Idiopathic pulmonary artery dissection: a case report

<p>Abstract</p> <p>Introduction</p> <p>The occurrence of pulmonary artery dissection is extremely rare in patients without pulmonary hypertension, congenital cardiac abnormalities or cardiac intervention. A diagnosis of pulmonary artery dissection is rarely made during life because it generally leads to cardiogenic shock and sudden death. The progression or natural course of pulmonary artery dissection is not known and the optimum management is not defined because of the paucity of cases in the literature.</p> <p>Case presentation</p> <p>We report a rare case of a 51-year-old female patient, without pulmonary hypertension or other cardiac abnormalities, who presented with acute chest pain and was found to have a pulmonary artery dissection.. The diagnosis of pulmonary artery dissection was confirmed by computed tomography scan of the chest and cardiac magnetic resonance imaging. The patient declined surgical intervention and was followed up closely with medical therapy. At almost a year after her initial presentation, the patient is stable with no complications.</p> <p>Conclusions</p> <p>To our knowledge, there are no similar cases reported in the literature of people with pulmonary artery dissection who have been followed up and who have not had surgical intervention. We review the etiology, pathophysiology, clinical associations, diagnosis and management of patients with pulmonary artery dissection.</p

A Review of Social and Relational Aspects of Deep Brain Stimulation in Parkinson's Disease Informed by Healthcare Provider Experiences

Background. Although the clinical effectiveness of deep brain stimulation (DBS) in Parkinson's disease is established, there has been less examination of its social aspects. Methods and Results. Building on qualitative comments provided by healthcare providers, we present four different social and relational issues (need for social support, changes in relationships (with self and partner) and challenges with regards to occupation and the social system). We review the literature from multiple disciplines on each issue. We comment on their ethical implications and conclude by establishing the future prospects for research with the possible expansion of DBS for psychiatric indications. Conclusions. Our review demonstrates that there are varied social issues involved in DBS. These issues may have significant impacts on the perceived outcome of DBS by patients. Moreover, the fact that the social impact of DBS is still not well understood in emerging psychiatric indications presents an important area for future examination

Effects of HIV Proteins on Macrophage Response to MAI

https://digitalcommons.unmc.edu/surp2023/1006/thumbnail.jp

Ergodic encoding for single-element ultrasound imaging in vivo

Conventional ultrasound imaging relies on the computation of geometric time delay from multiple sensors to detect the position of a scatterer. In this paper, we present Ergodic Relay Ultrasound Imaging (ERUI), a method that utilizes an ergodic cavity down to a single ultrasonic sensor for ultrasound imaging. With the proposed method, the ergodic cavity creates a unique temporal signature that encodes the position of a scatterer. When compared to standard approaches, ERUI enables the generation of images of comparable quality while utilizing fewer detector elements. Our results suggest that ERUI has the potential to achieve image resolution similar to that of traditional imaging techniques, shifting the complexity from hardware to sofware. The demonstrated feasibility offers a promising path towards ultrasound probes with reduced costs and complexity for more portable scanning devices.Comment: 5 pages, 4 figures, Lette

Creation of Computerized 3D MRI-Integrated Atlases of the Human Basal Ganglia and Thalamus

Functional brain imaging and neurosurgery in subcortical areas often requires visualization of brain nuclei beyond the resolution of current magnetic resonance imaging (MRI) methods. We present techniques used to create: (1) a lower resolution 3D atlas, based on the Schaltenbrand and Wahren print atlas, which was integrated into a stereotactic neurosurgery planning and visualization platform (VIPER); and (2) a higher resolution 3D atlas derived from a single set of manually segmented histological slices containing nuclei of the basal ganglia, thalamus, basal forebrain, and medial temporal lobe. Both atlases were integrated to a canonical MRI (Colin27) from a young male participant by manually identifying homologous landmarks. The lower resolution atlas was then warped to fit the MRI based on the identified landmarks. A pseudo-MRI representation of the high-resolution atlas was created, and a non-linear transformation was calculated in order to match the atlas to the template MRI. The atlas can then be warped to match the anatomy of Parkinson's disease surgical candidates by using 3D automated non-linear deformation methods. By way of functional validation of the atlas, the location of the sensory thalamus was correlated with stereotactic intraoperative physiological data. The position of subthalamic electrode positions in patients with Parkinson's disease was also evaluated in the atlas-integrated MRI space. Finally, probabilistic maps of subthalamic stimulation electrodes were developed, in order to allow group analysis of the location of contacts associated with the best motor outcomes. We have therefore developed, and are continuing to validate, a high-resolution computerized MRI-integrated 3D histological atlas, which is useful in functional neurosurgery, and for functional and anatomical studies of the human basal ganglia, thalamus, and basal forebrain

GPCRs and Fibroblast Heterogeneity in Fibroblast-Associated Diseases

G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of most targeted receptors . About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic pulmonary fibrosis, cardiac fibrosis, pancreatic fibrosis, hepatic fibrosis, and cancer as opposed to the GPCR signaling of fibroblasts in physiological conditions. Understanding the dynamics of GPCR signaling in fibroblasts with disease progression can help in the recognition of the complex interplay of different GPCR subtypes in fibroblast-mediated diseases. This review highlights the importance of designing and adaptation of next-generation strategies such as GPCR-omics, focused target identification, polypharmacology, and effective personalized medicine approaches to achieve better therapeutic outcomes for fibrosis and fibrosis associated malignancies

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

Background: The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells. Methods: PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies. Results: KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model. Conclusions: Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer

Ehrlichia chaffeensis Infections among HIV-infected Patients in Human Monocytic Ehrlichiosis–Endemic Area

Manifestations of human monocytic ehrlichiosis (HME), a tick-borne infection caused by Ehrlichia chaffeensis, range from asymptomatic disease to fulminant infection and may be particularly severe in persons infected with HIV. We conducted a serologic study to determine the epidemiology of HME in HIV-positive patients residing in an HME-endemic area. We reviewed charts from a cohort of 133 HIV-positive patients who were seen during the 1999 tick season with symptoms compatible with HME (n=36) or who were asymptomatic (n=97). When available, paired plasma samples obtained before and after the tick season were tested by using an indirect immunofluorescence assay (IFA) to detect antibodies reactive to E. chaffeensis. Two symptomatic incident cases were identified by IFA, resulting in a seroincidence of 6.67% among symptomatic HIV-positive participants with paired samples available for testing and 1.64% overall. The baseline seroprevalence of HME was 0%. In contrast to infection in immunocompetent patients, E. chaffeensis infection in HIV-positive persons typically causes symptomatic disease

Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease

Fas (CD95), a member of the tumor necrosis factor-receptor superfamily, has been studied extensively as a death-inducing receptor in the immune system. However, Fas is also widely expressed in a number of other tissues, including in neurons. Here, we report that defects in the Fas/Fas ligand system unexpectedly render mice highly susceptible to neural degeneration in a model of Parkinson's disease. We found that Fas-deficient lymphoproliferative mice develop a dramatic phenotype resembling clinical Parkinson's disease, characterized by extensive nigrostriatal degeneration accompanied by tremor, hypokinesia, and loss of motor coordination, when treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose that causes no neural degeneration or behavioral impairment in WT mice. Mice with generalized lymphoproliferative disease, which express a mutated Fas ligand, display an intermediate phenotype between that of lymphoproliferative and WT mice. Moreover, Fas engagement directly protects neuronal cells from MPTP/1-methyl-4-phenylpyridinium ion toxicity in vitro. Our data show that decreased Fas expression renders dopaminergic neurons highly susceptible to degeneration in response to a Parkinson-causing neurotoxin. These findings constitute the first evidence for a neuroprotective role for Fas in vivo