Ecologies, synergies, and biological systems shaping human milk composition—a report from “Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)” Working Group 2

Human milk is universally recognized as the preferred food for infants during the first 6 mo of life because it provides not only essential and conditionally essential nutrients in necessary amounts but also other biologically active components that are instrumental in protecting, communicating important information to support, and promoting optimal development and growth in infants. Despite decades of research, however, the multifaceted impacts of human milk consumption on infant health are far from understood on a biological or physiological basis. Reasons for this lack of comprehensive knowledge of human milk functions are numerous, including the fact that milk components tend to be studied in isolation, although there is reason to believe that they interact. In addition, milk composition can vary greatly within an individual as well as within and among populations. The objective of this working group within the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to provide an overview of human milk composition, factors impacting its variation, and how its components may function to coordinately nourish, protect, and communicate complex information to the recipient infant. Moreover, we discuss the ways whereby milk components might interact such that the benefits of an intact milk matrix are greater than the sum of its parts. We then apply several examples to illustrate how milk is better thought of as a biological system rather than a more simplistic “mixture” of independent components to synergistically support optimal infant health

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Attributes of Effective Head Start Mental Health Consultants : a Mixed Method Study of Rural and Urban Programs

Early childhood mental health consultation (ECMHC) is the primary strategy implemented by Head Start programs to address the social and emotional needs of children and their families, but little is known about the attributes of early childhood mental health consultants (MHCs) that contribute to consultants\u27 relationships with Head Start staff and to consultation outcomes. The present study examined how attributes of MHCs contribute to positive relationships between the MHCs and Head Start staff and to improved consultation outcomes. Seven attributes of rural and urban mental health consultants were examined: MHC training, supervision, and support; MHC understanding of consultant role; MHC relationship with Head Start staff; relationships with Head Start families; knowledge of and experience with Head Start; knowledge of early childhood best practices; and cultural sensitivity. This mixed methods study combined a secondary analysis of a national survey (Green, Everhart, Gordon, & Gettman, 2006) of 407 Head Start staff and 57 mental health consultants with a qualitative study using telephone focus groups with 26 rural and urban MHCs who worked with Head Start programs in Alaska and Oregon. Hierarchical linear models of the national survey of Head Start staff and MHCs suggested that Head Start staff reports of positive relationships with MHCs were associated with MHCs who reported positive relationships with families and staff and who reported that they received training, supervision, and support. Qualitative results indicated that effective MHCs share a mutual understanding of their role with the Head Start staff and provide culturally sensitive services. In addition, the focus groups provided specific information about how MHCs develop relationships with Head Start staff and families and about MHCs\u27 need for need for training, support, and supervision. Finally, the focus groups revealed that MHCs who provide services in rural areas must understand the role of relationships in rural communities, respect the rural lifestyle, and overcome the challenge of isolation. The findings of this mixed methods study provide valuable information about the nature of relationships between MHCs, Head Start staff, and families and have implications for ECMHC practice, policy, and research

Early Childhood Mental Health Consultation: A Developing Profession

As a career path, early childhood mental health consultation MHC is an emerging and growing work force opportunity. In keeping with the vision of an effective transformed service system expressed in the final report of the Presidents\u27 New Freedom Commission, and communities are expanding capacity to meet the mental health needs of young children and caregivers through mental health sultation. ECMHC supports children in naturalistic community and avoids the excessively expert tude9 and works through collaboration with families and other providers who care for them. In addition, is growing experience and research evidence to suggest that ECMHC an effective service that, from a license health perspective, promotes and emotional development and vents or reduces the impact of mental health problems in young children. The early childhood mental health consultation workforce is in transition from one of broad diversity in terms of training, experience, roles, responsibilities, and work expectations to one that has specific expertise in early childhood mental health and the specific skills required to take on the role of consultant. The purpose of this article is to support the development of a transformed workforce with the attitudes, knowledge, skills, and behaviors to work as early childhood mental health consultants in a changing children\u27s mental health field

Early Childhood Mental Health Consultation: An Evaluation Tool Kit

For states, communities, agencies and programs investing in early childhood mental health consultation and committed to quality data. This web-based resource combines a brief review of the literature and current research addressing the effectiveness of early childhood mental health consultation with guidance for designing and implementing program evaluation. It will help states, communities, and programs increase their capacity for high-quality evaluation of early childhood mental health consultation in community-based settings. Researchers, policy makers and program evaluation teams will find: A brief review of the evidence base, current issues, and questions; Defining characteristics of early childhood mental health consultation; Components of high quality evaluation and sample logic models; Evaluation tools to measure both process and outcome, including outcomes for children, families, staff and programs; and Guidance for using evaluation data for program improvement and communicating outcomes

Ecologies, synergies, and biological systems shaping human milk composition—a report from “Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)” Working Group 2

Human milk is universally recognized as the preferred food for infants during the first 6 mo of life because it provides not only essential and conditionally essential nutrients in necessary amounts but also other biologically active components that are instrumental in protecting, communicating important information to support, and promoting optimal development and growth in infants. Despite decades of research, however, the multifaceted impacts of human milk consumption on infant health are far from understood on a biological or physiological basis. Reasons for this lack of comprehensive knowledge of human milk functions are numerous, including the fact that milk components tend to be studied in isolation, although there is reason to believe that they interact. In addition, milk composition can vary greatly within an individual as well as within and among populations. The objective of this working group within the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to provide an overview of human milk composition, factors impacting its variation, and how its components may function to coordinately nourish, protect, and communicate complex information to the recipient infant. Moreover, we discuss the ways whereby milk components might interact such that the benefits of an intact milk matrix are greater than the sum of its parts. We then apply several examples to illustrate how milk is better thought of as a biological system rather than a more simplistic "mixture" of independent components to synergistically support optimal infant health