Among culturally and linguistically diverse students with disabilities, Asian American and Pacific Islander (AAPI) students comprise the third-largest group. In order to address the diversity of the special education student population and ensure that parents are involved in the decision-making process, the Individuals with Disabilities Education Improvement Act of 2004 requires schools to translate students’ Individualized Education Program (IEP) into their parents’ native language. The quality and accuracy of translated IEPs is a critical concern for limited-English-speaking parents who rely on such document for information that they miss in meetings. Discrepancies in the poorly translated documents prevent families from accurately understanding their child’s IEPs and knowing when they should advocate for their children for appropriate services and placement. This article exposes existing problems of translated IEPs and highlights the importance of hiring high-quality translators to help bridge the communication gap between schools and linguistically diverse parents of children with disabilities.

A 2-year-old male pediatric patient experienced a partial occlusion of the internal carotid and subsequent asphyxiation resulting in hypoxic brain injury that was later misdiagnosed as primary attention deficient hyperactivity disorder (ADHD). Imaging analyses using diffusion tensor imaging (DTI), positron emission tomography (PET), and magnetic resonance imaging (MRI) quantitative volumetrics (QV) were used nine years following the incident to identify whether his development of ADHD is of a primary heritability or secondary hypoxic brain injury sequelae. The patient's DTI analysis generated decreases in fractional anisotropy (FA) values in the anterior corpus callosum, bilateral internal capsule, and hippocampus. Decreases in FA are seen in ADHD patients, but the degree of FA decrease in the patient under study is several orders of magnitude greater than in ADHD patients. Also, not normally observed in ADHD patients were decreases in the metabolism of the orbitofrontal cortex, anterior cingulate, left anterior insular cortex, and left striatum. Additionally, QV showed enlargements of various regions of the brain including the amygdala which is often cited in the literature to be reduced in ADHD patients. The diagnosis of this patient despite having non-characteristic neuroimaging data suggests a unique specificity of the hypoxic injury to the development of a secondary hypoxic brain injury caused ADHD.

Vascular smooth muscle cells (VSMCs), a highly mosaic tissue, arise from multiple distinct embryonic origins and populate different regions of our vascular network with defined boundaries. Accumulating evidence has revealed that the heterogeneity of VSMC origins contributes to region-specific vascular diseases such as atherosclerosis and aortic aneurysm. These findings highlight the necessity of taking into account lineage-dependent responses of VSMCs to common vascular risk factors when studying vascular diseases. This chapter describes a reproducible, stepwise protocol for the generation of isogenic VSMC subtypes originated from proepicardium, second heart field, cardiac neural crest, and ventral somite using human induced pluripotent stem cells. By leveraging this robust induction protocol, patient-derived VSMC subtypes of desired embryonic origins can be generated for disease modeling as well as drug screening and development for vasculopathies with regional susceptibility.

Myocardial fibrosis is a hallmark of cardiac remodeling, which can progressively lead to heart failure, a leading cause of death worldwide. The effector cells of fibrosis in the heart are cardiac fibroblasts (CFs). There is currently no effective therapeutic strategy clinically available to specifically attenuate maladaptive responses of CFs. Large-scale applications such as high-throughput drug screening are difficult due to the limited availability of human primary CFs, thus limiting the development of future treatments. Here, we describe a robust induction protocol that can be used to generate a scalable, consistent, genetically defined source of quiescent CFs from human induced pluripotent stem cells for cardiac fibrosis modeling, drug discovery, and tissue engineering.

Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modelling, drug discovery and cell therapy development. Novel pathological mechanisms have been elucidated, new drugs originating from iPSC screens are in the pipeline and the first clinical trial using human iPSC-derived products has been initiated. In particular, the combination of human iPSC technology with recent developments in gene editing and 3D organoids makes iPSC-based platforms even more powerful in each area of their application, including precision medicine. In this Review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in the field.

Background

While obesity has been shown to be a risk factor for Alzheimer's disease, the potential mechanisms underlying this risk may be clarified with better understanding of underlying physiology in obese persons.

Objective

To identify patterns of cerebral perfusion abnormality in adults as a function of body mass index (BMI) defined weight categories, including overweight or obese status.

Methods

A large psychiatric cohort of 35,442 brain scans across 17,721 adults (mean age 40.8±16.2 years, range 18-94 years) were imaged with SPECT during baseline and concentration scans, the latter done after each participant completed the Connors Continuous Performance Test II. ANOVA was done to identify patterns of perfusion abnormality in this cohort across BMI designations of underweight (BMI < 18.5), normal weight (BMI = 18.5 to 24.9), overweight (BMI 24.9 to 29.9), obesity (BMI≥30), and morbid obesity (BMI≥40). This analysis was done for 128 brain regions quantifying SPECT perfusion using the automated anatomical labeling (AAL) atlas.

Results

Across adulthood, higher BMI correlated with decreased perfusion on both resting and concentration brain SPECT scans. These are seen in virtually all brain regions, including those influenced by AD pathology such as the hippocampus.

Conclusion

Greater BMI is associated with cerebral perfusion decreases in both resting and concentration SPECT scans across adulthood.

Many novel CRISPR-based genome-editing tools, with a wide variety of applications, have been developed in the past few years. The original CRISPR-Cas9 system was developed as a tool to alter genomic sequences in living organisms in a simple way. However, the functions of new CRISPR tools are not limited to conventional genome editing mediated by non-homologous end-joining or homology-directed repair but expand into gene-expression control, epigenome editing, single-nucleotide editing, RNA editing and live-cell imaging. Furthermore, genetic perturbation screening by multiplexing guide RNAs is gaining popularity as a method to identify causative genes and pathways in an unbiased manner. New CRISPR tools can also be applied to ex vivo or in vivo therapeutic genome editing for the treatment of conditions such as hyperlipidaemia. In this Review, we first provide an overview of the diverse new CRISPR tools that have been developed to date. Second, we summarize how these new CRISPR tools are being used to study biological processes and disease mechanisms in cardiovascular research and medicine. Finally, we discuss the prospect of therapeutic genome editing by CRISPR tools to cure genetic cardiovascular diseases.