Rapid Prototyping of Thermoplastic Microfluidic 3D Cell Culture Devices by Creating Regional Hydrophilicity Discrepancy.

Microfluidic 3D cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microenvironment. Traditional fabrication strategies lack the scalability, cost-effectiveness, and rapid prototyping capabilities required for industrial applications, especially for processes involving thermoplastic materials. Here, an approach to pattern fluid guides inside microchannels is introduced by establishing differential hydrophilicity using pressure-sensitive adhesives as masks and a subsequent selective coating with a biocompatible polymer. Optimal coating conditions are identified using polyvinylpyrrolidone, which resulted in rapid and consistent hydrogel flow in both the open-chip prototype and the fully bonded device containing additional features for medium perfusion. The suitability of the device for dynamic 3D cell culture is tested by growing human hepatocytes in the device under controlled fluid flow for a 14-day period. Additionally, the study demonstrated the potential of using the device for pharmaceutical high-throughput screening applications, such as predicting drug-induced liver injury. The approach offers a facile strategy of rapid prototyping thermoplastic microfluidic organ chips with varying geometries, microstructures, and substrate materials.

Unpacking the black box of survey costs.

Survey costs are a critically important input to and constraint on the quality of data collected from surveys. Much about survey costs is unknown, leading to lack of understanding of the drivers of survey costs, the relationship between survey costs and survey errors, and difficulty in justifying the importance of survey data versus other available administrative or organic data. This commentary outlines a recently developed typology for survey costs, illustrates this typology using methodological articles that report on costs in pharmacy surveys, and provides recommendations for research on the relationship between fixed and variable costs as a major area for further reporting and research, as well as the relationship between costs and errors.

Short Message Service Surveying With Homeless Youth: Findings From a 30-Day Study of Sleeping Arrangements and Well-Being.

Little is known about the location and consistency of sleeping arrangements among youth experiencing homelessness (YEH) and how this is linked to their well-being. This study addresses this gap using ecological momentary assessment (EMA) via short message service (SMS) surveying with 150 YEH over 30 days, to examine how various sleeping arrangements are associated with depression, marijuana use, support received, and service utilization. Results revealed that the average number of consecutive days youth stayed at any particular location varied considerably. Youth who stayed more frequently with a friend/partner or in a transitional living facility (TLF) reported fewer days of being depressed, whereas staying with a friend/ partner was associated with using marijuana more frequently. Finally, youth staying with a friend/partner, stranger, or TLF reported using services on fewer days. Because sleeping arrangements change almost daily, on average, this has important public health implications for agencies finding permanent housing for YEH.

A comparison of frequency of alcohol and marijuana use using short message service surveying and survey questionnaires among homeless youth.

BACKGROUND: There are several benefits to using short message service surveying (SMS) to gather data on substance use from homeless youth, including capturing data "in the moment" and verifying the timing of one behavior relative to another. Though SMS is a valuable data collection tool with highly mobile populations that otherwise are difficult to longitudinally sample, the reliability of SMS compared with surveys is largely unknown with homeless youth. Examining the reliability of SMS is important because these data can provide a more nuanced understanding of the relationships between various risk behaviors, which may lead to better intervention strategies with these youth. OBJECTIVES: We compared past 30-day survey and SMS data for youth's alcohol and marijuana use. METHODS: Interviewed 150 homeless youth (51% female) using surveys and SMS. RESULTS: Past 30-day survey and SMS data revealed moderately strong correlations for alcohol (rs  = .563) and marijuana (rs  = .564). Regression analysis revealed that independent variables were similarly associated with alcohol and marijuana use when comparing survey and SMS data with two exceptions: heterosexual youth reported less alcohol use in SMS data compared to survey data (ß = -.212; p < .05 vs. ß = -.006; p > .05, respectively) and youth whose parents had alcohol problems reported less marijuana use in survey data compared to SMS data (ß = -.277; p < .01 vs. ß = -.150; p > .05, respectively). CONCLUSION: Findings indicate SMS and surveys are both reliable methods of gathering data from homeless youth on substance use.

Understanding Daily Depression, Drinking, and Marijuana Use among Homeless Youth using Short Message Service Surveying.

We used short message service surveying (SMS) with 150 homeless youth to examine the time ordering of feeling depressed with drinking alcohol, using marijuana, and using substances with friends. Multilevel binary logistic regression results revealed that youth who were depressed earlier in the day were more likely to drink alcohol later that day. Among depressed youth, heterosexual youth were less likely to drink alcohol than lesbian, gay, and bisexual (LGB) youth. Depressed youth had increased odds of using marijuana by a factor of 1.6, while heterosexual youth, compared to LGB youth, were 80% less likely to use marijuana. Females were 82% less likely and heterosexual youth 75% less likely to use substances with friends compared to males and LGB youth, respectively. These findings improve upon prior retrospective studies by using SMS to understand time ordering between feeling depressed and substance use in the same day.

Examining the Feasibility of Ecological Momentary Assessment Using Short Message Service Surveying with Homeless Youth: Lessons Learned.

We assessed the feasibility of ecological momentary assessment using short message service (SMS) surveying with 150 homeless youth. We found that on average, participants completed 18.8 days of texts, but 30% of youth (N = 44) had texting data on 28 or more days. The average number of texts answered per day was 8.49 (of a possible 11). Forty-three percent of days had answers to all 11 texts sent that day, and 69.4% of days had answers to eight or more texts. We found significant differences in response rates by phone type. Seventy-three percent of youth reported that responding to our texts was very easy or somewhat easy and 69% endorsed the response option "just enough," regarding the number of texts sent per day. The 30-day texting period was deemed "about right" by 74% of youth. Details of using SMS with homeless youth are provided, and results indicate that this data collection technique is feasible with this population.

Understanding the Link between Victimization and Alcohol Use among Homeless Youth Using Ecological Momentary Assessment.

Most prior research on victimization and alcohol use among homeless youth is retrospective and thus does not allow researchers to determine the sequencing of these events. We address this gap using ecological momentary assessment via short message service surveying with homeless youth during 30 days. Multilevel binary logistic regression results revealed that experiencing physical or sexual victimization on a specific day was positively associated with youth's drinking alcohol later that day. Because ecological momentary assessment via short message service allows for such specificity, we can link a specific victimization experience with a current drinking episode. Thus, the time ordering of daily events in the current study is a significant improvement over prior research. Understanding the timing between victimization and drinking alcohol is also important for intervention with this underserved population.

Social isolation, survey nonresponse, and nonresponse bias: An empirical evaluation using social network data within an organization.

Survey researchers have long hypothesized that social isolation negatively affects the probability of survey participation and biases survey estimates. Previous research, however, has relied on proxy measures of isolation, such as being a marginalized group member within a population. We re-examine the relationship between social isolation and survey participation using direct measures of social isolation derived from social network data; specifically, instrumental research and expressive friendship connections among faculty within academic departments. Using a reconceptualization of social isolation, we find that social network isolation is negatively associated with unit response. Among women (a numerical minority group within the organization), we further find that social group isolation (i.e., lacking instrumental network connections to men, the majority group in the organization) is negatively associated with survey participation. Finally, we show that some survey estimates are systematically biased due to nonparticipation from socially isolated people.

Risk Factors for HIV among Zambian Street Youth.

The sub-Saharan African region has been disproportionately affected by Human Immunodeficiency Virus (HIV) and Zambia has one of the highest HIV prevalence rates within this region. Moreover, new incidences of HIV infection are increasing most rapidly among those 15 to 24 years of age. Though young people are at high risk for HIV infection, street youth are even more vulnerable given their exposure to high risk behaviors. The current study examines multiple levels of social influence on HIV infection among 250 street youth in Zambia. Results reveal that though the majority of youth understand what behaviors increase their risk for HIV, youth still hold many misconceptions about HIV/AIDS. Additionally, youth who do not have a home to return to and those who report parental drug misuse were significantly more likely to be HIV positive. This study underscores the need for further education among street youth regarding HIV knowledge.

Identifying predictors of survey mode preference.

To increase the likelihood of response, many survey organizations attempt to provide sample members with a mode they are thought to prefer. Mode assignment is typically based on conventional wisdom or results from mode choice studies that presented only limited options. In this paper we draw heavily on research and theory from the mode effects and the survey participation literatures to develop a framework for understanding what characteristics should predict mode preferences. We then test these characteristics using data from two different surveys. We find that measures of familiarity with and access to a mode are the strongest predictors of mode preference and measures of safety concerns, physical abilities, and normative concerns are unexpectedly weak predictors. Our findings suggest that variables that may exist on sample frames can be used to inform the assignment of "preferred" modes to sample members.

The University of Michigan Dioxin Exposure Study: methods for an environmental exposure study of polychlorinated dioxins, furans, and biphenyls.

BACKGROUND: The University of Michigan Dioxin Exposure Study (UMDES) was undertaken in response to concerns that the discharge of dioxin-like compounds from the Dow Chemical Company facilities in Midland, Michigan, resulted in contamination of soils in the Tittabawassee River floodplain and areas of the city of Midland, leading to an increase in residents' body burdens of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. OBJECTIVES: The UMDES is a hypothesis-driven study designed to answer important questions about human exposure to dioxins in the environment of Midland, where the Dow Chemical Company has operated for > 100 years, and in neighboring Saginaw, Michigan. In addition, the UMDES includes a referent population from an area of Michigan in which there are no unusual sources of dioxin exposure and from which inferences regarding the general Michigan population can be derived. A central goal of the study is to determine which factors explain variation in serum dioxin levels and to quantify how much variation each factor explains. CONCLUSIONS: In this article we describe the study design and methods for a large population-based study of dioxin contamination and its relationship to blood dioxin levels. The study collected questionnaire, blood, dust, and soil samples on 731 people. This study provides a foundation for understanding the exposure pathways by which dioxins in soils, sediments, fish and game, and homegrown produce lead to increased body burdens of these compounds.

The University of Michigan Dioxin Exposure Study: population survey results and serum concentrations for polychlorinated dioxins, furans, and biphenyls.

BACKGROUND: The University of Michigan Dioxin Exposure Study was undertaken to address concerns that the discharge of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo furans (PCDFs) from the Dow Chemical Company in the Midland, Michigan, area had resulted in contamination of soils in the Tittabawassee River floodplain and the city of Midland, leading to an increase in residents' body burdens of these compounds. OBJECTIVE: In this article we present descriptive statistics from the resident survey and sampling of human serum, household dust, and soil and compare them with other published values. METHODS: From a multistage random sample of populations in four areas of Midland and Saginaw counties and from a distant referent population, we interviewed 946 adults, who also donated blood for analysis of PCDDs, PCDFs, and polychlorinated biphenyls (PCBs). Samples of household dust and house perimeter soil were collected from consenting subjects who owned their property. RESULTS: All five study populations were comparable in age, race, sex, and length of residence in their current home. Regional differences existed in employment history, personal contact with contaminated soils, and consumption of fish and game from contaminated areas. Median soil concentrations were significantly increased around homes in the Tittabawassee River floodplain (11.4 ppt) and within the city of Midland (58.2 ppt) compared with the referent population (3.6 ppt). Median serum toxic equivalencies were significantly increased in people who lived in the floodplain (23.2 ppt) compared with the referent population (18.5 ppt). CONCLUSIONS: Differences in serum dioxin concentrations among the populations were small but statistically significant. Regression modeling is needed to identify whether the serum concentrations of PCDDs, PCDFs, and PCBs are associated with contaminated soils, household dust, and other factors.

The University of Michigan Dioxin Exposure Study: predictors of human serum dioxin concentrations in Midland and Saginaw, Michigan.

BACKGROUND: We conducted a population-based human exposure study in response to concerns among the population of Midland and Saginaw counties, Michigan, that discharges by the Dow Chemical Company of dioxin-like compounds into the nearby river and air had led to an increase in residents' body burdens of polychlorinated dibenzofurans (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs), here collectively referred to as "dioxins." OBJECTIVES: We sought to identify factors that explained variation in serum dioxin concentrations among the residents of Midland and Saginaw counties. Exposures to dioxins in soil, river sediments, household dust, historic emissions, and contaminated fish and game were of primary interest. METHODS: We studied 946 people in four populations in the contaminated area and in a referent population, by interview and by collection of serum, household dust, and residential soil. Linear regression was used to identify factors associated with serum dioxins. RESULTS: Demographic factors explained a large proportion of variation in serum dioxin concentrations. Historic exposures before 1980, including living in the Midland/Saginaw area, hunting and fishing in the contaminated areas, and working at Dow, contributed to serum dioxin levels. Exposures since 1980 in Midland and Saginaw counties contributed little to serum dioxins. CONCLUSIONS: This study provides valuable insights into the relationships between serum dioxins and environmental factors, age, sex, body mass index, smoking, and breast-feeding. These factors together explain a substantial proportion of the variation in serum dioxin concentrations in the general population. Historic exposures to environmental contamination appeared to be of greater importance than recent exposures for dioxins.

Simvastatin and L-arginine preserve renal function after ischemia/reperfusion injury.

BACKGROUND: HMG-CoA reductase inhibitors have been shown to have beneficial renal hemodynamic effects by increasing renal blood flow, independent of their lipid-lowering properties. Currently in organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its use is limited by its nephrotoxic effects, namely its renal vasoconstrictor properties. The purpose of this study was to determine the effect of an HMG-CoA reductase inhibitor, simvastatin (Zocor), on renal function in rats and on urinary nitrite/nitrate production following ischemia/reperfusion injury (I/R) with concomitant cyclosporine treatment. In addition, L-NAME (N(G)-nitro-L-arginine methyl ester) and L-arginine were administered with CyA to the rats to test the hypothesis that simvastatin's beneficial effects were due to nitric oxide. METHODS: Male Wistar rats (250 g) were anesthetized and the supra-aorta clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into five groups: 1) controls, no ischemia, no treatment (CTRL, n = 8); 2) ischemia (ISCH) plus cyclosporine A only (CyA, 5 mg/kg/day i.p., n = 8); 3) ischemia plus CyA and simvastatin (SIM, 10 mg/kg/day, gavage, n = 8); 4) ischemia plus simvastatin plus L-NAME plus CyA (10 mg/kg/day, gavage, n = 8), and 5) ischemia plus simvastatin plus L-arginine (2% in drinking water, n = 7) plus CyA. Five to 7 days after I/R injury, the glomerular filtration rate (GFR) was determined using urinary iohexol clearance. Urinary nitrite/nitrate production was determined using nitrate reductase and the Greiss reaction. Data are expressed as mean +/- SEM, and intergroup comparisons were made using one-way analysis of variance. RESULTS: The GFR values (mL/min) for all five groups are as follows: 1) CTRL = 1.25 +/- 0.10; 2) ISCH plus CyA only = 0.45 +/- 0.06 (P < 0.05 versus CTRL, ISCH only and simvastatin and cyclosporine and simvastatin plus L-arginine and cyclosporine); 3) CyA and SIM = 0.78 +/- 0.09, CyA and L-NAME = 0.62 +/- 0.12, and CyA and L-arginine and SIM = 1.57 +/- 0.12. Results in the control were significantly different from results in the ischemic only and the L-NAME groups (P < 0.05). The L-arginine plus cyclosporine and simvastatin group was significantly higher than the ischemic only group, ischemic plus simvastatin and cyclosporine and the L-NAME plus cyclosporine group (P < 0.05). No significant differences could be detected in the urinary nitric oxide concentrations. CONCLUSIONS: : After I/R injury and cyclosporine treatment, simvastatin and L-arginine preserved renal function, compared with cyclosporine treatment alone, because simvastatin and L-arginine may not have a direct vasoconstrictor effect on the renal microcirculation. They may be suppressing endothelin or increasing other vasodilator mediators such as the vasodilator prostaglandins and/or nitric oxide.

Rapamycin preserves renal function compared with cyclosporine A after ischemia/reperfusion injury.

OBJECTIVES: To determine the effect of cyclosporine and rapamycin administration on renal function after ischemia/reperfusion injury (I/R). Cyclosporine A has known nephrotoxic effects. Thus, cyclosporine therapy subsequent to I/R injury may further exacerbate graft dysfunction. Rapamycin is a newer agent that suppresses the immune system by a different mechanism. METHODS: Male Wistar rats (250 g) were anesthetized, and the suprarenal aorta was clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into four groups: group 1, controls, no ischemia and no treatment (n = 10); group 2, ischemia with no treatment (n = 8); group 3, ischemia plus rapamycin (0.17 mg/kg/day gavage, n = 8); and group 4, ischemia plus cyclosporine A (30 mg/kg/day intraperitoneally, n = 9). The glomerular filtration rate was measured 5 to 7 days after I/R injury using urinary iohexol clearance. Data are expressed as the mean +/- SEM, and intergroup comparisons were made using one-way analysis of variance. RESULTS: The mean GFR value for the controls (no ischemia, no treatment) was 1.23 +/- 0.08 mL/min; for group 2 (ischemia, no treatment), it was 1.05 +/- 0.10 mL/min; for group 3 (ischemia plus rapamycin) 1.06 +/- 0.14 mL/min; and for group 4 (ischemia plus cyclosporine A) 0.44 +/- 0.06 mL/min (P <0.05 versus the other three groups). The mean arterial pressure was significantly lower in the ischemic rats treated with cyclosporine A (P <0.05 versus the other three groups). CONCLUSIONS: After I/R injury, rapamycin may preserve renal function compared with cyclosporine treatment, because it does not have a direct vasoconstrictor effect on the renal microcirculation.

Simvastatin attenuates renal ischemia/reperfusion injury in rats administered cyclosporine A.

BACKGROUND: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors increase renal blood flow independent of their lipid-lowering properties. In organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its renal vasoconstrictor properties limit its use. This study aimed to determine the effect of an HMG-CoA reductase inhibitor, simvastatin (Zocor), on renal function in rats after ischemia/reperfusion injury (I/R) with concomitant CyA treatment. METHODS: Male Wistar rats (250 g) were anesthetized and the suprarenal aorta clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into 5 groups: (1) control rats, no ischemia, no treatment; (2) ischemia with no treatment; (3) ischemia plus CyA only; (4) ischemia plus CyA and low-dose simvastatin; and (5) ischemia plus CyA and high-dose simvastatin. Five to 7 days after I/R injury, glomerular filtration rate (GFR) was determined using urinary iohexol clearance. RESULTS: The GFR values (mL/min) for all 5 groups were as follows: (1) 1.23 +/- 0.08; (2) 1.05 +/- 0.10; (3) 0.44 +/- 0.06 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); (4) 0.51 +/- 0.04 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); and (5) 0.85 +/- 0.11. CONCLUSIONS: After I/R injury and cyclosporine treatment, simvastatin preserved renal function compared with cyclosporine treatment alone because it may not have a direct vasoconstrictor effect on the renal microcirculation. In fact, it may exhibit vasodilator properties on the renal microcirculation mediated by nitric oxide.