Microscale strain concentrations in tissue-engineered osteochondral implants are dictated by local compositional thresholds and architecture.

Tissue-engineered osteochondral implants manufactured from condensed mesenchymal stem cell bodies have shown promise for treating focal cartilage defects. Notably, such manufacturing techniques have shown to successfully recapture the bulk mechanical properties of native cartilage. However, the relationships among the architectural features, local composition, and micromechanical environment within tissue-engineered cartilage from cell-based aggregates remain unclear. Understanding such relationships is crucial for identifying critical parameters that can predict in vivo performance. Therefore, this study investigated the relationship among architectural features, composition, and micromechanical behavior of tissue-engineered osteochondral implants. We utilized fast-confocal microscopy combined with a strain mapping technique to analyze the micromechanical behavior under quasi-static loading, as well as Fourier Transform Infrared Spectroscopy to analyze the local compositions. More specifically, we investigated the architectural features and compositional distributions generated from tissue maturation, along with macro- and micro-level strain distributions. Our results showed that under compression, cell-based aggregates underwent deformation followed by body movement, generating high local strain around the boundaries, where local aggrecan concentration was low and local collagen concentration was high. By analyzing the micromechanics and composition at the single aggregate length scale, we identified a strong threshold relationship between local strain and compositions. Namely at the aggrecan concentration below 0.015 arbitrary unit (A.U.) and the collagen concentration above 0.15 A.U., the constructs experienced greater than threefold increase in compressive strain. Overall, this study suggests that local compositional features are the primary driver of the local mechanical environment in tissue-engineered cartilage constructs, providing insight into potential quality control parameters for manufacturing tissue-engineered constructs.

Long-term mediation of a sexual risk-reduction intervention for South African adolescents.

OBJECTIVE: Black adolescents in South Africa are disproportionately affected by HIV. A cluster-randomized controlled experiment examining the effects of a sexual risk-reduction intervention successfully reduced self-reported intercourse and unprotected intercourse. Based on long-term follow-up assessments, the present research examines theoretical constructs that could potentially mediate the intervention effects and how time and gender, respectively, moderated the mediation. METHOD: The behavioral outcome was measured by asking whether participants had had any vaginal sex in the past 3 months. Mediation and moderated mediation were tested based on the 3-, 6-, 12-, 42-, and 54-month postintervention outcomes. RESULTS: Three variables through which the sexual risk-reduction intervention had a significant mediated effect on the behavioral outcome were identified: abstinence career opportunities outcome expectancy (α × ß product = -0.086, 95% asymmetric confidence interval [ACI] [-0.126, -0.047]), expected parental approval of sexual intercourse (α × ß product = -0.061, [-0.102, -0.025]), and self-efficacy to avoid sexual-risk situations (α × ß product = -0.022, [-0.049, -0.001]). The moderated mediation analysis showed that gender moderated the intervention's effects on abstinence prevention outcome expectancy (B = -0.186, SEB = 0.079, p = .019), expected parental approval of sexual intercourse (B = 0.143, SEB = 0.058, p = .013), and self-efficacy to avoid sexual-risk situations (B = -0.293, SEB = 0.112, p = .009). The moderated mediation analysis also revealed that time moderated the effects of the intervention on abstinence career opportunities outcome expectancy (B = -0.293, SEB = 0.106, p = .006), self-efficacy to avoid sexual-risk situations (B = 0.335, SEB = 0.060, p < .001), and cultural myths regarding HIV transmission (B = 0.138, SEB = 0.042, p = .001); and the association between four theoretical constructs and the behavioral outcome: abstinence career opportunities outcome expectancy (B = -0.267, SEB = 0.104, p = .001), self-efficacy to refuse sex (B = -0.132, SEB = 0.043, p = .002), self-efficacy to avoid sexual-risk situations (B = -0.093, SEB = 0.055, p = .009), and HIV risk-reduction knowledge (B = -0.286, SEB = 0.134, p = .003). CONCLUSIONS: The present study identifies theoretical constructs that mediated the intervention effects on the sexual behavior among South African adolescents for an extended period of time. The findings also reveal gender differences in psychological mechanisms initiated by a sexual risk-reduction intervention and the long-term temporal dynamics of the intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prospective Predictors of Blood Pressure Among African American Men Living with HIV.

Little is known about the predictors of blood pressure (BP) among African American men living with HIV. We examined whether age and body mass index (BMI) are associated with higher blood pressure (BP) and whether being married and muscular endurance are associated with lower BP among African American men living with HIV. Second, we examined whether being married moderated the effects of the other predictors on BP. Finally, we examined whether BMI mediated the relationship between muscular endurance and BP. This article is a prospective secondary analysis of data from a randomized controlled trial of a health-promotion intervention for African American men living with HIV. We measured the participants' BP pre-intervention and three, six, and 12 months post-intervention. Generalized estimating equations linear regression analyses examined whether marital status, age, BMI, and muscular endurance predicted BP post-intervention, adjusting for pre-intervention BP and the intervention. Older age, higher BMI, and lower muscular endurance predicted higher BP post-intervention, adjusting for the intervention and baseline BP. Although marital status did not predict post-intervention BP, it moderated the negative effect of higher BMI. The positive relation of BMI to BP was weaker among married men than unmarried men. Muscular endurance had an indirect impact on BP mediated through BMI. Public health efforts targeting older African American men with HIV should focus on increasing muscular endurance in this population to lower BMI as a strategy to reduce cardiovascular disease risk in this population.

Physical Activity Intervention Effects on Waist-to-Hip Ratio in African American Men Living With HIV.

People living with HIV on antiretroviral therapy have an increased risk of developing metabolic disturbances and central adiposity. Adequate engagement in physical activity (PA) could reduce the risk of chronic diseases associated with central adiposity. We conducted a secondary analysis of data from a randomized controlled trial of a PA intervention with 302 African American men aged 40 or older (53.9±7.2 years) living with HIV to assess whether the intervention reduced the waist-to-hip ratio (WHR). Generalized estimating equation analyses tested whether the PA intervention reduced WHR compared with the control group and whether age moderated its effect, adjusting for follow-up assessment time (3, 6, and 12 months postintervention) and baseline WHR and age. The analysis revealed that the intervention's effect on WHR was not significant (B = -0.008, p = .097). However, a significant interaction between age and the intervention (B = 0.001, p = .046) indicated that the intervention's effect in reducing WHR waned with increasing age. For instance, when dividing participants into three age subgroups, the intervention reduced WHR for men ages 40 to 50 (B = -0.020, p = .013) and ages 50 and 60 (B = -0.007, p = .315) but increased it among those older than 60 (B = 0.013, p = .252). The intervention's effects on WHR differed by participants' age, suggesting that different PA strategies may be needed based on age to improve the metabolic profile and reduce chronic disease risk in African American men living with HIV.

Beliefs and willingness towards participating in genetic testing for depression in low-income and racial/ethnic minority mothers at-risk.

PURPOSE: To identify mothers' salient normative, behavioral and control beliefs and willingness towards participating in genetic salivary testing for depression. DESIGN: A qualitative, descriptive design was employed. 41 multi-ethnic mothers completed surveys that underwent directed content analysis according to The Theory of Planned Behavior. Percentages and frequency counts were used to categorize responses and calculate willingness. FINDINGS: Salient beliefs included: Behavioral: Finding a cure/treatment for depression (29.3 %), Normative: Family would approve (46.3 %), and Church associates would disapprove (19.5 %). CONTROL: Lacking information/explanations (34.1 %) as barriers, convenient locations (24.4 %) as facilitators. Most mothers indicated a willingness to participate (90.2 %). CONCLUSIONS: Interventions should target families, emphasize benefits, explain purposes and procedures, and use community based participatory methods.

Predicting intentions to meet fruit & vegetable recommendations among black emerging adult women.

ObjectiveTo examine Black emerging adult women's (ages 18-29) intention to meet the recommended daily intake of fruits and vegetables using the Theory of Planned Behavior (TPB). Participants: Black emerging adult women (BEAW; N = 100). Methods: A cross-sectional survey design. Results: Hierarchical regression analyses revealed that in Model 1, attitudes (p<.0001) and subjective norms (p<.05) were significant predictors of intentions to meet the recommended daily intake of fruits and vegetables. In Model 2, attitudes (p=.0001) and perceived behavioral control (p<.0001) were revealed to be significant predictors of intentions. The change in R squared from Model 1 (R2=.304) and Model 2 (R2=.559), was 0.255 (F = 40.08, p<.0001) with the addition of perceived behavioral control to the second model. Conclusion: The TPB may be a suitable framework to assess factors associated with fruit and vegetable intentions among BEAW. Interventions designed to increase fruit and vegetable intake in BEAW should prioritize modifying perceived behavioral control.

The Effects of a Community-Based, Multicomponent, Depression Prevention Intervention in Mothers At-Risk.

The purpose of this study was to develop a 12-week multicomponent, depression prevention pilot intervention and evaluate its feasibility and preliminary effects on improving levels and correlates of depressive symptoms, including anger, self-esteem perceived stress, social support, and racism. A quasi-experimental, mixed-methods design and a community-based participatory research (CBPR) approach was employed. University faculty, students and community residents collaborated at a low-income housing complex in a low-resourced, urban community. Fifteen low-income, ethnic minority mothers ages 23-46 years completed the intervention and evaluation surveys. Eight mothers participated in a focus group. The intervention included social group-dance, health education, and socialization. t-Tests, sign-tests, and thematic analysis was employed. Mothers identified barriers and facilitators of program engagement. Depressive symptoms were significantly reduced (t(14) = 2.41, p = .030). Self-esteem (t(14) = 2.28, p = .039) and social support levels (M = 4.5, p = .035) were significantly increased. This multicomponent intervention is feasible. Preliminary efficacy evidence was mixed.

Effects of a Health Promotion Intervention on Physical Activity in African American Men Living with HIV: Randomized Controlled Trial.

HIV and its treatment with antiretroviral therapy increase the risk of noncommunicable diseases (NCDs) tied to physical inactivity. Older African American men are also at high risk for NCDs. We tested the efficacy of a theory-based intervention to increase adherence to federal aerobic and muscle-strengthening physical activity (PA) guidelines among African American men aged 40 years and older living with HIV. We randomized African American men aged 40 years and older living with HIV to a three-session social cognitive theory-informed health promotion intervention targeting PA or a one-session health awareness control condition. The primary outcome was PA guideline adherence assessed (self-reported) preintervention, immediate postintervention, and 3, 6, and 12 months postintervention. Secondary outcomes were the number of days on which participants reported moderate-intensity aerobic PA, vigorous-intensity aerobic PA, and muscle-strengthening PA in the past 7 days. Of 302 participants, 255 completed the 12-month postintervention measures. Generalized estimated equation logistic regression indicated that the health promotion intervention participants had higher odds of meeting PA guidelines than health awareness control participants, adjusting for baseline adherence (p = 0.011). Health promotion intervention participants also reported more muscle-strengthening PA (p = 0.001), vigorous-intensity aerobic PA (p = 0.049), and moderate-intensity aerobic PA (p = 0.010) than control participants. The rise in self-reported adherence to PA guidelines and improvements in muscle-strengthening and aerobic PA considered separately suggest that a relatively brief behavioral intervention can increase PA among African American men aged 40 years and older living with HIV and potentially curb their risk of NCDs that PA can prevent.

Predictors of Colorectal Cancer Screening Among African American Men Living with HIV.

African American men living with HIV are at high risk of colorectal cancer (CRC). Screening to detect CRC is associated with a reduced risk of CRC mortality. However, little is known about CRC screening predictors in this population. This study examined the relation of self-efficacy, a potential mediator of screening that interventions could target, to CRC screening. It also investigated several variables that might identify subpopulations of African American men non-adherent to CRC screening recommendations. We report a secondary analysis on baseline data from a randomized controlled trial of a health promotion intervention for African American men living with HIV. Before their intervention, they completed measures of CRC screening, self-efficacy, marital status, age, education, and adherence to physical activity guidelines and were assessed for obesity. A total of 270 African American men aged 45 to 88 (Mean = 55.07; SD = 6.46) living with HIV participated. About 30% reported CRC screening in the past six months. Multiple logistic regression revealed greater CRC screening self-efficacy and meeting physical activity guidelines were associated with receiving CRC screening. Obese men and men reporting higher education were less likely to report screening. Age and marital status were unrelated to screening. The results of this study suggest CRC screening rates may be low among African American men living with HIV, and interventions targeting self-efficacy may improve their screening uptake. Moreover, public-health efforts to increase screening should prioritize interventions with subpopulations of African American men living with HIV who are physically inactive and obese.

Reasoned Action Approach Correlates of Fruit and Vegetable Diet Among African American Men Living With HIV: A Cross-Sectional Study.

Epidemiological evidence of the protective role of fruits and vegetables for a host of chronic health conditions is well-documented. However, there is a dearth of studies examining predictors of fruit and vegetable intake among African American men living with HIV. We report secondary analyses-multiple regression and logistic regression models fitted to examine the strength of the relationships between the reasoned action approach constructs; namely, attitudes, subjective norms, descriptive norms, self-efficacy and intention to consume fruits and vegetables, and self-reported adherence to 5-A-DAY guidelines. We used baseline data from a randomized controlled trial of a physical activity intervention trial with 302 African American men aged 40 years or older (M = 53.9; SD = 7.2) living with HIV. Attitudes, subjective norms, descriptive norms, and self-efficacy were positively associated with intention to meet 5-A-DAY guidelines. More positive attitudes toward 5-A-DAY guidelines were associated with higher odds of meeting 5-A-DAY guidelines. More positive attitudes and self-efficacy were also positively associated with meeting the guidelines for intake of vegetable servings and fruit-and-vegetable servings combined. To increase fruit and vegetable intake among African American men living with HIV, interventions should be tailored to address the perceived benefits of consumption.

Reasoned Action Approach Correlates of Physical Activity Among African American Men Living With HIV: A Cross-Sectional Study.

ABSTRACT: Physical activity (PA) is associated with a reduced incidence of chronic diseases. However, little is known about the predictors of PA among African American men living with HIV. We report secondary analyses examining the strength of the relationships between the reasoned action approach constructs, attitude, subjective norm, descriptive norm, and self-efficacy and intention to exercise and self-reported adherence to Department of Health and Human Services PA guidelines using baseline data from a trial of a PA intervention with 302 African American men, between 40 and 88 years of age (M = 53.9; SD = 7.2) living with HIV. Multiple regression revealed that attitude, subjective norm, and self-efficacy were positively associated with intention. Logistic regression revealed higher odds of meeting PA guidelines as self-efficacy increased. Self-efficacy and descriptive norm predicted meeting the aerobic guideline. Self-efficacy predicted meeting the muscle-strengthening guideline. Interventions targeting reasoned action approach variables may contribute to efforts to improve PA among African American men living with HIV.

Eliciting Willingness and Beliefs towards Participation in Genetic Psychiatric Testing in Black/African American Mothers at Risk for Depression.

Black/African American women are at high risk for depression, yet are underrepresented in psychiatric genetic research for depression prevention and treatment. Little is known about the factors that influence participation in genetic testing for Black/African American women at risk. The purpose of this study was to elicit the beliefs that underlie participation in genetic testing for depression in Black/African American mothers, a subgroup at high risk. Willingness to participate in genetic testing procedures was also determined. A qualitative, descriptive design was employed. Exactly 19 mothers aged 21-42 completed open-ended questionnaires. Directed content and descriptive analyses of the text were conducted based on the Theory of Planned Behavior. Salient beliefs included: behavioral advantages-diagnosing/detecting depression (31.6%), finding cure/treatment (21.1%); disadvantages-not finding follow-up treatment/help (21.1%); salient referents, who approves-family members (47.4%), agencies/organizations (26.3%); who disapproves-church associates (21.1%). Control beliefs included: barriers-unpleasant/difficult testing procedures (42.1%), limited knowledge about the purpose of testing (26.3%); facilitator-a convenient location (21.1%). Most mothers (89.5%) indicated willingness to participate in testing. Interventions can target families, address barriers, emphasize future benefits, and use convenient locations and community-based participatory research methods. Policies can address social determinants of participation to increase inclusion of these mothers in psychiatric genetic research.

The Use of Closing Questions in Qualitative Research: Results of a Web-Based Survey.

BACKGROUND: Scarce and differing reasons for including closing questions in qualitative research exist, but how data generated from these questions are used remains uncertain. OBJECTIVES: The purpose of the study was to understand if and how researchers use closing questions in qualitative research, specifically the research questions were: (a) "Why do qualitative researchers include or exclude closing questions during interviews?" and (b) "How do qualitative researchers use data from closing questions?" METHODS: A qualitative descriptive design using a single, asynchronous, web-based, investigator-designed survey containing 14 items was used to collect data. Convenience and snowball sampling were used to recruit participants. Data were analyzed using descriptive statistics and qualitative content analysis. Codes were developed from the qualitative data. Subcategories were derived from similar codes, and these subcategories were further scrutinized and were used to create broad categories. RESULTS: The number of respondents per question ranged from 76 to 99; most identified nursing and sociology as their academic disciplines, lived in the United States, and were involved in qualitative research for 1-10 years. Data, the interview, the interviewee, and the interviewer were broad categories to emerge as reasons for including closing questions. Only one respondent reported a reason for excluding closing questions. The uses of closing question data were described in four broad categories: analysis, data, the interview guide, and inquiry. DISCUSSION: Researchers frequently included closing questions in qualitative studies. The reasons for including these questions and how data are used vary, and support limited previously published literature. One unique reason, adding "new breath" to the interview, emerged. Study findings can aid qualitative researchers in deciding whether to include closing questions.

Exploring Expressions of Depression in Black Single Mothers.

PROBLEM: This study investigates the experience of depression from the perspective of Black single mothers, an understudied diverse-sub-group who consistently report high levels of depressive symptoms that go undetected and untreated. PARTICIPANTS: The sample consisted of 210 Black single mothers aged 18-45 who reside in urban communities. METHODS: A descriptive, cross-sectional design was used to categorize the responses of Black single mothers to an open-ended question that asks about feelings of depression according to the four domains of the Centers for Epidemiologic Studies Depression Scale. Percentages and frequencies were used to describe the results of the analysis. FINDINGS: The 303 usable responses were most consistent with the depressed affect domain (N = 172), followed by somatic activity (N = 108), interpersonal symptoms (N = 21), and lack of positive affect (N = 2). The most prevalent raw responses included sadness (N = 59), forms of anger (N = 48), depressed (N = 24), cry (N = 23), do not want to be around people (N = 21), lonely (N = 17), tired (N = 16), and stressed (N = 12). CONCLUSIONS/IMPLICATIONS: Consider culture and individualized assessments to explore feelings of anger and sadness when screening for depressive symptoms in specific sub-groups of Black single mothers. Consider the use of appropriate screening tools.

Co-creation of a pedagogical space to support qualitative inquiry: An advanced qualitative collective.

BACKGROUND: Situated in a research-intensive School of Nursing, the Advanced Qualitative Collective (AQC) provides an innovative educational forum for the study of qualitative research by doctoral and postdoctoral scholars. This long-standing collective is guided by a faculty facilitator using a collaborative co-learning approach to address individual and group needs, from the conception of research projects through dissemination of completed qualitative research. This article describes the dynamics of the AQC and the ways a co-created pedagogical entity supports professional development among its diverse members. The informal, participatory style, and dynamic content used by the AQC resists a course structure typical of doctoral education in health sciences, and promotes engagement and self-direction. The AQC provides opportunities for members to examine theoretical frameworks and methodologies rarely addressed within a positivism-dominant learning environment while simultaneously serving as an alternative exemplar for the pedagogy of research.

Hedgehog signalling does not stimulate cartilage catabolism and is inhibited by Interleukin-1ß.

BACKGROUND: In osteoarthritis, chondrocytes adopt an abnormal hypertrophic morphology and upregulate the expression of the extracellular matrix-degrading enzymes, MMP-13 and ADAMTS-5. The activation of the hedgehog signalling pathway has been established in osteoarthritis and is thought to influence both of these processes. However, the role of this pathway in the initiation and progression of osteoarthritis is unclear as previous studies have been unable to isolate the effects of hedgehog pathway activation from other pathological processes. In this study we test the hypothesis that hedgehog pathway activation causes cartilage degradation in healthy cartilage and in an in vitro model of inflammatory arthritis. METHODS: Isolated articular chondrocytes from the bovine metacarpal-phalangeal joint were stimulated for up to 24 hours with the agonist, recombinant Indian hedgehog (r-Ihh). ADAMTS-5 and MMP-13 gene expression was quantified by real-time PCR. In addition, healthy bovine cartilage explants were treated with r-Ihh or the hedgehog antagonist, cyclopamine, and sGAG release into the media was measured over 72 hours. Studies were repeated using chondrocytes and cartilage explants from human knee joint. Finally, studies were conducted to determine the effect of hedgehog pathway activation on matrix catabolism in the presence of the pro-inflammatory cytokine, IL-1ß. RESULTS: Addition of r-Ihh activated hedgehog signalling, confirmed by upregulation of Gli1 and Ptch1 expression, but did not increase ADAMTS-5 or MMP-13 expression in bovine or human chondrocytes. Furthermore, r-Ihh did not induce sGAG release in healthy bovine or human cartilage explants. IL-1ß treatment induced sGAG release, but this response was not altered by the stimulation or inhibition of hedgehog signalling. Hedgehog pathway activation was downregulated by IL-1ß. Conversely, r-Ihh weakly suppressed IL-1ß-induced ADAMTS-5 expression. CONCLUSION: Our results show for the first time that Indian hedgehog does not cause extracellular matrix degradation in healthy ex vivo cartilage or in the presence of IL-1ß and that IL-1ß downregulates Indian hedgehog induced signalling. Thus, we suggest reported hedgehog induced matrix catabolism in osteoarthritis must be due to its interaction with pathological factors other than IL-1ß. Hence, hedgehog signalling and its downstream effects are highly context-dependent.

Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair.

Cartilage tissue lacks an intrinsic capacity for self-regeneration due to slow matrix turnover, a limited supply of mature chondrocytes and insufficient vasculature. Although cartilage tissue engineering has achieved some success using agarose as a scaffolding material, major challenges of agarose-based cartilage repair, including non-degradability, poor tissue-scaffold integration and limited processing capability, have prompted the search for an alternative biomaterial. In this study, silk fiber-hydrogel composites (SF-silk hydrogels) made from silk microfibers and silk hydrogels were investigated for their potential use as a support material for engineered cartilage. We demonstrated the use of 100% silk-based fiber-hydrogel composite scaffolds for the development of cartilage constructs with properties comparable to those made with agarose. Cartilage constructs with an equilibrium modulus in the native tissue range were fabricated by mimicking the collagen fiber and proteoglycan composite architecture of native cartilage using biocompatible, biodegradable silk fibroin from Bombyx mori. Excellent chondrocyte response was observed on SF-silk hydrogels, and fiber reinforcement resulted in the development of more mechanically robust constructs after 42 days in culture compared to silk hydrogels alone. Thus, we demonstrate the versatility of silk fibroin as a composite scaffolding material for use in cartilage tissue repair to create functional cartilage constructs that overcome the limitations of agarose biomaterials, and provide a much-needed alternative to the agarose standard.

Tissue-engineered articular cartilage exhibits tension-compression nonlinearity reminiscent of the native cartilage.

The tensile modulus of articular cartilage is much larger than its compressive modulus. This tension-compression nonlinearity enhances interstitial fluid pressurization and decreases the frictional coefficient. The current set of studies examines the tensile and compressive properties of cylindrical chondrocyte-seeded agarose constructs over different developmental stages through a novel method that combines osmotic loading, video microscopy, and uniaxial unconfined compression testing. This method was previously used to examine tension-compression nonlinearity in native cartilage. Engineered cartilage, cultured under free-swelling (FS) or dynamically loaded (DL) conditions, was tested in unconfined compression in hypertonic and hypotonic salt solutions. The apparent equilibrium modulus decreased with increasing salt concentration, indicating that increasing the bath solution osmolarity shielded the fixed charges within the tissue, shifting the measured moduli along the tension-compression curve and revealing the intrinsic properties of the tissue. With this method, we were able to measure the tensile (401±83kPa for FS and 678±473kPa for DL) and compressive (161±33kPa for FS and 348±203kPa for DL) moduli of the same engineered cartilage specimens. These moduli are comparable to values obtained from traditional methods, validating this technique for measuring the tensile and compressive properties of hydrogel-based constructs. This study shows that engineered cartilage exhibits tension-compression nonlinearity reminiscent of the native tissue, and that dynamic deformational loading can yield significantly higher tensile properties.

Treatment of alcohol-dependent college students.

A report by the Centers for Disease Control and Prevention noted that excessive alcohol consumption is responsible for more than 4,600 deaths in underage youth annually. Alcohol abuse is common among college-age youth and may progress to alcohol dependence, which includes tolerance, craving, physical dependence, and loss of control. Although treatment for alcohol dependence is effective, like all other chronic disorders, relapse is common. The purpose of this article is to examine the issues surrounding alcohol abuse and dependence as well as maintaining sobriety in light of the high-risk college student drinking environment.

Localized alteration of microtubule polymerization in response to guidance cues.

Inhibition of microtubule dynamic instability prevents growth cone turning in response to guidance cues, yet specific changes in microtubule polymerization as growth cones encounter boundaries have not been investigated. In this study, we examined the rate and direction of microtubule polymerization in response to soluble nerve growth factor (NGF) and immobilized chondroitin sulfate proteoglycans (CSPGs) by expressing enhanced GFP-EB3 in rat pheochromocytoma (PC12) cells. GFP-EB3 comets were monitored in live cells using time-lapse epifluorescent microscopy. With an automated tracking system, the rate of microtubule polymerization was calculated as the frame-to-frame displacement of EB3 comets. Our results demonstrate that the rate of microtubule polymerization is increased following NGF treatment, whereas contact with CSPGs decreases microtubule polymerization rates. This reduction in microtubule polymerization rates was specifically localized to neurites in direct contact with CSPGs and not at noncontacting neurites. Additionally, we found an increase in the percentage of microtubules polymerizing in the retrograde direction in neurites at CSPG boundaries, with a concomitant decrease in the rate of retrograde microtubule polymerization. These results implicate localized changes in microtubule dynamics as an important component of the growth cone response to guidance cues.