Perceptions of clinical care and research among African-American patients with lymphoma.

Across lymphoma subtypes, African Americans experience disparities in clinical trial enrollment and outcomes. Understanding the needs of this population can aid addressing these disparities. Semi-structured interviews were conducted with 14 self-identified Black/African-American lymphoma patients to determine their perceptions and attitudes about aspects of treatment and research. Constant-comparative methods identified themes including trust in medical staff, lack of diagnosis information, interest in research, research priorities, and potentially unaddressed emotional needs. Patients trusted their doctors and desired more diagnosis information. Participants often did not consider the emotions surrounding their diagnoses and concentrated on positive attitudes during treatment. Most participants were interested in clinical trials to help future lymphoma patients. Participants suggested a range of future research topics emphasizing lymphoma etiology. Building on trusting doctor-patient relationships, expanding clinical trials information, addressing emotional needs, and aligning research objectives with patient concerns are potential strategies for increasing clinical trial enrollment among Black lymphoma patients.

Priorities for Rural Lymphoma Survivors: A Qualitative Study.

BACKGROUND: We gathered rural patient perspectives on lymphoma care and unmet needs throughout the treatment course to better understand their attitudes toward treatment and their barriers to participating in clinical research studies. PATIENTS AND METHODS: We conducted 12 individual semi-structured telephone interviews in the spring of 2018 with lymphoma survivors from rural counties in Georgia. Patients were identified by a residential address in counties classified as rural according to the Rural-Urban Commuting Areas codes. Participants were recruited from regional patient education conferences and from current research participants at a university research hospital in Georgia. The interviews were recorded and transcribed verbatim. Thematic analysis and MAXQDA, version 18.0.8, were used to facilitate a constant comparative coding process during theme development. RESULTS: The greatest barrier to care was the travel distance. The participants described difficulty navigating between local clinics and larger cancer centers. The lack of communication between the local and specialized clinics complicated the process, and participants had difficulty contacting or seeking advice from the team at the larger cancer centers. Seeking treatment from specialized clinics farther away introduced additional barriers. Most participants agreed that the use of technology was important for improved communication. Participants described lymphoma etiology, subtype-specific studies, alternative therapies, and quality of life as key research priorities. CONCLUSION: These findings suggest that targeted research and interventions are necessary to address the specific needs of rural patients with and survivors of lymphoma. To address the disparity in health outcomes within rural populations, healthcare professionals and investigators can use these data to engage rural patients in treatment decision-making and research planning.

Evidence for negative thermal expansion in the superconducting precursor phase SmFeAsO.

The fluorine-doped rare-earth iron oxypnictide series SmFeAsO1-x F x (0 [Formula: see text] 0.10) was investigated with high resolution powder x-ray scattering. In agreement with previous studies (Margadonna et al 2009 Phys. Rev. B. 79 014503), the parent compound SmFeAsO exhibits a tetragonal-to-orthorhombic structural distortion at [Formula: see text] = 130 K which is rapidly suppressed by [Formula: see text] 0.10 deep within the superconducting dome. The change in unit cell symmetry is followed by a previously unreported magnetoelastic distortion at 120 K. The temperature dependence of the thermal expansion coefficient [Formula: see text] reveals a rich phase diagram for SmFeAsO: (i) a global minimum at 125 K corresponds to the opening of a spin-density wave instability as measured by pump-probe femtosecond spectroscopy (Mertelj et al 2010 Phys. Rev. B 81 224504) whilst (ii) a global maximum at 110 K corresponds to magnetic ordering of the Sm and Fe sublattices as measured by magnetic x-ray scattering (Nandi et al 2011 Phys. Rev. B 84 055419). At much lower temperatures than [Formula: see text], SmFeAsO exhibits a significant negative thermal expansion on the order of -40 ppm · K-1 in contrast to the behaviour of other rare-earth oxypnictides such as PrFeAsO (Kimber et al 2008 Phys. Rev. B 78 140503) and the actinide oxypnictide NpFeAsO (Klimczuk et al 2012 Phys. Rev. B 85 174506) where the onset of [Formula: see text] 0 only appears in the vicinity of magnetic ordering. Correlating this feature with the temperature and doping dependence of the resistivity and the unit cell parameters, we interpret the negative thermal expansion as being indicative of the possible condensation of itinerant electrons accompanying the opening of a SDW gap, consistent with transport measurements (Tropeano et al 2009 Supercond. Sci. Technol. 22 034004).

Tales of diversity: Genomic and morphological characteristics of forty-six Arthrobacter phages.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.

Forskolin stimulation promotes urea transporter UT-A1 ubiquitination, endocytosis, and degradation in MDCK cells.

The adenylyl cyclase stimulator forskolin (FSK) stimulates UT-A1 phosphorylation, membrane trafficking, and urea transport activity. Here, we found that FSK stimulation induces UT-A1 ubiquitination in UT-A1 Madin-Darby canine kidney (MDCK) cells. This suggests that phosphorylation by FSK also triggers the protein degradation machinery for UT-A1. UT-A1-MDCK cells were treated with 100 µg/ml cycloheximide to inhibit protein synthesis, with or without 10 µM FSK. Total UT-A1 protein abundance was significantly reduced after FSK treatment, concomitantly ubiquitinated UT-A1 was increased. We then specifically investigated the effect of FSK on UT-A1 expressed on the cell plasma membrane. FSK treatment accelerated UT-A1 removal from the cell plasma membrane by increasing UT-A1 endocytosis as judged by biotinylation/MesNa treatment and confocal microscopy. We further found that inhibition of the clathrin-mediated endocytic pathway, but not the caveolin-mediated endocytic pathway, significantly blocks FSK-stimulated UT-A1 endocytosis. The PKA inhibitor H89 and the proteasome inhibitors MG132 and lactacystin reduced FSK-induced membrane UT-A1 reduction. Our study shows that FSK activates the UT-A1 urea transporter and the activation/phosphorylation subsequently triggers the downregulation of UT-A1, which represents an important mechanism for the cell to return to the basal conditions after vasopressin stimulation.

Glycoforms of UT-A3 urea transporter with poly-N-acetyllactosamine glycosylation have enhanced transport activity.

Urea transporters UT-A1 and UT-A3 are both expressed in the kidney inner medulla. However, the function of UT-A3 remains unclear. Here, we found that UT-A3, which comprises only the NH(2)-terminal half of UT-A1, has a higher urea transport activity than UT-A1 in the oocyte and that this difference was associated with differences in N-glycosylation. Heterologously expressed UT-A3 is fully glycosylated with two glycoforms of 65 and 45 kDa. By contrast, UT-A1 expressed in HEK293 cells and oocytes exhibits only a 97-kDa glycosylation form. We further found that N-glycans of UT-A3 contain a large amount of poly-N-acetyllactosamine. This highly glycosylated UT-A3 is more stable and is enriched in lipid raft domains on the cell membrane. Kifunensine, an inhibitor of α-mannosidase that inhibits N-glycan processing beyond high-mannose-type N-glycans, significantly reduced UT-A3 urea transport activity. We then examined the native UT-A1 and UT-A3 glycosylation states from kidney inner medulla and found the ratio of 65 to 45 kDa in UT-A3 is higher than that of 117 to 97 kDa in UT-A1. The highly stable expression of highly glycosylated UT-A3 on the cell membrane in kidney inner medulla suggests that UT-A3 may have an important function in urea reabsorption.

Depolymerization of cortical actin inhibits UT-A1 urea transporter endocytosis but promotes forskolin-stimulated membrane trafficking.

The cytoskeleton participates in many aspects of transporter protein regulation. In this study, by using yeast two-hybrid screening, we identified the cytoskeletal protein actin as a binding partner with the UT-A1 urea transporter. This suggests that actin plays a role in regulating UT-A1 activity. Actin specifically binds to the carboxyl terminus of UT-A1. A serial mutation study shows that actin binding to UT-A1's carboxyl terminus was abolished when serine 918 was mutated to alanine. In polarized UT-A1-MDCK cells, cortical filamentous (F) actin colocalizes with UT-A1 at the apical membrane and the subapical cytoplasm. In the cell surface, both actin and UT-A1 are distributed in the lipid raft microdomains. Disruption of the F-actin cytoskeleton by latrunculin B resulted in UT-A1 accumulation in the cell membrane as measured by biotinylation. This effect was mainly due to inhibition of UT-A1 endocytosis in both clathrin and caveolin-mediated endocytic pathways. In contrast, actin depolymerization facilitated forskolin-stimulated UT-A1 trafficking to the cell surface. Functionally, depolymerization of actin by latrunculin B significantly increased UT-A1 urea transport activity in an oocyte expression system. Our study shows that cortical F-actin not only serves as a structural protein, but directly interacts with UT-A1 and plays an important role in controlling UT-A1 cell surface expression by affecting both endocytosis and trafficking, therefore regulating UT-A1 bioactivity.

Orbital-ordering transition in Sr2VO4.

Temperature-dependent dc susceptibility and x-ray powder diffraction on a pure tetragonal sample of Sr(2)VO(4) show an antiferromagnetic orbital-ordering transition at T(oo) = 97 K, in which the occupied orbitals lie along the c axis. The unusual broadening of the x-ray Bragg peaks throughout the orbital-ordering transition temperature region indicates that this process occurs in stages, and the onset of short-range orbital ordering occurs at T(1) approximately 122 K. The study of the order parameter associated with this transition by analyzing the spontaneous strain results in a critical exponent beta = 0.35(2) consistent with 3D Heisenberg behavior. These results experimentally confirm the orbital-ordering state in Sr(2)VO(4) predicted by first-principles calculations using combinations of the local-density approximation and the GW method.

Effect of pyrolysis temperature on the mutagenicity of tobacco smoke condensate.

Tobacco smoke aerosols with fewer mutagens in the particulate fraction may present reduced risk to the smoker. The objective of this study was to test the hypothesis that the temperature at which tobacco is pyrolyzed or combusted can affect the mutagenicity of the particulate fraction of the smoke aerosol. Tobacco smoke aerosol was generated under precisely controlled temperature conditions from 250 to 550 degrees C by heating compressed tobacco tablets in air. The tobacco aerosols generated had a cigarette smoke-like appearance and aroma. The tobacco smoke aerosol was passed through a Cambridge filter pad to collect the particulate fraction, termed the smoke condensate. Although condensates of tobacco smoke and whole cigarette mainstream smoke share many of the same chemical components, there are physical and chemical differences between the two complex mixtures. The condensates from smoke aerosols prepared at different temperatures were assayed in the Ames Salmonella microsome test with metabolic activation by rat liver S9 using tester strains TA98 and TA100. Tobacco smoke condensates were not detectably mutagenic in strain TA98 when the tobacco smoke aerosol was generated at temperatures below 400 degrees C. Above 400 degrees C, condensates were mutagenic in strain TA98. Similarly, condensates prepared from tobacco smoke aerosols generated at temperatures below 475 degrees C were not detectably mutagenic in strain TA100. In contrast, tobacco tablets heated to temperatures of 475 degrees C or greater generated smoke aerosol that was detectably mutagenic as measured in TA100. Therefore, heating and pyrolyzing tobacco at temperatures below those found in tobacco burning cigarettes reduces the mutagenicity of the smoke condensate. Highly mutagenic heterocyclic amines derived from the pyrolysis of tobacco leaf protein may be important contributors to the high temperature production of tobacco smoke Ames Salmonella mutagens. The relevance of these findings regarding cancer risk in humans is difficult to assess because of the lack of a direct correlation between mutagenicity in the Ames Salmonella test and carcinogenicity.

Dependence of insulin secretion from permeabilized pancreatic beta-cells on the activation of Ca(2+)/calmodulin-dependent protein kinase II. A re-evaluation of inhibitor studies.

Previous studies utilizing inhibitors of the Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) to address the role of this enzyme in insulin secretion have produced contradictory results. In the current study, these inconsistencies have been addressed by evaluating the effect of various CaM kinase II inhibitors to decrease Ca(2+)-induced insulin secretion from permeabilized beta-cells. KN-93 (2-[N-(2-hydroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlo rocinnamyl)-N-methylbenzylamine) markedly inhibited both CaM kinase II activation and insulin secretion in parallel in alpha-toxin-permeabilized beta-cells. These effects were specific since they were not mimicked by the inactive analog, KN-92 (2-[N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methy lbenzylamine). In contrast, KN-62 (1-[N, O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine) , while reported to be similar to KN-93 with respect to mechanism of action, did not inhibit Ca(2+)-induced activation of CaM kinase II or insulin secretion in these cell preparations. All three agents suppressed Ca(2+) influx in intact beta-cells induced by depolarization in the presence of elevated extracellular potassium although to different extents. The synthetic peptide inhibitors of CaM kinase II, [Ala(286)]CaMK 281-302 and AIP (autocamtide-2-related inhibitory peptide), strongly inhibited Ca(2+)-induced insulin secretion from electropermeabilized islets, an effect that also correlated with an equivalent inhibition of CaM kinase II activation. This re-evaluation (i) explains a lack of effect of KN-62 on insulin secretion from permeabilized cells based on its inability to inhibit CaM kinase II activation in these preparations; (ii) has revealed that CaM inhibitors, either chemical or peptide in nature, that are capable of preventing enzyme activation uniformly suppress Ca(2+)-sensitive insulin secretion; and (iii) cautions the use of KN-62/93/92 as selective inhibitors of CaM kinase II in intact cell studies. These observations reinforce the suggestion that CaM kinase II plays an important role in insulin exocytosis in the beta-cell.

Acute respiratory distress syndrome. Potential pharmacologic interventions.

Remarkable progress has been made in the past 10 years with regard to understanding the interplay of potent physiologic mediators in patients with acute lung injury. Because there are so many mediators and the interaction of these agents is complex, true insight into the process has been slow in coming. Clinical studies in ARDS, as well as sepsis, the leading cause of ARDS, have increased in number, size, and quality over this same period. Although none of these studies has produced an accepted new therapy for ARDS, each has laid the groundwork for more efficient and more elegant studies of the problem. The stage is now set for the real advances to be brought forward and put to rigorous, efficient clinical testing.

A software application that answers the need for an enterprise budgeting tool.

A prototype software application developed for the Vanderbilt University School of Medicine answered our need for an enterprise budgeting tool--one that has application across the entire organization. This application, built on Microsoft Access, provides a flexible user interface without requiring sophisticated technical support.

Accuracy of judgments of sexual orientation from thin slices of behavior.

In this research the authors examined the accuracy of judging sexual orientation on the basis of brief observations or "thin slices" of nonverbal behavior. In Study 1, sexual orientation was judged more accurately than chance, with judgments being more accurate when based on dynamic nonverbal behavior (10-s and 1-s silent video segments) than on static information (a series of 8 still photographs). Gay men and lesbians were more accurate than heterosexuals in judging still photographs and 1-s clips but not in 10-s clips. In Study 2, judgments based on 10-s dynamic figural outline displays containing primarily gestural information were more accurate than chance.

Restenosis following angioplasty in the swine coronary artery is inhibited by an orally active PDGF-receptor tyrosine kinase inhibitor, RPR101511A.

BACKGROUND: Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis. METHODS AND RESULTS: RPR101511A is a novel compound which selectively and potently inhibits the cell-free and in situ PDGFr-TK and PDGFr-dependent proliferation and chemotaxis in vascular smooth muscle cells (VSMC). To evaluate the effect of RPR101511A (30 mg. kg-1. d-1 BID for 28 days following PTCA) on coronary restenosis, PTCA was performed in hypercholesterolemic minipigs whose left anterior descending (LAD) coronary artery had been injured by overdilation and denudation, yielding a previously existing lesion. Angiographically determined prePTCA minimal lumen diameters (MLD) were similar in vehicle and RPR101511A-treated pigs (1.98+/-0.09 versus 2.01+/-0.08 mm) and increased to the same extent in the 2 groups following successful PTCA (2.30+/-0.06 versus 2.52+/-0.13). At termination, there was an average 50% loss of gain in the vehicle-treated group but no loss of gain with RPR101511A (2.16+/-0. 05 versus 2.59+/-0.11, P<0.001). Morphometric analysis of the LAD showed that RPR101511A caused a significant decrease in total intimal/medial ratio (0.96+/-0.58 versus 0.67+/-0.09, P<0.05). CONCLUSIONS: RPR101511A, which acts by inhibition of the PDGFr-TK, completely prevented angiographic loss of gain following PTCA and significantly reduced histological intimal hyperplasia.

Associations between drug abuse treatment and cigarette use: evidence of substance replacement.

The influence of risk-behavior bias, drug use, prior cigarette use, and prior and current participation in drug treatment on cigarette use was analyzed using a 3-wave survey of 346 drug abusers. Participation in drug treatment and a risk-behavior bias were hypothesized to predict greater cigarette use. After controlling for prior levels of cigarette use with a longitudinal path model, it was found that participation in drug treatment at Wave 2 significantly predicted increased cigarette use at Wave 2. There were similar results at Wave 3. Additional analyses indicated that reduced heroin use was especially associated with more smoking. Risk-behavior bias predicted more drug and cigarette use and predicted less participation in drug treatment at Wave 3. These results suggest that drug treatment, reduced heroin use, and a tendency toward risky behavior may lead to increased cigarette use, which may represent a form of substance replacement.

Linkage of typical pseudoachondroplasia to chromosome 19.

Pseudoachondroplasia (PSACH) is an autosomal dominant dwarfing condition associated with disproportionate short stature, marked joint deformities, and early onset osteoarthritis. Previous linkage studies have excluded linkage to cartilage and noncartilagenous extracellular matrix candidate genes. Here, we report mapping the pseudoachondroplasia gene to chromosome 19. Maximum lod scores of 4.70, 4.15, and 4.86 at theta = 0.00 were found for D19S212, D19S215, and D19S49, respectively. Multipoint analysis suggests the following order: D19S253-D19S199-(D19S212/PSACH/D19S215)-++ +D19S222-D19S49.

Utilizing lung sounds analysis for the evaluation of acute asthma in small children.

One of the most difficult aspects of management of acute asthma in the small child is the clinician's inability to quantitate the response or lack of response to bronchodilator agents because of the inability of a child this age to perform objective lung measurements in the acute state. The present study was designed to evaluate bronchodilator responsiveness in children between 2 and 6 years of age with wheezing by means of a computerized lung sound analysis, computer digitized airway phonopneumonography. Children between ages 2 and 6 who were experiencing acute exacerbations of asthma were included in this study population. The 43 children were evaluated by physical examination, pulmonary function testing, if possible, by use of (spirometry or peak flow meter) and transmission of lung sounds to a computer using an electronic stethoscope to obtain a phonopneumograph with sound intensity level determinations during tidal breathing. A control group of 20 known asthmatic patients between the ages of 8 and 52 years who also presented to the office with acute asthma were evaluated similarly. In each of these individuals, a physical examination was followed by complete spirometry as well as computer digitized airway phonopneumonography recordings. Following initial measurements, all patients were treated with nebulized albuterol (0.25 mL in 2 mL of saline). Five minutes after completion of the nebulization all patients were reexamined and repeat pulmonary function tests were performed followed by CDAP recordings. In the study group of children, the mean pretreatment sound intensity level was 1,694 (range 557 to 4,950 SD +/- 745).(ABSTRACT TRUNCATED AT 250 WORDS)