Innate Immune Function in Placenta and Cord Blood of Hepatitis C – Seropositive Mother-Infant Dyads

Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in ∼80% of cases following exposure, the rate of mother-to-child transmission (2–6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and γδ-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells

Feasibility of a mHealth Approach to Nutrition Counseling in an Appalachian State

Abstract: West Virginia is a rural state with an aging population that may experience barriers to accessing nutritional and lifestyle counseling. This study examined feasibility of an online personalized nutrition tracking application, Good Measures (GM), with patients at seven health care clinics throughout the state. Fourteen healthcare providers and 64 patients 18 years or older with a Body Mass Index (BMI) greater than or equal to 30 and access to the Internet were recruited for this 12-week feasibility study. Patient participants logged meals and exercise into the GM application via smart phone, tablet, or computer and virtually engaged with a Registered Dietitian Nutritionist (RDN) in one-on-one sessions. The primary endpoint was to examine feasibility of the program by usage of the application and feedback questions regarding the benefits and challenges of the application. Participants were predominately white (92%) and female (76%). Minimal improvements in weight and systolic blood pressure were found. Participant attitude survey data declined from 4-weeks to 12-weeks of the intervention. Interestingly though, patients in a rural clinic had lesser declines in attitudes than peri-urban participants. Qualitative feedback data identified participants predominately had a positive overall feeling toward the approach. Participants expressed favorability of RDN access, the variety of foods, but did give suggestions for in-person meetings and more updating of the application. Implementing a technology approach to nutrition in rural areas of West Virginia using a mobile application with RDN access may be one strategy to address public health issues such as obesity

Collinear and Soft Limits of Multi-Loop Integrands in N=4 Yang-Mills

It has been argued in arXiv:1112.6432 that the planar four-point integrand in N=4 super Yang-Mills theory is uniquely determined by dual conformal invariance together with the absence of a double pole in the integrand of the logarithm in the limit as a loop integration variable becomes collinear with an external momentum. In this paper we reformulate this condition in a simple way in terms of the amplitude itself, rather than its logarithm, and verify that it holds for two- and three-loop MHV integrands for n>4. We investigate the extent to which this collinear constraint and a constraint on the soft behavior of integrands can be used to determine integrands. We find an interesting complementarity whereby the soft constraint becomes stronger while the collinear constraint becomes weaker at larger n. For certain reasonable choices of basis at two and three loops the two constraints in unison appear strong enough to determine MHV integrands uniquely for all n.Comment: 27 pages, 14 figures; v2: very minor change

Cortisol does not mediate the suppressive effects of psychiatric morbidity on natural killer cell activity: a cross-sectional study of patients with early breast cancer

Background. There is evidence that depression impairs natural killer cell activity (NKA); this could have implications for anti-tumour immunity. Our aim was to examine the role of the hypothalamicâpituitaryâadrenal (HPA) axis in suppressing NKA in a population of patients with early breast cancer, screened for depression. Secondary aims were to study the relationship between psychological, endocrine and immune variables and baseline tumour characteristics. Methods. A cross-sectional population of female patients (n=55) with early breast cancer was sampled prior to primary surgery. Structured interview and psychometric instruments measured psychological distress. Flow cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning saliva samples were collected to measure free cortisol levels. Tumour characteristics were obtained from hospital laboratory data. Results. A high rate of psychological morbidity (40%) was observed in the population. NKA was reduced in those with past or current psychiatric illness compared to those without (344 v. 553 LU20 and 455 v. 569 LU20 respectively, p<0·05 for both). Cortisol was not related to psychological status but was modestly positively correlated to NKA. A positive correlation was observed between the Fighting Spirit subscale of the Mental Adjustment to Cancer Scale and tumour size (r=0·383, p=0·012) Conclusions. Our data support the evidence that psychological morbidity is associated with immune dysfunction; however, the most obvious candidate mediator of this effect, the HPA axis, does not appear responsible for this effect. Possible reasons for this are discussed

Cortisol does not mediate the suppressive effects of psychiatric morbidity on natural killer cell activity: a cross-sectional study of patients with early breast cancer

Background. There is evidence that depression impairs natural killer cell activity (NKA); this could have implications for anti-tumour immunity. Our aim was to examine the role of the hypothalamicâpituitaryâadrenal (HPA) axis in suppressing NKA in a population of patients with early breast cancer, screened for depression. Secondary aims were to study the relationship between psychological, endocrine and immune variables and baseline tumour characteristics. Methods. A cross-sectional population of female patients (n=55) with early breast cancer was sampled prior to primary surgery. Structured interview and psychometric instruments measured psychological distress. Flow cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning saliva samples were collected to measure free cortisol levels. Tumour characteristics were obtained from hospital laboratory data. Results. A high rate of psychological morbidity (40%) was observed in the population. NKA was reduced in those with past or current psychiatric illness compared to those without (344 v. 553 LU20 and 455 v. 569 LU20 respectively, p<0·05 for both). Cortisol was not related to psychological status but was modestly positively correlated to NKA. A positive correlation was observed between the Fighting Spirit subscale of the Mental Adjustment to Cancer Scale and tumour size (r=0·383, p=0·012) Conclusions. Our data support the evidence that psychological morbidity is associated with immune dysfunction; however, the most obvious candidate mediator of this effect, the HPA axis, does not appear responsible for this effect. Possible reasons for this are discussed

Balloon Measurements of Cosmic Ray Muon Spectra in the Atmosphere along with those of Primary Protons and Helium Nuclei over Mid-Latitude

We report here the measurements of the energy spectra of atmospheric muons and of the cosmic ray primary proton and helium nuclei in a single experiment. These were carried out using the MASS superconducting spectrometer in a balloon flight experiment in 1991. The relevance of these results to the atmospheric neutrino anomaly is emphasized. In particular, this approach allows uncertainties caused by the level of solar modulation, the geomagnetic cut-off of the primaries and possible experimental systematics to be decoupled in the comparison of calculated fluxes of muons to measured muon fluxes. The muon observations cover the momentum and depth ranges of 0.3-40 GeV/c and 5-886 g/cmsquared, respectively. The proton and helium primary measurements cover the rigidity range from 3 to 100 GV, in which both the solar modulation and the geomagnetic cut-off affect the energy spectra at low energies.Comment: 31 pages, including 17 figures, simplified apparatus figure, to appear in Phys. Rev.

The Hidden Curriculum of Veterinary Education: Mediators and Moderators of Its Effects

The “hidden curriculum” has long been supposed to have an effect on students' learning during their clinical education, and in particular in shaping their ideas of what it means to be a professional. Despite this, there has been little evidence linking specific changes in professional attitudes to the individual components of the hidden curriculum. This study aimed to recognize those components that led to a change in students' professional attitudes at a UK veterinary school, as well as to identify the attitudes most affected. Observations were made of 11 student groups across five clinical rotations, followed by semi-structured interviews with 23 students at the end of their rotation experience. Data were combined and analyzed thematically, taking both an inductive and deductive approach. Views about the importance of technical competence and communication skills were promoted as a result of students' interaction with the hidden curriculum, and tensions were revealed in relation to their attitudes toward compassion and empathy, autonomy and responsibility, and lifestyle ethic. The assessment processes of rotations and the clinical service organization served to communicate the messages of the hidden curriculum, bringing about changes in student professional attitudes, while student-selected role models and the student rotation groups moderated the effects of these influences

Multi-Regge kinematics and the moduli space of Riemann spheres with marked points

We show that scattering amplitudes in planar N = 4 Super Yang-Mills in multi-Regge kinematics can naturally be expressed in terms of single-valued iterated integrals on the moduli space of Riemann spheres with marked points. As a consequence, scattering amplitudes in this limit can be expressed as convolutions that can easily be computed using Stokes' theorem. We apply this framework to MHV amplitudes to leading-logarithmic accuracy (LLA), and we prove that at L loops all MHV amplitudes are determined by amplitudes with up to L + 4 external legs. We also investigate non-MHV amplitudes, and we show that they can be obtained by convoluting the MHV results with a certain helicity flip kernel. We classify all leading singularities that appear at LLA in the Regge limit for arbitrary helicity configurations and any number of external legs. Finally, we use our new framework to obtain explicit analytic results at LLA for all MHV amplitudes up to five loops and all non-MHV amplitudes with up to eight external legs and four loops.Comment: 104 pages, six awesome figures and ancillary files containing the results in Mathematica forma