Ocular manifestations in Gorlin-Goltz syndrome

Background: Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients. Results: Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients. Conclusions: The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients

Treatment plan comparison in acute and chronic respiratory tract diseases : an observational study of doxophylline vs. theophylline

BACKGROUND: The main objective of this article is to estimate the global cost related to the use of the two drugs (associated drugs, specialist visits, hospital admissions, plasma drug monitoring). METHODS: The drug prescriptions were extracted from the Information System of the Pharmaceutical Prescriptions of the Marche Region for each ATC code in the years 2008-2012 and the number of patients per year and other outcomes measure were obtained. RESULTS: 13,574 patients were treated with theophylline and 19,426 patients with doxophylline. The number of patients treated was approximately 5,000 per year. Co-prescription with other drugs, use of corticosteroids, mean number of visits and hospital admissions (per 100 patients) were lower for doxophylline vs theophylline (1.55vs5.50, 0.3vs0.7, 2.05vs3.73 and 1.57vs3.3 respectively). The annual mean cost per patient was €187.4 for those treated with doxophylline and €513.5 for theophylline. CONCLUSIONS: In our study, doxophylline resulted to be associated with a reduction of the overall cost

Self-sealing posterior scleral perforation in airgun ocular trauma, surgical tip: A case report

Background: Intraorbital metallic foreign bodies have varied clinical presentations. Here, we report the unusual case of intraoperative evidence of spontaneously healed posterior scleral perforation in a severe ballistic trauma without previous instrumental signs of penetrating wound and complete visual restoration after surgery. Case presentation: The patient was hit by several lead hunting pellets in the chest, abdomen, limbs, face and orbit. Computed Tomography (CT) images revealed the presence of a pellet within the orbitary cavity, close to the optic nerve, with no signs of penetrating ocular wound. While performing vitrectomy for severe vitreous hemorrhage, a point of strong adherence between a old hemorrhage and retinal surface was identified and managed conservatively, as it was attributed to trauma related-impact area. So, lead foreign body took an unusual trajectory impacting the globe and finally lodging back in the deep orbitary cavity, in absence of significant ocular injury and with visual prognosis preservation. Conclusions: Our findings provide further information on orbital injuries from airguns, a theme of growing popularity and concern. Intraoperative recognition of hardly removable old hemorrhagic clot as self-blockage site of posterior scleral penetrating trauma, allowed for surgical stabilization and minimal solicitation of the area to avoid inadvertent perforation

X-linked dominant RPGR gene mutation in a familial Coats angiomatosis

Background: Retinitis Pigmentosa (RP) is the most frequent retinal hereditary disease and every kind of transmission pattern has been described. The genetic etiology of RP is extremely heterogeneous and in the last few years the large application of Next Generation Sequencing (NGS) approaches improved the diagnostic yield, elucidating previously unexplained RP causes and new genotype-phenotype correlations. The objective of this study was to reevaluate a previously reported family affected by Coats’-type RP without genetic diagnosis and to describe the new genetic findings. Case presentation: Cohort, prospective, and single-center observational family case. Three individuals of a family, consisting of a mother and four sons, with a Coats phenotype were revaluated after 25 years of clinical follow-up using visual acuity tests, ophthalmoscopy, Goldmann visual field, electroretinography (ERG), and spectral domain-optical coherence tomography (SD-OCT). Specifically, a RP NGS panel was performed on one member of the family and segregation analysis was required for the other affected and unaffected members. NGS analysis disclosed a RPGR (Retinitis Pigmentosa GTPase Regulator) gene truncating variant segregating with the phenotype in all the three affected members. RPGR mutations are reported as causative of an X-linked RP. Conclusions: This is the first reported family with a Coats’-type RP associated to a RPGR mutation and segregating as a dominant X-linked disease, confirming the hypothesis of the genetic origin of this condition and expanding the phenotypic spectrum of diseases caused by RPGR gene mutations. The Authors suggest RPGR gene screening mutations in patients presenting this phenotype

Arterial hypertension in aortic valve stenosis: A critical update

Aortic stenosis (AS) is a very common valve disease and is associated with high mortality once it becomes symptomatic. Arterial hypertension (HT) has a high prevalence among patients with AS leading to worse left ventricle remodeling and faster degeneration of the valve. HT also interferes with the assessment of the severity of AS, leading to an underestimation of the real degree of stenosis. Treatment of HT in AS has not historically been pursued due to the fear of excess reduction in afterload without a possibility of increasing stroke volume due to the fixed aortic valve, but most recent evidence shows that several drugs are safe and effective in reducing BP in patients with HT and AS. RAAS inhibitors and beta‐blockers provide benefit in selected populations based on their profile of pharmacokinetics and pharmacodynamics. Different drugs, on the other hand, have proved to be unsafe, such as calcium channel blockers, or simply not easy enough to handle to be recommended in clinical practice, such as PDE5i, MRA or sodium nitroprusside. The present review highlights all available studies on HT and AS to guide antihypertensive treatment

Neuroprotective role of phosphoserine in primary open-angle glaucoma patients

OBJECTIVE: To evaluate the neuroprotective role of phosphoserine (P-Ser) in primary open-angle glaucoma (POAG) patients and to compare its therapeutic effectiveness to placebo treatment. PATIENTS AND METHODS: Fifty-one patients (24 males and 27 females) between 35 and 61 years (average 46 years ± 3.8 SD) affected by POAG were enrolled in this study. Patients were divided in two groups: group A included 28 subjects that received an oral P-Ser treatment for 12 months; and group B included 23 subjects that received an oral placebo treatment for 12 months. Complete ophthalmological examination, standard automated perimetric examination, analysis of ON fibers via scanning laser polarimetry and glaucoma staging was performed in all patients at enrolment and 1, 3, 6, and 12 months after. Statistical analysis was performed using STATA 14.0 (Collage Station, TX, USA). RESULTS: Mean deviation (MD) and pattern standard deviation (PSD) analysis by means of 30-2 full threshold of the visual fields (VFs), retinal nerve fiber layer (RNFL) thickness by means of GDx, and IOP were considered to evaluate P-Ser therapy effectiveness in both groups. A statistically significant improvement (p<0.05) in VF, RNFL thickness and IOP compared to pre-treatment was found in patients in group A. CONCLUSIONS: Our study shows a significant improvement in several variables in patients with glaucoma treated with P-Ser compared to placebo and suggests a potential neuroprotective effect of P-Ser in treating glaucoma patients in association with the traditional hypotonic topical therapy

Incorporating Inductances in Tissue-Scale Models of Cardiac Electrophysiology

In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and [...].Comment: 20 pages, 12 figure

The impact of behavioural skills training on the knowledge, skills and well-being of front line staff in the intellectual disability sector: a clustered randomised control trial

© 2019 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd Background: Staff with varying backgrounds and educational qualifications can be effectively trained to implement procedures in line with evidence-based practice. Behavioural skills training (BST) is a competency-based training model used to effectively educate a broad selection of professionals, including front line staff, in a range of work-related skills. However, BST has yet to be evaluated in a large group-based experiment. Methods: This study involved a parallel cluster randomised control trial. Six service sites, with a total of 54 participants, were randomised to the intervention condition using the ‘coin toss’ method. The intervention condition used BST to coach intellectual disability staff in reinforcement, systematic prompting, functional communication training and task analysis. Six service sites, with a total of 50 participants, were also randomised to a control condition in which generalised training in behavioural interventions was restricted. Recruited service sites were randomly assigned to the intervention condition (N = 6, n = 54) or the control condition (N = 6, n = 50) at one point in time, immediately after recruitment and before baseline testing took place. Allocations were stratified by service type (residential or day) and geographical region. One member of the research team allocated service sites using the ‘coin toss’ method, and another member, blind to the allocations, decided which experimental arm would receive the intervention and which would be designated as control. It was not possible to mask the intervention from participants, but they were recruited prior to randomisation. Results: Participants in the intervention condition demonstrated statistically significant improvements in their knowledge scores over the study period. Participants in the control condition showed no change or a statistically significant decrease in their knowledge scores. No statistically significant changes to well-being were observed for either group. There was clear evidence of knowledge maintenance, as well as skill acquisition and subsequent generalisation to the workplace environment, among participants in the intervention condition. Participants also evaluated the BST intervention positively. Conclusions: Results support BST as a method for disseminating evidence-based practice to front line staff working with adults with intellectual and developmental disabilities

Cardiac anisotropy in boundary-element models for the electrocardiogram

The boundary-element method (BEM) is widely used for electrocardiogram (ECG) simulation. Its major disadvantage is its perceived inability to deal with the anisotropic electric conductivity of the myocardial interstitium, which led researchers to represent only intracellular anisotropy or neglect anisotropy altogether. We computed ECGs with a BEM model based on dipole sources that accounted for a “compound” anisotropy ratio. The ECGs were compared with those computed by a finite-difference model, in which intracellular and interstitial anisotropy could be represented without compromise. For a given set of conductivities, we always found a compound anisotropy value that led to acceptable differences between BEM and finite-difference results. In contrast, a fully isotropic model produced unacceptably large differences. A model that accounted only for intracellular anisotropy showed intermediate performance. We conclude that using a compound anisotropy ratio allows BEM-based ECG models to more accurately represent both anisotropies