Rush University Medical Center

About: Rush University Medical Center is a healthcare organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 13915 authors who have published 29027 publications receiving 1379216 citations. The organization is also known as: Rush Presbyterian St. Luke's Medical Center.

Idiopathic congenital central hypoventilation syndrome: Analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b

Abstract: Idiopathic congenital central hypoventilation syndrome (CCHS) has been linked to autonomic nervous system dysregulation and/or dysfunction (ANSD) since it was first described in 1970 A genetic basis of CCHS has been proposed because of the reports of four families with two affected children, because of mother-child transmission, and because of a recent report of a polyalanine expansion mutation in PHOX2b in a subset of CCHS subjects We, therefore, studied genes pertinent to early embryologic development of the ANS including mammalian achaete-scute homolog-1 (MASH1), bone morphogenic protein-2 (BMP2), engrailed-1 (EN1), TLX3, endothelin converting enzyme-1 (ECE1), endothelin-1 (EDN1), PHOX2a, and PHOX2b in 67 probands with CCHS, and gender- and ethnicity-matched controls No disease-defining mutations were identified in MASH1, BMP2, EN1, TLX3, ECE1, EDN1, or PHOX2a The 65/67 CCHS probands (97%) were found to be heterozygous for the exon 3 polyalanine expansion mutation identified previously in PHOX2b Further, there was an association between repeat mutation length and severity of the CCHS/ANSD phenotype Of the two probands who did not carry the expansion mutation, one had a nonsense mutation in exon 3 which truncated the protein and the other had no mutation in PHOX2b but had a previously reported EDN3 frameshift point mutation The polyalanine expansion mutation was not found in any of 67 matched controls Of 54 available families (including 97 unaffected parents), whose child carried the PHOX2b mutation, 4 parents demonstrated mosaicism for an expansion mutation identical to that seen in the CCHS cases, suggesting that not all mutations in affected probands with unaffected parents are de novo We also studied four women with CCHS who were heterozygous for the PHOX2b mutation, each with one child Three of the four children were also affected and had the same mutation, demonstrating autosomal dominant inheritance of the mutation Assay of the PHOX2b polyalanine repeat mutation represents a highly sensitive and specific technique for confirming the diagnosis of CCHS Identification of the CCHS mutation will lead to clarification of the phenotype, allow for prenatal diagnosis for parents of CCHS probands and adults with CCHS in future pregnancies, and potentially direct intervention strategies for the treatment of CCHS

Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer’s disease related cognitive functioning

Abstract: There is an urgent need to develop molecular biomarkers of brain age in order to advance our understanding of age related neurodegeneration. Recently, we developed a highly accurate epigenetic biomarker of tissue age (known as epigenetic clock) which is based on DNA methylation levels. Here we use n=700 dorsolateral prefrontal cortex (DLPFC) samples from Caucasian subjects of the Religious Order Study and the Rush Memory and Aging Project to examine the association between epigenetic age and Alzheimer's disease (AD) related cognitive decline, and AD related neuropathological markers. Epigenetic age acceleration of DLPFC is correlated with several neuropathological measurements including diffuse plaques (r=0.12, p=0.0015), neuritic plaques (r=0.11, p=0.0036), and amyloid load (r=0.091, p=0.016). Further, it is associated with a decline in global cognitive functioning (β=-0.500, p=0.009), episodic memory (β=-0.411, p=0.009) and working memory (β=-0.405, p=0.011) among individuals with AD. The neuropathological markers may mediate the association between epigenetic age and cognitive decline. Genetic complex trait analysis (GCTA) revealed that epigenetic age acceleration is heritable (h2=0.41) and has significant genetic correlations with diffuse plaques (r=0.24, p=0.010) and possibly working memory (r=-0.35, p=0.065). Overall, these results suggest that the epigenetic clock may lend itself as a molecular biomarker of brain age.

Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study

Abstract: Summary Background Few data on the pathology of cerebral vessel disease, dementia, and cognition are available. We examined the association of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer's disease dementia and cognitive function. Methods This cross-sectional study included men and women aged 65 years or older who had yearly clinical assessments and had agreed to brain autopsy at the time of death, as part of one of two cohort studies of ageing (The Religious Orders Study and the Rush Memory and Aging Project). Individuals without dementia or with Alzheimer's disease dementia, and with complete neuropathological data, are included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Clinical data recorded between 1994 and 2015 were used to determine presence of Alzheimer's disease dementia. Systematic neuropathological assessments documented the severity of cerebral large vessel (atherosclerosis) and small vessel (arteriolosclerosis) disease. By use of regression analyses adjusted for demographics, gross and microscopic infarcts, and Alzheimer's disease pathology, we examined associations of vessel disease severity (mild, moderate, and severe) with odds of probable and possible Alzheimer's disease dementia and cognitive function. Findings Study enrolment began in January, 1994, and two cohort studies are ongoing. 1143 individuals were included in our analyses (median age at death 88·8 years; 478 [42%] with Alzheimer's disease dementia). Moderate-to-severe atherosclerosis was present in 445 (39%) individuals, and arteriolosclerosis in 401 (35%) individuals. Each level increase in the severity of atherosclerosis or arteriolosclerosis was associated with significantly higher odds of Alzheimer's disease dementia (odds ratio [OR] for atherosclerosis 1·33, 95% CI 1·11–1·58; OR for arteriolosclerosis 1·20, 1·04–1·40). Atherosclerosis was associated with lower scores for global cognition (estimate −0·10 [SE 0·04], p=0·0096) and four cognitive domains (episodic memory −0·10 [0·04], p=0·017; semantic memory −0·11 [0·05], p=0·018; perceptual speed −0·14 [0·04], p=0·00080; and visuospatial abilities −0·13 [0·04], p=0·0080), but not working memory (−0·05 [0·04], p=0·21). Arteriolosclerosis was associated with lower scores for global cognition (estimate −0·10 [0·03], p=0·0015) and four domains (episodic memory −0·12 [0·04], p=0·00090; semantic memory −0·10 [0·04], p=0·013; working memory −0·07 [0·03], p=0·045; perceptual speed −0·12 [0·04], p=0·0012), and a non-significant association was noted for visuospatial abilities (−0·07 [0·03], p=0·052). Findings were unchanged in analyses controlling for the presence of APOE e4 allele or vascular risk factors. Interpretation Cerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer's disease dementia, and are also associated with low scores in most cognitive domains. Cerebral vessel pathology might be an under-recognised risk factor for Alzheimer's disease dementia. Funding US National Institutes of Health.

Cervical laminoplasty: a critical review

Abstract: Object. The technique of cervical laminoplasty was developed to decompress the spinal canal in patients with multilevel anterior compression caused by ossification of the posterior longitudinal ligament or cervical spondylosis. There is a paucity of data confirming its superiority to laminectomy with regard to neurological outcome, preserving spinal stability, preventing postlaminectomy kyphosis, and the development of the “postlaminectomy membrane.” Methods. The authors conducted a metaanalysis of the English-language laminoplasty literature, assessing neurological outcome, change in range of motion (ROM), development of spinal deformity, and complications. Seventy-one series were reviewed, comprising more than 2000 patients. All studies were retrospective, uncontrolled, nonrandomized case series. Forty-one series provided postoperative recovery rate data in which the Japanese Orthopaedic Association Scale was used for assessing myelopathy. The mean recovery rate was 55% (range 20–80%). The authors of 23...