Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features.

Purpose:To report atypical presentation of neuronal ceroid lipofuscinoses type 8 (CLN8) to the eye clinic and review clinical features of CLN8. Observations:Detailed eye exam by slit lamp exam, indirect ophthalmoscopy, fundus photography, optical coherence tomography, visual fields and electroretinogram (ERG). Molecular genetic testing using Next Generation Sequencing panel (NGS) and array Comparative Genomic Hybridization (aCGH).The siblings in this study presented to the eye clinic with retinitis pigmentosa and cystoid macular edema, and a history of seizures but no severe neurocognitive deficits or regression. Genetic testing identified a c.200C > T (p.A67V) variant in the CLN8 gene and a deletion encompassing the entire gene. Electron microscopy of lymphocytes revealed fingerprint inclusions in both siblings. Conclusions:and Importance: Pathogenic variants in CLN8 account for the retinitis pigmentosa and seizures in our patients however, currently, they do not have regression or neurocognitive decline. The presentation of NCL can be very diverse and it is important for ophthalmologists to consider this in the differential diagnosis of retinal disorders with seizures or other neurological features. Molecular genetic testing of multiple genes causing isolated and syndromic eye disorders using NGS panels and aCGH along with additional complementary testing may often be required to arrive at a definitive diagnosis

Principles of Chemistry I & II (GHC)

This Grants Collection for Principles of Chemistry I & II was created under a Round Eight ALG Textbook Transformation Grant. Affordable Learning Georgia Grants Collections are intended to provide faculty with the frameworks to quickly implement or revise the same materials as a Textbook Transformation Grants team, along with the aims and lessons learned from project teams during the implementation process. Documents are in .pdf format, with a separate .docx (Word) version available for download. Each collection contains the following materials: Linked Syllabus Initial Proposal Final Reporthttps://oer.galileo.usg.edu/chemistry-collections/1016/thumbnail.jp

Foundations of Biology (GHC)

This Grants Collection for Foundations of Biology was created under a Round Five ALG Textbook Transformation Grant. Affordable Learning Georgia Grants Collections are intended to provide faculty with the frameworks to quickly implement or revise the same materials as a Textbook Transformation Grants team, along with the aims and lessons learned from project teams during the implementation process. Documents are in .pdf format, with a separate .docx (Word) version available for download. Each collection contains the following materials: Linked Syllabus Initial Proposal Final Reporthttps://oer.galileo.usg.edu/biology-collections/1011/thumbnail.jp

Walking and Jogging for Fitness (GHC)

This Grants Collection for Walking and Jogging for Fitness was created under a Round Seven ALG Textbook Transformation Grant. Affordable Learning Georgia Grants Collections are intended to provide faculty with the frameworks to quickly implement or revise the same materials as a Textbook Transformation Grants team, along with the aims and lessons learned from project teams during the implementation process. Documents are in .pdf format, with a separate .docx (Word) version available for download. Each collection contains the following materials: Linked Syllabus Initial Proposal Final Reporthttps://oer.galileo.usg.edu/health-collections/1006/thumbnail.jp

Concepts of Fitness and Wellness (GHC)

This Grants Collection for Concepts of Fitness and Wellness was created under a Round Seven ALG Textbook Transformation Grant. Affordable Learning Georgia Grants Collections are intended to provide faculty with the frameworks to quickly implement or revise the same materials as a Textbook Transformation Grants team, along with the aims and lessons learned from project teams during the implementation process. Documents are in .pdf format, with a separate .docx (Word) version available for download. Each collection contains the following materials: Linked Syllabus Initial Proposal Final Reporthttps://oer.galileo.usg.edu/health-collections/1005/thumbnail.jp

Walking and Jogging for Fitness

This open textbook for Walking and Jogging for Fitness at Georgia Highlands College was created through a Round Seven ALG Textbook Transformation Grant and updated with a Round 14 Mini-Grant. Topics covered include: Benefits of Walking and Jogging for Exercise Getting Started in a Walking and Jogging Program Adaptations to Stress Technique: The Art of Walking and Jogging Nutrition and Energy Requirements Injuries and Injury Prevention Appendix on Flexibility 2nd Edition: Editors\u27 Description: The deliverables of the mini grant were: 1. Mini-lecture recordings to aid in focusing the efforts of students by offering an overview of the chapter content. 2. PowerPoint slides for all chapters which align with the textbook to augment the content and increase the learning experience for students. 3. Chapter terminology checklists to provide an informational foundation for content. 4. Homework test questions for all chapters so that students can test their knowledge and identify content gaps. 5. Recorded visual demonstrations for activity-based exercise Labs that can be accessed as many times as is necessary to increase the understanding of performance expectations, and serve as a clear reference point for students.https://oer.galileo.usg.edu/health-textbooks/1004/thumbnail.jp

Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes

BACKGROUND: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4). METHODS: We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction. RESULTS: Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes. CONCLUSION: Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4

Divergent dysregulation of gene expression in murine models of fragile X syndrome and tuberous sclerosis

Background: Fragile X syndrome and tuberous sclerosis are genetic syndromes that both have a high rate of comorbidity with autism spectrum disorder (ASD). Several lines of evidence suggest that these two monogenic disorders may converge at a molecular level through the dysfunction of activity-dependent synaptic plasticity. Methods: To explore the characteristics of transcriptomic changes in these monogenic disorders, we profiled genome-wide gene expression levels in cerebellum and blood from murine models of fragile X syndrome and tuberous sclerosis. Results: Differentially expressed genes and enriched pathways were distinct for the two murine models examined, with the exception of immune response-related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO) model, the neuroactive ligand receptor interaction pathway and gene sets associated with synaptic plasticity such as long-term potentiation, gap junction, and axon guidance were the most significantly perturbed pathways. The phosphatidylinositol signaling pathway was significantly dysregulated in both cerebellum and blood of Fmr1-KO mice. In Tsc2 heterozygous (+/−) mice, immune system-related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly changed in both tissues. Conclusions: Our data suggest that distinct molecular pathways may be involved in ASD with known but different genetic causes and that blood gene expression profiles of Fmr1-KO and Tsc2+/− mice mirror some, but not all, of the perturbed molecular pathways in the brain

Reproducibility of the lung anatomy under active breathing coordinator control:Dosimetric consequences for scanned proton treatments

Purpose The treatment of moving targets with scanned proton beams is challenging. For motion mitigation, an Active Breathing Coordinator (ABC) can be used to assist breath-holding. The delivery of pencil beam scanning fields often exceeds feasible breath-hold durations, requiring high breath-hold reproducibility. We evaluated the robustness of scanned proton therapy against anatomical uncertainties when treating nonsmall-cell lung cancer (NSCLC) patients during ABC controlled breath-hold. Methods Four subsequent MRIs of five healthy volunteers (3 male, 2 female, age: 25-58, BMI: 19-29) were acquired under ABC controlled breath-hold during two simulated treatment fractions, providing both intrafractional and interfractional information about breath-hold reproducibility. Deformation vector fields between these MRIs were used to deform CTs of five NSCLC patients. Per patient, four or five cases with different tumor locations were modeled, simulating a total of 23 NSCLC patients. Robustly optimized (3 and 5 mm setup uncertainty respectively and 3% density perturbation) intensity-modulated proton plans (IMPT) were created and split into subplans of 20 s duration (assumed breath-hold duration). A fully fractionated treatment was recalculated on the deformed CTs. For each treatment fraction the deformed CTs representing multiple breath-hold geometries were alternated to simulate repeated ABC breath-holding during irradiation. Also a worst-case scenario was simulated by recalculating the complete treatment plan on the deformed CT scan showing the largest deviation with the first deformed CT scan, introducing a systematic error. Both the fractionated breath-hold scenario and worst-case scenario were dosimetrically evaluated. Results Looking at the deformation vector fields between the MRIs of the volunteers, up to 8 mm median intra- and interfraction displacements (without outliers) were found for all lung segments. The dosimetric evaluation showed a median difference in D-98% between the planned and breath-hold scenarios of -0.1 Gy (range: -4.1 Gy to 2.0 Gy). D-98% target coverage was more than 57.0 Gy for 22/23 cases. The D-1 cc of the CTV increased for 21/23 simulations, with a median difference of 0.9 Gy (range: -0.3 to 4.6 Gy). For 14/23 simulations the increment was beyond the allowed maximum dose of 63.0 Gy, though remained under 66.0 Gy (110% of the prescribed dose of 60.0 Gy). Organs at risk doses differed little compared to the planned doses (difference in mean doses <0.9 Gy for the heart and lungs, <1.4% difference in V-35 [%] and V-20 [%] to the esophagus and lung). Conclusions When treating under ABC controlled breath-hold, robustly optimized IMPT plans show limited dosimetric consequences due to anatomical variations between repeated ABC breath-holds for most cases. Thus, the combination of robustly optimized IMPT plans and the delivery under ABC controlled breath-hold presents a safe approach for PBS lung treatments

Using a model-based geostatistical approach to design and analyse the prevalence of schistosomiasis in Kenya

BackgroundInfections caused by both Schistosoma mansoni and Schistosoma haematobium are endemic in Kenya, with over six million children at risk. A national school-based deworming programme was launched in 2012 with the goal of eliminating parasitic worms as a public health problem. This study used a model-based geostatistical (MBG) approach to design and analyse the impact of the programme and inform treatment strategy changes for schistosomiasis (SCH).MethodsA cross-sectional survey of 200 schools across 27 counties of Kenya was utilised. The study design, selection of the schools, and analysis followed the MBG approach, which incorporated historical data on treatment, morbidity, and environmental covariates.ResultsThe overall SCH prevalence was 5.0% (95% CI 4.9%–5.2%) and was estimated, with a high predictive probability of 0.999, to be between 1% and&lt; 10%. The predictive probabilities at county level revealed county heterogeneity, with that of four counties estimated to be between 0% and&lt; 1%, that of 20 counties estimated to be between 1% and&lt; 10%, that of two counties estimated to be between 10% and&lt; 20%, and that of one county estimated to be between 20% and&lt; 50%.ConclusionSCH treatment requirements can now be confidently refined based on the World Health Organization’s guidelines. The four counties with prevalences of between 0% and&lt; 1% may consider suspending treatment only in areas (i.e., sub-counties and wards) where the prevalence is&lt; 1%