The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Hypertension Awareness and Control Among Young Adults in the National Longitudinal Study of Adolescent Health

BACKGROUND

Young adults are less likely than older adults to be aware they have hypertension or to be treated for hypertension.

OBJECTIVE

To describe rates of hypertension awareness and control in a cohort of young adults and understand the impact of health insurance, utilization of preventive care, and self-perception of health on rates of hypertension awareness and control in this age group.

DESIGN AND PARTICIPANTS

Cross-sectional study of 13,512 young adults participating in Wave IV of the National Longitudinal Study of Adolescent Health in 2007–2008.

MAIN MEASURES

We defined hypertension as an average of two measured systolic blood pressures (SBP) ≥ 140 mmHg, diastolic blood pressures (DBP) ≥ 90 mmHg, or self-report of hypertension. We defined hypertension awareness as reporting having been told by a health care provider that one had high blood pressure, and assessed awareness among those with uncontrolled hypertension. We considered those aware of having hypertension controlled if their average measured SBP was < 140 mmHg and DBP was < 90 mmHg.

KEY RESULTS

Of the 3,303 young adults with hypertension, 2,531 (76 %) were uncontrolled, and 1,893 (75 %) of those with uncontrolled hypertension were unaware they had hypertension. After adjustment for age, sex, race/ethnicity, weight status, income, education, alcohol and tobacco use, young adults with uncontrolled hypertension who had (vs. didn’t have) routine preventive care in the past 2 years were 2.4 times more likely (95 % confidence interval [CI] 1.68–3.55) to be aware, but young adults who believed they were in excellent (vs. less than excellent) health were 64 % less likely to be aware they had hypertension (OR 0.36, 95 % CI 0.23–0.57). Neither preventive care utilization nor self-rated health was associated with blood pressure control.

CONCLUSIONS

In this nationally representative group of young adults, rates of hypertension awareness and control were low. Efforts to increase detection of hypertension must address young adults’ access to preventive care and perception of their need for care.     

Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort

Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM_2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied.Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM_2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data.Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m³ for PM_2.5 and from 0.1 to 1.7 μg/m³ for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM_2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM.Conclusions: Greater exposure to PM_2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy.Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose tolerance during pregnancy: the Project Viva Cohort. Environ Health Perspect 122:378–383; http://dx.doi.org/10.1289/ehp.1307065     

Construct validity of individual and summary performance metrics associated with a computer-based laparoscopic simulator

Background

Computer-based surgical simulators capture a multitude of metrics based on different aspects of performance, such as speed, accuracy, and movement efficiency. However, without rigorous assessment, it may be unclear whether all, some, or none of these metrics actually reflect technical skill, which can compromise educational efforts on these simulators. We assessed the construct validity of individual performance metrics on the LapVR simulator (Immersion Medical, San Jose, CA, USA) and used these data to create task-specific summary metrics.

Methods

Medical students with no prior laparoscopic experience (novices, N = 12), junior surgical residents with some laparoscopic experience (intermediates, N = 12), and experienced surgeons (experts, N = 11) all completed three repetitions of four LapVR simulator tasks. The tasks included three basic skills (peg transfer, cutting, clipping) and one procedural skill (adhesiolysis).

Results

We selected 36 individual metrics on the four tasks that assessed six different aspects of performance, including speed, motion path length, respect for tissue, accuracy, task-specific errors, and successful task completion. Four of seven individual metrics assessed for peg transfer, six of ten metrics for cutting, four of nine metrics for clipping, and three of ten metrics for adhesiolysis discriminated between experience levels. Time and motion path length were significant on all four tasks. We used the validated individual metrics to create summary equations for each task, which successfully distinguished between the different experience levels.

Conclusion

Educators should maintain some skepticism when reviewing the plethora of metrics captured by computer-based simulators, as some but not all are valid. We showed the construct validity of a limited number of individual metrics and developed summary metrics for the LapVR. The summary metrics provide a succinct way of assessing skill with a single metric for each task, but require further validation.     

抗血管生成因子Angiostatin与Endostatin作用下肿瘤血管生成的二维数值模拟

目的数值模拟抗血管生成因子Angiostatin和Endostatin对肿瘤血管生成的影响。方法建立肿瘤内外血管生成的二维离散数学模型。模型耦合两种抗血管生成因子Angiostatin和Endostatin的抑制效应,数值模拟在促血管生成因子诱导下肿瘤微血管网生成,讨论血管生成抑制因子的影响。结果抗血管生成因子Angiostatin对肿瘤内外血管网络生成的速度和成熟度有抑制作用。抗血管生成因子Angiostatin和Endostatin耦合作用时,在肿瘤血管生成的早期有明显的抑制效应;在肿瘤血管生成的中后期,它们可以降低肿瘤血管化程度。结论本文模型能够较好的模拟抗血管生成因子Angiostatin和Endostatin对内皮细胞迁移和增殖的抑制作用。     

Cholecystokinin: induced suppression of feeding in fed, fasting and hypothalamic island rats

Experiments were undertaken to examine the involvement of CCK in the regulation of feeding behavior. The results indicate that 1) intact normal animals exhibited rhythmic circadian feeding behavior, with onset of feedings starting about two hr prior to dark period and continuing until 1 to 2 hr prior to the light period; 2) food deprivation and surgical isolation of the hypothalamus after this pattern of feeding behavior, to the point that animals spend more time eating with no identifiable pattern; 3) administration of CCK to either fed, fasted or hypothalamic island animals has a profound dose related effect on suppressing feeding behavior and in modifying the eating pattern over 24 hr. A possible involvement of CCK with the opiate system in controlling feeding behavior is discussed.