Severity of Schistosoma haematobium co-infection with malaria in school-children is potentially modulated by host CD14 gene variants.

OBJECTIVE: Schistosomiasis remains a chronic disease of global importance, especially in many rural areas of the world where co-infection with Plasmodium falciparum is common. It is critical to decipher the role of single or co-infected disease scenarios on immune system regulation in such individuals and how such co-infections can either ameliorate or complicate immune response and the consequent disease outcome. First, 10 ml of urine samples, collected between 10:00 am and 2:00 pm, was filtered for diagnosis of schistosomiasis, while egg count, indicative of disease severity, was determined by microscopy. Furthermore, genomic DNA samples extracted from dried blood spots collected on filter paper from one hundred and forty-four Schistosoma haematobium-infected school-children was tested for P. falciparum parasite positivity by an allele-specific nested-PCR analysis of merozoite surface protein (msp)-1 and -2 genes and a real-time PCR assay. In addition, among P. falciparum parasite-positive individuals, we carried out a Taqman SNP genotyping assay to extrapolate the effect of host CD14 (-159 C/T; rs2569190) genetic variants on schistosome egg count. RESULTS: Of the 144 individuals recruited, P. falciparum parasite positivity with msp-1 gene were 34%, 43% and 55% for MAD20, RO33 and K1 alleles respectively. Of the co-infected individuals, CD14 genetic variants ranged from 18.8% vs 21.5%, 33.3% vs 44.4%, 9.7% vs 11.8% for single versus schistosome co-infection for the wild type (CC), heterozygous (CT) and mutant (TT) variants respectively. Though the mean egg count for co-infected individuals with CD14 wild type (33.7 eggs per 10 ml of urine) and heterozygote variants (37.5 eggs per 10 ml of urine) were lower than that of schistosome infection alone (52.48 and 48.08 eggs/10 ml of urine respectively), it lacked statistical significance (p-value 0.12 and 0.29), possibly reflecting the benefit of the CD14 activation in schistosome plus malaria co-infection and not schistosome infection alone. In addition, the lower mean egg count in co-infected individuals reveal the benefit of downstream Th1 immune response mitigated by CD14 innate activation that is absent in schistosome infection alone.

Differences in Anatomical Outcomes Between Early Chronic and Far Chronic Time-Points After Transplantation of Spinal Cord Neural Progenitor Cells in Mice.

Spinal cord injury (SCI) affects millions of people worldwide. Neural progenitor cell (NPC) transplantation is a promising treatment for regenerating lost spinal cord tissue and restoring neurological function after SCI. We conducted a literature search and found that less than a quarter of experimental rodent cell and tissue transplantation studies have investigated anatomical outcomes at longer than 4 months post-transplantation. This is a critical topic to investigate, given that stem and progenitor cell therapies would need to remain in place throughout the lifetime of an individual. We sought to determine how commonly assessed anatomical outcomes evolve between early and far chronic time-points post-NPC transplantation. At either 8 weeks or 26 weeks following transplantation of NPCs into sites of cervical SCI, we evaluated graft neuronal density, astroglial cell density, graft axon outgrowth, and regeneration of host axon populations into grafts in male and female mice. We found that graft neuronal density does not change over time, but the numbers of graft-associated astrocytes and glial fibrillary acidic protein intensity is significantly increased in the far chronic phase compared with the early chronic time-point. In addition, graft axon outgrowth was significantly decreased at 26 weeks post-transplantation compared with 8 weeks post-transplantation. In contrast, corticospinal axon regeneration into grafts was not diminished over time, but rather increased significantly from early to far chronic periods. Interestingly, we found that graft neuronal density is significantly influenced by sex of the host animal, suggesting that sex-dependent processes may shape graft composition over time. Collectively, these results demonstrate that NPC transplants are dynamic and that commonly assessed outcome measures associated with graft efficacy evolve over the weeks to months post-transplantation into the spinal cord.

Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after spinal cord injury in mice.

Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery of motor and sensory functions after SCI, is poorly understood. We transplanted developmentally-restricted spinal cord NPCs, isolated from E11.5-E13.5 mouse embryos, into sites of adult mouse SCI and analyzed graft axon outgrowth, cellular composition, host axon regeneration, and behavior. Earlier-stage grafts exhibited greater axon outgrowth, enrichment for ventral spinal cord interneurons and Group-Z spinal interneurons, and enhanced host 5-HT+ axon regeneration. Later-stage grafts were enriched for late-born dorsal horn interneuronal subtypes and Group-N spinal interneurons, supported more extensive host CGRP+ axon ingrowth, and exacerbated thermal hypersensitivity. Locomotor function was not affected by any type of NPC graft. These findings showcase the role of spinal cord graft cellular composition in determining anatomical and functional outcomes following SCI.

Effects of biological sex mismatch on neural progenitor cell transplantation for spinal cord injury in mice.

Despite advancement of neural progenitor cell transplantation to spinal cord injury clinical trials, there remains a lack of understanding of how biological sex of transplanted cells influences outcomes after transplantation. To address this, we transplanted GFP-expressing sex-matched, sex-mismatched, or mixed donor cells into sites of spinal cord injury in adult male and female mice. Biological sex of the donor cells does not influence graft neuron density, glial differentiation, formation of the reactive glial cell border, or graft axon outgrowth. However, male grafts in female hosts feature extensive hypervascularization accompanied by increased vascular diameter and perivascular cell density. We show greater T-cell infiltration within male-to-female grafts than other graft types. Together, these findings indicate a biological sex-specific immune response of female mice to male donor cells. Our work suggests that biological sex should be considered in the design of future clinical trials for cell transplantation in human injury.

Adoption of Evidence-Based Interventions in Local Health Departments: "1-2-3 Pap NC".

Descriptions of barriers and facilitators to adoption of evidence-based interventions in local health departments (LHDs) are limited. This study was conducted by the North Carolina Public Health Practice-Based Research Network to identify factors associated with adoption of an evidence-based human papillomavirus video intervention, "1-2-3 Pap NC," in North Carolina LHDs. A sequential mixed-method study design was used. Data from the 2013 National Profile of Local Health Departments were used to test associations between LHD characteristics and adoption of the intervention. Qualitative, key stakeholder interviews with LHD directors provided the context for quantitative data. Data collection and analysis continued from March 3, 2014, to September 15, 2014. Overall, 28% of North Carolina health jurisdictions (33 of 100 counties) implemented the intervention. Of the three channels used to deliver the intervention to clients, most LHDs opted to show the video in the exam room (42%), followed by website/other social media (36%) and video loop in the lobby/waiting room (22%). In logistic regression, gender of the director (female) was significantly and positively associated with adoption of the intervention (AOR=4.44, p<0.05). Being a first-time director was marginally significant (AOR=0.28, p=0.074), suggesting first-time directors were less likely to adopt. Qualitative results suggested that aspects of communication (awareness and positive attitudes) and agency directors' evaluation of resources, balanced against intervention complexity and flexibility, competing priorities, and mandates, influenced adoption. Adoption of evidence-based interventions by LHDs is critical to improve population health. Practice-based research can contribute to understanding facilitators and modifying barriers to this process.

CT Utilization for Pediatric Orthopedic Trauma.

BACKGROUND: The use of computed tomography (CT) scanning in trauma has tripled in the past decade in adults and children alike. There is growing concern about the long-term risks of radiation delivery in childhood. There is little information in the literature on radiation exposure during extremity CT in children. This study evaluated the radiation dose and geographic bodily exposure to the child/adolescent during extremity CT. METHODS: A retrospective review of 163 patients (girls aged 0.5-19 years and boys aged 3.1-19 years) who sustained an orthopedic extremity injury that required a CT scan in 2012 was performed. Data collected included sex, age, height, weight, body mass index (BMI), joint, upper extremity position, body position, scout start, scout end, CTDIvol (mGy), and dose length product (CTDLP (mGy-cm)). RESULTS: Lower extremity scans were more frequent (124/163, 76 percent) and had higher radiation doses overall. Only the elbow varied for upper extermity positioning. Five of nine were on the side of body with a corresponding 66 percent lower mean radiation dose. All lower extremity scans were in the supine position. Scout CT start and end varied among all joints except for femur to tibia. CONCLUSIONS: Lower extremity CT scans had the highest radiation doses. Variability in positioning and delineation of scout contributed to variation in radiation exposure of extremity and adjacent body area. Improved localization and consistent positioning can effectively lower radiation exposure in children undergoing extremity CT scan.