Search

Staff travel required to provide home visiting services can be a barrier to quality service provision. This may be of particular concern to rural programs, where the demands of staff travel are often thought to be greater than in urban settings. As part of a statewide needs assessment of the Infants and Toddlers with Disabilities Program in Kansas (Kansas Part C), a time study was conducted to examine travel time in rural and urban programs. While in the field, Part C providers spent 29.9% of their time traveling, over half (51.4%) of their time in direct service, 5.5% preparing documentation, and 2.0% communicating with clients and partners. Travel time did not differ significantly between urban and rural programs. This suggests that caution is warranted when adopting policy approaches, such as funding formula differences, designed to account for assumed (but not documented) differences in rural and urban programs, such as staff travel time. [ABSTRACT FROM AUTHOR]

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with an increased risk of Parkinson's disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 wk of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points—birth, 6, 12, and 36 wk old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial–neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of differential modification of cytosines with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late-life diseases, including PD. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms are mediators of interactions between aging, genetics, and environmental factors in sporadic Parkinson's disease (PD). Multiple studies have explored the DNA modifications in PD, but few focus on 5-hydroxymethylcytosine (5-hmC), which is important in the central nervous system and sensitive to environmental exposures. To date, studies have not differentiated between 5-methylcytosine (5-mC) and 5-hmC or have analyzed them separately. In this study, we modeled paired 5-mC and 5-hmC data simultaneously. We identified 108 cytosines with significant PD-associated shifts between these marks in an enriched neuronal population from PD postmortem parietal cortex, within 83 genes and 34 enhancers associated with 67 genes. These data potentially link epigenetic regulation of genes related to LRRK2 and endolysosomal sort ( RAB32 and AGAP1 ), and genes involved in neuroinflammation, the inflammasome, and neurodevelopment with early changes in PD and suggest that there are significant shifts between 5mC and 5hmC associated with PD in genes not captured by standard methods., Competing Interests: Competing interests: All authors declare that they have no competing interests

Background: The majority of Parkinson's disease (PD) cases are due to a complex interaction between aging, genetics, and environmental factors; epigenetic mechanisms are thought to act as important mediators of these risk factors. While multiple studies to date have explored the role of DNA modifications in PD, few focus on 5-hydroxymethylcytosine (5hmC). Because 5hmC occurs at its highest levels in the brain and is thought to be particularly important in the central nervous system, particularly in the response to neurotoxicants, it is important to explore the potential role of 5hmC in PD. This study expands on our previously published epigenome-wide association study (EWAS) performed on DNA isolated from neuron-enriched nuclei from human postmortem parietal cortex from the Banner Sun Health Research Institute Brain Bank. The study aimed to identify paired changes in 5hmC and 5mC in PD in enriched neuronal nuclei isolated from PD post-mortem parietal cortex and age- and sex-matched controls. We performed oxidative bisulfite (oxBS) conversion and paired it with our previously published bisulfite (BS)-based EWAS on the same samples to identify cytosines with significant shifts between these two related epigenetic marks. Interaction differentially modified cytosines (iDMCs) were identified using our recently published mixed-effects model for co-analyzing β mC and β hmC data., Results: We identified 1,030 iDMCs with paired changes in 5mC and 5hmC (FDR < 0.05) that map to 695 genes, including PARK19 (DNAJC6), a familial PD gene, and PTPRN2 (IA-2), which has been previously implicated in PD in both epigenetic and mechanistic studies. The majority of iDMC-containing genes have not previously been implicated in PD and were not identified in our previous BS-based EWAS., Conclusions: These data potentially link epigenetic regulation of the PARK19 and PTPRN2 loci in the pathogenesis of idiopathic PD. In addition, iDMC-containing genes have known functions in synaptic formation and function, cell cycle and senescence, neuroinflammation, and epigenetic regulation. These data suggest that there are significant shifts between 5mC and 5hmC associated with PD in genes relevant to PD pathogenesis that are not captured by analyzing BS-based data alone or by analyzing each mark as a distinct dataset., Competing Interests: Competing interests: All authors declare that they have no competing interests

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson's disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril (α-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 weeks of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points - birth, 6 weeks, 12 weeks, and 36 weeks old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of DMCs with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late life diseases, including PD., Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Today any researcher with the desire can easily purchase a viral vector. However, despite the availability of viral vectors themselves, the requisite knowledge that is absolutely essential to conducting a gene therapy experiment remains somewhat obscure and esoteric. To utilize viral vectors to their full potential, a large number of decisions must be made, in some instances prior to even obtaining the vector itself. For example, critical decisions include selection of the proper virus, selection of the proper expression cassette, whether to produce or purchase a viral vector, proper viral handling and storage, the most appropriate delivery method, selecting the proper controls, how to ensure your virus is expressing properly, and many other complex decisions that are essential to performing a successful gene therapy experiment. The need to make so many important decisions can be overwhelming and potentially prohibitive, especially to the novice gene therapist. In order to aid in this challenging process, here we provide an overview of basic gene therapy modalities and a decision tree that can be used to make oneself aware of the options available to the beginning gene therapist. This information can be used as a road map to help navigate the complex and perhaps confusing process of designing a successful gene therapy experiment.