EEG Characterization During Motor Tasks That Are Difficult for Movement Disorder Patients

Movement disorders are a group of syndromes that often arise due to neurological abnormalities. Approximately 40 million Americans are affected by some form of movement disorder, significantly impacting patients’ quality of life and their ability to live independently. Deep brain stimulation (DBS) is one treatment that has shown promising results in the past couple decades, however, the currently used open-loop system has several drawbacks. By implementing a closed-loop or adaptive DBS (aDBS) system, the need for expensive parameter reprogramming sessions would be reduced, side-effects may be relieved, and habituation could be avoided. Several biomarkers, for example signals or activity derived from electroencephalogram (EEG), could potentially be used as a feedback source for aDBS. Here, we attempted to characterize cortical EEG potentials in healthy subjects performing six tasks that are difficult for those with movement disorders. Using a 32-channel EEG cap with an amplifier sampling at 500 Hz, we performed our protocol on 11 college-aged volunteers lacking any known movement disorder. For each task, we analyzed task-related power (TRP) changes, spectrograms, and topographical maps. In a finger movement exercise, we found task-related depression (TRD) in the delta band at the F4 electrode, as well as TRD at the C3 electrode in the alpha band during a pencil-pickup task, and TRD at the F3 electrode in the beta band during voluntary swallowing. While delta-ERD in the finger movement exercise was likely due to ocular artifact, the other significant results were in line with what relevant literature would predict. The findings from the work, in conjunction with a future study involving movement disorder patients, can provide insight into the use of EEG as a feedback source for aDBS. Keywords: EEG, electroencephalography, neurostimulation, deep brain stimulation, movement disorders, closed-loop DBS, adaptive DBS, aDB

A combination of curcumin and ginger extract improves abrasion wound healing in corticosteroid-impaired hairless rat skin

Hairless rats were topically treated with a combination of 10% curcumin and 3% ginger extract (or with each agent alone) for a 21-day period. Following this, the rats were treated topically with Temovate (corticosteroid) for an additional 15 days. At the end of the treatment period, superficial abrasion wounds were induced in the treated skin. Abrasion wounds healed more slowly in the skin of Temovate-treated rats than in skin of control animals. Healing was more rapid in skin of rats that had been pretreated with either curcumin or ginger extract alone or with the combination of curcumin–ginger extract (along with Temovate) than in the skin of rats treated with Temovate and vehicle alone. Skin samples were obtained at the time of wound closure. Collagen production was increased and matrix metalloproteinase-9 production was decreased in the recently healed skin from rats treated with the botanical preparation relative to rats treated with Temovate plus vehicle. In none of the rats was there any indication of skin irritation during the treatment phase or during wounding and repair. Taken together, these data suggest that a combination of curcumin and ginger extract might provide a novel approach to improving structure and function in skin and, concomitantly, reducing formation of nonhealing wounds in “at-risk” skin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74673/1/j.1524-475X.2009.00483.x.pd

BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH), positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH

Prevalence and characteristics of resistant hypertensive patients in an Asian population

Background: Resistant hypertension is a well-recognized clinical challenge yet there are no reported data on its prevalence in Pakistan. These patients are subjected to a higher risk of developing hypertensive complications. The objective of our study was to evaluate the prevalence and determinants of resistant hypertension in an Asian cohort of hypertensive patients.Methods: This cross-sectional study was carried out among hypertensive patients visiting a tertiary care hospital in Karachi from September-December 2015. Patient data and characteristics were recorded using a pre-coded questionnaire. Morisky and Berlin questionnaires were used to assess compliance to medications and determine the risk of developing obstructive sleep apnea, respectively. Pearson\u27s chi-square test was used to analyze statistical differences between hypertensive patients and related factors.Results: A total of 515 patients were included in the study. Overall, 12% of the total patients (n=62) were resistant hypertensives and 25% (n=129) had pseudo-resistant hypertension. Resistant patients were more often females, older and had a higher body mass index (all P\u3c0.001). Use of painkillers and noncompliance to dietary recommendations were found to be significant determinants of resistant hypertension. Prevalence of comorbid conditions, including diabetes (p=0.33), hyperlipidemia (p=0.46), and chronic kidney disease (p=0.23), was not significantly higher in patients with resistant hypertension.Conclusion: Nearly one in ten hypertensive patients had true resistant hypertension, and twenty-five percent of patients had pseudo-resistance. Resistance hypertensions is significantly associated with female gender, older age, obesity, dietary noncompliance and increased use of NSAIDs

The landscape of RNA polymerase II-associated chromatin interactions in prostate cancer

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing the total number of chromatin interaction modules comprising the AR gene and its distal enhancer. We deconvoluted the transcription control modules of several PCa genes, notably the biomarker KLK3, lineage-restricted genes (KRT8, KRT18, HOXB13, FOXA1, ZBTB16), the drug target EZH2, and the oncogene MYC. By integrating clinical PCa data, we defined a germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion in the transcriptional regulation of multiple target genes - VPS53, FAM57A, and GEMIN4. Our studies implicate changes in genome organization as a critical determinant of aberrant transcriptional regulation in PCa

Nuclear data for medical applications: An overview of present status and future needs

A brief overview of nuclear data required for medical applications is given. The major emphasis is on radionuclides for internal applications, both for diagnosis and therapy. The status of the presently available data is discussed and some of the emerging needs are outlined. Most of the needs are associated with the development of non-standard positron emitters and novel therapeutic radionuclides. Some new developments in application of radionuclides, e.g. theranostic approach, multimode imaging, radionanoparticles, etc. are described and the related nuclear data needs are discussed. The possible use of newer irradiation technologies for medical radionuclide production, e.g. intermediate energy charged-particle accelerators, high-power electron accelerators for photon production, and spallation neutron sources, will place heavy demands on nuclear data

Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer.

Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions. The transcriptional status and epigenetic features of the target genes influence this effect. Importantly, inflammation-induced de novo genomic rearrangements are blocked by homologous recombination (HR) and promoted by non-homologous end-joining (NHEJ) pathways. In conjunction with the association of proliferative inflammatory atrophy (PIA) with human prostate cancer, our results support a working model in which recurrent genomic rearrangements induced by inflammatory stimuli lead to the development of prostate cancer