IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23

Vicarious Antitrust Liability in the Health Care Field

In order to understand the interface between vicarious antitrust liability and the decline of the independent contractor defense in the health care field, it is necessary to understand the complex relationship between the hospital and the physician, as well as the recent changes that have taken place in that relationship. Therefore, this article will briefly trace the changes that have occurred in the traditional rules of the hospital\u27s relationship with its physicians. Then, the current relationship between hospital and staff physician will be examined in light of legal requirements, accreditation standards and practical considerations. After a brief introduction to the health care marketplace as a context for antitrust law, the new theories of liability will be applied to the health care field, in order to give examples of claims likely to be asserted by plaintiffs and defenses that can be raised by health care institutions

Cross-sectional survey of Good Samaritan behaviour by physicians in North Carolina

ObjectiveTo assess the responses of physicians to providing emergency medical assistance outside of routine clinical care. We assessed the percentage who reported previous Good Samaritan behaviour, their responses to hypothetical situations, their comfort providing specific interventions and the most likely reason they would not intervene.SettingPhysicians residing in North Carolina.ParticipantsConvenience sample of 1000 licensed physicians.InterventionMailed survey.DesignCross-sectional study conducted May 2015 to September 2015.Main outcome and measuresWillingness of physicians to act as Good Samaritans as determined by the last opportunity to intervene in an out-of-office emergency.ResultsThe adjusted response rate was 26.1% (253/970 delivered). 4 out of 5 physicians reported previous opportunities to act as Good Samaritans. Approximately, 93% reported acting as a Good Samaritan during their last opportunity. There were no differences in this outcome between sexes, practice setting, specialty type or experience level. Doctors with greater perceived knowledge of Good Samaritan law were more likely to have intervened during a recent opportunity (p=0.02). The most commonly cited reason for potentially not intervening was that another health provider had taken charge.ConclusionsWe found the frequency of Good Samaritan behaviour among physicians to be much higher than reported in previous studies. Greater helping behaviour was exhibited by those who expressed more familiarity with Good Samaritan law. These findings suggest that physicians may respond to legal protections

Assessment of Kinematics and Electromyography Following Arthroscopic Single-Tendon Rotator Cuff Repair

Background The increasing demand for rotator cuff (RC) repair patients to return to work as soon as they are physically able has led to exploration of when this is feasible. Current guidelines from our orthopedic surgery clinic recommend a return to work at 9 weeks postoperation. To more fully define capacity to return to work, the current study was conducted using a unique series of quantitative tools. To date, no study has combined 3-dimensional (3D) motion analysis with electromyography (EMG) assessment during activities of daily living (ADLs), including desk tasks, and commonly prescribed rehabilitation exercise. Objective To apply a quantitative, validated upper extremity model to assess the kinematics and muscle activity of the shoulder following repair of the supraspinatus RC tendon compared to that in healthy shoulders. Design A prospective, cross-sectional comparison study. Setting All participants were evaluated during a single session at the Medical College of Wisconsin Department of Orthopaedic Surgery\u27s Motion Analysis Laboratory. Participants Ten participants who were 9-12 weeks post–operative repair of a supraspinatus RC tendon tear and 10 participants with healthy shoulders (HS) were evaluated. Methods All participants were evaluated with 3D motion analysis using a validated upper extremity model and synchronized EMG. Data from the 2 groups were compared using multivariate Hotelling T2 tests with post hoc analyses based on Welch t-tests. Main Outcome Measurements Participants\u27 thoracic and thoracohumeral joint kinematics, temporal-spatial parameters, and RC muscle activity were measured by applying a quantitative upper extremity model during 10 activities of daily living and 3 rehabilitation exercises. These included tasks of hair combing, drinking, writing, computer mouse use, typing, calling, reaching to back pocket, pushing a door open, pulling a door closed, external rotation, internal rotation, and rowing. Results There were significant differences of the thoracohumeral joint motion in only a few of the tested tasks: comb maximal flexion angle (P = .004), pull door internal/external rotation range of motion (P = .020), reach abduction/adduction range of motion (P = .001), reach flexion/extension range of motion (P = .001), reach extension minimal angle (P = .025), active external rotation maximal angle (P = .012), and active external rotation minimal angle (P = .004). The thorax showed significantly different kinematics of maximal flexion angle during the call (P = .011), mouse (P = .007), and drink tasks (P = .005) between the 2 groups. The EMG data analysis showed significantly increased subscapularis activity in the RC repair group during active external rotation. Conclusions Although limited abduction was expected due to repair of the supraspinatus tendon, only a single ADL (reaching to back pocket) had a significantly reduced abduction range of motion. Thoracic motion was shown to be used as a compensatory strategy during seated ADLs. Less flexion of the thorax may create passive shoulder flexion at the thoracohumeral joint in efforts to avoid active flexion. The RC repair group participants were able to accomplish the ADLs within the same time frame and through thoracohumeral joint kinematics similar to those in the healthy shoulder group participants. In summary, this study presents a quantification of the effects of RC repair and rehabilitation on the ability to perform ADLs. It may also point to a need for increased rehabilitation focus on either regaining external rotation strength or range of motion following RC repair to enhance recovery and return to the workforce

Characterization of ENU-induced mutations in red blood cell structural proteins

Murine models with modified gene function as a result of N-ethyl-N-nitrosourea (ENU) mutagenesis have been used to study phenotypes resulting from genetic change. This study investigated genetic factors associated with red blood cell (RBC) physiology an

Magnetic excitations in stripe-ordered La1.875_{1.875}Ba0.125_{0.125}CuO4_4 studied using resonant inelastic x-ray scattering

The charge and spin correlations in La$_{1.875}$Ba$_{0.125}$CuO$_4$ (LBCO 1/8) are studied using Cu $L_3$ edge resonant inelastic x-ray scattering (RIXS). The static charge order (CO) is observed at a wavevector of $(0.24,0)$ and its charge nature confirmed by measuring the dependence of this peak on the incident x-ray polarization. The paramagnon excitation in LBCO 1/8 is then measured as it disperses through the CO wavevector. Within the experimental uncertainty no changes are observed in the paramagnon due to the static CO, and the paramagnon seems to be similar to that measured in other cuprates, which have no static CO. Given that the stripe correlation modulates both the charge and spin degrees of freedom, it is likely that subtle changes do occur in the paramagnon due to CO. Consequently, we propose that future RIXS measurements, realized with higher energy resolution and sensitivity, should be performed to test for these effects.Comment: 5 pages, 4 figure

Synthetic properties of bright metal-poor variables. II. BL Her stars

We investigate the properties of the so-called BL Her stars, i.e., Population II Cepheids with periods shorter than 8 days, using updated pulsation models and evolutionary tracks computed adopting a metal abundance in the range of Z=0.0001 to Z=0.004. We derive the predicted Period-Magnitude (PM) and Period-Wesenheit (PW) relations at the various photometric bands and we show that the slopes of these relations are in good agreement with the slopes determined by observed variables in Galactic globular clusters, independently of the adopted M_V(RR)-[Fe/H] relation to get the cluster RR Lyrae-based distance. Moreover, we show that also the distances provided by the predicted PM and PW relations for BL Her stars agree within the errors with the RR Lyrae based values. The use of the predicted relations with W Vir stars, which are Population II Cepheids with periods longer than 8 days, provides no clear evidence for or against a change in the PM and PW slopes around P~10 days.Comment: 12 pages, 6 figures, 6 tables, accepted for publication in A&A on date 16/05/200

The Andromeda Project. I. Deep HST-WFPC2 V,I photometry of 16 fields toward the disk and the halo of the M31 galaxy. Probing the stellar content and metallicity distribution

HST-WFPC2 F555W and F814W photometry were obtained for 16 fields of the luminous nearby spiral galaxy M31, sampling the stellar content of the disk and the halo at different distances from the center, from ~ 20 to ~ 150 arcmin (i.e. ~ 4.5 to 35 kpc), down to limiting V and I magnitudes of ~ 27. The Color-Magnitude diagrams (CMD) show the presence of complex stellar populations, including an intermediate age/young population and older populations with a wide range of metallicity. Those fields superposed on the disk of M31 generally show a blue plume of stars which we identify with main sequence members. Accordingly, the star formation rate over the last 0.5 Gyr appears to have varied dramatically with location in the disk. All the CMDs show a prominent Red Giant Branch (RGB) with a descending tip in the V band, characteristic of metallicity higher than 1/10 Solar. A red clump is detected in all of the fields, and a weak blue horizontal branch is frequently present. The metallicity distributions (MDs), obtained by comparison of the RGB stars with globular cluster templates, are basically similar in all the sampled fields: they all show a long, albeit scantly populated metal-poor tail and a main component at [Fe/H] ~ -0.6. However, some differences also exist, e.g. in some fields a very metal-rich ([Fe/H] >= -0.2) component is present. Whereas the fraction of metal-poor stars seems to be approximately constant in all fields, the fraction of very-metal-rich stars varies with position and seems to be more prominent in those fields superposed on the disk and/or with the presence of streams or substructures. This might indicate and possibly trace interaction effects with some companion, e.g. M32.Comment: 23 pages (including 5 tables), 22 figures, submitted to A&

The 2015 Middle Childhood Survey (MCS) of mental health and well-being at age 11 years in an Australian population cohort

Purpose: The Middle Childhood Survey (MCS) was designed as a computerised self-report assessment of children's mental health and well-being at approximately 11 years of age, conducted with a population cohort of 87 026 children being studied longitudinally within the New South Wales (NSW) Child Development Study. Participants: School Principals provided written consent for teachers to administer the MCS in class to year 6 students at 829 NSW schools (35.0% of eligible schools). Parent or child opt-outs from participation were received for 4.3% of children, and MCS data obtained from 27 808 children (mean age 11.5 years, SD 0.5; 49.5% female), representing 85.9% of students at participating schools. Findings to date: Demographic characteristics of participating schools and children are representative of the NSW population. Children completed items measuring Social Integration, Prosocial Behaviour, Peer Relationship Problems, Supportive Relationships (at Home, School and in the Community), Empathy, Emotional Symptoms, Conduct Problems, Aggression, Attention, Inhibitory Control, Hyperactivity-Inattention, Total Difficulties (internalising and externalising psychopathology), Perceptual Sensitivity, Psychotic-Like Experiences, Personality, Self-esteem, Daytime Sleepiness and Connection to Nature. Distributions of responses on each item and construct demarcate competencies and vulnerabilities within the population: most children report mental health and well-being, but the population distribution spanned the full range of possible scores on every construct. Future plans: Multiagency, intergenerational linkage of the MCS data with health, education, child protection, justice and early childhood development records took place late in 2016. Linked data were used to elucidate patterns of risk and protection across early and middle child development, and these data will provide a foundation for future record linkages in the cohort that will track mental and physical health, social and educational/occupational outcomes into adolescence and early adulthood.Kristin R Laurens, Stacy Tzoumakis, Kimberlie Dean, Sally A Brinkman, Miles Bore, Rhoshel K Lenroot, Maxwell Smith, Allyson Holbrook, Kim M Robinson, Robert Stevens, Felicity Harris, Vaughan J Carr, Melissa J Gree