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

Rhodacyanine Derivative Selectively Targets Cancer Cells and Overcomes Tamoxifen Resistance

MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family

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

Biosynthesis of silver nanoparticles from Aeromonas sobria and antibacterial activity against fish pathogens

4th International Conference on Computational and Experimental Science and Engineering (ICCESEN) -- OCT 04-08, 2017 -- Kemer, TURKEYWOS: 000478894500021Fish diseases are a major obstacle to the development of the fisheries industry. Aeromonas sobria is an infectious waterborne bacterium that causes ulcers, tail rot and hemorrhagic septicemia in fishes and resistant to many existing antibiotics. In this context, A. sobria-AgNPs were synthesized by A. sobria using AgNO3. A. sobria-AgNPs were characterized using UV-Vis spectroscopy, and a peak was obtained at a range of 420-480 nm. A. sobria-AgNPs were evaluated for antibacterial activities against different fish pathogens. The highest antibacterial activity was observed against A. hydrophila, E. cloacae and E. coli. The lower activity was found against C. braakii and E. hermannii, but against H. alvei, P. rettger and M. morganii subsp. sibonii no zone of inhibition was recorded. The results indicated that the A. sobria-AgNPs can be used to develop antibacterial agent and as a therapeutic agent in the fishing industry and water disinfection. The antibacterial efficacy against the fish pathogen A. hydrophila of silver nanoparticles is a hope for possible application as a disinfectant or antimicrobial agent for better fish health management.Ahi Evran University Scientific Research Projects Coordination UnitAhi Evran University [FEF.E2.17.038]This work was supported by the Ahi Evran University Scientific Research Projects Coordination Unit. Project Number FEF.E2.17.038

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

Nursing students' self-reported knowledge of genetics and genetic education.

INTRODUCTION: Nurses need to use genetic information in care; several areas of current need include primary care, public health, cardiovascular, geriatric and oncology nursing. Nursing faculties may be reluctant to add genetics to existing courses, let alone tackle the work of teaching an entire course in genetics. OBJECTIVES: The purpose of this study was to describe the current genetic knowledge of nursing students regarding genetics and genetic education. METHODS: This is a self-administered cross-sectional survey. A total of 162 of 209 nursing students returned a questionnaire. Data from the surveys reflect the students' self-reported knowledge regarding medical genetics (response rate = 77.5%). RESULTS: The majority of students noted 'some' to 'minimal' knowledge of Mendelian inheritance and human chromosome abnormalities. In terms of awareness of genetic abnormalities and disorders, students claimed to have 'high' knowledge of breast cancer, phenylketonuria, thalassemia, colon cancer, Rh factor, cleft lip/palate, hemophilia, color blindness, and polydactyly. Students stated that they would like to receive more education related to genetic diseases and genetic counseling (93.9%). CONCLUSIONS: The majority of students reported very little knowledge of genetics and genetic disorders. Most of students responded positively to all the education methods suggested in the questionnaire, adding that they would like more education about genetics. The results from this study may help to reform and upgrade the educational strategy concerning genetics in the Schools of Health

Positive effects of deprenyl and estradiol on spatial memory and oxidant stress in aged female rat brains

Increasing age decreases spatial learning and memory. Spatial learning is coordinated with different brain regions. Since the oxidative damage may play a role in the aging process, including the associated cognitive decline, age-related impairment in spatial learning and memory may be alleviated by antioxidant treatment. The present study examined the effects of the monoamine oxidase B inhibitor L-deprenyl, alone and in combination with estradiol, on spatial memory using the Morris water maze and oxidant stress in aged female rat brains. We demonstrated that co-administration of deprenyl and estradiol caused a synergistic effect on spatial memory. However, use of either deprenyl or estradiol alone increased antioxidant enzyme activities in brain and reduced lipid peroxidation. Therefore, positive effects of deprenyl and estradiol on spatial memory may occur due not only to their antioxidant activities but also to the different actions. (C) 2003 Elsevier Ireland Ltd. All rights reserved