Service-learning across an accelerated curriculum

In support of the community-based education philosophy, nursing faculty at a small health careers college in the midwestern United States incorporated a service-learning experience involving Sudanese refugee families and Latino community members into its accelerated community-based nursing program (ACE) curriculum. The purpose of the service-learning experience is to allow students the opportunity develop relationships through which they may gain an understanding of unique needs within a community. This article describes the development and benefits of the service-learning experience across the ACE curriculum. Through reflection, students broaden and deepen their understanding about the health of individuals in the community and acquire a more sophisticated understanding of risk     

Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests.     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.     

Implicit strategy affects learning in children with heavy prenatal alcohol exposure

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.     

Meal frequency and timing in health and disease

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.     

Metabolic abnormalities and hypoleptinemia in α-synuclein A53T mutant mice

Parkinson's disease (PD) patients frequently display loss of body fat mass and increased energy expenditure, and several studies have outlined a relationship between these metabolic abnormalities and disease severity, yet energy metabolism is largely unstudied in mouse models of PD. Here we characterize metabolic and physiologic responses to a high calorie diet (HCD) in mice expressing in neurons a mutant form of human α-synuclein (A53T) that causes dominantly inherited familial forms of the disease. A53T (SNCA) and wild type (WT) littermate mice were placed on a HCD for 12 weeks and evaluated for weight gain, food intake, body fat, blood plasma leptin, hunger, glucose tolerance, and energy expenditure. Results were compared with both SNCA and WT mice on a control diet. Despite consuming similar amounts of food, WT mice gained up to 66% of their original body weight on a HCD, whereas SNCA mice gained only 17%. Further, after 12 weeks on a HCD, magnetic resonance imaging analysis revealed that WT mice had significantly greater total and visceral body fat compared with SNCA mice (p < 0.007). At the age of 24 weeks SNCA mice displayed significantly increased hunger compared with WT (p < 0.03). At the age of 36 weeks, SNCA mice displayed significant hypoleptinemia compared with WT, both on a normal diet and a HCD (p < 0.03). The HCD induced insulin insensitivity in WT, but not SNCA mice, as indicated by an oral glucose tolerance test. Finally, SNCA mice displayed greater energy expenditure compared with WT, as measured in a Comprehensive Laboratory Animal Monitoring System, after 12 weeks on a HCD. Thus, SNCA mice are resistant to HCD-induced obesity and insulin resistance and display reduced body fat, increased hunger, hypoleptinemia and increased energy expenditure. Our findings reveal a profile of metabolic dysfunction in a mouse model of PD that is similar to that of human PD patients, thus providing evidence that α-synuclein pathology is sufficient to drive such metabolic abnormalities and providing an animal model for discovery of the underlying mechanisms and potential therapeutic interventions.     

Different degradation rates of nanofiber vascular grafts in small and large animal models

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.     

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer

Background Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy.Methods One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress.Results Primary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063).Conclusions IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials.Clinical trial registration ISRCTN04156504.Subject terms: Randomized controlled trials, Breast cancer, Nutrition, Weight management, Breast cancer     

Anterior, Total, and Two-Stage Corpus Callosum Section: Differential and Incremental Seizure Responses

Summary: Published reports suggest that control of generalized seizures is improved by callosotomy but do not necessarily indicate that completion of failed anterior callosotomy is beneficial. We studied 42 patients after anterior callosotomy and 22 after total callosotomy, of whom 14 underwent a two-stage procedure. Cure or marked diminution of seizures was most dramatic for atonic and tonic-clonic seizures after anterior callosotomy (100 and 83%), and for tonic-clonic and tonic seizures after total callosotomy (68 and 57%). For the 14 patients who failed to improve after anterior section and then underwent total section, incremental responses were noted for all seizure types, with cure or marked diminution of partial seizures in 2 of 14 patients, of tonic-clonic seizures in 6 of 10, of tonic seizures in 2 of 4, of atonic seizures in 2 of 5, and of myoclonic seizures in 1 of 1. More than two seizure types, verbal IQ <80, and diffuse ictal EEG patterns were significantly more common in the anterior callosotomy failures. Total callosotomy can be of benefit when anterior callosotomy fails, especially for persistent tonic- clonic and tonic seizures, and will most often be necessary in patients with diffuse cerebral abnormalities.