The glass is half full: evidence for efficacy of alcohol-wise at one university but not the other.

This research extends the growing literature about online alcohol prevention programs for first-year college students. Two independent randomized control studies, conducted at separate universities, evaluated the short-term effectiveness of Alcohol-Wise, an online alcohol prevention program not previously studied. It was hypothesized the prevention program would increase alcohol knowledge and reduce alcohol consumption, including high-risk alcohol-related behaviors, among first-year college students. At both universities, the intervention significantly increased alcohol-related knowledge. At one university, the prevention program also significantly reduced alcohol consumption and high-risk drinking behaviors, such as playing drinking games, heavy drinking, and extreme ritualistic alcohol consumption. Implications for the use of online alcohol prevention programs and student affairs are discussed.

Endorsement of a Personal Responsibility to Adhere to the Minimum Drinking Age Law Predicts Consumption, Risky Behaviors, and Alcohol-Related Harms.

Despite minimum drinking age laws, underage college students engage in high levels of risky drinking and reach peak lifetime levels of alcohol dependence. A group of presidents of universities and colleges has argued that these laws promote disrespect for laws in general, and do not prevent drinking or related negative consequences. However, no study has investigated the policy-relevant question of whether students who endorse a personal responsibility to obey drinking laws, regardless of their opinions about the laws, are less likely to drink or to experience negative consequences. Therefore, we compared endorsers to non-endorsers, controlling for race, gender, and baseline outcomes, at two universities (Ns = 2007 and 2027). Neither sample yielded a majority (49% and 38% endorsement), but for both universities, all 17 outcome measures were significantly associated with endorsement across all types of analyses. Endorsers were less likely to drink, drank less, engaged in less high-risk behavior (e.g., heavy/binge drinking), and experienced fewer harms (e.g., physical injury), even when controlling for covariates. Racial/ethnic minority groups were more likely to endorse, compared to White students. By isolating a small window of time between high school and college that produces large changes in drinking behavior, and controlling for covariates, we can begin to hone in on factors that might explain relations among laws, risky behaviors, and harms. Internalization of a social norm to adhere to drinking laws could offer benefits to students and society, but subsequent research is needed to pin down causation and causal mechanisms.

Impact of an online alcohol education course on behavior and harm for incoming first-year college students: short-term evaluation of a randomized trial.

OBJECTIVE: The authors assessed short-term effectiveness of a Web-based alcohol education program on entering freshmen. PARTICIPANTS: 3,216 incoming first-year students were randomized to a control or intervention group. METHODS: Controls completed a survey and knowledge test the summer before college; 4 to 6 weeks after arrival on campus, they completed a follow-up survey of behaviors and harms followed by an invitation to complete the online course. Intervention students completed the precourse survey and test, the online course, and final exam prior to coming to campus. This was followed by a survey 4 to 6 weeks after arrival on campus. RESULTS: Although the intervention group showed significantly higher alcohol-related postcourse knowledge compared to the control group, protective behavior, risk-related behavior, high-risk drinking, and alcohol-related harm did not favor the intervention group, with the sole exception of playing drinking games. CONCLUSIONS: Alcohol knowledge alone was insufficient to mitigate alcohol-related high-risk behaviors in this student population.

Diabetes and burns: retrospective cohort study.

Burn injuries are often associated with multisystemic complications, even in otherwise healthy individuals. It is therefore intuitive that for the diabetic patient, the underlying pathophysiologic alterations in vascular supply, peripheral neuropathy, and immune function could have a profoundly devastating impact on patient outcome. The effects of diabetes on morbidity and mortality of the burn-injured patient have not been examined in great detail. The purpose of this retrospective study was to compare clinical outcomes between diabetic and nondiabetic burn patients. We reviewed the charts of 181 diabetic (DM) and 190 nondiabetic (nDM) patients admitted with burns between January 1996 and May 2000, matched by sex and date of admission. Burn cause and size, time to presentation, clinical course, and outcomes were evaluated. Because age was a factor, the analysis was done by three age groups: younger than 18 years, 18 to 65 years, and older than 65 years. Of patients 18 to 65 years, 51% (98/191) were diabetic, whereas 84% (81/96) of those older than 65 and only 4% (3/85) of patients younger than 18 were diabetic. Because of the disproportion in numbers of diabetics compared with nondiabetics in the younger than 18 and older than 65 years-old groups, these patients will not be discussed. Diabetics were more likely to incur scald injury from tub or shower water rather than hot fluid spills (33% DM vs 15% nDM; P < or = 0.01), and have a delayed presentation (45 vs 23%; P = 0.00001). There was no difference in total burn size in all groups. Diabetics in the 18 to 65 years group had a higher rate of full-thickness burns (51 vs 31%; P = 0.025), skin grafts (50 vs 28%; P = 0.01) and burn-related procedures (57 vs 32%; P = 0.001), infections (65 vs 51%; P = 0.05), and longer lengths of stay (23 vs 12 days; P = 0.0001). Although there was no statistically significant difference in incidence of specific infections, the rates of cellulitis, wound infection, urinary tract infection, line infection, and osteomyelitis, were consistently higher in the diabetic population. Partial graft slough was 6% in diabetics 18 to 65 years with a 3% regraft rate, whereas nondiabetics had a 1% regraft rate. Comparing diabetics with controlled vs uncontrolled glucose levels, diabetics with uncontrolled glucose had higher rates of infection (72 vs 55%; P < or = 0.025), all burn-related procedures (68 vs 45%; P < or = 0.025), and longer ICU stays (24 vs 10 days; P = 0.048). Mortality rate was 2% for diabetics and for nondiabetics. In summary, presence of diabetes in the burn patient was associated with a worse outcome. A predilection for burn injuries in the diabetic was noted in the older adult population. Deeper burns, delayed presentation, higher rates of infection, graft failure and operations, and longer lengths of stay translate into an increased cost to society both economically and in lives. This data would suggest a need for better burn education for diabetics and health care professionals, recognizing the elderly population as a "high-risk" group. We believe that targeted prevention measures and treatment strategies, emphasizing earlier and more aggressive intervention for this population, may have a favorable effect on morbidity and mortality.

The slope of change: an environmental management approach to reduce drinking on a day of celebration at a US college.

OBJECTIVE: This research extends the literature on event-specific environmental management with a case study evaluation of an intervention designed to reduce student drinking at a university's year-end celebration. PARTICIPANTS: Cornell University undergraduates were surveyed each May from 2001 through 2009. Sample sizes ranged from 322 to 1,973. METHODS: Randomly sampled surveys were conducted after a large, annual spring campus celebration. An environmental management plan was initiated in 2003 that included increased enforcement of the minimum legal drinking age (MLDA) law. RESULTS: In the short term, drinking at the campus celebration decreased while drinking before the event increased. Over time, the intervention significantly reduced high-risk drinking on the day of the event, especially among those under the age of 21. CONCLUSION: These findings are contrary to the argument that enforcement of MLDA laws simply leads to increased high-risk drinking, and therefore have implications for how colleges approach the challenge of student alcohol misuse.

Impact of diabetes on burn injury: preliminary results from prospective study.

Reducing diabetes mellitus complications has been a major focus for Healthy People 2010. A prior retrospective cohort of our burn center's admissions revealed worse outcomes among diabetic patients, that is, increased infection rates, grafting and graft complications, and increased length of hospital stay. Therefore, a prospective study has been designed to carefully assess wound repair and recovery of diabetic and nondiabetic burn patients. Our long-term aim is to determine the characteristics of the wound milieu along with global responses to injury that may predict poor outcome among diabetic patients. This is an initial phase of a larger observational study of in-hospital diabetic (types 1 and 2) and nondiabetic patients, prospectively matched for age (18-70 and >70 years) and burn size (<5, 5-15, and 16-25%). Time (days) to complete index wound closure, documented through serial photography, is the main outcome measure. Secondary measures compare delays in presentation, prevalence of infections, graft rates, wound and graft complications, adverse events, and length of hospital stay. Detailed history, physical, and baseline hemoglobin A1C are elicited from all subjects who are assessed daily over the initial 72 hours poststudy entry, then weekly until complete index wound closure, and finally monthly through 3 months. Forty subjects are presented herein, 24 diabetic and 16 nondiabetic patients. Time to index wound closure was significantly prolonged in diabetic patients, despite increased grafting. These findings suggest that excision and grafting in diabetic patients may not alone be sufficient to ensure rapid closure, as graft complications may contribute to protracted closure. Evaluating graft need may be more complex among diabetic patients, suggesting the need for alternative management strategies. The current prospective study confirms our previous retrospective analysis, notably manifested by significant delays in index wound closure. Our efforts continue in identifying the most important predictors of outcome, especially modifiable factors that would create a basis of intervention to improve care.

PAI-1 transcriptional regulation during the G0 --> G1 transition in human epidermal keratinocytes.

Plasminogen activator inhibitor type-1 (PAI-1) is the major negative regulator of the plasmin-dependent pericellular proteolytic cascade. PAI-1 gene expression is normally growth state regulated but frequently elevated in chronic fibroproliferative and neoplastic diseases affecting both stromal restructuring and cellular migratory activities. Kinetic modeling of cell cycle transit in synchronized human keratinocytes (HaCaT cells) indicated that PAI-1 transcription occurred early after serum stimulation of quiescent (G0) cells and prior to entry into a cycling G1 condition. PAI-1 repression (in G0) was associated with upstream stimulatory factor-1 (USF-1) occupancy of two consensus E box motifs (5'-CACGTG-3') at the PE1 and PE2 domains in the PF1 region (nucleotides -794 to -532) of the PAI-1 promoter. Chromatin immunoprecipitation (ChIP) analysis established that the PE1 and PE2 site E boxes were occupied by USF-1 in quiescent cells and by USF-2 in serum-activated, PAI-1-expressing keratinocytes. This reciprocal and growth state-dependent residence of USF family members (USF-1 vs. USF-2) at PE1/PE2 region chromatin characterized the G0 --> G1 transition period and the transcriptional status of the PAI-1 gene. A consensus E box motif was required for USF/E box interactions, as a CG --> AT substitution at the two central nucleotides inhibited formation of USF/probe complexes. The 5' flanking sites (AAT or AGAC) in the PE2 segment were not necessary for USF binding. USF recognition of the PE1/PE2 region E box sites required phosphorylation with several potential involved residues, including T153, maping to the USF-specific region (USR). A T153A substitution in USF-1 did not repress serum-induced PAI-1 expression whereas the T153D mutant was an effective suppressor. As anticipated from the ChIP results, transfection of wild-type USF-2 failed to inhibit PAI-1 induction. Collectively, these data suggest that USF family members are important regulators of PAI-1 gene control during serum-stimulated recruitment of quiescent human epithelial cells into the growth cycle.

Epithelial monolayer wounding stimulates binding of USF-1 to an E-box motif in the plasminogen activator inhibitor type 1 gene.

Several proteases and their co-expressed inhibitors modulate the interdependent processes of cell migration and matrix proteolysis during wound repair. Transcription of the gene encoding plasminogen activator inhibitor type 1 (PAI-1), a serine protease inhibitor important in the control of barrier proteolysis and cell-to-matrix adhesion, is spatially-temporally regulated following epithelial denudation injury in vitro as well as in vivo. Using a well-defined culture model of acute epidermal wounding and reepithelialization, PAI-1 mRNA/protein synthesis was induced early after monolayer scraping and restricted to cells comprising the motile cohort. PAI-1 levels in locomoting cells remained elevated (relative to the distal, contact-inhibited monolayer regions) throughout the time course of trauma repair. Targeted PAI-1 downregulation by transfection of antisense PAI-1 expression constructs significantly impaired keratinocyte migration and monolayer scrape wound closure. Injury-induced PAI-1 transcription closely paralleled growth state-dependent controls on the PAI-1 gene. An E-box motif (CACGTG) in the PAI-1 proximal promoter (located at nucleotides -160 to -165), previously shown to be necessary for serum-induced PAI-1 expression, was bound by nuclear factors from wound-stimulated but not quiescent, contact-inhibited, keratinocytes. UV crosslinking approaches to identify E-box-binding factors coupled with deoxyoligonucleotide affinity chromatography and gel retardation assays confirmed at least one major E-box-binding protein in both serum- and wound-activated cells to be USF-1, a member of the helix-loop-helix family of transcription factors. An intact hexanucleotide E-box motif was necessary and sufficient for USF-1 binding using nuclear extracts from both serum- and wound-simulated cells. Two species of immunoreactive USF-1 were identified by western blotting of total cellular lysates that corresponded to the previously characterized phosphorylated and non-phosphorylated forms of the protein. USF-1 isolated by PAI-1 promoter-DNA affinity chromatography was almost exclusively phosphorylated. Only a fraction of the total cellular USF-1 in proliferating cultures, by comparison, was phosphorylated at any given time. PAI-1 E-box binding activity, assessed by probe mobility shift criteria, increased within 2 hours of monolayer scrape injury, a time frame consistent with wound-stimulated increases in PAI-1 transcription. Relative to intact cultures, scrape site-juxtaposed cells had significantly greater cytoplasmic and nuclear USF-1 immunoreactivity correlating with the specific in situ-restricted expression of PAI-1 transcripts/protein in the wound-edge cohort. USF-1 immunocytochemical staining declined significantly with increasing distance from the denudation site. These data are the first to indicate that binding of USF-1 to its target motif can be induced by 'tissue' injury in vitro and implicate USF-1 as a transcriptional regulator of genes (e.g. PAI-1) involved in wound repair.

Gallium nitrate accelerates partial thickness wound repair and alters keratinocyte integrin expression to favor a motile phenotype.

The nitrate form of the Group III transitional element gallium (GN) increases expression of specific structural components of the provisional wound matrix (i.e., collagen type I, fibronectin) in human dermal fibroblasts. To evaluate the potential of GN as a therapeutic option in management of cutaneous trauma, GN-treated partial thickness porcine wounds and experimentally "injured" human keratinocyte (NHK) monolayer cultures were compared with mirror image control (i.e., saline-treated) sites. GN suppressed cell proliferation in both models, as determined by reduced Ki-67 reactivity and significant lengthening of keratinocyte cell cycle transit times, while effectively promoting reepithelialization. The primary effect of GN was apparently to promote cell migration, as neither epidermal thickness nor epidermal differentiation was altered as a result of GN exposure in vivo or in vitro. Significantly enhanced epidermal reepithelialization was associated with alterations in expression of several keratinocyte integrin subunits. GN induced a significant increase in alpha5 expression. alpha5beta1 switching is a characteristic of the motile phenotype in the setting of cutaneous injury. Concomitantly, GN treatment also induced a dramatic (70%) decrease in the expression of the alpha3 subunit; alpha3beta1 binds laminin 5 and is associated with hemidesmosome formation and reestablishment of a nonmotile phenotype. Taken together, the GN-induced changes in integrin expression favor acellular migration. While the molecular mechanism of GN action on resident cells of the skin remains to be defined, these data suggest that GN administration which represses MMP activity in the wound and increases matrix synthesis also accelerates NHK motility and, thereby, may be a useful therapeutic agent for wound repair.