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

Iliolumbar veins have a high frequency of variations

The spectrum of individual anatomic variations of the vascular structures are broad, however, the exact incidence of variations of the lumbosacral vein is obscure. In the current study, 38 iliolumbar veins were dissected from 19 formaldehyde-preserved male cadavers. The drainage pattern of the iliolumbar vein was determined. The diameter and the length of the iliolumbar vein were measured, and the relationships of the iliolumbar vein with the lumbosacral trunk, obturator nerve, and iliolumbar artery were ascertained. Means and standard deviations were used as descriptive measures to define variations among the cases. The iliolumbar vein or veins were detected in both sides of all 19 cadavers. Five drainage patterns were seen between the iliolumbar vein and the lumbosacral major veins. In only five cadavers, symmetric drainage patterns were seen on the left and the right sides. In our study, two drainage patterns were seen that were not previously reported. Anatomic variations of the iliolumbar vein are numerous and should be considered to avoid complications when doing surgery

Surgical anatomy of the cervical sympathetic trunk

Lack of knowledge of the anatomy of the cervical sympathetic trunk (CST) may complicate surgical procedures on the cervical spine. This study aims to define linear and angular relations of the CST with respect to consistent Structures around it, including the number and size of the cervical ganglia, the distances between the CST and the longus colli muscle and the anterior tubercles of the transverse processes of cervical vertebrae. Morphometric parameters of the 24 CSTs of 12 adults were measured on both sides. The CST had superior, middle, and inferior (or cervicothoracic) ganglia in 20.8% of specimens; superior and inferior (or cervicothoracic) ganglia in 45.8%; superior, middle, vertebral, inferior, or cervicothoracic ganglia in 12.5%, and superior, vertebral, inferior or cervicothoracic ganglia in 20.8% of specimens. The superior ganglion was observed in all specimens, the middle ganglion and vertebral ganglion were each observed in 33.3%. There was no difference between the number of superior and vertebral Ganglia between the right and left sides. The average distance between the CST and the medial border of the ipsilateral longus colli muscle (LCM) was 17.2 mm at C3 and 12.4 mm at C7. As the CSTs converged caudally, the LCMs diverged. The average distance between the anterior tubercles of transverse processes of the cervical vertebrae and the lateral borders of the ipsilateral CST was 3.4 mm at C4, 3.2 min at C5, and 3.9 min at C6. The presence of a vertebral ganglion and variations, such as the localization of the CST within the carotid sheath, are important. The anatomical landmarks described should assist the spinal surgeon to avoid injury of the CST. (c) 2005 Wiley-Liss. Inc

The V2 segment of the vertebral artery in anterior and anterolateral cervical spinal surgery: A cadaver angiographic study

Objective: The second segment of the vertebral artery is under the risk of injury during anterior and anterolateral cervical spine procedures. To avoid such a risk, one needs to be familiar with the regional anatomy. The aim of this study was to measure the distance between the vertebral artery and the uncinate process, midline, and the medial side of the longus colli muscle using vertebral artery angiograms at the level of C6, C5, C4, and C3 vertebrae

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