32), who were institutionalized, was collected. The curves of contrast sensitivity and stereopsis are the most accurate (area under the curves were 0.814−p = 0.001, C.I.95%[0.653;0.975]— and 0.713−p = 0.027, C.I.95%[0,540;0,887], respectively). The scores with the best diagnostic validity for the stereopsis test were 0.605 (sensitivity 0.87, specificity 0.54; LR+ 1.89, LR−0.24) and 0.610 (sensitivity 0.81, specificity 0.54; LR+1.75, LR−0.36). The scores with higher diagnostic validity for the contrast sensibility test were 0.530 (sensitivity 0.94, specificity 0.69; LR+ 3.04, LR−0.09). The contrast sensitivity and stereopsis test's proved to be clinically useful in detecting vision loss in the elderly.

Diagnostic performance of visual screening tests in the elderly

The aging of Portuguese population is characterized by an increase of individuals aged older than 65 years. Preventable visual loss in older persons is an important public health problem. Tests used for vision screening should have a high degree of diagnostic validity confirmed by means of clinical trials. The primary aim of a screening program is the early detection of visual diseases. Between 20% and 50% of older people in the UK have undetected reduced vision and in most cases is correctable. Elderly patients do not receive a systematic eye examination unless a problem arises with their glasses or suspicion vision loss. This study aimed to determine and evaluate the diagnostic accuracy of visual screening tests for detecting vision loss in elderly. Furthermore, it pretends to define the ability to find the subjects affected with vision loss as positive and the subjects not affected with the same disease as negative. The ideal vision screening method should have high sensitivity and specificity for early detection of risk factors. It should be also low cost and easy to implement in all geographic and socioeconomic regions. Sensitivity is the ability of an examination to identify the presence of a given disease and specificity is the ability of the examination to identify the absence of a given disease. It was not an aim of this study to detect abnormalities that affect visual acuity. The aim of this study was to find out what´s the best test for the identification of any vision loss.

In vitro toxicity screening of silica-coated superparamagnetic iron oxide nanoparticles in glial cells

Nanotechnology industry is progressing with prospects of substantial benefits to economics and science. Superparamagnetic iron oxide nanoparticles (ION) have been showing excellent magnetic properties, biocompatibility and biodegradability, broadening their potential applications and importance in the biomedical field

Survey of cyclopids (Crustacea, Copepoda) in Brazil and preliminary screening of their potential as dengue vector predators

INTRODUCTION: Cyclopid copepods are known to be good mosquito controllers, specially as regards the larvae of the dengue vectors Aedes aegypti and Ae. albopictus. MATERIAL AND METHOD: The objective of the study was to survey the local copepod fauna and search for new strains of M. longisetus var. longisetus, comparing the potential of the samples found with the current strain ML-01 against Ae. albopictus larvae, under laboratory conditions. Eleven bodies of water in Campinas, SP, Brazil, were screened for copepods by collecting 1.5 l of water from each of then. The predatory potential of adults copepods was evaluated over 24 h, in the laboratory, for groups of 5 individuals preying upon 30 first instar Ae. albopictus larvae. RESULTS AND CONCLUSION: The following cyclopid species were found: Metacyclops mendocinus, Tropocyclops prasinus, Eucyclops sp, Eucyclops serrulatus, Eucyclops solitarius, Eucyclops ensifer, Macrocyclops albidus var. albidus and Mesocyclops longisetus var. longisetus. The predatory potential of these copepods ranged from nil to 97.3%. A sample collected in the field containing only M. longisetus var. longisetus showed the best control efficiency with no significant difference from a three-year old laboratory culture (ML-01) of the same species evaluated for comparison. The sample with few M. albidus var. albidus was ranked in second place showing an average 25.9% efficiency. The use of copepods in trap tires as dengue vector controllers is discussed.

Children visual screening protocol: validation by a focus group panel of experts

Screening programs, particularly the inclusion of specific orthoptic tests to detect visual abnormalities, varies among countries. This study aims to: 1) describes expert perception of issues related with children visual screening; 2) identify specific orthoptic tests to detect visual abnormalities in children visual screening.

Visual Screening Competencies Questionnaire (VSCQ) and orthoptic practice

The identification of core competencies which are important for undertaking accurate visual screening by orthoptists is considered in this study. The aim was to construct and validate a questionnaire for orthoptists to assess visual screening competency. This study comprised three steps. The first step involved a 69-item self-assessment questionnaire constructed to assess orthoptists' perception of their competencies in visual screening programs for children. This questionnaire was constructed with statements from the Orthoptic Benchmark Statement for Health Care Programmes (Quality Assurance Agency for Higher Education, UK) and included three competency dimensions: interpersonal (IP), instrumental (IT) and systemic (ST). The second step involved questionnaire translation.