A Novel Adaptive Deformable Model for Automated Optic Disc and Cup Segmentation to Aid Glaucoma Diagnosis

This paper proposes a novel Adaptive Region-based Edge Smoothing Model (ARESM) for automatic boundary detection of optic disc and cup to aid automatic glaucoma diagnosis. The novelty of our approach consists of two aspects: 1) automatic detection of initial optimum object boundary based on a Region Classification Model (RCM) in a pixel-level multidimensional feature space; 2) an Adaptive Edge Smoothing Update model (AESU) of contour points (e.g. misclassified or irregular points) based on iterative force field calculations with contours obtained from the RCM by minimising energy function (an approach that does not require predefined geometric templates to guide auto-segmentation). Such an approach provides robustness in capturing a range of variations and shapes. We have conducted a comprehensive comparison between our approach and the state-of-the-art existing deformable models and validated it with publicly available datasets. The experimental evaluation shows that the proposed approach significantly outperforms existing methods. The generality of the proposed approach will enable segmentation and detection of other object boundaries and provide added value in the field of medical image processing and analysis.     

Age as an independent risk factor for secondary headaches

OBJECTIVE: To verify if the age is a risk factor for secondary headaches, regardless the time interval since the onset of the headache complaint. METHOD: 1131 patients were selected, with the main complaint of headache. The ratio of secondary headaches was evaluated and compared between young and elderly patients in general; between individuals with headache starting before and after 60 years of age; and between young and elderly subjects with headache having started for less than one year. RESULTS: Elderly patients in general and individuals with headache having started after 60 years of age presented a higher ratio of secondary headaches than the young subjects and the ones whose pain started before 60 years of age. Elderly subjects with headache of recent start presented a higher ratio of secondary headaches than young individuals with the same time of pain evolution. CONCLUSION: Age is an independent risk factor for secondary headaches, regardless the time interval since the onset of the complaint.     

Synchronous gastric and sebaceous cancers,a rare manifestation of MLH1-related Muir-Torre syndrome

Muir-Torre syndrome (MTS), a rare variant of the hereditary non polyposis colorectal cancer syndrome, is an autosomal dominant genodermatosis characterised by coincidence of sebaceous gland neoplasms (sebaceous adenoma, epithelioma, or carcinoma) and at least one internal malignancy. The underlying cause of MTS is a germline mutation in DNA mismatch repair genes MSH2, MLH1 and MSH6. We report the case of a 52-year-old caucasian woman with the development of metachronous colon cancer at the age of 38 years, uterine cancer at the age of 43 years, and unique occurrence of synchronous gastric and sebaceous carcinomas related to germline point mutation c. 2194A>T in the last exon of MLH1 gene, resulting in truncated protein in C-terminal region p. Lys732X due to premature stop codon. This mutation, not previously reported in MTS, disrupts the function of MutL complexes presumably by preventing the interaction with PMS1/PMS2 and impairing the endonuclease active site. This case points out the importance of sebaceous neoplasia, especially sebaceous adenocarcinoma, as cutaneous markers of MTS for timely implementation of cancer screening programs.     

Cystathionine β‐synthase mutations: effect of mutation topology on folding and activity

Misfolding of mutant enzymes may play an important role in the pathogenesis of cystathionine β‐synthase (CBS) deficiency. We examined properties of a series of 27 mutant variants, which together represent 70% of known alleles observed in patients with homocystinuria due to CBS deficiency. The median amount of SDS‐soluble mutant CBS polypeptides in the pellet after centrifugation of bacterial extracts was increased by 50% compared to the wild type. Moreover, mutants formed on average only 12% of tetramers and their median activity reached only 3% of the wild‐type enzyme. In contrast to the wild‐type CBS about half of mutants were not activated by S‐adenosylmethionine. Expression at 18°C substantially increased the activity of five mutants in parallel with increasing the amounts of tetramers. We further analyzed the role of solvent accessibility of mutants as a determinant of their folding and activity. Buried mutations formed on average less tetramers and exhibited 23 times lower activity than the solvent exposed mutations. In summary, our results show that topology of mutations predicts in part the behavior of mutant CBS, and that misfolding may be an important and frequent pathogenic mechanism in CBS deficiency. Hum Mutat 31:1–11, 2010. © 2010 Wiley‐Liss, Inc.     

Blood vessel segmentation and width estimation in ultra-wide field scanning laser ophthalmoscopy

Features of the retinal vasculature, such as vessel widths, are considered biomarkers for systemic disease. The aim of this work is to present a supervised approach to vessel segmentation in ultra-wide field of view scanning laser ophthalmoscope (UWFoV SLO) images and to evaluate its performance in terms of segmentation and vessel width estimation accuracy. The results of the proposed method are compared with ground truth measurements from human observers and with existing state-of-the-art techniques developed for fundus camera images that we optimized for UWFoV SLO images. Our algorithm is based on multi-scale matched filters, a neural network classifier and hysteresis thresholding. After spline-based refinement of the detected vessel contours, the vessel widths are estimated from the binary maps. Such analysis is performed on SLO images for the first time. The proposed method achieves the best results, both in vessel segmentation and in width estimation, in comparison to other automatic techniques.OCIS codes: (100.2960) Image analysis, (100.3008) Image recognition, algorithms and filters, (100.4996) Pattern recognition, neural networks, (170.4470) Ophthalmology     

Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease

Histamine is a central neurotransmitter degraded by histamine-N-methyltransferase (HNMT). Several abnormalities in the histaminergic system were found in patients with Parkinson's disease (PD), thus we tested the possible association of a Thr105Ile functional polymorphism in HNMT with PD. A total of 913 patients with PD and 958 controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster City, California, USA). Lower frequency of HNMT Ile105 allele that is associated with decreased enzymatic activity was found in patients compared with controls (χ(2) = 11.65; p = 0.0006). We performed meta-analysis to confirm the association of Thr105Ile functional polymorphism with PD. Our results indicate that lower HNMT activity plays a role in the pathogenesis of PD.     

A nationwide population-based study of tension-type headache in Brazil

Objectives.— To estimate the 1-year prevalence of tension-type headache (TTH) and the degree of the association of TTH with some sociodemographic characteristics of a representative sample of the adult population of Brazil.
Methods.— This was an observational, cross-sectional, population-based study. We conducted telephone interviews on 3848 people, aged 18-79 years, randomly selected from the 27 states of Brazil. Trained lay interviewers administered the structured questionnaire. It included questions about the sociodemographic characteristics of the population, as well as questions about headache. The degree of the association was calculated through prevalence ratios, adjusted with Poisson regression by gender, age, years of education, marital status, household income, job status, body mass index (BMI), and physical exercise.
Results.— The estimated 1-year gender- and-age-adjusted prevalence of TTH was 13.0% (95% CI: 11.8-14.2%); 15.4% in males and 9.5% in females. The prevalence of probable TTH was 22.6% (95% CI: 21.1-24.1%). Most (86.2%) subjects reported episodic TTH; 6.4% had chronic TTH. The prevalence was higher at 18-29 years of age (16.2%). TTH was 1.6 times more prevalent in men, and 1.54 times more in subjects with more than 11 years of education. There was no significant association of TTH with marital or job status, household income, BMI, and physical activity.
Conclusion.— This is the first nationwide epidemiological study of TTH in Brazil. The overall prevalence of TTH in Brazil is low, at 13%. TTH is significantly more prevalent in males and subjects with higher education level.     

Slower cortisol response during ACTH stimulation test in autistic children

Autism is a hereditary, pervasive neurodevelopmental disorder that starts early in life. The main characteristics of the autism are impairment in social interactions, difficulties in adapting to novel environmental situations and improper reaction to stress. Since the Hypothalamic-Pituitary-Adrenocortical (HPA) axis plays a key role in the response to stress and because the previous research found abnormalities in HPA system, we conducted a study to test several elements of the HPA axis. Because autism is a heritable disorder, autistic subjects were studied as well as their parents. Cortisol circadian rhythm, cortisol daily secretion and its suppression response to dexamethasone had been measured from saliva or urine samples of the autistic children and their parents. Cortisol secretion response after ACTH stimulation was done with the autistic children only. The cortisol elevation after ACTH stimulation among the autistic individuals was slower (P = 0.017) than in healthy controls. No differences were found in salivary cortisol circadian rhythm or suppression response, as well as in cortisol daily excretion. These data indicate that, compared to healthy subjects, autistic individuals have fine differences in cortisol response to ACTH stimulation or possibly to other types of stress.