Functional Identification of Dendritic Cells in the Teleost Model, Rainbow Trout (Oncorhynchus mykiss)

Dendritic cells are specialized antigen presenting cells that bridge innate and adaptive immunity in mammals. This link between the ancient innate immune system and the more evolutionarily recent adaptive immune system is of particular interest in fish, the oldest vertebrates to have both innate and adaptive immunity. It is unknown whether dendritic cells co-evolved with the adaptive response, or if the connection between innate and adaptive immunity relied on a fundamentally different cell type early in evolution. We approached this question using the teleost model organism, rainbow trout (Oncorhynchus mykiss), with the aim of identifying dendritic cells based on their ability to stimulate naïve T cells. Adapting mammalian protocols for the generation of dendritic cells, we established a method of culturing highly motile, non-adherent cells from trout hematopoietic tissue that had irregular membrane processes and expressed surface MHCII. When side-by-side mixed leukocyte reactions were performed, these cells stimulated greater proliferation than B cells or macrophages, demonstrating their specialized ability to present antigen and therefore their functional homology to mammalian dendritic cells. Trout dendritic cells were then further analyzed to determine if they exhibited other features of mammalian dendritic cells. Trout dendritic cells were found to have many of the hallmarks of mammalian DCs including tree-like morphology, the expression of dendritic cell markers, the ability to phagocytose small particles, activation by toll-like receptor-ligands, and the ability to migrate in vivo. As in mammals, trout dendritic cells could be isolated directly from the spleen, or larger numbers could be derived from hematopoietic tissue and peripheral blood mononuclear cells in vitro

Behavioral Therapy for Rural Substance Abusers

The problems and needs of rural substance abusers vary from those of abusers in urban areas. Accordingly, the means of treatment must acknowledge and address these differences. Despite this call for specialized care, no theoretically grounded therapy has yet been made available to rural patients. Behavioral Therapy for Rural Substance Abusers, developed and piloted over three years by University of Kentucky faculty and staff and substance abuse counselors in rural eastern Kentucky, provides a model for effective treatment for this segment of the population. A two-phase outpatient treatment, this approach combines group and individual sessions in an environment that is both comfortable and useful for the client. The success of this method lies in its regional approach to therapy. Rather than using role-playing techniques to examine old behaviors, therapy is designed around storytelling activities. Rural patients respond more positively to such time-honored traditions and thus become active participants in their own treatment. This manual offers a clear and well-constructed guide through the strategies of Structured Behavioral Outpatient Rural Therapy (SBORT). Supplemented with illustrations, sample exercises, and case studies, Behavioral Therapy for Rural Substance Abusers is a vital tool in meeting the treatment needs of an otherwise ignored rural population. Carl Leukefeld, professor at the University of Kentucky College of Medicine, Center on Drug and Alcohol Research, is a co-author of Reducing the Risks for Substance Abuse: A Lifespan Approach. Theodore Godlaski is assistant professor of psychiatry at the University of Kentucky Medical Center. James Clark is a professor in the College of Social Work at the University of Kentucky. Cynthia Brown is a research assistant at the Center on Drug and Alcohol Research. Lon Hays is professor and chair of the department of psychiatry at the University of Kentucky Medical Center. An extremely useful eclectic approach to the treatment of substance use disorders. —Drug and Alcohol Reviewhttps://uknowledge.uky.edu/upk_medicine_and_health_sciences/1008/thumbnail.jp

The Borrego Mountain, California, earthquake of 9 April 1968: A preliminary report

The largest earthquake to hit California in more than 15 years occurred at 02:28:58.9 GCT on 9 April 1968 near Borrego Mountain, on the western edge of the Imperial Valley. The Seismological Laboratory at Pasadena has tentatively assigned the shock a magnitude of 6.5, an epicentral location of 33 ° 08.8' N, 116 ° 07.5' W, and a focal depth of 20 km. The earthquake was felt throughout most of southern California and adjacent areas, but the absence of severe damage and casualties was in large part due to the relatively undeveloped nature of the epicentral region. Indeed, it would have been difficult to pick a location in the southernmost part of the State more remote from centers of population

Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) significantly reduces the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (SP), the current standard of care, but its impact on the incidence of malaria during infancy is unknown. METHODS: We conducted a double-blind randomized trial to compare the incidence of malaria during infancy among infants born to HIV-uninfected pregnant women who were randomized to monthly IPTp with either DP or SP. Infants were followed for all their medical care in a dedicated study clinic, and routine assessments were conducted every 4 weeks. At all visits, infants with fever and a positive thick blood smear were diagnosed and treated for malaria. The primary outcome was malaria incidence during the first 12 months of life. All analyses were done by modified intention to treat. RESULTS: Of the 782 women enrolled, 687 were followed through delivery from December 9, 2016, to December 5, 2017, resulting in 678 live births: 339 born to mothers randomized to SP and 339 born to those randomized to DP. Of these, 581 infants (85.7%) were followed up to 12 months of age. Overall, the incidence of malaria was lower among infants born to mothers randomized to DP compared to SP, but the difference was not statistically significant (1.71 vs 1.98 episodes per person-year, incidence rate ratio (IRR) 0.87, 95% confidence interval (CI) 0.73-1.03, p = 0.11). Stratifying by infant sex, IPTp with DP was associated with a lower incidence of malaria among male infants (IRR 0.75, 95% CI 0.58-0.98, p = 0.03) but not female infants (IRR 0.99, 95% CI 0.79-1.24, p = 0.93). CONCLUSION: Despite the superiority of DP for IPTp, there was no evidence of a difference in malaria incidence during infancy in infants born to mothers who received DP compared to those born to mothers who received SP. Only male infants appeared to benefit from IPTp-DP suggesting that IPTp-DP may provide additional benefits beyond birth. Further research is needed to further explore the benefits of DP versus SP for IPTp on the health outcomes of infants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02793622 . Registered on June 8, 2016

Comparative genomics of the pathogenic ciliate Ichthyophthirius multifiliis, its free-living relatives and a host species provide insights into adoption of a parasitic lifestyle and prospects for disease control

BACKGROUND: Ichthyophthirius multifiliis, commonly known as Ich, is a highly pathogenic ciliate responsible for 'white spot', a disease causing significant economic losses to the global aquaculture industry. Options for disease control are extremely limited, and Ich's obligate parasitic lifestyle makes experimental studies challenging. Unlike most well-studied protozoan parasites, Ich belongs to a phylum composed primarily of free-living members. Indeed, it is closely related to the model organism Tetrahymena thermophila. Genomic studies represent a promising strategy to reduce the impact of this disease and to understand the evolutionary transition to parasitism. RESULTS: We report the sequencing, assembly and annotation of the Ich macronuclear genome. Compared with its free-living relative T. thermophila, the Ich genome is reduced approximately two-fold in length and gene density and three-fold in gene content. We analyzed in detail several gene classes with diverse functions in behavior, cellular function and host immunogenicity, including protein kinases, membrane transporters, proteases, surface antigens and cytoskeletal components and regulators. We also mapped by orthology Ich's metabolic pathways in comparison with other ciliates and a potential host organism, the zebrafish Danio rerio. CONCLUSIONS: Knowledge of the complete protein-coding and metabolic potential of Ich opens avenues for rational testing of therapeutic drugs that target functions essential to this parasite but not to its fish hosts. Also, a catalog of surface protein-encoding genes will facilitate development of more effective vaccines. The potential to use T. thermophila as a surrogate model offers promise toward controlling 'white spot' disease and understanding the adaptation to a parasitic lifestyle