Automatic Glaucoma Detection Based on Optic Disc Segmentation and Texture Feature Extraction

The use of digital image processing techniques is prominent in medical settings for the automatic diagnosis of diseases. Glaucoma is the second leading cause of blindness in the world and it has no cure. Currently, there are treatments to prevent vision loss, but the disease must be detected in the early stages. Thus, the objective of this work is to develop an automatic detection method of Glaucoma in retinal images. The methodology used in the study were: acquisition of image database, Optic Disc segmentation, texture feature extraction in different color models and classification of images in glaucomatous or not. We obtained results of 93% accuracy

Acousto-optic modulation of optical reflection properties in fiber Bragg gratings and the application in fiber lasers

This thesis aims to investigate the interaction of acoustic waves and fiber Bragg gratings (FBGs) in standard and suspended-core fibers (SCFs), to evaluate the influence of the fiber, grating and modulator design on the increase of the modulation efficiency, bandwidth and frequency. Initially, the frequency response and the resonant acoustic modes of a low frequency acousto-optic modulator (f < 1.2 MHz) are numerically investigated by using the finite element method. Later, the interaction of longitudinal acoustic waves and FBGs in SCFs is also numerically investigated. The fiber geometric parameters are varied and the strain and grating properties are simulated by means of the finite element method and the transfer matrix method. The study indicates that the air holes composing the SCF cause a significant reduction of the amount of silica in the fiber cross section increasing acousto-optic interaction in the core. Experimental modulation of the reflectivity of FBGs inscribed in two distinct SCFs indicates evidences of this increased interaction. Besides, a method to acoustically induce a dynamic phase-shift in a chirped FBG employing an optimized design of modulator is shown. Afterwards, a combination of this modulator and a FBG inscribed in a three air holes SCF is applied to mode-lock an ytterbium doped fiber laser. To improve the modulator design for future applications, two other distinct devices are investigated to increase the acousto-optic interaction, bandwidth and frequency (f > 10 MHz). A high reflectivity modulation has been achieved for a modulator based on a tapered fiber. Moreover, an increased modulated bandwidth (320 pm) has been obtained for a modulator based on interaction of a radial long period grating (RLPG) and a FBG inscribed in a standard fiber. In summary, the results show a considerable reduction of the grating/fiber length and the modulator size, indicating possibilities for compact and faster acousto-optic fiber devices. Additionally, the increased interaction efficiency, modulated bandwidth and frequency can be useful to shorten the pulse width of future all-fiber mode-locked fiber lasers, as well, to other photonic devices which require the control of the light in optical fibers by electrically tunable acoustic waves.

Fresh Frozen Plasma in Hereditary Angioedema Crisis: To Give or Not To Give?

Objectives: Fresh frozen plasma (FFP) has been used in angioedema crises, however there is a risk of aggravating the symptoms as well as transmitting infections. In this report, the authors emphasize the dangers of this therapy. Materials and methods: A 25-year-old woman with hereditary angioedema (HAE) was treated with FFP after which her symptoms escalated. Results: Administration of purified C1-inhibitor (C1-INH) resulted in relief of her symptoms. Conclusions: FFP is to be avoided in a HAE crisis. Newer therapies for angioedema are preferred.

Hansen Neuropathy: Still a Possible Diagnosis in the Investigation of a Peripheral Neuropathy

INTRODUCTION: Leprosy is still one of the most frequent causes of peripheral neuropathy. Although regarded as eradicated in Portugal, is still documented in neuropathological study of patients with clinical peripheral neuropathy without proper diagnosis.

Next-generation sequencing of hereditary hemochromatosis-related genes: novel likely pathogenic variants found in the Portuguese population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1GNC)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5′-UTR of HAMP gene(c.-25GNA). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.

Oxidative Stress in Diabetic Neuropathy

For treating chronic pain, a multifactorial condition, is needed a suitable diagnosis which allows the differentiation in its many components. Diabetic neuropathy is a worldwide disease with great impact in the modern society. Diabetes may leads to the production of reactive oxygen species that are associated to oxidative stress, which may be a key factor in the development of diabetic neuropathy. The main goal is to inquire a potential association between chronic pain, diabetic neuropathy and oxidative stress. Thus, was performed a meta-analysis that permitted the causal evaluation between oxidative stress and diabetic neuropathy, and, a pain evaluation was accomplished in a convenience sample using validated surveys – Brief Pain Inventory (BPI) and Douleur Neuropathique 4 (DN4). Through the meta-analysis it was possible evaluate oxidative stress biomarkers, such lipid peroxidation, superoxide dismutase and catalase activities, and reduced glutathione. 9 studies were selected and all were performed in mouse models. The levels of lipid peroxidation were increased in all the studies, however the levels of the other biomarkers were diminished in diabetic models comparatively to healthy controls. In the evaluation of convenience sample, 84 surveys were collected along the four seasons: summer, autumn, winter and spring. The pain complaints were described in terms of local, intensity, impact, relief by medication and its effect on daily activities using BPI questionnaire. The scores obtained in BPI indicate the presence of moderate to severe pain, with increased complaints in autumn and spring, and implications in daily activities, transversal to all groups. To determine the main features associated with neuropathic pain it was used DN4 questionnaire. The DN4 indicated the presence of nearly 50% of patients with neuropathic pain. The results suggest that being female, the increased age and being retired can influence chronic pain and neuropathic pain in patients. As main conclusions, it was possible to verify an association between oxidative stress, and neuropathic pain, and, also, that weather conditions may influence the pain complaints and its prevalence.

Do hereditary syndrome-related gynecologic cancers have any specific features?

Hereditary syndromes are responsible for 10 % of gynaecologic cancers, among which hereditary breastovarian cancer and hereditary non-polyposis colon cancer syndromes, known as HBOC and Lynch syndromes respectively, present the highest relative risk. The latter predisposes to endometrial cancer and both contribute to ovarian cancer. Cowden syndrome-related endometrial cancer and the increased risk of ovarian, uterine and cervical cancers associated with Peutz-Jeghers syndrome, are also demonstrated, while Li-Fraumeni syndrome patients are prone to develop ovarian and endometrial cancers. Despite these syndromes’ susceptibility to gynaecologic cancers being consensual, it is still not clear whether these tumours have any epidemiologic, clinical, pathologic or imaging specific features that could allow any of the intervening physicians to raise suspicion of a hereditary syndrome in patients without known genetic risk. Moreover, controversy exists regarding both screening and surveillance schemes. Our literature review provides an updated perspective on the evidence-based specific features of tumours related to each of these syndromes as well as on the most accepted screening and surveillance guidelines. In addition, some illustrative cases are presented.

A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

International audience

FREQUENCY DOMAIN CHARACTERIZATION OF OPTIC FLOW AND VISION-BASED OCELLAR SENSING FOR ROTATIONAL MOTION

The structure of an animal’s eye is determined by the tasks it must perform. While vertebrates rely on their two eyes for all visual functions, insects have evolved a wide range of specialized visual organs to support behaviors such as prey capture, predator evasion, mate pursuit, flight stabilization, and navigation. Compound eyes and ocelli constitute the vision forming and sensing mechanisms of some flying insects. They provide signals useful for flight stabilization and navigation. In contrast to the well-studied compound eye, the ocelli, seen as the second visual system, sense fast luminance changes and allows for fast visual processing. Using a luminance-based sensor that mimics the insect ocelli and a camera-based motion detection system, a frequency-domain characterization of an ocellar sensor and optic flow (due to rotational motion) are analyzed. Inspired by the insect neurons that make use of signals from both vision sensing mechanisms, advantages, disadvantages and complementary properties of ocellar and optic flow estimates are discussed.

Experience of a Single Center in NTBC Use in Management of Hereditary Tyrosinemia Type I in Libya

Background: Hereditary Tyrosinemia type I (HTI) is a metabolic disease caused by deficiency of fumarylacetoacetate hydrolase enzyme. Objectives: This study reports beside its clinical and biochemical presentation, the outcome of NTBC [2- (2-nitro-4-trifloro-methylbenzoyl)-1, 3-cyclohexanedion] treatment of the disease and evaluates its biochemical markers in 16 pediatric Libyan patients. Patients and Methods: The diagnosis was based on presence of high tyrosine levels in blood and succinylacetone in urine. Results: The consanguinity rate was 81.2%, the median age at onset, at diagnosis and at starting treatment were 4.5, 8, and 9.5 months respectively. At presentation hepatomegaly, jaundice, rickets and high gamma glutamyl transferase (GGT) were observed in 87.5% of patients. All patients had extremely high alpha fetoprotein (AFP) and high alkaline phosphatase (ALP) levels. Fifteen patients were treated with NTBC, normalization of PT (Prothrombine time) was achieved in average in 14 days. The other biochemical parameters of liver function (transaminases, GGT, ALP, bilirubin and albumin) took longer to improve and several months to be normalized. Survival rate with NTBC was 86.6%. Patients who started treatment in a median of 3 months post onset observed a fast drop of AFP in 90.6% of patients (P = 0.003). Abnormal liver function and rickets were the common presentations, GGT was an early cholestatic sensitive test. ALP was constantly high even in asymptomatic patients. Conclusions: In HT1 a faster dropping of AFP is a marker of good prognosis.

Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a colombian family

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. Objective: We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. Methods: We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A. Results: The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.

Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a colombian family

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. Objective: we describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. Methods: We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A. Results: The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.

Does cochlear implantation improve speech recognition in children with auditory neuropathy spectrum disorder? A systematic review

OBJECTIVE: Cochlear implantation (CI) is a standard treatment for severe-profound sensorineural hearing loss (SNHL). However, consensus has yet to be reached on its effectiveness for hearing loss caused by auditory neuropathy spectrum disorder (ANSD). This review aims to summarize and synthesize current evidence of the effectiveness of CI in improving speech recognition in children with ANSD. DESIGN: Systematic review. STUDY SAMPLE: A total of 27 studies from an initial selection of 237. RESULTS: All selected studies were observational in design, including case studies, cohort studies, and comparisons between children with ANSD and SNHL. Most children with ANSD achieved open-set speech recognition with their CI. Speech recognition ability was found to be equivalent in CI users (who previously performed poorly with hearing aids) and hearing-aid users. Outcomes following CI generally appeared similar in children with ANSD and SNHL. Assessment of study quality, however, suggested substantial methodological concerns, particularly in relation to issues of bias and confounding, limiting the robustness of any conclusions around effectiveness. CONCLUSIONS: Currently available evidence is compatible with favourable outcomes from CI in children with ANSD. However, this evidence is weak. Stronger evidence is needed to support cost-effective clinical policy and practice in this area.

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography

Purpose: The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). Methods: Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. Results: The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911–0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. Conclusions: Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

Neurodegeneration and the m-AAA protease: pathogenic cascades in neurons and myelinating cells

The m-AAA protease is a hexameric complex involved in processing of specific substrates and turnover of misfolded polypeptides in the mitochondrial inner membrane. In humans, the m-AAA protease is composed of AFG3L2 and paraplegin. Mutations in AFG3L2 have been implicated in dominant spinocerebellar ataxia (SCA28) and recessive spastic ataxia-neuropathy syndrome (SPAX5). Mutations of SPG7, encoding paraplegin, are linked to hereditary spastic paraplegia. In the mouse, a third subunit AFG3L1 is expressed. Various mouse models recapitulate the phenotype of these neurodegenerative disorders, however, the pathogenic mechanism of neurodegeneration is not completely understood. Here, we studied several mouse models and focused on cell-autonomous role of the m-AAA protease in neurons and myelinating cells. We show that lack of Afg3l2 triggers mitochondrial fragmentation and swelling, tau hyperphosphorylation and pathology in Afg3l2 full-body and forebrain neuron-specific knockout mice. Moreover, deletion of Afg3l2 in adult myelinating cells causes early-onset mitochondrial abnormalities as in the neurons, but the survival of these cells is not affected, which is a contrast to early neuronal death. Despite the fact that myelinating cells have been previously shown to survive respiratory deficiency by glycolysis, total ablation of the m-AAA protease by deleting Afg3l2 in an Afg3l1 null background (DKO), leads to myelinating cell demise and subsequently progressive axonal demyelination. Interestingly, DKO mice show premature hair greying due to loss of melanoblasts. Together, our data demonstrate cell-autonomous survival thresholds to m-AAA protease deficiency, and an essential role of the m-AAA protease to prevent cell death independent from mitochondrial dynamics and the oxidative capacity of the cell. Thus, our findings provide novel insights to the pathogenesis of diseases linked to m-AAA protease deficiency, and also establish valuable mitochondrial dysfunctional mouse models to study other neurodegenerative diseases, such as tauopathies and demyelinating diseases.