Comparison of gene expression in CD34+ cells from bone marrow and G-CSF-mobilized peripheral blood by high-density oligonucleotide array analysis - Supplemental Materials Only.

A prospective randomized trial has shown that there is a survival advantage for allogeneic transplant recipients who received granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral blood mononuclear cells (GPBMC) versus those who received bone marrow (BM) as a source of stem cells. The biological basis for this advantage is not clear and may be attributable to qualitative as well as quantitative differences in the CD34 cells, T cells, and/or the monocytes transplanted. To begin to address this issue, gene expression patterns in CD34 cells isolated from these 2 stem cell sources were compared to identify functional pathways that may distinguish these 2 populations. CD34 cells were isolated to purity from the BM and peripheral blood stem cells of multiple healthy donors. (The complete data set will be available at http://parma.fhcrc.org/lgraf upon publication.) Two separate RNA preparations from pooled samples from both sources were analyzed by Affymetrix Oligonucleotide Array chips for expression of over 6400 human genes. Comparative analyses among the samples showed that a small set of 28 sequences increased and 38 sequences decreased in expression more than 3-fold in both of the GPBMC samples compared to those in BM samples. More highly expressed genes include several for nuclear proteins and transcriptional factors. Functional categorization of the genes decreased in expression indicated sequences influential in cell cycle progression, in agreement with the recognized quiescence of circulating CD34 cells. Multiple transcriptional regulators and chemokines were also found to be decreased. These data emphasize that in addition to increased numbers of CD34 cells, G-CSF mobilization also results in significant qualitative changes. Whether they impact engraftment remains to be determined

The Electromagnetic Self-Energy Contribution to M_p - M_n and the Isovector Nucleon Magnetic Polarizability

We update the determination of the isovector nucleon electromagnetic self-energy, valid to leading order in QED. A technical oversight in the literature concerning the elastic contribution to Cottingham's formula is corrected and modern knowledge of the structure functions is used to precisely determine the inelastic contribution. We find \delta M_{p-n}^\gamma = 1.30(03)(47) MeV. The largest uncertainty arises from a subtraction term required in the dispersive analysis, which can be related to the isovector magnetic polarizability. With plausible model assumptions, we can combine our calculation with additional input from lattice QCD to constrain this polarizability as: \beta_{p-n} = -0.87(85) x 10^{-4} fm^3.Comment: 5 pages, version accepted for publication in PR

Effects of Acute Exercise on Affect in Females with Substance Use Disorder

International Journal of Exercise Science 16(5): 95-108, 2023. Negative mood states experienced during the withdrawal stage of substance dependence have been associated with relapse in persons suffering from substance use disorder (SUD). Exercise is gaining attention as an adjunct therapy for SUD due to its ability to alleviate negative mood states experienced during withdrawal. The purpose of this study was to investigate the effects of acute, controlled bouts of aerobic and resistance exercise versus sedentary control (quiet reading) on positive affect (PA) and negative affect (NA) in females undergoing SUD treatment at inpatient facilities. Females (n=11; 34 + 8 yrs) were randomly assigned to each condition in counterbalanced fashion. Aerobic exercise (AE) consisted of 20 minutes of steady-state moderate intensity (40-60% HRR) treadmill walking. Resistance exercise (RE) consisted of 20 minutes of standardized circuit weight training (1:1 work to rest ratio). The Positive and Negative Affect Scale (PANAS) was used to assess PA and NA pre- and post-interventions. Repeated measures ANOVAs indicated AE and RE significantly increased PA (p \u3c 0.05) versus control, with no significant difference between AE and RE. Friedman’s test revealed AE and RE significantly reduced NA (p \u3c 0.05) versus control. Results indicate short bouts of aerobic and resistance exercise are equally effective for acute mood regulation and superior to a sedentary control in females undergoing inpatient SUD treatment

Coronal magnetic reconnection driven by CME expansion -- the 2011 June 7 event

Coronal mass ejections (CMEs) erupt and expand in a magnetically structured solar corona. Various indirect observational pieces of evidence have shown that the magnetic field of CMEs reconnects with surrounding magnetic fields, forming, e.g., dimming regions distant from the CME source regions. Analyzing Solar Dynamics Observatory (SDO) observations of the eruption from AR 11226 on 2011 June 7, we present the first direct evidence of coronal magnetic reconnection between the fields of two adjacent ARs during a CME. The observations are presented jointly with a data-constrained numerical simulation, demonstrating the formation/intensification of current sheets along a hyperbolic flux tube (HFT) at the interface between the CME and the neighbouring AR 11227. Reconnection resulted in the formation of new magnetic connections between the erupting magnetic structure from AR 11226 and the neighboring active region AR 11227 about 200 Mm from the eruption site. The onset of reconnection first becomes apparent in the SDO/AIA images when filament plasma, originally contained within the erupting flux rope, is re-directed towards remote areas in AR 11227, tracing the change of large-scale magnetic connectivity. The location of the coronal reconnection region becomes bright and directly observable at SDO/AIA wavelengths, owing to the presence of down-flowing cool, dense (10^{10} cm^{-3}) filament plasma in its vicinity. The high-density plasma around the reconnection region is heated to coronal temperatures, presumably by slow-mode shocks and Coulomb collisions. These results provide the first direct observational evidence that CMEs reconnect with surrounding magnetic structures, leading to a large-scale re-configuration of the coronal magnetic field.Comment: 12 pages, 12 figure

Present Constraints on the H-dibaryon at the Physical Point from Lattice QCD

The current constraints from lattice QCD on the existence of the H-dibaryon are discussed. With only two significant lattice QCD calculations of the H-dibaryon binding energy at approximately the same lattice spacing, the forms of the chiral and continuum extrapolations to the physical point are not determined. In this brief report, we consider the constraints on the H-dibaryon imposed by two simple chiral extrapolations. In both instances, the extrapolation to the physical pion mass allows for a bound H-dibaryon or a near-threshold scattering state. Further lattice QCD calculations are required to clarify this situation.Comment: 8 pages, 2 figures, 1 table; revised for the journa

Genomic surveillance reveals low prevalence of livestock-associated methicillin-resistant Staphylococcus aureus in the East of England

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an emerging problem in many parts of the world. LA-MRSA has been isolated previously from animals and humans in the United Kingdom (UK), but the prevalence is unknown. The aim of this study was to determine the prevalence and to describe the molecular epidemiology of LA-MRSA isolated in the East of England (broadly Cambridge and the surrounding area). We accessed whole genome sequence data for 2,283 MRSA isolates from 1,465 people identified during a 12-month prospective study between 2012 and 2013 conducted in the East of England, United Kingdom. This laboratory serves four hospitals and 75 general practices. We screened the collection for multilocus sequence types (STs) and for host specific resistance and virulence factors previously associated with LA-MRSA. We identified 13 putative LA-MRSA isolates from 12 individuals, giving an estimated prevalence of 0.82% (95% CI 0.47% to 1.43%). Twelve isolates were mecC-MRSA (ten CC130, one ST425 and one ST1943) and single isolate was ST398. Our data demonstrate a low burden of LA-MRSA in the East of England, but the detection of mecC-MRSA and ST398 indicates the need for vigilance. Genomic surveillance provides a mechanism to detect and track the emergence and spread of MRSA clones of human importance.Supported by grants from the UKCRC Translational Infection Research (TIR) Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Ofce of the Scottish Government Health Directorate (to Prof. Peacock); a Hospital Infection Society Major Research Grant, and by Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute. Tis work was supported by the Wellcome Trust 201344/Z/16/Z. M.E.T. is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation, and by the NIHR Cambridge Biomedical Research Centre

Effect of axillary brachial plexus blockade on baroreflex-induced skin vasomotor responses: Assessing the effectiveness of sympathetic blockade

Background: The combination of laser Doppler flowmetry and non-invasive blood pressure monitoring allows the continuous observation of cutaneous vascular resistance (CVR). Continuous recording of unmodulated skin blood flow (SBF) is very sensitive to artefacts, rendering the method unreliable. In contrast, intermittent short lasting challenges of the CVR by cardiovascular autonomic reflexes may provide information about the responsiveness of the sympathetic nervous system in the skin. Methods: Eleven patients with below-wrist hand surgery (six males and five females; aged 35.2 ± 7.1 years) performed Valsalva maneuver following axillary blockade. Skin blood flow was continuously monitored on the forearm of the side axillary blockade, as well as on the contra-lateral forearm, which was used as the control. The responses were expressed as changes compared with the baseline level derived from a resting period of 30s. The maxima

Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community

Genome sequencing has provided snapshots of the transmission of methicillin-resistant Staphylococcus aureus (MRSA) during suspected outbreaks in isolated hospital wards. Scale-up to populations is now required to establish the full potential of this technology for surveillance. We prospectively identified all individuals over a 12-month period who had at least one MRSA-positive sample processed by a routine diagnostic microbiology laboratory in the East of England, which received samples from three hospitals and 75 general practitioner (GP) practices. We sequenced at least 1 MRSA isolate from 1465 individuals (2282 MRSA isolates) and recorded epidemiological data. An integrated epidemiological and phylogenetic analysis revealed 173 transmission clusters containing between 2 and 44 cases and involving 598 people (40.8%). Of these, 118 clusters (371 people) involved hospital contacts alone, 27 clusters (72 people) involved community contacts alone, and 28 clusters (157 people) had both types of contact. Community- and hospital-associated MRSA lineages were equally capable of transmission in the community, with instances of spread in households, long-term care facilities, and GP practices. Our study provides a comprehensive picture of MRSA transmission in a sampled population of 1465 people and suggests the need to review existing infection control policy and practice.This work was supported by grants from the UK Clinical Research Collaboration Translational Infection Research Initiative and the Medical Research Council (grant no. G1000803) with contributions to the grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research (NIHR) on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to S.J.P.); by a Hospital Infection Society Major Research Grant; by Wellcome Trust grant no. 098051 awarded to the Wellcome Trust Sanger Institute; and by Wellcome Trust 201344/Z/16/Z awarded to F.C. M.S.T. is a Wellcome Trust Clinical PhD fellow. M.E.T. is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation and by the NIHR Cambridge Biomedical Research Centr

Aplastic Crisis as Primary Manifestation of Systemic Lupus Erythematosus

Aplastic crisis is an unusual feature of systemic lupus erythematosus (SLE). We report the case of a 54-year-old woman presenting with both (extravascular) Coombs-positive hemolytic anemia and laboratory findings of bone marrow hyporegeneration with concomitant severe neutropenia. A bone marrow biopsy confirmed aplastic crisis. Diagnostic work-up revealed soaring titers of autoantibodies (anti-nuclear, anti-double-stranded DNA, anti-cardiolipin-IgM, and anti-beta 2-glykoprotein-IgM antibodies), indicating a connective tissue disease as the most plausible reason for bone marrow insufficiency. As the criteria for SLE were fulfilled, we initiated an immunosuppressive therapy by steroids, which led to a rapid complete hematologic and clinical remission in our patient. In this case, we could report on one of the rare cases of SLE-induced aplastic crisis showing that this condition can be entirely reversed by immunosuppressive treatment and that SLE-induced aplastic crisis yields a good prognosis. In conclusion, in a case of aplastic crisis, physicians should be aware that SLE can be a rare cause that is accessible to specific treatment