Clues from Crouzon: Insights into the potential role of growth factors in the pathogenesis of myelinated retinal nerve fibers.

PurposeWe present a case of bilateral extensive peripapillary myelinated retinal nerve fibers (MRNF) in an individual with Crouzon syndrome, an inherited form of craniosynostosis caused by overactivation of fibroblast growth factor receptor 2. As a secondary aim, we examine the utility of optical coherence tomography (OCT) angiography for visualization of peripapillary vasculature obscured by myelination on other imaging modalities.MethodsA 24-year-old woman with Crouzon syndrome was evaluated for suspected optic neuritis in the right eye.ResultsFunduscopic examination and photography revealed the incidental finding of bilateral extensive peripapillary MRNF. OCT angiography provided excellent visualization of peripapillary retinal vessels, which were partially obscured by myelination on other imaging modalities.ConclusionsThis association of Crouzon syndrome with bilateral peripapillary MRNF may lend insight into the developmental control of optic nerve myelination, the pathogenesis of MRNF, and the potential role of growth factors in these processes. Further, OCT angiography allowed for excellent blood vessel visualization in this case of MRNF

Profound vision loss impairs psychological well-being in young and middle-aged individuals.

PurposeThe aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support.MethodsA questionnaire was issued to individuals aged 13-65 years with profound vision loss resulting from Leber's hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from -10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support.ResultsA total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = -5) and career goals (median IR = -6) were observed; both ratings were worse (P<0.001) for depressed versus nondepressed subjects. Older age at diagnosis corresponded to higher depression prevalence and increased incidence of negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids (P=0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist.ConclusionProfound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by age and use of electronic vision aids. Ophthalmologists, in addition to managing vision loss, may serve an important role in the emotional adaptation of these patients

Anomalous relaxations and chemical trends at III-V nitride non-polar surfaces

Relaxations at nonpolar surfaces of III-V compounds result from a competition between dehybridization and charge transfer. First principles calculations for the (110) and (10$\bar{1}$0) faces of zincblende and wurtzite AlN, GaN and InN reveal an anomalous behavior as compared with ordinary III-V semiconductors. Additional calculations for GaAs and ZnO suggest close analogies with the latter. We interpret our results in terms of the larger ionicity (charge asymmetry) and bonding strength (cohesive energy) in the nitrides with respect to other III-V compounds, both essentially due to the strong valence potential and absence of $p$ core states in the lighter anion. The same interpretation applies to Zn II-VI compounds.Comment: RevTeX 7 pages, 8 figures included; also available at http://kalix.dsf.unica.it/preprints/; improved after revie

A novel approach to simulate gene-environment interactions in complex diseases

Background: Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results: We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions: By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study

Profound vision loss impairs psychological well-being in young and middle-aged individuals

PURPOSE: The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. METHODS: A questionnaire was issued to individuals aged 13–65 years with profound vision loss resulting from Leber’s hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from −10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. RESULTS: A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = −5) and career goals (median IR = −6) were observed; both ratings were worse (P<0.001) for depressed versus nondepressed subjects. Older age at diagnosis corresponded to higher depression prevalence and increased incidence of negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids (P=0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. CONCLUSION: Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by age and use of electronic vision aids. Ophthalmologists, in addition to managing vision loss, may serve an important role in the emotional adaptation of these patients

Immune Regulatory Neural Stem/Precursor Cells Protect from Central Nervous System Autoimmunity by Restraining Dendritic Cell Function

The systemic injection of neural stem/precursor cells (NPCs) provides remarkable amelioration of the clinico-pathological features of experimental autoimmune encephalomyelitis (EAE). This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains the immune modulatory capacity of transplanted NPCs.To achieve the exclusive targeting of the peripheral immune system, SJL mice with PLP-induced EAE were injected subcutaneously with NPCs and the treatment commenced prior to disease onset. NPC-injected EAE mice showed significant clinical improvement, as compared to controls. Exogenous NPCs lacking the expression of major neural antigens were reliably (and for long-term) found at the level of draining lymph nodes, while establishing sophisticated anatomical interactions with lymph node cells. Importantly, injected NPCs were never found in organs other than lymph nodes, including the brain and the spinal cord. Draining lymph nodes from transplanted mice showed focal up-regulation of major developmental stem cell regulators, such as BMP-4, Noggin and Sonic hedgehog. In lymph nodes, injected NPCs hampered the activation of myeloid dendritic cells (DCs) and steadily restrained the expansion of antigen-specific encephalitogenic T cells. Both ex vivo and in vitro experiments identified a novel highly NPC-specific–BMP-4-dependent–mechanism hindering the DC maturation.The study described herein, identifies the first member of the TGF β/BMP family of stem cell regulators as a novel tolerogenic factor released by NPCs. Full exploitation of this pathway as an efficient tool for vaccination therapy in autoimmune inflammatory conditions is underway

Age at menopause and lung function: a Mendelian randomisation study

In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.We included 94\u200a742 naturally post-menopausal women from the UK Biobank and performed MR analyses on the effect of age at menopause on forced expiratory volume in 1\u2005s (FEV1), FVC, FEV1/FVC, spirometric restriction (FV

Automatic assessment of the 2-minute walk distance for remote monitoring of people with multiple sclerosis

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes