Posterior fossa arachnoid cysts (PFACs) are rare congenital abnormalities observed in 0.3 to 1.7% of the population and are traditionally thought to be benign. While conducting a neuroimaging study ...investigating cerebellar structure in bipolar disorder, we observed a higher incidence of PFACs in bipolar patients (5 of 75; 6.6%) compared to the neuronormative control group (1 of 54; 1.8%). In this report, we detail the cases of the five patients with bipolar disorder who presented with PFACs. Additionally, we compare neuropsychiatric measures and cerebellar volumes of these patients to neuronormative controls and bipolar controls (those with bipolar disorder without neuroanatomical abnormalities). Our findings suggest that patients with bipolar disorder who also present with PFACs may have a milder symptom constellation relative to patients with bipolar disorder and no neuroanatomical abnormalities. Furthermore, our observations align with prior literature suggesting an association between PFACs and psychiatric symptoms that warrants further study. While acknowledging sample size limitations, our primary aim in the present work is to highlight a connection between PFACs and BD-associated symptoms and encourage further study of cerebellar abnormalities in psychiatry.
Stroke is one of the leading causes of impairment in the world. Many of those who have suffered a stroke experience long-term loss of upper-limb function as a result. BLUE SABINO is an exoskeleton ...device being developed at the University of Idaho to help assess these patients and aid in their rehabilitation. One of the central design challenges with exoskeletons is limiting the overall weight of the device. Motors used in actuation of these devices are often oversized to allow gravity balancing of the device and user and the creation of torques to facilitate patient movements. If the torques required for gravity balancing are achieved through elastic elements, the motor and other upstream components can be lighter, potentially greatly reducing the overall weight of the device. In this paper, constant-force springs may provide an effective method of generating a constant offsetting torque to compensate for gravity. In experimental testing of multiple mounting configurations of C-shaped constant-force springs (single, back-to-back, double-wrapped), the force output fluctuated less than 8.6% over 180° of wrapping, with friction values below 2.6%, validating the viability of constant-force springs for this application. The results suggest the back-to-back configuration provides a simpler implementation with better force consistency while the double-wrapped configuration adds less friction to the system.
The purpose of this article is to evaluate single-source dual-energy CT (DECT) for distinguishing benign and indeterminate adrenal nodules, with attention to the effects of phase of IV contrast ...enhancement.
A retrospective review revealed 273 contrast-enhanced abdominal DECT examinations from November 2009 through March 2012. Fifty adrenal nodules 0.8 cm or larger were identified in 41 patients (22 women and 19 men; average age, 66 years; age range, 36-88 years). CT postprocessing and measurements were independently performed by two radiologists (readers 1 and 2) for each nodule, as follows: attenuation (in Hounsfield units) on true unenhanced images; contrast-enhanced attenuation (in Hounsfield units) on monochromatic spectral images at 40, 75, and 140 keV; and contrast-enhanced material density (in milligrams per milliliter) on virtual unenhanced images. Nodules were classified as benign (< 10 HU) and indeterminate (≥ 10 HU) according to true unenhanced images.
Interreader agreement regarding benign and indeterminate nodules was high (κ = 0.92; 95% CI, 0.8-1.0). At 140 keV, the attenuation of benign nodules was significantly lower (reader 1, 7.0 ± 12.5 HU; reader 2, 7.8 ± 9.2 HU) than that of indeterminate nodules (reader 1, 15.7 ± 20.5 HU p = 0.004; reader 2, 17.5 ± 13.4 HU p < 0.0001). On virtual unenhanced images, benign nodules had significantly lower material density (reader 1, 992.4 ± 9.9 mg/mL; reader 2, 992.7 ± 9.6 mg/mL) than did indeterminate nodules (reader 1, 1001.1 ± 20.5 mg/mL p = 0.038; reader 2, 1007.6 ± 13.4 mg/mL p < 0.0001).
DECT tools can mathematically subtract iodine or minimize its effects in high-energy reconstructions, approximating unenhanced imaging and potentially reducing the need for additional studies to triage adrenal nodules detected on contrast-enhanced DECT examinations.
Prior cross-sectional studies have shown that cancer patients have sleep-wake activity cycles that show little distinction between daytime and nighttime, a pattern indicative of circadian disruption. ...This pattern is seen both before and during cancer treatment. Long-term data are needed, however, to assess to what extent circadian rhythm impairments evolve over the course of chemotherapy. The goal of this study was to assess the longitudinal course of sleep-wake activity rhythms before and during chemotherapy for breast cancer.
Ninety-five women scheduled to receive neoadjuvant or adjuvant anthracycline based chemotherapy for a stage I-III breast cancer participated. The participants wore a wrist actigraph for 72 consecutive hours at baseline (pre-chemotherapy), as well as during the weeks 1, 2 and 3 (W1, W2, W3) of cycle 1 and cycle 4 of chemotherapy. Sleep-wake circadian activity variables were computed based on actigraphic data.
Compared to baseline, with the exception of acrophase, all circadian rhythm variables examined, including amplitude, mesor, up-mesor, down-mesor, and rhythmicity were significantly impaired during the first week of both chemotherapy cycles. Although the circadian variables approached baseline values during W2 and W3 of cycle 1, most remained significantly more impaired during W2 and W3 of cycle 4.
These data suggest that the first administration of chemotherapy is associated with transient disruption of sleep-wake rhythm, while repeated administration of chemotherapy results in progressively worse and more enduring impairments in sleep-wake activity rhythms.
Abstract
Introduction: The presence of the t(11;19) chromosomal translocation and its CRTC1-MAML2 (C1/M2) fusion product occurs frequently in salivary mucoepidermoid carcinoma (MEC) and has been ...correlated with a favorable prognosis. Recently, whole-exome sequencing studies found genomic alterations in MEC to be infrequent, which supports the role of C1/M2 as an early driver event. However, when present, TP53 and PIK3CA alterations may represent alternative driver mutations in fusion-negative cases. To better understand the MEC transcriptional landscape by fusion status and histologic grade, we performed RNA deep sequencing.
Methods: 16 parotid MEC (8 low-grade and 8-high grade) tumors, 12 adjacent normal, and 6 age-matched normal parotid tissues were retrospectively analyzed from UNC Surgical Pathology specimens collected from 2000-2019. H&E and mucicarmine stained slides were independently reviewed by pathology for diagnostic confirmation. The Air Force Institute of Pathology (AFIP) classification system by Ellis and Auclair was utilized for histologic grading. RNA was extracted from FFPE tissue sections and quality checked prior to library preparation. RNA-seq (HS2500) was then performed on all samples and computational methods were used to determine C1/M2 fusion status. Gene set variation analyses (GSVA) were performed on genes differentially expressed between MEC tumor versus normal, or according to tumor grade, and/or fusion status.
Results: Compared to matched normals, MEC tumors display significant changes in ERBB2 and PI3K signaling cascades (FC=-3.2, p=0.049). We also noted significant upregulation of inflammatory and apoptosis markers including interferon gamma, IL-4, NOS1, and programmed cell death (p<0.05). Moreover, compared to low-grade, high-grade MEC tumors had significant upregulation of angiogenesis pathways, including the VEGF-VEGF receptor signaling network (FC=4, p=0.007) and activation of developmental pathways such as TGF-β signaling (FC=3.62, p=0.015). Notably, we report the expression of C1/M2 fusion transcripts in both low- and high-grade MEC. Further, p53 signaling pathway is downregulated in C1/M2 fusion-positive cases compared to fusion-negative cases (p<0.05).
Discussion: This is the first study to perform transcriptome analyses of salivary MEC comparing to normal parotid tissue, while accounting for histologic grade. While C1/M2 fusion status is considered pathognomonic of low-grade MEC, we identified the expression of C1/M2 fusion transcripts in high-grade MEC. This confirms recent reports challenging the prognostic value of fusion status. Our study also confirms that reprogramming TP53 and PI3K signaling is a universal feature of MEC and epigenetic mechanisms may repress p53 in the absence of TP53 driver mutations seen in fusion negative tumors. Lastly, we report that VEGF and TGF-β pathway activation are associated with cancer pathogenesis in high-grade MEC. The evaluation of anticancer therapies targeting these pathways should be evaluated further.
Citation Format: Siddharth Sheth, Renee Betancourt, Joel Parker, Kshitij Sharma, Adele Musicant, Wendell Yarbrough, Trevor Hackman, Antonio Amelio. RNA sequencing of salivary mucoepidermoid carcinoma reveals distinct molecular profiles based on histologic grade abstract. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr PR04.
Left ventricular (LV) systolic dysfunction may lead to mitral regurgitation (MR) in the absence of structural mitral valve abnormalities and may be related to LV dilatation, stretching of the mitral ...annulus, sphericity, and regional wall motion abnormalities. Although the presence and degree of MR in patients with LV dysfunction may have important prognostic and therapeutic implications, the available data are scarce.
Prior to its close encounter with the Kuiper Belt object (KBO) (486958) 2014 MU69 on 2019 January 1, NASA's New Horizons spacecraft observed other KBOs from distances greater than 0.1 au at solar ...phase angles far larger than those attainable from Earth. The expanded range in phase angle afforded by these distant KBO (DKBO) observations enables comparisons between their phase functions and those of other solar system objects. Here we present extended New Horizons phase angle coverage of plutino (15810) Arawn (1994 JR1) to 131°, resonant KBO 2012 HE85 to 64°, scattered disk KBO 2011 HK103 to 124°, hot classical (515977) 2012 HZ84 to 73°, and cold classical KBOs 2011 HJ103 and 2011 JY31 to 27° and 122°, respectively. In general, DKBO solar phase curves have slopes (i.e., phase coefficients) and shapes (with corresponding phase integrals q) similar to those of other dark, small solar system objects including comet nuclei, asteroids, and satellites. Until stellar occultations by these DKBOs provide information about their size, geometric albedos p (and Bond albedos A = pq) must be inferred from the median albedos measured by thermal radiometry for each dynamical class. Bond albedos for these DKBOs range from 0.01 to 0.04. Cold classical JY31 has a slightly lower slope and higher phase integral than the other DKBOs, and its slope and phase integral come closest to matching those of cold classical MU69, suggesting that cold classical KBOs share surface scattering characteristics that are distinct from those of other KBOs.
Ehlers-Danlos Syndrome (EDS) are a heterogeneous group of genetic connective tissue disorders, and typically manifests as weak joints that subluxate/dislocate, stretchy and/or fragile skin, ...organ/systems dysfunction, and significant widespread pain. Historically, this syndrome has been poorly understood and often overlooked. As a result, people living with EDS had difficulty obtaining an accurate diagnosis and appropriate treatment, leading to untold personal suffering as well as ineffective health care utilization. The GoodHope EDS clinic addresses systemic gaps in the diagnosis and treatment of EDS. This paper describes a leap forward--from lack of awareness, diagnosis, and treatment--to expert care that is tailored to meet the specific needs of patients with EDS. The GoodHope EDS clinic consists of experts from various medical specialties who work together to provide comprehensive care that addresses the multi-systemic nature of the syndrome. In addition, EDS-specific self-management programs have been developed that draw on exercise science, rehabilitation, and health psychology to improve physical and psychosocial wellbeing and overall quality of life. Embedded into the program are research initiatives to shed light on the clinical presentation, underlying mechanisms of pathophysiology, and syndrome management. We also lead regular educational activities for community health care providers to increase awareness and competence in the interprofessional management of EDS beyond our doors and throughout the province and country.
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