Effect of High Strength Food Wastes on Anaerobic Codigestion of Sewage Sludge.

Anaerobic codigestion has been practiced at water resource recovery facilities to increase methane production, but the impact of many variables is still not well understood. In this study, the feasibility of codigesting fats, oils, and grease (FOG), and other high strength wastes (HSWs) with municipal sewage sludge was investigated. Four laboratory-scale digesters were operated at a working volume of 9.75 L, 15 days solids retention time (SRT), and at a temperature of 37 °C. Wastes including whey (cheese), juice, grease trap waste (GTW), and dissolved air flotation waste (DAF), along with municipal sewage sludge, were fed to the digesters in varying amounts. The addition of HSWs led to higher methane production at lower organic loadings. However, at higher organic loadings, the GTW appeared to be toxic to methanogens, leading to a decrease in digester pH and biogas production, and an accumulation of volatile fatty acids within the digester.

Green tea component EGCG, insulin and IGF-1 promote nuclear efflux of atrophy-associated transcription factor Foxo1 in skeletal muscle fibers.

Prevention and slowing of skeletal muscle atrophy with nutritional approaches offers the potential to provide far-reaching improvements in the quality of life for our increasingly aging population. Here we show that polyphenol flavonoid epigallocatechin 3-gallate (EGCG), found in the popular beverage green tea (Camellia sinensis), demonstrates similar effects to the endogenous hormones insulin-like growth factor 1 (IGF-1) and insulin in the ability to suppress action of the atrophy-promoting transcription factor Foxo1 through a net translocation of Foxo1 out of the nucleus as monitored by nucleo-cytoplasmic movement of Foxo1-green fluorescent protein (GFP) in live skeletal muscle fibers. Foxo1-GFP nuclear efflux is rapid in IGF-1 or insulin, but delayed by an additional 30 min for EGCG. Once activated, kinetic analysis with a simple mathematical model shows EGCG, IGF-1 and insulin all produce similar apparent rate constants for Foxo1-GFP unidirectional nuclear influx and efflux. Interestingly, EGCG appears to have its effect at least partially via parallel signaling pathways that are independent of IGF-1's (and insulin's) downstream PI3K/Akt/Foxo1 signaling axis. Using the live fiber model system, we also determine the dose-response curve for both IGF-1 and insulin on Foxo1 nucleo-cytoplasmic distribution. The continued understanding of the activation mechanisms of EGCG could allow for nutritional promotion of green tea's antiatrophy skeletal muscle benefits and have implications in the development of a clinically significant parallel pathway for new drugs to target muscle wasting and the reduced insulin receptor sensitivity which causes type II diabetes mellitus.

Mathematical modeling reveals modulation of both nuclear influx and efflux of Foxo1 by the IGF-I/PI3K/Akt pathway in skeletal muscle fibers.

Foxo family transcription factors contribute to muscle atrophy by promoting transcription of the ubiquitin ligases muscle-specific RING finger protein and muscle atrophy F-box/atrogin-1. Foxo transcriptional effectiveness is largely determined by its nuclear-cytoplasmic distribution, with unphosphorylated Foxo1 transported into nuclei and phosphorylated Foxo1 transported out of nuclei. We expressed the fluorescent fusion protein Foxo1-green fluorescent protein (GFP) in cultured adult mouse flexor digitorum brevis muscle fibers and tracked the time course of the nuclear-to-cytoplasmic Foxo1-GFP mean pixel fluorescence ratio (N/C) in living fibers by confocal imaging. We previously showed that IGF-I, which activates the Foxo kinase Akt/PKB, caused a rapid marked decline in N/C, whereas inhibition of Akt caused a modest increase in N/C. Here we develop a two-state mathematical model for Foxo1 nuclear-cytoplasmic redistribution, where Foxo phosphorylation/dephosphorylation is assumed to be fast compared with nuclear influx and efflux. Cytoplasmic Foxo1-GFP mean pixel fluorescence is constant due to the much larger cytoplasmic than nuclear volume. Analysis of N/C time courses reveals that IGF-I strongly increased unidirectional nuclear efflux, indicating similarly increased fractional phosphorylation of Foxo1 within nuclei, and decreased unidirectional nuclear influx, indicating increased cytoplasmic fractional phosphorylation of Foxo1. Inhibition of Akt increased Foxo1 unidirectional nuclear influx, consistent with block of Foxo1 cytoplasmic phosphorylation, but did not decrease Foxo1 unidirectional nuclear efflux, indicating that Akt may not be involved in Foxo1 nuclear efflux under control conditions. New media change experiments show that cultured fibers release IGF-I-like factors, which maintain low nuclear Foxo1 in the medium. This study demonstrates the power of quantitative modeling of observed nuclear fluxes.

A pediatric residency experience with surgical co-management.

BACKGROUND AND OBJECTIVE: Acquisition of knowledge and skills in the care of surgical patients is defined as an essential element of training by the Pediatric Residency Review Committee. The pediatric-surgical comanagement model of care is increasingly utilized, yet its impact on residency training has not been described. The goal of this study was to describe a 5-year experience with a co-management model in a pediatric residency program. METHODS: We describe the planning and implementation of a surgical co-management model in a pediatric residency program and report on case volume and diversity from 2005 to 2010. We assessed the experience of pediatric residents and faculty through rotation evaluations, program leadership meetings, and an anonymous online survey. In the survey, residents rated the value of their exposure on knowledge and skills in selected perioperative domains and their experience with interprofessional teamwork. RESULTS: The volume of co-managed patients increased threefold from 2005 to 2010; most (79%) had concurrent medical conditions, and one-third (36%) were children with special health care needs (CYSHCN). Residents reported that co-management helped them gain knowledge and skills in pain management, fluid and electrolytes, respiratory, and nutritional support, as well as in interprofessional teamwork. Other strengths included greater exposure to CYSHCN and subspecialty faculty, and preparedness for critical care rotations. Challenges included clarity of roles and responsibilities between pediatric and surgery residents and interservice communication. CONCLUSIONS: A surgical co-management model in pediatric residency training presented important opportunities for development of residents' knowledge and skills in perioperative care and interprofessional teamwork.

A collaborative model for inpatient training in a small pediatric residency program.

BACKGROUND: The nationwide decline in pediatric admissions to community hospitals threatens the sustainability of small pediatric residency programs. Little is known about the response of small programs to this challenge. OBJECTIVES: We report on the design and evaluation of an innovative, collaborative model for pediatric inpatient training between an academic community medical center and a children's hospital. METHODS: We describe the operational, academic, and financial features of the model. Outcome measures include patient volume and subspecialty mix, resident and faculty perceptions as reported in an anonymous survey, and Accreditation Council for Graduate Medical Education Residency Review Committee (RRC) review. RESULTS: In 2003, Albert Einstein Medical Center (Einstein) closed its pediatric inpatient unit and established an independent teaching service at St Christopher's Hospital for Children (St Christopher's) in Philadelphia, Pennsylvania. Under the new model, patient volume and subspecialty mix more than tripled. Einstein residents and faculty identified 5 major strengths: level of responsibility and decision making, caring for medically complex children, quality of teaching, teamwork, and opportunity to participate in academic activities at a children's hospital. St Christopher's leadership reported increased volume, no disruption of their residency program, and no dilution of clinical teaching material. The Einstein program was reaccredited by the RRC in 2006 for 2 years and in 2009 for 4 years. CONCLUSION: A collaborative model for inpatient training was successful in maintaining a community hospital-based pediatric residency program. Positive outcomes were documented for the residency program, the parent community hospital, and the collaborating children's hospital.

APE chemotherapy for children with relapsed Hodgkin disease: a Pediatric Oncology Group trial.

BACKGROUND: MOPP (mechlorethamine, vincristine, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) are effective therapies for Hodgkin disease (HD) that may cause long-term toxicities in children. APE (cytosine arabinoside, cisplatin, etoposide) is a non-cross-resistant regimen with limited toxicities. We evaluated this regimen for patients with recurrent or refractory disease. METHODS: Patients with recurrent Hodgkin disease who were

Antibiotics in the human food chain: establishing no effect levels of tetracycline, neomycin, and erythromycin using a chemostat model of the human colonic microflora.

A chemostat model of the healthy human large bowel ecosystem was used to establish no effect levels for tetracycline, neomycin, and erythromycin. For each compound, the equivalent to four oral doses (0, 1.5, 15, and 150 mg/60 kg person/d) was studied. Concentrations of the test compounds in the chemostat medium were intended to simulate fecal levels that might be expected following consumption of food containing antibiotic residue and were based on published oral doses and fecal levels. We monitored the following parameters: short chain fatty acids, bile acids, sulfate reduction, azoreductase and nitroreductase activities, beta-glucosidase and beta-glucuronidase activities, a range of bacterial counts and, lastly, the susceptibility among sentinel bacteria to each test compound. Neomycin and erythromycin reduced bile acid metabolism. Neomycin elevated propionate levels and caused a marginal diminution in azoreductase activity. Based on our results, the no observed effect level (NOEL) of both tetracycline and erythromycin was 15 mg/60 kg person/d. The NOEL for neomycin was 1.5 mg/60 kg person/d.

Activated sludge deflocculation in response to chlorine addition: the potassium connection.

Chlorination is often used to control filamentous bulking in activated sludge systems. Pure culture and mixed-liquor experiments showed that soluble potassium (K+) concentrations increased by 2.4 mg/L (80%) and 1.5 to 3.6 mg/L (11 to 30%) in the bulk liquid phase of pure and activated sludge cultures that were exposed to chlorine, relative to unchlorinated controls. Effluent turbidity and total suspended solids from settled mixed liquor increased significantly in both short-term batch and sequencing batch reactor experiments when chlorine mass load increased above 6 milligrams of chlorine per gram mixed liquor volatile suspended solids (mg Cl2/g MLVSS) in a single dose, which correlated with a localized chlorine concentration at the dose point of 10 mg/L as Cl2 or greater. The results support the hypothesis that the glutathione-gated potassium efflux (GGKE) bacterial stress response may contribute to increased effluent turbidity associated with high doses of mixed-liquor chlorination. It is suggested that potassium is a useful parameter to monitor at full-scale facilities when determining chlorine mass doses that should be used to control filaments and minimize increases in effluent turbidity.

Double-delayed intensification improves event-free survival for children with intermediate-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Addition of a delayed-intensification (DI) phase after standard induction/consolidation therapy was previously shown to improve outcome for patients younger than 10 years of age with intermediate-risk acute lymphoblastic leukemia (ALL). The current trial randomized 1204 patients to regimens containing a single DI phase (405 patients), 2 DI phases (DDI) (402 patients), or a single DI phase in conjunction with increased vincristine and prednisone pulses during maintenance (DIVPI) (397 patients). Estimates of event-free survival (EFS) and survival at 6 years are 79% +/- 1% and 89% +/- 1%, respectively. EFS was improved on DDI compared with either DI (log-rank P =.04; Kaplan-Meier [KM] P =.04; relative risk [RR] = 1.38) or DIVPI (log-rank P =.04; KM P =.01; RR = 1.39). There was no difference in EFS for the DI and DIVPI regimens (log-rank P =.96; KM P =.75). Survival estimates at 6 years were 87% (SD = 2%) for DI; 91% (SD = 2%) for DDI; and 90% (SD = 2%) for DIVPI (P =.17). Significant univariate risk factors for the overall cohort included poor day-7 marrow response, black race, and age of at least 5 years. These data demonstrate that DDI improves EFS of patients younger than 10 years of age with intermediate-risk ALL.