Interpretable deep learning as a means for decrypting disease signature in multiple sclerosis.

Objective.The mechanisms driving multiple sclerosis (MS) are still largely unknown, calling for new methods allowing to detect and characterize tissue degeneration since the early stages of the disease. Our aim is to decrypt the microstructural signatures of the Primary Progressive versus the Relapsing-Remitting state of disease based on diffusion and structural magnetic resonance imaging data.Approach.A selection of microstructural descriptors, based on the 3D-Simple Harmonics Oscillator Based Reconstruction and Estimation and the set of new algebraically independent Rotation Invariant spherical harmonics Features, was considered and used to feed convolutional neural networks (CNNs) models. Classical measures derived from diffusion tensor imaging, that are fractional anisotropy and mean diffusivity, were used as benchmark for diffusion MRI (dMRI). Finally, T1-weighted images were also considered for the sake of comparison with the state-of-the-art. A CNN model was fit to each feature map and layerwise relevance propagation (LRP) heatmaps were generated for each model, target class and subject in the test set. Average heatmaps were calculated across correctly classified patients and size-corrected metrics were derived on a set of regions of interest to assess the LRP contrast between the two classes.Main results.Our results demonstrated that dMRI features extracted in grey matter tissues can help in disambiguating primary progressive multiple sclerosis from relapsing-remitting multiple sclerosis patients and, moreover, that LRP heatmaps highlight areas of high relevance which relate well with what is known from literature for MS disease.Significance.Within a patient stratification task, LRP allows detecting the input voxels that mostly contribute to the classification of the patients in either of the two classes for each feature, potentially bringing to light hidden data properties which might reveal peculiar disease-state factors.

The combined effect of surgeon and hospital volume on health outcomes: a systematic review.

OBJECTIVES: To explore the interaction between surgeon volumes (SVs) and hospital volumes (HVs) on health outcomes. MATERIALS AND METHODS: We searched MEDLINE, Embase, CINAHL, Web of Science as of May 2017. We included studies investigating the interaction between high or low SVs operating in high or low HVs. Review process follows the PRISMA guidelines. We assessed the methodological quality of the included studies using validated critical appraisal checklists. RESULTS: Sixteen studies were included. Due to the heterogeneity of studies, it was not possible to perform a quantitative analysis. Heath outcome are worse when high SV operating in low HV vs high HV, for the majority of the conditions (colorectal cancer, cystectomy, liver resection, mitral valve surgery, pancreatico-duodenectomy). Results for low SV are better when operating in high HV vs low HV for patients undergoing pancreatic-duodenectomy for mortality, 30 days complications and length of stay. Results for low SV are worse vs high SV when operating in high HV for most considered conditions. Results were in favour of higher SV vs low SV when operating in low HV for digital replantation success after injuries, 30 days mortality and complications after pancreatic-duodenectomy. CONCLUSIONS: The available evidence is limited. It is necessary to increase the monitoring of the association between surgeons volumes and hospitals volumes in which they operate, to ensure fairness and accuracy of care for better health outcomes.

Rich context information for just-in-time adaptive intervention promoting physical activity.

Sedentary lifestyle and inadequate levels of physical activity represent two serious health risk factors. Nevertheless, within developed countries, 60% of people aged over 60 are deemed to be sedentary. Consequently, interest in behavior change to promote physical activity is increasing. In particular, the role of emerging mobile apps to facilitate behavior change has shown promising results. Smart technologies can help in providing rich context information including an objective assessment of the level of physical activity and information on the emotional and physiological state of the person. Collectively, this can be used to develop innovative persuasive solutions for adaptive behavior change. Such solutions offer potential in reducing levels of sedentary behavior. This work presents a study exploring new ways of employing smart technologies to facilitate behavior change. It is achieved by means of (i) developing a knowledge base on sedentary behaviors and recommended physical activity guidelines, and (ii) a context model able to combine information on physical activity, location, and a user's diary to develop a context-aware virtual coach with the ability to select the most appropriate behavior change strategy on a case by case basis.

Intracameral epinephrine without the addition of intracameral lidocaine in the management of tamsulosin associated intraoperative floppy iris syndrome.

OBJECTIVE: Intracameral mydriatics using epinephrine associated with lidocaine have been reported as efficacious in reducing intraoperative floppy iris syndrome (IFIS) complications during cataract surgery. The aim of this study was to verify the efficacy of intracameral epinephrine without intracameral lidocaine as prophylaxis against IFIS in patients on tamsulosin. MATERIALS AND METHODS: This was a retrospective study on the results of cataract surgery in 18 patients on therapy with tamsulosin. Patients had undergone routine phacoemulsification in one eye. Successively, they underwent phacoemulsifcation in the fellow eye using non preserved intracameral epinephrine 1:4000 diluted with BSS. Intraoperative complications during cataract surgery had been documented and IFIS was graded based on iris billowing, miosis or iris prolapse. Follow-up was 3 months. RESULTS: Thirty-six eyes of 18 patients were included in the evaluation. The incidence of IFIS was significantly higher in the eyes where routine phacoemulsificaton had been performed (100%) with respect to eyes where phacoemulsification was carried out using intracameral epinephrine (33%) (Chi Square test =15.12, p<0.001). In routine phacoemulsification 16 eyes showed iris billowing, 14 eyes had some extent of miosis and 14 eyes had tendency to iris prolapse. In phacoemulsification with the use of intracameral epinephrine 5 eyes showed iris billowing, 4 eyes presented some extent of miosis and 2 eyes had tendency to iris prolapse. There were no serious intraoperative complications. CONCLUSIONS: Intracameral epinephrine without the addition of lidocaine was efficacious in the management of IFIS in patients on tamsulosin.

Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis.

In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance ((1)H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA). To define the metabolomics signatures of BV, 100 discriminant analysis by projection on latent structure (PLS-DA) models were calculated. Bacterial signatures distinguishing the health condition and BV were identified by qPCR. Lactobacillus crispatus strongly featured the healthy vagina, while increased concentrations of Prevotella, Atopobium and Mycoplasma hominis specifically marked the infection. (1)H-NMR analysis has led to the identification and quantification of 17 previously unreported molecules. BV was associated with changes in the concentration of metabolites belonging to the families of amines, organic acids, short chain fatty acids, amino acids, nitrogenous bases and monosaccharides. In particular, maltose, kynurenine and NAD(+) primarily characterised the healthy status, while nicotinate, malonate and acetate were the best metabolic hallmarks of BV. This study helps to better understand the role of the vaginal microbiota and metabolome in the development of BV infection. We propose a molecular approach for the diagnosis of BV based on quantitative detection in the vaginal fluids of Atopobium, Prevotella and M. hominis, and nicotinate, malonate and acetate by combining qPCR and (1)H-NMR.

Positive emotional arousal increases duration of memory traces: different role of dopamine D1 receptor and ß-adrenoceptor activation.

We investigated the effects of post-training administration of dopamine D1 receptor antagonist SCH 23390 and ß-adrenergic receptor antagonist Propranolol on memory retention of an object sampled in a state of positive emotional arousal. Saline-treated mice trained and tested under high emotional/motivational arousal (High) showed discrimination of a novel object both 24 and 96 h post-training. Instead, mice trained and tested under low motivational arousal (Low) were unable to discriminate the novel object 96 h post-training. Both a high (2 mg/kg) and a low (1 mg/kg) dose of Propranolol reduced object discrimination in High mice tested 24 h post-training, whereas neither dose was effective in Low mice. A high dose of SCH 23390 (0.025 mg/kg) reduced discrimination of the novel object in High mice tested both 24 and 96 h post-training, whereas a low dose of the D1 antagonist (0.01 mg/kg) reduced discrimination in High mice tested 96 h post-training and abolished discrimination in Low mice tested 24h after training.

[Stabilometric analysis in patients affected by maculopathy]. / Analisi stabilometrica in pazienti maculopatici.

OBJECTIVES: The walk is strictly influenced by vision, that's essential for the position of the body in the space during the walk cycle and the postural control. The quality of life related to the vision is widely highlighted in literature: for example Brown et al. in 2005 underlined the comparison from DMLE and chronic ills, like HIV, angina, dialysis, advanced prostate tumor, stroke, and heart attack. Peripheral low vision appeared the most crippling aspect to the walk, but in recent years a lot of studies stressed the walk difficulty in patients with central low vision. MATERIALS AND METHODS: Our study has been carried out in partnership between Ophtalmic Department and Physiatrist Department. Its aim was to evaluate static posture in patients affected by maculopathy. We picked out subjects affected by maculopathy with central low vision due to a variety of causes but with preserved peripheral vision. RESULTS: Test trials had the purpose to investigate different aspects of static posture, in subjects affected by central low vision. It was related to risk of falling and faulty postures, that are pathologically in a long term. CONCLUSIONS: Our study claimed that in stabilometric analysis the differences between patients affected by maculopathy and control group aren't statistically significant.

Urrets- Zavalia Syndrome after glaucoma filtration device implantation.

We report a case of Urrets-Zavalia Syndrome after a glaucoma filtration device (g.f.d.) implantation. A 74-year-old woman with bilateral advanced glaucoma has been planned for surgery. The patient underwent to g.f.d. implantation in the right eye. On postoperative day 1, the patient had an edematous cornea with a dilated and non reactive pupil. In this article we describe the clinical history of this patient. To our knowledge, this is the first case of Urrets-Zavalia Syndrome after a g.f.d. implantation.

Botulinum toxin treatment in glaucomatous patients: a pilot study.

PURPOSE: The purpose was to evaluate the efficacy of the treatment of iatrogenic entropion (IE), in patients affected by primary open angle glaucoma (POAG), by botulinum toxin injections (BTI). PATIENTS AND METHODS: 20 patients of the "Glaucoma Center" of the Hospital "Umberto I" (Rome) were examined. These patients had POAG and used prostaglandin analogues (PA). Mean age was 75.5 years old (range 68-83); they had been suffering from PAOG since 10 years and were not affected by other relevant systemic diseases. One to three BTI were made into the lower orbicularis muscle using a 0.3 G needle (0.025 to 0.05 units for each injection site). RESULTS: The results were particularly significant in 18 out of 20 patients. Two patients showed slight improvements. A rating scale ranging from 0 to 6 points (0 corresponded to 'no effect' and 6 to the 'complete' resolution of the entropion) was used to evaluate the goals of the treatment. The average rating was 5.37 points. CONCLUSIONS: The entropion due to glaucoma therapy with PA can be successfully treated with BTI in the orbicularis muscle, despite offering temporary therapeutic effects.

Macular thickness changes evaluated with spectral domain optical coherence tomography after uncomplicated phacoemulsification.

PURPOSE: To determine macular thickness changes after uncomplicated cataract surgery using spectral domain optical coherence tomography (OCT). METHODS: This was a prospective non-randomized, clinical study. Data were analysed for 40 healthy patients undergoing uneventful phacoemulsification. OCT measurements were performed before surgery and postoperatively at day 1, week 1 and 2, and month 1, 2, 3, and 6. The retinal map was divided into central point thickness (CPT), central 1-mm subfield (CSF), and two peripheral ring areas with diameters of 3 and 6 m. Fellow eyes were used as controls. Retinal thickness change between the operated and fellow eyes were compared using unpaired t-test. Correlations were analysed using the Spearman or the Pearson analysis. RESULTS: There was a progressive significant increase in retinal thickness of the operated eyes compared with the fellow eyes, with a peak at 1 month (P<0.0001) for the 3- and 6-mm areas and a peak at 2 months for CPT and CSF (P=0.01 and P<0.0001, respectively). At 6 months, retinal thickness was still significantly increased only in the peripheral areas (P<0.0001). There was no significant correlation between macular thickness changes and preoperative factors (age, axial length, anterior chamber depth, posterior vitreous detachment, best-corrected visual acuity), intraoperative factors (length of surgery, effective phaco time, phaco energy) or BCVA change. CONCLUSIONS: The present study demonstrated a significant increase in macular thickness up to 6 months after uncomplicated cataract surgery. The most important finding was the regional pattern of retinal thickening with an early involvement of the parafoveal area.

Chitosan/alginate complexes for vaginal delivery of chlorhexidine digluconate.

Chitosan/alginate complexes were prepared at different polycation/polyanion molar ratios and freeze-dried vaginal inserts were obtained for chlorhexidine digluconate local delivery in genital infections. Complex yield, FT-IR spectra, and TGA thermograms were studied to confirm the interaction between the two polyions. The influence of different complexes on physical handling, morphology, and drug distribution in the samples were evaluated by friability test, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS), respectively. In vitro water-uptake, mucoadhesion and release tests were performed as well as microbiological tests toward pathogenic vaginal microorganisms. The results showed that the selection of suitable chitosan/alginate molar ratio and drug loading allowed modulate insert ability to hydrate, adhere to the mucosa, and release chlorhexidine digluconate. The insert containing an excess of alginate was found to be the best performing formulation and showed good antimicrobial activity toward the pathogens Candida albicans and Escherichia coli.

Investigation about causes of blindness and low vision among members of Blind and Visually Impaired Italian Union (UICI).

PURPOSE: To evaluate the prevalence of the most important causes of blindness among visually impaired and blind, members of UICI (Blind and Visually Impaired Italian Union). The main aim is to get information about the most important ocular diseases which make people blind or visually impaired in Italy. Further purpose is to make our data useful to provide economical evaluations about public expense due to blindness and low vision. MATERIALS AND METHODS: A retrospective analysis was carried out on UICI database to get information about members of the most important UICI Provincial Centers. The Centers were selected depending on specific inclusion criteria. The descriptive analysis was performed with SAS System 9.1.3 and Microsoft Excel 2007. RESULTS: Data were available for 15,725 UICI members, whose 39% (n=6,133) were visually impaired and 61% (n=9.592) were blind. Pathologic myopia was responsible for low vision and blindness in 11.78%, AMD in 11%, cataract in 8.92%, glaucoma in 8.31%, diabetic retinopathy in 8.23%, retinitis pigmentosa in 6.96%. DISCUSSION: The analyzed sample allows to get only a rough, although useful, estimate of low vision and blindness in Italy. The causes of visual impairment we found are quite in line with those provided by other international studies. The main difference from previous studies concerns pathologic myopia and retinitis pigmentosa as the most important causes of low vision and blindness among working-age people. Our epidemiological study should be mixed with economical cost-effectiveness evaluations in order to provide further impulses to efficient prevention programs.

Acute Myopia: could it be the presenting symptom of a rheumatic disease? A case report

This is a case-report of a patient who came to our Eye Emergency Room for acute onset of myopia and asthenia. The purpose is to evaluate the causes of acute myopia in a 28 year old woman with a family history of rheumatic diseases and a positive antibody titer (ANA). The UBM-study showed a 360° choroidal effusion and the hematological analysis showed mild anemia, lymphocytosis and ANA antibodies were positive. All that signs could suggest a vasculitis-like onset of an autoimmune disease, involving the eye first. Although the diagnosis of Systemic Lupus Erythematosus (SLE) or other autoimmune diseases cannot be confirmed according to the rheumatologic criteria, the vasculitic ocular manifestations with positive antibodies in the young woman need further evaluation because it seems to be enough to refer the patient to a rheumatology follow-up.

Association between striatal accumulation of FosB/ΔFosB and long-term psychomotor sensitization to amphetamine in mice depends on the genetic background.

Previous results demonstrated association between increased FosB/ΔFosB immunostaining in the ventromedial striatum and behavioral sensitization to amphetamine promoted by repeated stress or by repeated pairings of the psychostimulant and the testing cage in mice of the C57BL/6J strain. The present experiments tested this association in an additional protocol, its stability following the end of the sensitizing procedure and its generalization to mice from a different inbred strain. Eleven days after repeated administration of amphetamine within their home-cages, mice of the C57BL/6J strain expressed sensitization to the psychomotor effects of the psychostimulant when tested in a novel cage. At this time-point the same mice showed increased FosB/ΔFosB immunostaining in the ventromedial striatum. Instead, mice of the genetically unrelated DBA/2J inbred strain expressing robust sensitization in the same protocol did not show changes in FosB/ΔFosB immunostaining throughout the striatal complex. Lack of effects in FosB/ΔFosB immunostaining was also observed in DBA/2J mice behaviorally sensitized by repeated pairings of amphetamine with the test cage. These results demonstrate that mice, depending on the genetic background, can develop robust and long-lasting behavioral sensitization to amphetamine in the absence of striatal ΔFosB accumulation.

[Children's eye care in Italy through data provided by "Let's see clear" campaign]. / La salute oculare nell'infanzia in Italia attraverso i dati della campagna "Vediamoci Chiaro".

PURPOSE: To know children's visual conditions and assess the actual status of ophthalmological prevention in Italy, highlighting both positive and negative aspects and its variables. MATERIALS AND METHODS: Research was carried out in nine Italian regions (Sicilia, Calabria, Campania, Lazio, Abruzzo, Molise, Emilia Romagna, Lombardia, Friuli Venezia Giulia) by means of questionnaire filled in by preschool, elementary and junior high school children's parents. A different amount of questionnaires has been got for each region. For this reason a percentage distribution is used instead of absolute value, in order to remove distortion due to the different size of samples from region to region. Statistical analysis was carried out. RESULTS: 36.744 files were collected. Most important data were about (average):Parents' schooling (37% junior high school, 46% high school, 12% degree). 2. Spread of refractive errors (23% of children wear glasses). 3. Relation between children glasses (77% accepted glasses); 4. First ophthalmological examination: age (90% <6 yrs old in Lombardia), aim (77% prevention), who take the initiative (77% parents). 5. Relation between neonatal ophthalmological examination and premature birth or stay in incubator (Friuli: examination carried out on 63% of premature babies and on 79% of babies who needed the stay in the incubator). 6. The most common ocular diseases among children (subjective disorders 60%, motility disorders 20%, annexes' disorders 8%). DISCUSSION: There are no many examples of studies about childhood health and even less frequent are the investigations about prevention and the diffusion of ophthalmological examination among children. Our data result from a pretty representative sample of Italian reality. The main feature of visual health among the children included in our research is the great spread of refractive errors, according to most economically advanced countries. Parents play a key role regarding childhood prevention, because they seem to have a high level of awareness in most included regions. Therefore, the family should represent the recipient of efforts in order to move up further the ophthalmological examination on children, preferably at birth.

A simulation of cost-benefit analysis of blindness prevention in Italy.

PURPOSE: The most important purpose is to assess by a trial and error method the financial effects of efficient prevention programmes in our country. The study provides an empiric evidence that Government could reduce public spending thorough investments in projects of prevention about visual care. MATERIALS AND METHODS: Authors focus on the economic impact of four eye diseases that are the major cause of blindness (90%) and for this reason they were classificated as "diseases of social importance" (DSI from hereforth) according to the WHO: Age - related Macular Degeneration (AMD), Glaucoma, Diabetic Retinopathy (DR), Cataract. Authors use a three-stage approach in order to estimate the impact of blindness prevention on public accounts: 1. Calculation of aggregate costs of the DSI in Italy; 2. Use of the estimated figures in the first stage of the alanysis to estimate the individual average costs; 3. Use of the estimated figures in the second stage of the analysis to run a simulation in capital budgeting comparing the costs associated with taking one of two possible choices: investing or not in a blindness prevention programme. DISCUSSION: Authors simulate the economic effects of the adoption of a blindness prevention campaign and compare them to the calculated costs of blindness. This comparison was based on the creation of decision trees, which are typically used for the optimisation of investment portfolios, combined with another decision technique: the Net Present Value (NPV).

Positive and negative emotional arousal increases duration of memory traces: common and independent mechanisms.

We compared the ability of positive and negative emotional arousal to increase the duration of consolidated memory traces. Positive arousal was modulated by manipulating the motivational salience of the testing cage of an object recognition test. Negative emotional arousal was modulated by manipulating shock levels in a step-through inhibitory avoidance (IA). Mice trained in either a high (chocolate-associated) or a low (inedible object-associated) emotionally arousing cage showed discrimination of a novel object 24 h after training, but only mice trained in the more arousing cage showed retention 96 h after training. Mice trained with either low (0.35 mA) or high (0.7 mA) shock intensities showed increased step-through latencies when tested 24 h after training, but only mice trained with the higher shock intensity showed retention of the IA learning 1 week after training. Administration of the phosphodiesterase type IV inhibitor Rolipram immediately after training in the two low arousing conditions increases duration of both responses.

Incidental finding of double nodular microscopic hyperplasia versus adenoma of the retinal pigment epithelium in an eye eviscerated for phthisis bulbi.

Neoplasms of the retinal pigment epithelium (RPE) are very rare and can clinically simulate choroidal melanoma. The clinical, histopathological and immunohistochemical features of incidental double pseudo-neoplastic proliferation of the RPE in an eviscerated eye for phthisis bulbi are reported. The differential diagnosis of RPE neoplasms and the utility of histopatological examination of eviscerated/enucleated eyes are discussed.

Intravitreal bevacizumab for treatment of myopic choroidal neovascularization: the second year of a prospective study.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV). DESIGN: Prospective, non-randomized, interventional clinical study. METHODS: Twenty eyes from 20 patients with CNV secondary to pathologic myopia participated in this study. These patients had already completed 12 months of follow-up. All patients were scheduled for 3 monthly intravitreal bevacizumab 1.25 mg injections. ETDRS best-corrected visual acuity (BCVA), foveal center thickness (FCT) on OCT and CNV size as assessed by fluorescein angiography were examined before and after treatment. Patients were followed up for 24 months. RESULTS: Mean BCVA (+/- SD) at baseline was 24.8 (+/- 11.86) letters (Snellen equivalent: 20/80). At 24 months after treatment the mean BCVA (+/- SD) improved significantly (p less than 0.05) to 44 (+/- 13.99) letters (Snellen equivalent: 20/33). At 24 month follow-up, BCVA improved of 10 letters or more in 17 (85%) out of 20 treated eyes and improved of 15 letters or more in 15 (75%) eyes. No treated eyes experienced a worsening of BCVA from baseline. Mean foveal center thickness (FCT) (+/- SD) at baseline was 223 (+/- 47,43) microns. By month 24, mean FCT (+/-SD) reduced to 190 (+/- 29.01) microns (p less than 0.05). Mean area of the CNVs at baseline was 0.77 (+/- 0.78) mm2, which decreased to 0.31 +/- (0.51) mm2 and 0.30 (+/- 0.50) mm2 at 12 (p less than 0.05) and 24 months (p less than 0.05), respectively. At 24 months follow-up absence of fluoresce in leakage from the CNV was demonstrated in 18 (90%) out of 20 treated eyes. No ocular or systemic adverse effects from treatment were encountered. CONCLUSION: Eyes with myopic CNV treated with intravitreal bevacizumab over 2 years had significant anatomic and functional improvement. Further studies will be needed to confirm the long-term efficacy and safety of this treatment.

Causes of blind certification in an Italian province and comparison with other European countries.

PURPOSE: Low vision and blindness are significantly growing in both industrialized and developing countries. In Italy there are few epidemiological studies that provide data on this phenomenon. In this paper we report the main causes of blindness and the characteristics of the subjects who obtained a disability certification due to blindness in an Italian province. MATERIALS AND METHODS: Disability certificates issued by the Civil Blind Provincial Commission of the Viterbo province over a 2-year period (2002-2003) were analysed. The causes of blindness and the age of occurrence were investigated and divided into 12 groups. RESULTS: The four most frequent causes of blindness were age related macular degeneration (19%), cataract (14%), glaucoma (15%) and diabetic retinopathy (15%). The main eye pathology which caused partial blindness was age related macular degeneration (22.3%). Glaucoma (19.6%) was the main cause of total blindness. CONCLUSIONS: The estimates of blindness were based on certification for visual impairment with limited characteristics as our data was exclusively administrative. However, a general appraisal of the magnitude and causes of visual impairment was determined. This is important towards planning appropriate preventive and management measures.