The Relationship Between Attention, Dyslexia, and Convergence Insufficiency

Dyslexia and attention deficit hyperactivity disorder are two distinct conditions belonging to the same class of frequently and comorbidly diagnosed childhood and adolescent developmental disorders. Further complicating treatment and diagnoses is convergence insufficiency, a visual disorder, with symptoms that can appear similar to dyslexia’s diagnostic criteria. ADHD and dyslexia have a worldwide prevalence of 5-12% each among the school-age population and 4-10% of young adults. As many as 1 million U.S. ADHD diagnoses are situational with undocumented, pre-existing conditions (e.g., convergence insufficiency, dyslexia). Convergence insufficiency, characterized by an inability to converge the eyes smoothly as a focal object moves from distance to near, affects 2-8% of the worldwide population. Given the number of people worldwide who may be diagnosed, misdiagnosed, or undiagnosed by these three disorders, it is of value to explore the intersectionality of these conditions among college-aged students. This project investigated the relationship between self-reported scores on a standard ADHD measure, as well as ADHD diagnoses, dyslexia, and convergence insufficiency using optometric and neuropsychological assessments. We found ADHD diagnosis and its self-reported symptoms were significantly correlated with total scores on the Adult Reading History Questionnaire, dyslexia diagnoses, and the Convergence Insufficiency Symptom Survey. All three self-report assessments and near visual acuity significantly correlated; indicating that as visual acuity improves, total assessment scores decrease. These combined results highlight a distinct and important relationship between vision, attention, and reading and support a more holistic assessment in the identification, diagnosis, intervention, and treatment of cognitive problems pertaining to reading and learning.Faculty Sponsor: Dr. Heide Islan

The Relationship Between Attention, Dyslexia, and Convergence Insufficiency

Dyslexia and attention deficit hyperactivity disorder are two distinct conditions belonging to the same class of frequently and comorbidly diagnosed childhood and adolescent developmental disorders. Further complicating treatment and diagnoses is convergence insufficiency, a visual disorder, with symptoms that can appear similar to dyslexia’s diagnostic criteria. ADHD and dyslexia have a worldwide prevalence of 5-12% each among the school-age population and 4-10% of young adults. As many as 1 million U.S. ADHD diagnoses are situational with undocumented, pre-existing conditions (e.g., convergence insufficiency, dyslexia). Convergence insufficiency, characterized by an inability to converge the eyes smoothly as a focal object moves from distance to near, affects 2-8% of the worldwide population. Given the number of people worldwide who may be diagnosed, misdiagnosed, or undiagnosed by these three disorders, it is of value to explore the intersectionality of these conditions among college-aged students. This project investigated the relationship between self-reported scores on a standard ADHD measure, as well as ADHD diagnoses, dyslexia, and convergence insufficiency using optometric and neuropsychological assessments. We found ADHD diagnosis and its self-reported symptoms were significantly correlated with total scores on the Adult Reading History Questionnaire, dyslexia diagnoses, and the Convergence Insufficiency Symptom Survey. All three self-report assessments and near visual acuity significantly correlated; indicating that as visual acuity improves, total assessment scores decrease. These combined results highlight a distinct and important relationship between vision, attention, and reading and support a more holistic assessment in the identification, diagnosis, intervention, and treatment of cognitive problems pertaining to reading and learning

Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma

Purpose: Extracellular matrix (ECM) component hyaluronan (HA) facilitates malignant phenotypes of glioblastoma (GBM), however, whether HA impacts response to GBM immunotherapies is not known. Herein, we investigated whether degradation of HA enhances oncolytic virus immunotherapy for GBM. Experimental design: Presence of HA was examined in patient and murine GBM. Hyaluronidase-expressing oncolytic adenovirus, ICOVIR17, and its parental virus, ICOVIR15, without transgene, were tested to determine if they increased animal survival and modulated the immune tumor microenvironment (TME) in orthotopic GBM. HA regulation of NF-κB signaling was examined in virus-infected murine macrophages. We combined ICOVIR17 with PD-1 checkpoint blockade and assessed efficacy and determined mechanistic contributions of tumor-infiltrating myeloid and T cells. Results: Treatment of murine orthotopic GBM with ICOVIR17 increased tumor-infiltrating CD8+ T cells and macrophages, and upregulated PD-L1 on GBM cells and macrophages, leading to prolonged animal survival, compared with control virus ICOVIR15. High molecular weight HA inhibits adenovirus-induced NF-κB signaling in macrophages in vitro, linking HA degradation to macrophage activation. Combining ICOVIR17 with anti-PD-1 antibody further extended the survival of GBM-bearing mice, achieving long-term remission in some animals. Mechanistically, CD4+ T cells, CD8+ T cells, and macrophages all contributed to the combination therapy that induced tumor-associated proinflammatory macrophages and tumor-specific T-cell cytotoxicity locally and systemically. Conclusions: Our studies are the first to show that immune modulatory ICOVIR17 has a dual role of mediating degradation of HA within GBM ECM and subsequently modifying the immune landscape of the TME, and offers a mechanistic combination immunotherapy with PD-L1/PD-1 blockade that remodels innate and adaptive immune cells

p19Ink4d Is a Tumor Suppressor and Controls Pituitary Anterior Lobe Cell Proliferation

Pituitary tumors develop in about one-quarter of the population, and most arise from the anterior lobe (AL). The pituitary gland is particularly sensitive to genetic alteration of genes involved in the cyclin-dependent kinase (CDK) inhibitor (CKI)–CDK-retinoblastoma protein (Rb) pathway. Mice heterozygous for the Rb mutation develop pituitary tumors, with about 20% arising from the AL. Perplexingly, none of the CKI-deficient mice reported thus far develop pituitary AL tumors. In this study, we show that deletion of p19Ink4d (p19), a CKI gene, in mice results in spontaneous development of tumors in multiple organs and tissues. Specifically, more than one-half of the mutant mice developed pituitary hyperplasia or tumors predominantly in the AL. Tumor development is associated with increased cell proliferation and enhanced activity of Cdk4 and Cdk6 and phosphorylation of Rb protein. Though Cdk4 is indispensable for postnatal pituitary cell proliferation, it is not required for the hyperproliferative pituitary phenotype caused by p19 loss. Loss of p19 phosphorylates Rb in Cdk4−/− pituitary AL cells and mouse embryonic fibroblasts (MEFs) and rescues their proliferation defects, at least partially, through the activation of Cdk6. These results provide the first genetic evidence that p19 is a tumor suppressor and the major CKI gene that controls pituitary AL cell proliferation

Update on rare epithelial ovarian cancers: based on the Rare Ovarian Tumors Young Investigator Conference

There has been significant progress in the understanding of the pathology and molecular biology of rare ovarian cancers, which has helped both diagnosis and treatment. This paper provides an update on recent advances in the knowledge and treatment of rare ovarian cancers and identifies gaps that need to be addressed by further clinical research. The topics covered include: low-grade serous, mucinous, and clear cell carcinomas of the ovary. Given the molecular heterogeneity and the histopathological rarity of these ovarian cancers, the importance of designing adequately powered trials or finding statistically innovative ways to approach the treatment of these rare tumors has been emphasized. This paper is based on the Rare Ovarian Tumors Conference for Young Investigators which was presented in Tokyo 2015 prior to the 5th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG)

Geographical distribution of hepatitis C virus genotypes in blood donors:an international collaborative survey

The frequency of infection with the six classified major genotypes of hepatitis C virus (HCV) was investigated in 447 infected volunteer blood donors from the following nine countries: Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan. Viral sequences in plasma from blood donors infected with HCV were amplified in the 5'-noncoding region and were typed by restriction fragment length polymorphism analysis. Electrophoresis of DNA fragments produced by cleavage with HaeIII-RsaI and ScrFI-HinfI allowed HCV types 1 (or 5), 2, 3, 4, and 6 to be identified. Further analysis with MvaI-HinfI allowed sequences of the type 5 genotype to be distinguished from sequences of type 1 genotype. Types 1, 2, and 3 accounted for almost all infections in donors from Scotland, Finland, The Netherlands, and Australia. Types 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors were infected with type 1. Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4. Donors infected with HCV type 1 showed broad serological reactivity with all four antigens of the second generation Chiron RIBA-2 assay (Chiron Corporation, Emeryville, Calif.), while infection with divergent HCV genotypes elicited antibodies mainly reactive to c22-3 and c33c. Reactivities with antibodies 5-1-1 and c100-3 were infrequent and were generally weak, irrespective of the geographical origin of the donor. Because the envelope region of HCV is even more variable than the NS-4 region, it is likely that vaccines based on these proteins need to be multivalent and perhaps specifically adapted for different geographical regions.link_to_subscribed_fulltex

Cortisol coregulation in fish

Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations