Maria Rosaria Barillari

Spatio-temporal hotspots and application on a disease analysis case via GIS

Hotspot analysis is a spatial analysis that uses cluster techniques for determining areas with elevated concentrations of localized events. We use the consolidated Extended Fuzzy C-Means algorithm to determine the hotspot areas on the map as circles, moreover the advantages of this technique are the linear computational complexity, the robustness to noise and outliers, the automatic determination of the optimal number C of clusters (in the classical FCM algorithm C is chosen a priori). Furthermore it prevents the problem of shifting the clusters with low density area of data points in areas with higher density of such points. We apply this method to study the spatio-temporal variations of the hotspot areas by testing this process on a specific disease problem, precisely we have clusterized 5,000 point-events correspondent to cases of brain cancer detected in the state of New Mexico from 1973 to 1991. We also show that the same results are obtained by using the Extended Gustafson–Kessel algorithm which gives elliptical clusters. We have implemented both algorithms in a Geographic Information System environment. Thus we establish the areas which seem not interested from the incidence of the disease and those areas in which the phenomenon appears to be temporarily attenuated either increased or constant or quite disappeared.

Modulation of Matrix Metalloproteinases Activity in the Ventral Horn of the Spinal Cord Re-stores Neuroglial Synaptic Homeostasis and Neurotrophic Support following Peripheral Nerve Injury

Modulation of extracellular matrix (ECM) remodeling after peripheral nerve injury (PNI) could represent a valid therapeutic strategy to prevent maladaptive synaptic plasticity in central nervous system (CNS). Inhibition of matrix metalloproteinases (MMPs) and maintaining a neurotrophic support could represent two approaches to prevent or reduce the maladaptive plastic changes in the ventral horn of spinal cord following PNI. The purpose of our study was to analyze changes in the ventral horn produced by gliopathy determined by the suffering of motor neurons following spared nerve injury (SNI) of the sciatic nerve and how the intrathecal (i.t.) administration of GM6001 (a MMPs inhibitor) or the NGF mimetic peptide BB14 modulate these events. Immunohistochemical analysis of spinal cord sections revealed that motor neuron disease following SNI was associated with increased microglial (Iba1) and astrocytic (GFAP) response in the ventral horn of the spinal cord, indicative of reactive gliosis. These changes were paralleled by decreased glial aminoacid transporters (glutamate GLT1 and glycine GlyT1), increased levels of the neuronal glutamate transporter EAAC1, and a net increase of the Glutamate/GABA ratio, as measured by HPLC analysis. These molecular changes correlated to a significant reduction of mature NGF levels in the ventral horn. Continuous i.t. infusion of both GM6001 and BB14 reduced reactive astrogliosis, recovered the expression of neuronal and glial transporters, lowering the Glutamate/GABA ratio. Inhibition of MMPs by GM6001 significantly increased mature NGF levels, but it was absolutely ineffective in modifying the reactivity of microglia cells. Therefore, MMPs inhibition, although supplies neurotrophic support to ECM components and restores neuro-glial transporters expression, differently modulates astrocytic and microglial response after PNI.

Mutations in the PCYT1A gene are responsible for isolated forms of retinal dystrophy.

Mutations in the PCYT1A gene have been recently linked to two different phenotypes: one characterized by spondylometaphyseal dysplasia and cone-rod dystrophy (SMD-CRD) and the other by congenital lipodystrophy, severe fatty liver disease, and reduced HDL cholesterol without any retinal or skeletal involvement. Here, we identified, by next generation sequencing, sequence variants affecting function in the PCYT1A gene in three young patients with isolated retinal dystrophy from two different Italian families. A thorough clinical evaluation of the patients, with whole skeleton X-ray, metabolic assessment and liver ultrasound failed to reveal signs of skeletal dysplasia, metabolic and hepatic alterations. This is the first report showing that the PCYT1A gene can be responsible for isolated forms of retinal dystrophy, particularly without any skeletal involvement, thus further expanding the phenotypic spectrum induced by mutations in this gene.

Dysphagia in Amyotrophic Lateral Sclerosis: Relationships between disease progression and Fiberoptic Endoscopic Evaluation of Swallowing.

OBJECTIVE Our aim was to evaluate the relationship between the disease severity of Amyotrophic Lateral Sclerosis (ALS) and the following parameters of Fiberoptic Endoscopic Evaluation of Swallowing (FEES): premature spillage, post-swallowing residue and aspiration. METHODS We studied 202 patients (95 women and 107 men) with ALS; of these, 136 had spinal and 66 had bulbar onset. They were analyzed according to the Amyotrophic Lateral Sclerosis Functioning Rating Scale (ALSFRS) and the b-ALSFRS subscale (bulbar scale). All subjects underwent FEES. Post-swallowing residue was classified into four classes (0-3); premature spillage and aspiration were considered either present or absent. RESULTS Spearmans correlation test showed a highly significant correlation (p<0.0001) between the value of ALSFRS and b-ALSFRS and the FEES parameters as the following: disease severity and dysphagia severity are closely related, both in spinal and bulbar onset, no matter what bolus texture was used. Spearmans Rho was more significant for post-swallowing residue, ≤-0.500 with all three consistencies (p<0.0001) in spinal onset and -0.520 only with liquid bolus (p<0.0001) in bulbar onset. Independent T-Test revealed a significant difference (p<0.0001) between the mean ALSFRS and b-ALSFRS scores and the presence/absence of aspiration. For the premature spillage in spinal onset (ALSFRS), we found a statistically significant difference for all three bolus textures (p<0.0001). Analysis of variance for the post-swallowing residue in spinal onset (ALSFRS) revealed a statistically significant difference (p<0.0001) for most of the comparisons between groups for all three textures. For the premature spillage in bulbar onset (b-ALSFRS), we found a statistically significant difference for all three textures (p<0.0001). Analysis of variance for the post-swallowing residue in bulbar onset (b-ALSFRS) showed a statistically significant difference (p<0.0001) for most of the comparisons between groups for all three textures. Kruskal-Wallis test showed a highly significant association between the classes of severity in bulbar forms and all the FEES parameters, no matter what type of bolus was administered (p<0.0001), whereas a significant correlation in spinal forms only for post-swallowing residue with solid (p=0.026) and semisolid (p=0.031) boluses. CONCLUSION There is a highly significant relationship as the following between the FEES parameters and the disease severity assessed via ALSFRS and b-ALSFRS: classes of greater severity entail a greater deterioration of FEES parameters. FEES can be considered a good indicator of the dysphagia severity and a useful test for the follow-up of dysphagia in patients with ALS, whether of spinal or bulbar onset.

WebGIS based on spatio-temporal hot spots: an application to oto-laryngo-pharyngeal diseases

We present a web geo-spatial framework for analyzing and continuously monitoring the spatio-temporal evolution of disease hot spots for detecting spatial areas with high concentrations of events in a geographic information system (GIS). To detect the hot spots, we adopt Extended Fuzzy C-Means algorithm. Each event is given by the geo-positional coordinates of the place of residence of the patient. The analyst can insert event data directly on the map or digitizing the address of the residence of the patient and using geo-coding services for locating the event. In our experiments, the data consist of geo-referenced patterns corresponding to the residence of patients in the district of Naples (Italy) submitted to a surgical intervention concerning the oto-laryngo-pharyngeal apparatus between the years 2008 and 2012. The results show the presence of two greatest hot spots: the first covers a geographical area that affects the city of Naples, the second covers parts of various towns around the famous vulcan Vesuvius, respectively.

Reliability, validity and normative data of a quick repetition test for Italian children

OBJECTIVES A quick repetition test can be useful as a screening or preliminary investigation to select children who need to be assessed with a more specific articulation test. Schindlers repetition test lasts about 2 min and requires the repetition of a 30 words list, each word targeting a specific phoneme or cluster. The aims of the study are: to assess reliability of Schindlers repetition test; to establish normative data for speech development in Italian-speaking children; to analyse validity of this instrument. METHODS Six-hundred-two Italian children, aged range between 3;0 and 10;8 years, were included in the study: 557 without clinical sign of speech impairment and 45 had a speech sound disorder. Reliability. One-hundred-five children were tested the same day by two examiners (inter-rater reliability); the administration of the repetition test to 45 children was audio-recorded (intra-rater reliability); 105 children underwent the repetition test twice, with a 2 weeks interval (test-retest reliability). Data were compared through Intraclass Correlation Coefficient (ICC). Normative data. Percentages of children without clinical sign of speech impairment in each age group who repeated correctly, omitted or produced distorted target phonemes of Schindlers repetition test were reported. VALIDITY To assess the ability of the test to record improvement in mean values with age (construct validity), the proportion of correct repetitions obtained by children from different age groups were compared through logistic regression. The speech abilities of 45 children were also analysed through a more comprehensive articulation test (concurrent validity). Scores were compared through Bland-Altman plot. RESULTS Reliability. All ICC were superior to 0.9. Normative data. Despite language-specific pattern of acquisition emerged, data showed many similarities to data reported in international studies on speech sound development. VALIDITY Logistic regression demonstrated a significant effect of age groups. Bland-Altman plot showed relatively narrow limits of agreement between Schindlers repetition and Rossis articulation test. CONCLUSIONS Schindlers repetition test can be considered a reliable and valid instrument for preliminary assessment of speech abilities in Italian-speaking children aged from 3 to 6 years old. Application of Schindlers repetition test is recommended in clinical practice, as a screening test or as a first clinical assessment instrument.

Spatiotemporal hotspots analysis for exploring the evolution of diseases: an application to oto-laryngopharyngeal diseases

This paper presents a spatiotemporal analysis of hotspot areas based on the Extended Fuzzy C-Means method implemented in a geographic information system. This method has been adapted for detecting spatial areas with high concentrations of events and tested to study their temporal evolution. The data consist of georeferenced patterns corresponding to the residence of patients in the district of Naples (Italy) to whom a surgical intervention to the oto-laryngopharyngeal apparatus was carried out between the years 2008 and 2012.

Complications with Fiberoptic Endoscopic Evaluation of Swallowing in 2,820 Examinations

Objective: To perform a retrospective evaluation of the incidence of complications and adverse events during fiberoptic endoscopic evaluation of swallowing (FEES) in 2,820 examinations. Patients and Methods: Subjects included in- and outpatients at Pisa University Hospital referred for FEES by other physicians due to dysphagia symptoms. Neurologic diseases were the most commonly diagnosed conditions in the patients tested (48.3%). Informed consent was obtained from all subjects. Results: Our study showed minor side effects (discomfort, occasional gagging and vomiting) and a few complications [three cases of anterior epistaxis (0.1%), one case of posterior epistaxis (0.04%), three cases of vasovagal syncope (0.1%) and two cases of laryngospasm (0.07%)]. These cases of laryngospasm occurred in patients with amyotrophic lateral sclerosis (ALS) and spontaneously resolved after some difficulty. Conclusions: Our study confirms the published data regarding the safety of FEES and the incidence of complications with this procedure, but also highlights that in neurologic patients with neurodegenerative diseases such as ALS, laryngospasm is more likely to occur as a severe complication. The overall risk of FEES is minimal, but it is recommended that clinicians be well trained in recognising the signs and symptoms of adverse reactions and be ready to take appropriate action if these occur.

Normative and validation data of an articulation test for Italian-speaking children

OBJECTIVES As a standardized instrument to assess speech sound development in Italian-speaking children is currently lacking, norms used to diagnose speech sound disorders (SSD) are mainly based on studies including English-speaking participants. This application may result in misidentification of SSD due to linguistic differences. The aims of the study were to establish normative data on speech sound development of Italian-speaking children and to evaluate psychometric properties of Rossis articulation test, the picture-naming test selected to assess speech sound development. METHODS A cross-sectional study including 694 normally-developing Italian-speaking children aged from 3 to 7 years was conducted. Children were administered Rossis articulation test, and percentages of speech sound correct production were calculated. To evaluate inter-rater reliability of the test, audio-recordings of 50 children were scored by an additional examiner. The same rater scored the audio-recordings of 50 children twice with an interval of at least 1 week. To evaluate test-retest reliability, 144 participants were re-tested after 1-3 weeks by the same assessor. Scores were compared through Intraclass Correlation Coefficient (ICC). To assess construct validity, the developmental progression of total scores across age groups was verified by the estimation of the reference range for the test, using a regression procedure. RESULTS Almost all Italian children in the sample produced vowels and approximants correctly. Singleton consonants were acquired before consonant clusters. Ages of acquisition of each consonant were presented: plosives and nasals were early mastered by Italian children, while dental affricates, alveolar fricatives and the palatal lateral were the latest acquired segments. All ICCs were superior to 0.9 (reliability). A statistically significant improvement in test score with age was found (construct validity). CONCLUSIONS The paper provides normative data for speech sound development of Italian-speaking children; preliminary psychometric analysis of Rossis articulation test revealed satisfactory reliability and construct validity. Clinicians are recommended to use Rossis articulation test to assess speech sound development in Italian children.

Endoscopic and phoniatric evaluation in singing students

OBJECTIVES In To analyze laryngostroboscopic findings and ENT/phoniatric examination results in a group of singing students and in a control group of non-singing subjects to emphasize the importance of ENT/phoniatric examination and of laryngostroboscopy before taking up singing. METHODS 56 singing students and 60 healthy euphonic non-singer volunteers were recruited. In each subject a perceptual assessment and a self-assessment (VHI) of the voice were performed. The singing students filled out the Singing-VHI. All subjects underwent flexible fiberoptic endoscopy and laryngostroboscopy. All subjects were evaluated through the Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS). RESULTS At laryngostroboscopy, 60.7% of students presented pathological findings, versus 20% of controls (P < 0.0001). Incomplete glottic closure (35.7% vs. 13.3%), supraglottic hypertonus (16.1% vs. 5%), organic lesions (bilateral nodules, cysts, sulcus vergeture) (17.9% vs. 3.3%), posterior erythema (16.1% vs. 5%) and laryngeal edema (14.3% vs 3.3%) were more frequent in the students. The most common symptoms in singers were phonasthenia (37.5 % vs 6.7%; P =  0.0001) and mucus sensation (17.9% vs. 5%, P = 0.03). S-VHI showed higher values in students with pathological laryngostroboscopy (P < 0.0001). Finally, average RSI and RFS were higher in students. CONCLUSIONS Due to the high percentage of organic and functional voice disorders in singing students, it would be desirable that every subject who is going to start singing underwent an ENT/phoniatric investigation with videostrobolaryngoscopy to ascertain vocal folds healthy condition.