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

String Dilaton Fluid Cosmology

We investigate $(n+1)$-dimensional string-dilaton cosmology with effective dilaton potential in presence of perfect-fluid matter.We get exact solutions parametrized by the constant \gam of the state equation p=(\gam-1)\rho, the spatial dimension number $n$, the bulk of matter, and the spatial curvature constant $k$. Several interesting cosmological behaviours are selected. Finally we discuss the recovering of ordinary Einstein gravity starting from string dominated regime and a sort of asymptotic freedom due to string effective coupling.Comment: 16 pages, Latex, submitted to Int. Jou. Mod. Phys.

Fusion pacing with biventricular, left ventricular-only and multipoint pacing in cardiac resynchronisation therapy: Latest evidence and strategies for use

Despite advances in the field of cardiac resynchronisation therapy (CRT), response rates and durability of therapy remain relatively static. Optimising device timing intervals may be the most common modifiable factor influencing CRT efficacy after implantation. This review addresses the concept of fusion pacing as a method for improving patient outcomes with CRT. Fusion pacing describes the delivery of CRT pacing with a programming strategy to preserve intrinsic atrioventricular (AV) conduction and ventricular activation via the right bundle branch. Several methods have been assessed to achieve fusion pacing. QRS complex duration (QRSd) shortening with CRT is associated with improved clinical response. Dynamic algorithm-based optimisation targeting narrowest QRSd in patients with intact AV conduction has shown promise in people with heart failure with left bundle branch block. Individualised dynamic programming achieving fusion may achieve the greatest magnitude of electrical synchrony, measured by QRSd narrowing

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

Hyperpigmented spots at fundus examination: a new ocular sign in neurofibromatosis type I

Background: Neurofibromatosis Type I (NF1), also termed von Recklinghausen disease, is a rare genetic disorder that is transmitted by autosomal dominant inheritance, with complete penetrance and variable expressivity. It is caused by mutation in the NF1 gene on chromosome 17 encoding for neurofibromin, a protein with oncosuppressive activity, and it is 50% sporadic or inherited. The disease is characterized by a broad spectrum of clinical manifestations, mainly involving the nervous system, the eye and skin, and a predisposition to develop multiple benign and malignant neoplasms. Ocular diagnostic hallmarks of NF1 include optic gliomas, iris Lisch nodules, orbital and eyelid neurofibromas, eyelid café-au-lait spots. Choroidal nodules and microvascular abnormalities have recently been identified as additional NF1-related ocular manifestations. The present study was designed to describe the features and clinical significance of a new sign related to the visual apparatus in NF-1, represented by hyperpigmented spots (HSs) of the fundus oculi. Results: HSs were detected in 60 (24.1%) out of 249 patients with NF1, with a positive predictive value of 100% and a negative predictive value of 44.2%. None of the healthy subjects (150 subjects) showed the presence of HSs. HSs were visible under indirect ophthalmoscopy, ultra-wide field (UWF) pseudocolor imaging and red-only laser image, near-infrared reflectance (NIR)-OCT, but they were not appreciable on UWF green reflectance. The location and features of pigmentary lesions matched with the already studied NF1-related choroidal nodules. No significant difference was found between the group of patients (n = 60) with ocular HSs and the group of patients (n = 189) without ocular pigmented spots in terms of age, gender or severity grading of the disease. A statistically significant association was demonstrated between the presence of HSs and neurofibromas (p = 0.047), and between the presence of HSs and NF1-related retinal microvascular abnormalities (p = 0.017). Conclusions: We described a new ocular sign represented by HSs of the fundus in NF1. The presence of HSs was not a negative prognostic factor of the disease. Following multimodal imaging, we demonstrated that HSs and choroidal nodules were consistent with the same type of lesion, and simple indirect ophthalmoscopy allowed for screening of HSs in NF1

Electromagnetic shape resonances of a dielectric sphere and radiation of portable telephones

The frequency band used by cellular telephones includes the eigenfrequencies of a dielectric sphere with physical characteristics close to those of a human head. Proceeding from the spatial features of the natural modes of such a sphere we propose an independent and clear evident accuracy test for the complicated numerical calculations which are conducted when estimating the potential hazard due to the use of cellular telephones, in particular, for the check of a proper handling of the electromagnetic shape resonances of a human head.Comment: 10 pages, 1 figure with 2 eps file

Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins

Cancer Stem Cells (CSCs) are self-renewing cancer cells responsible for expansion of the malignant mass in a dynamic process shaping the tumor microenvironment. CSCs may hijack the host immune surveillance resulting in typically aggressive tumors with poor prognosis. In this review, we focus on neurotrophic control of cellular substrates and molecular mechanisms involved in CSC-driven tumor growth as well as in host immune surveillance. Neurotrophins have been demonstrated to be key tumor promoting signaling platforms. Particularly, Nerve Growth Factor (NGF) and its specific receptor Tropomyosin related kinase A (TrkA) have been implicated in initiation and progression of many aggressive cancers. On the other hand, an active NGF pathway has been recently proven to be critical to oncogenic inflammation control and in promoting immune response against cancer, pinpointing possible pro-tumoral effects of NGF/TrkA-inhibitory therapy. A better understanding of the molecular mechanisms involved in the control of tumor growth/immunoediting is essential to identify new predictive and prognostic intervention and to design more effective therapies. Fine and timely modulation of CSCs-driven tumor growth and of peripheral lymph nodes activation by the immune system will possibly open the way to precision medicine in neurotrophic therapy and improve patient's prognosis in both TrkA- dependent and independent cancers

Casimir energy of a non-uniform string

The Casimir energy of a non-uniform string built up from two pieces with different speed of sound is calculated. A standard procedure of subtracting the energy of an infinite uniform string is applied, the subtraction being interpreted as the renormalization of the string tension. It is shown that in the case of a homogeneous string this method is completely equivalent to the zeta renormalization.Comment: 11 pages, REVTeX, no figures and table

Cerenkov radiation and scalar stars

We explore the possibility that a charged particle moving in the gravitational field generated by a scalar star could radiate energy via a recently proposed gravitational \v{C}erenkov mechanism. We numerically prove that this is not possible for stable boson stars. We also show that soliton stars could have \v{C}erenkov radiation for particular values of the boson mass, although diluteness of the star grows and actual observational possibility decreases for the more usually discussed boson masses. These conclusions diminish, although do not completely rule out, the observational possibility of actually detecting scalar stars using this mechanism, and lead us to consider other forms, like gravitational lensing.Comment: Accepted for publication in Class. Quantum Gra

Achromobacter xylosoxidans respiratory tract infection in cystic fibrosis patients

The aims of this study were to evaluate the frequency of Achromobacter xylosoxidans infection in a cohort of cystic fibrosis patients, to investigate antimicrobial sensitivity, to establish possible clonal likeness among strains, and to address the clinical impact of this infection or colonization on the general outcome of these patients. The study was undertaken between January 2004 and December 2008 on 300 patients receiving care at the Regional Cystic Fibrosis Center of the Naples University “Federico II”. Sputum samples were checked for bacterial identification. For DNA fingerprinting, pulsed-field gel electrophoresis (PFGE) was carried out. Fifty-three patients (17.6%) had at least one positive culture for A. xylosoxidans; of these, 6/53 (11.3%) patients were defined as chronically infected and all were co-colonized by Pseudomonas aeruginosa. Of the patients, 18.8% persistently carried multidrug-resistant isolates. Macrorestriction analysis showed the presence of seven major clusters. DNA fingerprinting also showed a genetic relationship among strains isolated from the same patients at different times. The results of DNA fingerprinting indicate evidence of bacterial clonal likeness among the enrolled infected patients. We found no significant differences in the forced expiratory volume in 1 s (FEV1) and body mass index (BMI) when comparing the case group of A. xylosoxidans chronically infected patients with the control group of P. aeruginosa chronically infected patients