International and Interprofessional Collaboration: An Innovative Week of Learning Across Three Professions, Three Universities, and One Ocean.

ABSTRACT: As the COVID-19 pandemic prevented planned international travel opportunities for students and faculty, faculty at three universities from three professions created a four-day innovative, online learning experience. Each session included presentations from each country, small-group discussions, and evaluation. The topics appealed to students regardless of profession or nationality. Daily evaluations showed attendees valued the experience. The benefits of international and interprofessional learning were evident; students gained better understanding of other professions and health care systems through sessions that expanded their thinking. International appreciation and learning can be prioritized without physical travel.

Holistic Admissions: Strategies for Increasing Student Diversity in Occupational Therapy, Physical Therapy, and Physician Assistant Studies Programs.

To meet the healthcare needs of diverse populations, universities must implement strategies to recruit health professions students who are racially, ethnically, and culturally similar to the communities they serve. One strategy to increase diversity in the health professions is to implement a holistic admissions process. Inspired by the successful use of holistic admission practices in the College of Medicine at the Medical University of South Carolina, occupational therapy, physical therapy, and physician assistant studies programs implemented holistic reviews in their admissions processes. Although each program developed a different strategy, all were successful in increasing the percentage of diverse students in their respective programs. This paper describes the holistic admissions practices and outcomes and other lessons learned in the effort to achieve our goal of greater student diversity. These lessons included the need to increase the total number of applicants using centralized application services, develop mentoring programs to assist applicants with navigating the requirements for our programs and the admissions process, and provide more scholarship opportunities.

Beneficial effects of theophylline infusions in surgical patients with intra-abdominal hypertension.

BACKGROUND: Intra-abdominal hypertension (IAH) can cause high mortality. Recently, we found that IAH was associated with increased serum levels of adenosine and interleukin 10. Our present "hypothesis-generated study" was based on the above mentioned results. MATERIALS AND METHODS: In this uncontrolled clinical trial, a total of 78 patients with IAH were enrolled representing a 13-20 mmHg range of intra-abdominal pressure (IAP). Patients requiring surgical abdominal decompression were excluded. Patients were treated with the following protocols: standard supportive therapy (ST, n = 38) or ST plus infusion with the adenosine receptor antagonist theophylline (T, n = 40). Over the 5-day measurement period, IAP was monitored continuously and serum adenosine concentration and other clinical and laboratory measurements were monitored daily. Mortality was followed for the first 30 days following the diagnosis of IAH. RESULTS: Mortality of ST patients was 55%, which is compatible to other studies. Serum adenosine concentration was found to be directly proportional to IAP. Of the 40 patients receiving T treatment, survival was 100%. An increased survival related to theophylline infusion correlated with improving serum concentrations of IL-10, urea, and creatinine, as well as 24-h urine output, fluid balance, mean arterial pressure, and O(2)Sat. CONCLUSIONS: Adenosine receptor antagonism with T following IAH diagnosis resulted in markedly reduced mortality in patients with moderated IAH (<20 mmHg). Theophylline-associated mortality reduction may be related to improved renal perfusion and improved MAP, presumably caused by adenosine receptor blockade. Because this study was not a randomized controlled study, these compelling observations require further multicentric clinical confirmation.

Polyunsaturated fatty acids. Immunomodulators in older adults.

The immune system tends to become less efficient as people age, and nutrition plays a significant role in older adults' immune responses. In particular, dietary fatty acids are precursors to important immune system components. Certain fatty acids, predominantly those that are polyunsaturated, also tend to decrease the risk of certain neurological diseases in older adults. This article describes the impact of dietary polyunsaturated fatty acids (PUFA) on older adults' immune system and discusses the roles of age and immune status with regard to PUFA supplements.

Ex vivo detection of histone H1 modified with advanced glycation end products.

A number of oxidative stress agents cause DNA and protein damage, which may compromise genomic integrity. Whereas oxidant-induced DNA damage has been extensively studied, much less is known concerning the occurrence and fate of nuclear protein damage, particularly of proteins involved in the regulation and maintenance of chromatin structure. Protein damage may be caused by the formation of reactive carbonyl species such as glyoxal, which forms after lipid peroxide degradation. It may also result from degradation of early protein glycation adducts and from methylglyoxal, formed in the process of glycolytic intermediate degradation. Major adducts indicative of protein damage include the advanced glycation end product (AGE) carboxymethyllysine (CML) and argpyrimidine protein adducts. Thus, the formation of CML and argpyrimidine protein adducts represents potential biomarkers for nuclear protein damage deriving from a variety of sources. The purpose of this study was to identify and quantify AGE adducts formed in vivo in a nuclear protein, specifically histone H1, using CML and argpyrimidine as biomarkers. Histone H1 was isolated from calf thymus collected immediately after slaughter under conditions designed to minimize AGE formation before isolation. Using antibodies directed against oxidative protein adducts, we identified CML, argpyrimidine, and protein crosslinks present in the freshly isolated histone H1. Detailed mass spectroscopy analysis of histone H1 revealed the presence of two specific lysine residues modified by CML adducts. Our results strongly suggest that glycation of important nuclear protein targets such as histone H1 occurs in vivo and that these oxidative changes may alter chromatin structure, ultimately contributing to chronic changes associated with aging and diseases such as diabetes.

Rutin metabolites: novel inhibitors of nonoxidative advanced glycation end products.

Glycation is a nonenzymatic condensation reaction between reducing sugars and amino groups of proteins that undergo rearrangements to stable ketoamines, leading to the formation of advanced glycation end products (AGEs) including fluorescent (argpyrimidine) and nonfluorescent (N(epsilon)-carboxymethyllysine; CML) protein adducts and protein cross-links. AGEs are formed via protein glycation and correlate with processes resulting in aging and diabetes complications. Reactive carbonyl species such as glyoxal and methylglyoxal are ubiquitous by-products of cell metabolism that potently induce the formation of AGEs by nonenzymatic protein glycation and may achieve plasma concentrations of 0.3-1.5 micromol/L. In this in vitro study histone H1 glycation by glyoxal, methylglyoxal, or ADP-ribose was used to model nonoxidative protein glycation, permitting us to distinguish specific AGE inhibition from general antioxidant action. Rutin derivatives were tested as AGE inhibitors because rutin, a common dietary flavonoid that is consumed in fruits, vegetables, and plant-derived beverages, is metabolized by gut microflora to a range of phenolic compounds that are devoid of significant antioxidant activity and achieve blood concentrations in the mumol/L range. Our data show that in a 1:1 stoichiometry with glyoxal or methylglyoxal, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3,4-dihydroxytoluene (DHT) are powerful inhibitors of CML and argpyrimidine histone H1 adduct formation, respectively. Furthermore, when DHPAA and DHT were tested as inhibitors of histone H1 glycation by the powerful glycating agent ADP-ribose, they inhibited glycation as effectively as aminoguanidine. These results suggest that dietary flavonoids may serve as effective AGE inhibitors and suggest mechanisms whereby fruit- and vegetable-rich diets contribute to the prevention of processes resulting in aging and diabetes complications.

Increased serum adenosine and interleukin 10 levels as new laboratory markers of increased intra-abdominal pressure.

BACKGROUND: Increased intra-abdominal pressure (IAP), intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are severe complications of surgical interventions with a high rate of mortality. The technique of IAP measurement is accurate, precise, reproducible and cost-effective. However, laboratory measures for monitoring of IAH have not been defined. We investigated the linkage between the serum levels of adenosine and interleukin 10 (IL-10) with IAP. METHODS: The sera of 25 surgical patients with IAP <12 mmHg and of 45 surgical patients with IAP >12 mmHg were tested. Serum adenosine concentration was measured by HPLC. Serum IL-1ß, IL-2, IL-4, IL-10, TNFα, IFNγ and IL-10 were determined by enzyme linked immunosorbent assay (ELISA). CRP was measured by nephelometry. RESULTS: Significant correlations of IAP were found only with serum levels of adenosine and IL-10. In the sera of patients with IAP >12 mmHg, the levels of both adenosine (1.61 versus 0.06 µM, p < 0.01) and IL-10 (63.23 versus 27.27 pg/ml, p < 0.01) were significantly higher than those in patients with IAP <12 mmHg. Moreover, significant correlations were found between individual patient IAP-adenosine values (r = 0.766, p < 0.001), IAP-IL-10 values (r = 0.792, p < 0.001) and adenosine-IL-10 values (r = 0.888, p < 0.001). A direct linear correlation between IAP-adenosine and IAP-10 values was only observed with IAP >15 (Grade II-IV). CONCLUSION: We report associations between IAP and the serum adenosine and IL-10 levels providing new tools for the laboratory monitoring of IAH as well as further understanding of the pathomechanisms contributing to ACS.

Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites.

Several lines of evidence suggest that rutin, flavonoid in fruits and vegetables, or one of its metabolites may effectively modulate advanced glycation end product (AGE) formation. Following ingestion, rutin forms metabolites that include 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3,4-dihydroxytoluene (3,4-DHT), m-hydroxyphenylacetic acid (m-HPAA), 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA) and 3,5,7,3',5'-pentahydroxyflavonol (quercetin). We studied the effects of rutin and its metabolites on the formation of AGE biomarkers such as pentosidine, collagen-linked fluorescence, N(epsilon)-carboxymethyllysine (CML) adducts, glucose autoxidation and collagen glycation, using an in vitro model where collagen I was incubated with glucose. Rutin metabolites containing vicinyl dihydroxyl groups, i.e., 3,4-DHT, 3,4-DHPAA and quercetin, inhibited the formation of pentosidine and fluorescent adducts, glucose autoxidation and glycation of collagen I in a dose-dependent manner, whereas non-vicinyl dihydroxyl group-containing metabolites, i.e., HVA and m-HPAA, were much less effective. All five metabolites of rutin effectively inhibited CML formation. In contrast, during the initial stages of glycation and fluorescent AGE product accumulation, only vicinyl hydroxyl group-containing rutin metabolites were effective. These studies demonstrate that rutin and circulating metabolites of rutin can inhibit early glycation product formation, including both fluorescent and nonfluorescent AGEs induced by glucose glycation of collagen I in vitro. These effects likely contribute to the beneficial health effects associated with rutin consumption.

Patterns of colorectal cancer incidence, risk factors, and screening in Kentucky.

BACKGROUND: Colorectal cancer incidence rates are higher in Kentucky than in the United States in general, and there are regional variations within the state. METHODS: This study investigates these variations in relation to lifestyle and health behaviors, combining data from the Kentucky Behavioral Risk Factor Surveillance System (BRFSS), and from the Kentucky Cancer Registry. We used Kentucky's fifteen Area Development Districts (ADDs) as units of analysis across a five-year period from 1993 to 97. RESULTS: Differences were observed across ADDs. ADDs with a higher prevalence of risk factors, with the exception of chronic alcohol drinking, had lower CRC rates. ADDs with a higher proportion of respondents having had recent routine check-ups had higher CRC incidence rates. CONCLUSIONS: In general, healthier lifestyles and positive health-related behaviors were associated with increased colorectal cancer incidence. This may be explained by the tendency for healthier individuals to receive regular check-ups and screening, thus increasing the detection rate of colorectal cancer.