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In the Philippines, a total of 21,000 typhoid cases with 40 deaths caused by Salmonella typhi were reported in 2016. Previous studies have shown that multi-drug resistant Salmonella (MDRS) exists in fresh chicken meat purchased from retail stalls and supermarkets. MDRS has become a global health concern because of its resistance to treatment with the usual battery of antibiotics. Some studies show that gamma irradiation can eliminate antibiotic-resistant bacteria in food. This study was aimed at determining the radiation sensitivity and inactivation of antibiotic-resistant Salmonella spp. in fresh chicken legs. In phase one, four strains of freshly prepared Salmonella spp. were identified for resistance/susceptibility using disk diffusion method and minimum inhibitory concentration (MIC) with a different spectrum of Ampicillin (AMP), Chloramphenicol (CHL), Gentamicin (GN), Tetracycline (TET) Sulfamethoxazole/Trimethoprim (STX), based on the breakpoints established by CLSI (Clinical and Laboratory Standards Institute). Results showed that the S. enterica ser. Enteritidis 1963, S. enterica ser. Typhi 1768 and S. enterica ser. Typhimurium 1741were resistant to AMP and GN, while S. enterica ser. Typhimurium ATCC 14028 was resistant to GN. In phase two, the freshly prepared pure strains of antibiotic-resistant Salmonella spp. were grown in tryptic soy broth (TSB) for 24 h, centrifuged, and cell pellets were re-suspended in phosphate buffer saline (PBS) and adjusted at 0.5 McFarland (1.0 × 108 CFU per mL). One ml of Salmonella spp. was inoculated into fresh chicken meat then irradiated at different doses of control (0, 0.2, 0.4, 0.6, 0.8 1.0, and 2.0 kGy) at the Gamma Irradiation Facility of the Philippine Nuclear Research Institute. The D10-values, for the four strains of Salmonella, ranged from 0.14 to 0.19 kGy. This indicates that low dose radiation can induce a 1-log reduction of Salmonella spp. in fresh chicken legs and at 2 kGy doses, effectively eliminate the Salmonella spp. by 6 logs cycle. The four strains of Salmonella were mostly resistant to AMP and GN. Therefore, S. enterica serovar Enteritidis 1963, S. enterica serovar Typhi 1768, and S. enterica serovar Typhimurium 1741 exhibited multi-drug resistance. Gamma radiation can be used as a feasible technique to inactivate the presence of Salmonella spp. including the antibiotic-resistant Salmonella in fresh chicken meat.

This study investigated dyadic adrenocortical attunement within adolescent romantic relationships. An ethnically diverse sample (42% Latino) of adolescent heterosexual dating couples (N=91 dyads, Mage=16.5 years, SD=0.99) donated eight saliva samples (later assayed for cortisol) over the course of a 3-h laboratory session. Supportive behaviors were coded during a conflict and jealousy interaction task from video recordings, and participants completed pre-and-post task questionnaires. Parallel process latent growth models revealed a strong positive association between the couples' cortisol intercept, indicating that couples show attunement in initial levels of cortisol. Further, observed supportive behavior moderated the strength of the association between dyadic cortisol slopes. The results imply that low levels of supportive behavior predicted stronger adrenocortical attunement in the change in cortisol levels over time between adolescent romantic partners. These findings indicate that even early romantic relationships exhibit coordination of physiological activity. Findings raise the possibility that adrenocortical attunement may be a dyadic pathway through which the proximal social context of early romantic relationships is translated into risk or resilience in health and behavior.

Data on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P < .001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P = .04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML. Overall mortality risk (HR, 2.86; P < .001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks.

Acute myeloid leukemia (AML) is a heterogeneous group of leukemias that result from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. As a result of highly collaborative clinical research by pediatric cooperative cancer groups worldwide, disease-free survival has improved significantly during the past 3 decades. Further improvements in outcomes of children who have AML probably will reflect continued progress in understanding the biology of AML and the concomitant development of new molecularly targeted agents for use in combination with conventional chemotherapy drugs.

We reported previously that high levels of vascular endothelial growth factor (VEGF) were associated with shorter survival in adult acute myeloid leukemia (AML) patients. In this study, cellular VEGF and its receptor, VEGF-R2 (kinase domain receptor (KDR)), were analyzed in 45 pediatric AML patients using Western blot and solid-phase radioimmunoassay (RIA). Cellular VEGF levels were significantly lower in pediatric AML compared to adult AML patients. In contrast, there was no significant difference in VEGF-R2 levels between adult and pediatric AML. Higher VEGF and VEGF-R2 levels in pediatric AML patients correlated with higher white blood cell (WBC). Unlike in adults, VEGF and VEGF-R2 levels in pediatric AML patients did not correlate with survival. This data suggest that the role of VEGF and its receptor VEGF-R2 in pediatrics AML may be different from that in adult AML.

The successful use of allogeneic hematopoietic stem cell transplantation (HSCT) for children with malignant and nonmalignant diseases continues to be limited by the development of acute and chronic graft-versus-host disease (GVHD), infectious complications, delayed recovery of the immune system, acute and long-term toxicity, and relapse of disease. Significant advances have been made, particularly in the ability to identify suitable sources of HSC. Future advances will depend on a better understanding of the biology of HSC sources, GVHD, immune reconstitution, and common complications. Improved therapies are dependent on participation of children in well-designed, translational and clinical transplant studies.

Syngeneic (murine) and xenogeneic (canine) marrow-derived stromal cells were injected intravenously into SCID and normal mice to examine the homing pattern and persistence of these cells in vivo. By in situ hybridization, these stromal cells were detectable in the bone marrow cavity and the spleen 21 days after injection. Xenogeneic cells did not persist in normal mice but persisted in SCID mice. Conditioning of the recipients with irradiation or 5-fluorouracil (5-FU) treatment did not alter these results. In addition, syngeneic murine stromal cells were transfected with the genes for canine MHC class II (DRA + DRB) and transplanted into murine recipients to investigate their homing pattern and immunogenicity. These transfected syngeneic stromal cells did also home to marrow and spleen even in normal recipients. However, these cells led to sensitization of the host towards canine antigens as shown by accelerated skin graft rejection and delayed type hypersensitivity (DTH). Thus, immunodeficient (SCID) mice allow for the homing of xenogeneic stromal cells to hemopoietic organs and for prolonged persistence. In immunocompetent (normal) mice, no xenogeneic stromal cells were identified in spleen and marrow, either because of their inability to home or more likely because of immunological rejection. In contrast, syngeneic stromal cells expressing xenogeneic MHC class II genes did home to spleen and marrow and persisted even though the recipient had become sensitized. Their survival may be due to a loss of expression of the transfected gene. Alternatively, the presentation of these xenogeneic gene products in the hemopoietic organs was such that a cytotoxic response was not induced.(ABSTRACT TRUNCATED AT 250 WORDS)

Fanconi anemia (FA) is a genetic syndrome characterized by the uniform development of aplastic anemia. Current therapy for patients lacking HLA-identical sibling hematopoietic stem cell (HSC) donors are not optimal. We have opened two phase I clinical trials to determine if potentially useful numbers of CD34+ cells can be collected early in the course of the disease (collection study) and if these cells, once corrected, can engraft without cytoreduction and demonstrate proliferative advantage in vivo over un-corrected cells (gene transfer study). To date, 7 FA patients have undergone a 20 ml/kg bone marrow harvest (BMH) with an average of 1.9|[times]|106 CD34+ cells/kg (range 0.3|[ndash]|2.9|[times]|106 CD34+ cells/kg) collected, suggesting that collection of adequate numbers of cells is possible but challenging, even early in the disease. In the gene transfer study, 3 FA patients with genotype A (FAA) have enrolled, meeting eligibility criteria of FAA, no evidence of malignancy and a minimum of 1|[times]|105 viable CD34+ cells/kg for ex vivo culture and gene transfer. BMHs from the 3 patients (2 fresh and one previously cryopreserved) were CD34+ cell selected. Despite collection before significant pancytopenia, an average of only 5|[times]|105 CD34+ cells/kg (range 1.5|[ndash]|10|[times]|105 CD34+ cells/kg) was purified from these 3 cases representing |[sim]|10% of the expected yield from normal individuals. These cells underwent ex vivo gene transfer using cytokine prestimulation in serum-free medium followed 2 exposures to a GALV-MSCV-FANCA vector. Transduction efficiency of the final product determined by real-time PCR analysis of progenitors averaged 48% (range 40|[ndash]|62%). Equivalent correction of mitomycin C hypersensitivity in progenitor cells confirmed this analysis at the functional level. Nucleated cell recovery after ex vivo manipulation was 82|[ndash]|110% of input nucleated cells using freshly harvested bone marrow derived CD34+ cells (N=2). However, despite good CD34+ cell recovery and viability after CD34+ selection, only 6% of input nucleated cells were recovered utilizing CD34+ cells purified from the previously cryopreserved bone marrow and these cells were not re-infused. In the two patients who did receive gene corrected cells, the total cell dose re-infused was 2.5|[ndash]|3.5|[times]|105 nucleated cells/kg, reflecting the low number of initial CD34+ cells placed in culture. FAA vector sequences were detected in the PB of one patient early post-infusion (+4 weeks) but none was detected after 8 weeks. Despite no long term detection of the corrective gene in the PB and BM, both patients exhibited a transient but marked improvement (10|[ndash]|20% increase) in their peripheral blood hemoglobin (> 6 months) and platelets counts (2|[ndash]|3 months). The data demonstrates that gene transfer efficiency in the clinical setting has been significantly improved, however the collection of adequate numbers of HSC may be the critical barrier to the success of genetic correction attempts in FA.

s / Biol Blood Marrow Transplant 20 (2014) S104eS127 S106 Myeloma subtype, ISS, post-ASCT response and PET activity were significantly associated with PFS. Post-ASCT PET(-) CR had significantly longer PFS than patients with PET(+) CR (31.4 9.9 vs 18.4 3.5 months; p1⁄4.029). In conclusion, having an ISS-3 stage myeloma, pre and post-ASCT response