Detailed Clinical, Ophthalmic, and Genetic Characterization of ADGRV1-Associated Usher Syndrome

Purpose: To present the clinical characteristics, retinal features, natural history, and genetics of ADGRV1-Usher syndrome (USH). Design: Multicenter international retrospective cohort study. Methods: Clinical notes, hearing loss history, multimodal retinal imaging, and molecular diagnosis were reviewed. Thirty patients (28 families) with USH type 2 and disease-causing variants in ADGRV1 were identified. Visual function, retinal imaging, and genetics were evaluated and correlated, with retinal features also compared with those of the commonest cause of USH type 2, USH2A-USH. Results: The mean age at the first visit was 38.6 ± 12.0 years (range: 19-74 years), and the mean follow-up time was 9.0 ± 7.7 years. Hearing loss was reported in the first decade of life by all patients, 3 (10%) described progressive loss, and 93% had moderate-severe impairment. Visual symptom onset was at 17.0 ± 7.7 years of age (range: 6-32 years), with 13 patients noticing problems before the age of 16. At baseline, 90% of patients had no or mild visual impairment. The most frequent retinal features were a hyperautofluorescent ring at the posterior pole (70%), perimacular patches of decreased autofluorescence (59%), and mild-moderate peripheral bone-spicule–like deposits (63%). Twenty-six (53%) variants were previously unreported, 19 families (68%) had double-null genotypes, and 9 were not-double-null. Longitudinal analysis showed significant differences between baseline and follow-up central macular thickness (−1.25 µm/y), outer nuclear layer thickness (−1.19 µm/y), and ellipsoid zone width (−40.9 µm/y). The rate of visual acuity decline was 0.02 LogMAR (1 letter)/y, and the rate of constriction of the hyperautofluorescent ring was 0.23 mm2/y. Conclusions: ADGRV1-USH is characterized by early-onset, usually non-progressive, mild-to-severe hearing loss and generally good central vision until late adulthood. Perimacular atrophic patches and relatively retained ellipsoid zone and central macular thickness in later adulthood are more often seen in ADGRV1-USH than in USH2A-USH

Challenging the Science Curriculum Paradigm: TeachingPrimary Children Atomic-Molecular Theory

Solutions to global issues demand the involvement of scientists, yet concern exists about retention rates in science as students pass through school into University. Young children are curious about science, yet are considered incapable of grappling with abstract and microscopic concepts such as atoms, sub-atomic particles, molecules and DNA. School curricula for primary (elementary) aged children reflect this by their limitation to examining only what phenomena are without providing any explanatory frameworks for how or why they occur. This research challenges the assumption that atomic-molecular theory is too difficult for young children, examining new ways of introducing atomic theory to 9 year olds and seeks to verify their efficacy in producing genuine learning in the participants. Early results in three cases in different schools indicate these novel methods fostered further interest in science, allowed diverse children to engage and learn aspects of atomic theory, and satisfied the children’s desire for intellectual challenge. Learning exceeded expectations as demonstrated in the post-interview findings. Learning was also remarkably robust, as demonstrated in two schools eight weeks after the intervention, and in one school, one year after their first exposure to ideas about atoms, elements and molecules

No preliminary evidence of differences in astrocyte density within the white matter of the dorsolateral prefrontal cortex in autism

Background: While evidence for white matter and astrocytic abnormalities exist in autism, a detailed investigation of astrocytes has not been conducted. Such an investigation is further warranted by an increasing role for neuroinflammation in autism pathogenesis, with astrocytes being key players in this process. We present the first study of astrocyte density and morphology within the white matter of the dorsolateral prefrontal cortex (DLPFC) in individuals with autism. Methods: DLPFC formalin-fixed sections containing white matter from individuals with autism (n = 8, age = 4-51 years) and age-matched controls (n = 7, age = 4-46 years) were immunostained for glial fibrillary acidic protein (GFAP). Density of astrocytes and other glia were estimated via the optical fractionator, astrocyte somal size estimated via the nucleator, and astrocyte process length via the spaceballs probe. Results: We found no evidence for alteration in astrocyte density within DLPFC white matter of individuals with autism versus controls, together with no differences in astrocyte somal size and process length. Conclusion: Our results suggest that astrocyte abnormalities within the white matter in the DLPFC in autism may be less pronounced than previously thought. However, astrocytic dysregulation may still exist in autism, even in the absence of gross morphological changes. Our lack of evidence for astrocyte abnormalities could have been confounded to an extent by having a small sample size and wide age range, with pathological features potentially restricted to early stages of autism. Nonetheless, future investigations would benefit from assessing functional markers of astrocytes in light of the underlying pathophysiology of autism

Influence of Bacillus Calmette-Guerin vaccination at birth and 2 months old age on the peripheral blood T-cell subpopulations [gamma/delta (gamma delta) and alpha-beta (alpha beta) T cell]

The neonatal immune system is immature and may be affected by Bacillus Calmette-Guerin (BCG) vaccine. We investigated the influence of BCG given at two different ages on the peripheral blood (PB) T-cell subpopulations. Forty full term healthy newborns were randomly chosen. Twenty of them were vaccinated with BCG at birth (group 1) and the remaining at the age of 2 months (group II). The cell analysis were carried out before (pre-BCGI and pre-BCGII), and 2 months after (post-BCGI and post-BCGII) the vaccination. The analysis of the gamma/delta and alpha/beta T-cell receptor (TCR) antigens was done by two-colour flowcytometer. The purified protein derivative (PPD) response was investigated 2 months after vaccination. The results showed that although T-cell (TCR+ cell) counts showed no difference in PB before and after vaccination in both study groups, the total lymphocyte and non-T cell (TCR- cell) populations increased significantly whereas alpha beta T-cell population significantly decreased after vaccination. On the contrary, gamma delta T-cell counts in PB increased significantly 2 months after vaccination in group I but not in group II. Total lymphocyte and non-T cell counts in vaccinated infants at 2 months of age (post-BCGI) were significantly higher than in unvaccinated infants of the same age whereas alpha beta T-cell count in vaccinated infants was significantly low. However, total T-cell and gamma delta T-cell counts showed no difference. PPD positivity was similar in both study groups (61% in group I, 66% in group II). Neither alpha beta T- nor gamma delta T-cell counts were different in PPD positive and PPD negative infants. Our study shows that BCG causes marked quantitative changes in the PB T-cell subpopulations in young infants

The Relationships Between Craniofacial Structure and Frontal Sinus Morphology: Evaluation With Conventional Anthropometry and CT-Based Volumetry

The purpose of this study was to investigate the effects of craniofacial structure and nasal septal deviation on frontal sinus morphology 3-dimensionally. This study of anatomy, anthropology, morphology, and radiology included 74 dry skulls as study sample. The craniofacial measurements were made through conventional anthropometric methods by the use of calipers. The nasal septal deviation measurements were done by computerized software on photographs taken from frontal view. Frontal sinus volumes were estimated by the computerized tomography-based volumetry. The relationships between craniofacial structure, nasal septal deviation, and frontal sinus morphology were tested by linear regression and correlation analysis. The analysis of numerical variables and categorical variables within different groups was done by Mann-WhitneyU/Kruskal-Wallis, and chi(2)tests, respectively. There appeared a positive relationship between the dimensions of the frontal sinuses and the maximal cranial length and the nasal height especially on the left side (P< .05). However, after multivariate linear regression model for both factors was created, solely the nasal height kept being a positive factor for frontal sinus size as an independent variable. No statistical relevance was detected between the presence of metopic suture and frontal sinus morphology. Septal deviation itself affected frontal sinus morphometry, but the morphometry did not differ between the deviation side and the opposite side. In conclusion, the cranial structure does not affect the frontal sinus morphology but nasal structure affects. The true influences, among measured craniofacial elements, in relationship with the pneumatization of frontal sinus are appeared to be the nasal structure related

Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: Nerve growth factor beta and vascular endothelial growth factor

PubMed ID: 24771956Background. It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-ß) are important neurotrophic factors for male reproductive system. Objective. We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-ß levels in diabetic rats. Methods. Diabetes was induced by streptozotocin (STZ, 45mg/kg/i.p.) in adult rats. Fiveweeks later testicular tissuewas removed; testicular VEGF and NGF-ß levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid- Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsens score. Results. In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-ß were decreased in diabetic testes. Correlation between VEGF and NGF-ß levels was strong. Conclusion. These results suggest that the decrease of VEGF and NGF-ß levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-ß levels could be potential novel biomarkers for diabetes induced testicular damage. © Copyright 2014 Magorzata Guz et al

The effects of resveratrol on chronic constriction injury of sciatic nerve in rats.

The aim of this study was to investigate the effects of resveratrol (RVT) in chronic constriction injury (CCI) of sciatic nerve by behavioral, histomorphological and immunohistochemical evaluations in rats. In this study, male Wistar rats were divided into three groups: sham (n = 7), CCI+saline (n = 7) and CCI+RVT (n = 7). After inducing CCI, treatment with 10 mg/kg/day of RVT or saline for 14 days was given. Locomotor function was assessed with rota-rod and open field tests. Morphologic alterations of sciatic nerve were assessed histologically by light and electron microscopy. Immunohistochemistry for insulin-like growth factor-1 (IGF-1) were performed. RVT treatment prevented motor impairment and histomorphological alterations caused by chronic constriction injury of sciatic nerve. IGF-1 immunoreactivity was significantly higher in RVT treated group then CCI induced group and positive correlated with morphometric parameters. These results indicate that RVT may reduce CCI induced damage and this effect may be mediated through the restoration of IGF-1 immunoreactivity. Crown Copyright (C) 2013 Published by Elsevier Ireland Ltd. All rights reserved

Carnosine attenuates oxidative stress and apoptosis in transient cerebral ischemia in rats

Cerebral ischemia leads to cognitive decline and neuronal damage in the hippocampus. Reactive oxygen species (ROS) play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Carnosine has both antioxidant and neuroprotective effects against ROS. In the present study, the effects of carnosine on oxidative stress, apoptotic neuronal cell death and spatial memory following transient cerebral ischemia in rats were investigated. Transient ischemia was induced by occlusion of right common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 250 mg/kg carnosine or saline 30 min prior to experiment. Determination of antioxidant enzyme activities was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed using an In Situ Cell Death Detection Kit. Carnosine treatment elicited a significant decrease in lipid peroxidation and increase in antioxidant enzyme activities in ischemic rat brains. The number of TUNEL-positive cells was decreased significantly in carnosine-treated group when compared with the ischemia-induction group. Carnosine treatment did not provide significant protection from ischemia induced deficits in spatial learning. The results show that carnosine is effective as a prophylactic treatment for brain tissue when it is administered before ischemia without affecting spatial memory

Antioxidant and antiapoptotic activities of deprenyl and estradiol co-administration in aged rat kidney

Aging is a progressive degeneration process in living organisms. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has antioxidant, antiapoptotic and neuroprotective effects. Estradiol is also a neuroprotective and antioxidant hormone. The objective of this study was to determine whether the antioxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat kidney. Wistar Albino female rats were divided into six groups as follows; young (3 months old) control, aged (24 months old) control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and sham. All rats except for the sham group were injected for 21 days. Determination of oxidative stress parameter was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining and caspase-3 immunohistochemistry were performed. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation relative to aged control and sham-injected rats. The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. Deprenyl and estradiol replacement attenuated age-related changes in renal morphology. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat kidney by decreasing oxidative stress