To Mesh or Not to Mesh: What Is the Ideal Meshing Ratio for Split Thickness Skin Grafting of the Lower Extremity?

Split-thickness skin grafts can provide effective autologous wound closure in patients with dysvascular comorbidities. Meshing the graft allows for reduced donor site morbidity and expanded coverage. This study directly compares outcomes across varying meshing ratios used to treat chronic lower extremity wounds. Patients who received split-thickness skin grafts to their lower extremity for chronic ulcers from December 2014 to December 2019 at a single center were retrospectively reviewed. Patients were stratified by meshing ratios: nonmeshed (including pie crusting), 1.5:1, and 3:1. The primary outcome was clinical "healing" as determined by surgeon discretion at 30 days, 60 days, and the latest follow-up. Secondary outcomes included postoperative complications, graft loss, ulcer recurrence, progression to amputation, and mortality. A total of 321 patients were identified. Wound sizes and location differed significantly, with 3:1 meshing applied to the largest wounds (187.8 ± 157.6 cm2; 1.5:1 meshed, 110.4 ± 103.9 cm2; nonmeshed 38.7 ± 55.5 cm2; p < .0001) mostly of the lower leg (n = 18, 75%; 1.5:1 meshed, n = 23, 43.4%; nonmeshed n = 62, 25.7%; p < .0001). Meshed grafts displayed a significantly higher proportion of healing at 30 and 60 days, but no differences persisted by the final follow-up (16.5 ± 20.5 months). Longitudinally, nonmeshed STSG was associated with most graft loss (46, 19.1%; p = .011) and ulcer recurrence (44, 18.3%; p = .011). Of the 3 meshing ratios, 3:1 exhibited the lowest rates of complications. Our results suggest that 3:1 meshing is a safe option for coverage of large lower extremity wounds to minimize donor site morbidity.

Free Tissue Transfer to the Lower Extremity in the Setting of Thrombocytosis and the Role of Antiplatelet Therapy: A Propensity Score-Matched Analysis.

BACKGROUND: Free tissue transfer (FTT) provides a versatile method to achieve successful lower limb salvage. Thrombocytosis in patients undergoing lower extremity (LE) FTT is associated with increased risk of complications. The aims of this study were to assess the feasibility of performing LE FTT in patients with preoperative thrombocytosis, and whether antiplatelet (AP) therapy on the day of surgery (DOS) affects outcomes. METHODS: A retrospective review of thrombocytotic patients who underwent LE FTT between 2011 and 2022 was performed. Patients were stratified into groups based on the receipt of AP therapy on the DOS. Patients were propensity score matched for comorbidity burden and postoperative risk stratification. Outcomes of interest included perioperative transfusion requirements, postoperative flap-related complications, rates of flap success, limb salvage, and ambulatory status. RESULTS: Of the 279 patients who underwent LE FTT, 65 (23.3%) were found to have preoperative thrombocytosis. Fifty-three patients remained following propensity score matching; of which, 32 (60.4%) received AP therapy on the DOS and 21 (39.6%) did not. Overall flap success rate was 96.2% (n = 51). The likelihoods of thrombosis and hematoma development were similar between cohorts (p = 0.949 and 0.574, respectively). Receipt of DOS AP therapy was associated an additional 2.77 units and 990.10 mL of transfused blood (p = 0.020 and 0.018, respectively). At a mean follow-up of 20.7 months, overall limb salvage and ambulatory rates were 81.1% (n = 43) and 79.2% (n = 42), respectively, with no differences between cohorts. CONCLUSION: Preoperative thrombocytosis is not an absolute contraindication to LE FTT. DOS AP therapy may be protective in comorbid patients with elevated platelet counts but must be weighed against possible short-term bleeding as suggested by significant increases in postoperative transfusion requirements.

The application of targeted muscle reinnervation in lower extremity amputations: A systematic review.

BACKGROUND: Targeted muscle reinnervation (TMR) is a promising surgical modality for reducing post-amputation pain. We sought to provide a succinct overview of TMR specific to the lower extremity (LE) amputation population. METHODS: A systematic review was performed per PRISMA guidelines. Ovid MEDLINE, PubMed, and Web of Science were queried for records using various combinations of Medical Subject Heading (MeSH) terms such as "LE "amputation," "below-knee amputation" (BKA), "above-knee amputation" (AKA), and "TMR." Primary outcomes included (1) operative techniques, (2) changes in neuroma, phantom limb pain (PLP), or residual limb pain (RLP), and (3) postoperative complications. Studies were only included if outcomes data were discretely provided for LE patients. RESULTS: Eleven articles examining 318 patients were identified. Average patient age was 47.5 ± 9.3 years, and most patients were male (n = 246, 77.4%). Eight manuscripts (72.7%) described TMR at the index amputation. The average number of nerve transfers performed per TMR case was 2.1 ± 0.8, and the most commonly employed nerve was the tibial (178/498; 35.7%). Nine (81.8%) articles incorporated patient-reported outcomes after TMR, with common methods including the Numerical Rating Scale (NRS) and questionnaires. Four studies (33.3%) reported functional outcomes such as ambulation ability and prosthesis tolerance. Complications were described in seven manuscripts (58.3%), with postoperative neuroma development being the most common (21/371; 7.2%). CONCLUSIONS: The application of TMR to LE amputations is effective in reducing PLP and RLP with limited complications. Continued investigations are warranted to better understand patient outcomes specific to anatomic location using validated patient-reported outcome measures (PROM).

Perioperative evaluation of nutritional status to predict complications in patients with major lower extremity amputation.

INTRODUCTION: Optimization of nutritional status is critical in postoperative wound healing. Perioperative Alb and pAlb levels have been used as proxies for overall nutritional status. OBJECTIVE: This study examines if such biomarkers correlate with postoperative complications after MLEA for chronic wounds. MATERIALS AND METHODS: A retrospective review of patients undergoing MLEA at a single institution from January 2017 through October 2021 was performed. Data collection included demographics, comorbidities, and perioperative laboratory values. The primary outcomes were surgical dehiscence, hematoma, and infection within 30 days of surgery. RESULTS: A total of 303 patients undergoing MLEA met the inclusion criteria. At the threshold of less than 3.2 g/dL for low Alb, no significance was found for any postoperative complications. The threshold of less than 10 mg/dL for low pAlb was associated with significantly increased infection rates. At the threshold of less than 9 mg/dL for low pAlb, hematoma and infection were significantly increased compared with the defined normal perioperative pAlb. Alternatively, low Alb (<3.2 g/dL) did not correlate with postoperative complications. CONCLUSIONS: Further investigation of validated biomarkers and their thresholds is needed to guide perioperative optimization of nutritional status after MLEA for chronic wounds.

A Pilot Investigation into Targeted Muscle Reinnervation for Complex Regional Pain Syndrome, Type II.

Complex regional pain syndrome (CRPS) is a debilitating condition, characterized by severe pain with vascular, motor, or trophic changes. Varied presentations make this a diagnostic and therapeutic challenge. There is a lack of high-quality evidence demonstrating efficacy for most existing therapies, particularly with surgical intervention for type II CRPS (CRPS-II). Targeted muscle reinnervation (TMR) is a surgical technique to transfer the terminal end of a divided nerve to a recipient motor nerve, shown to limit phantom limb pain, residual limb pain, and postamputation neuroma pain. Methods: Herein, we describe a series of 13 patients undergoing TMR for CRPS-II by a single surgeon from 2018 to 2021 in the upper (38%) and lower extremities (62%). All patients had a diagnosis of CRPS-II with either traumatic or postsurgical etiology, each seeking TMR with or without concomitant treatment to control their pain after previous therapies had failed. Three patients had previous lower extremity amputation, whereas three others received lower extremity amputation at the time of TMR, each indicated for control of CRPS pain. Results: Of the patients receiving TMR within 1 year of CRPS diagnosis, all three reported improved function, and two patients were able to tolerate a prosthetic for ambulation after previous pain prevented prosthetic use. Of the entire cohort, all but one patient reported reduced pain interference or improved function. Conclusions: These outcomes suggest that TMR may provide some benefit to reducing pain severity patients with CRPS, even after a more chronic disease course. Further prospective trials are warranted.

Postoperative Outcomes following a Multidisciplinary Approach to HIV-positive Breast Cancer Patients.

Improvements in human immunodeficiency virus (HIV) treatment resulted in drastic increases in the lifespan of HIV-positive individuals, resulting in higher rates of non-AIDS-defining cancers. We describe our postoperative outcomes in HIV+ breast cancer (BC) patients, highlighting our multidisciplinary experience with this high-risk population. Methods: A 7-year multi-institutional retrospective review of all HIV+ BC patients who underwent surgical intervention was performed. Patient demographics, therapeutic interventions, and treatment outcomes were collected. Results: Twenty-four patients were identified, including one male patient (4.2%). Most patients were African American (83.3%). Mean age was 52.1 + 9.7 years at the time of diagnosis in HIV+ BC patients. Surgical interventions included lumpectomy (n = 16, 66.7%), simple mastectomy (n = 3, 12.5%), and skin-sparing mastectomy (n = 5. 20.8%). All patients were on antiretroviral therapy, and 81.3% had undetectable viral loads at the time of operation. Seventeen patients (70.8%) underwent breast reconstruction, with three (17.7%) undergoing delayed reconstruction. Thirty-day postoperative complications occurred in three patients (17.6%), including flap necrosis (11.8%), infection (11.8%), dehiscence (5.9%), and return to OR (11.8%). Three patients (12.5%) experienced recurrence at a median of 18 months since operation. Mean follow-up was 51.4 + 33.3 months since BC diagnosis. Conclusions: While postoperative complication rates in HIV+ patients trended higher (17.6%) compared with the existing data on breast reconstruction patients overall (10.1%), HIV+ patients did not exhibit increased risk of BC recurrence (12.5%) compared with BC patients overall (12-27%). This highlights the importance of a combined multidisciplinary approach involving infectious disease, breast surgery, and plastic and reconstructive surgery to optimize surgical and oncologic outcomes in these high-risk patients.

SARS-CoV-2 Infection in Pediatric Solid Organ Transplant Recipients: A Single Center Observation.

OBJECTIVES: This is a descriptive study to characterize rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in pediatric SOT recipients. METHODS: We queried Organ Transplant Tracking Record (OTTR) for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 and June 30, 2021. Patients were tested by polymerase chain reaction (PCR): prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (1) acute infection versus convalescence; (2) acute infection versus SOT recipients without infection (called healthy controls); (3) liver transplant (LT) versus small bowel (SB)/multivisceral transplant (MVT); (4) positive versus negative test result. RESULTS: Of 257 LT recipients, 99 were tested: 6 were PCR positive, 13 were antibody positive. Of 150 SB/MVT recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs 10.0 years; P = 0.017). We observed a rapid decline in viral load within 96 hours without a change in immunosuppression. Antibody lasted >8 months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 T EM cell frequency ( P = 0.04, P = 0.03, respectively), decreased interferon (IFN)-γ production from T-cells (2.8% vs 11.3%; P = 0.006), and decreased CD8 TEMRA frequency (4.56% vs 11.70%; P = 0.006). CONCLUSIONS: Early in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed.

Pediatric Vulvovaginal Graft-Versus-Host Disease: A Retrospective Cohort Study and Literature Review.

STUDY OBJECTIVE: To assess genital symptomatology, characterize the findings of genital examination, and describe the incidence and treatment of vulvovaginal graft-versus-host disease (vvGvHD) in girls and adolescents after allogeneic hematopoietic stem cell transplantation (HSCT). DESIGN: Retrospective cohort. SETTING: Metropolitan-area children's hospital. PARTICIPANTS: Female allogeneic HSCT recipients ages 0 to 22 years. MAIN OUTCOME MEASURES: Genital symptoms, genital examination, diagnosis, and treatment of vvGvHD. RESULTS: A total of 57 participants were included in the analysis. The median age at the time of HSCT was 10 years (range 4 months-23 years). Most (n = 40, 71%) underwent transplant for a nonmalignant condition, most commonly sickle cell anemia (n = 19, 33%). The median time of onset of GvHD post HSCT was 62 days (IQR = 42 to 151 days). The most common initial site of GvHD was skin (n = 21, 64%), followed by GI tract (n = 10, 30%). Three patients (5%) were diagnosed with vvGvHD. The time of onset of vvGvHD post HSCT ranged from 62 to 1565 days. One patient (33%) was asymptomatic at the time of diagnosis. There was no difference in diagnosis of vvGvHD when race (P = 0.15), age at allogeneic HSCT (P = 0.64), nonmalignant vs malignant indication (P = 0.21), source of stem cells (P = 0.25), partial vs full human leukocyte antigens (HLA) donor match (P = 0.34), and GvHD prophylaxis regimen (P = 0.18) were compared. None had isolated vvGvHD. Vulvovaginal GvHD was preceded by skin GvHD in 1 patient, was preceded by lung GvHD in 1 patient, and occurred concurrently with skin GvHD in the third patient. CONCLUSIONS: Pediatric vvGvHD can occur within the first 100 days after transplant and can be asymptomatic. Routine gynecologic evaluation post allogeneic HSCT in children and adolescents should include a thorough review of vulvovaginal symptoms and a gynecologic exam for the detection and treatment of vvGvHD.

Mismatch epitope load predicts de novo-DSA-free survival in pediatric liver transplantation.

BACKGROUND: Our knowledge of de novo anti-HLA donor-specific antibodies (dnDSA) in liver transplantation continues to be defined. We hypothesized that differences of HLA-DR/DQ mismatches can improve precision in alloimmune risk categorization and be applied to tailor immunosuppression. METHODS: A retrospective chart review of 244 pediatric patients consecutively transplanted at our center between 2003 and 2019 was performed to identify patients tested for dnDSA. Records were queried for: demographics, pre-transplant diagnosis, biopsy-proven T-cell-mediated rejection (TCMR), radiology proven biliary complications, tacrolimus trough levels, dnDSA characteristics, and HLA typing. The eplet mismatch analyses were performed using HLAMatchmaker™ 3.1. All statistical analyses were conducted using R software version 3.40. RESULTS: There were 99 dnDSA-negative patients and 73 dnDSA-positive patients (n = 70 against class II and n = 3 against class I and II). ROC analysis identified optimal cutoff of eplet mismatch load for dnDSA and defined risk groups for an alloimmune outcome. Kaplan-Meier curves and log-rank tests showed high eplet mismatch load was associated with shorter dnDSA-free survival (log-rank p = .001). Multivariable Cox regression models showed that tacrolimus coefficient of variation and tacrolimus mean levels were significantly associated with dnDSA-free survival (p < .001 and p = .036). Fisher's exact test showed that dnDSA was associated with an increased likelihood of TCMR (OR 14.94; 95% CI 3.65 - 61.19; p < .001). Patients without TCMR were more likely to have dnDSA to HLA-DQ7 and less likely to have dnDSA to HLA-DQ2 (p = .03, p = .080). CONCLUSIONS: Mismatched epitope load predicts dnDSA-free survival in pediatric liver transplant, while dnDSA specificity may determine alloimmune outcome.

Stenotrophomonas maltophilia Necrotizing Soft Tissue Infection in an Immunocompromised Patient.

INTRODUCTION: To report on the first recorded case of necrotizing soft tissue infection (NSTI) in an immunocompromised individual caused by Stenotrophomonas maltophilia in the Western Hemisphere and highlight the challenges that medical providers face in promptly diagnosing and treating NSTI in this highly vulnerable patient population. CASE PRESENTATION: We report a case of NSTI caused by S. maltophilia in a neutropenic patient admitted for treatment of acute lymphoblastic leukemia. The patient presented with laboratory and clinical findings atypical for a NSTI that may have confounded its diagnosis and delayed surgical intervention. Despite aggressive medical care and surgical debridement, the patient unfortunately passed away due to overwhelming septic shock. CONCLUSIONS: Providers should consider atypical organisms as causative in NSTI in immunocompromised patients and recognize that these patients may present without classic clinical and laboratory findings.

SCH79797 improves outcomes in experimental bacterial pneumonia by boosting neutrophil killing and direct antibiotic activity.

Objectives: The role of protease-activated receptor 1 (PAR1) in the pathogenesis of pneumonia and sepsis is ambiguous given the existing literature. As PAR1 is classically activated by the coagulation-based protease thrombin and leads to vascular leakage, our hypothesis was that PAR1 blockade with SCH79797 would be therapeutically beneficial in an experimental model of murine Gram-negative pneumonia. Methods: In this study, we administered SCH79797 via the intrapulmonary route 6 h after the establishment of Escherichia coli pneumonia and observed a significant improvement in survival, lung injury, bacterial clearance and inflammation. We focused on neutrophils as a potential target of the PAR1 antagonist, since they are the predominant inflammatory cell type in the infected lung. Results: Neutrophils appear to express PAR1 at low levels and the PAR1 antagonist SCH79797 enhanced neutrophil killing. Part of this effect may be explained by alterations in the generation of reactive oxygen species (ROS). SCH79797 also led to robust neutrophil extracellular trap (NET) generation and cathelicidin-related antimicrobial peptide (CRAMP) release by neutrophils. Surprisingly, SCH79797 also had a potent, direct antibiotic effect with disruption of the E. coli cell membrane. However, the newer-generation PAR1 antagonist, vorapaxar (SCH530348), had no appreciable effect on neutrophil activity or direct bacterial killing, which suggests the effects seen with SCH79797 may be PAR1 independent. Conclusions: In summary, we observed that intrapulmonary treatment with SCH79797 has significant therapeutic effects in a model of E. coli pneumonia that appear to be due, in part, to both neutrophil-stimulating and direct antibacterial effects of SCH79797.

Hypoxia-inducible factor-1α inhibition modulates airway hyperresponsiveness and nitric oxide levels in a BALB/c mouse model of asthma.

Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-1α regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-1α inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype. Systemic treatment with HIF-1α antagonist YC-1 suppressed the increase in HIF-1α expression seen in control AIAD mice. Treatment with YC-1 also decreased AHR, blood eosinophilia, and allergic inflammatory gene expression: IL-5, IL-13, myeloperoxidase and iNOS. AIAD mice had elevated BAL levels of NO, and treatment with YC-1 eliminated this response. However, YC-1 did not decrease BAL, lung or bone marrow eosinophilia. We conclude that HIF-1α inhibition in different genetic backgrounds, and thus different AIAD phenotypes, decreases airway resistance and markers of inflammation in a background specific manner. CAPSULE SUMMARY: Asthma is a common disease that can be difficult to control with current therapeutics. We describe how pharmacologic targeting of a specific transcription factor, HIF-1α, suppresses asthmatic airway reactivity and inflammation.

Pulmonary artery size as a predictor of outcomes in idiopathic pulmonary fibrosis.

UNLABELLED: IPF patients have heightened propensity for pulmonary hypertension, which portends a worse outcome. Presence of pulmonary hypertension may be reflected in an enlarged pulmonary artery. We investigated pulmonary artery size measured on high-resolution computed tomography (HRCT) as an outcome predictor in IPF.We retrospectively reviewed all IPF patients evaluated at a tertiary-care centre between 2008 and 2013. Pulmonary artery and ascending aorta diameters were measured from chest HRCT with pulmonary artery:ascending aorta diameter (PA:A) ratio calculations. Outcome analysis defined by either death or lung transplant based on pulmonary artery size and PA:A ratio over 60 months was performed. Independent effects of different variables on overall outcomes were evaluated using the Cox proportional hazards model.98 IPF patients with available HRCT scans had a mean pulmonary artery diameter and PA:A ratio of 32.8 mm and 0.94, respectively. Patients with a PA:A ratio >1 had higher risk of death or transplant compared with a PA:A ratio ≤1 (p<0.001). A PA:A ratio >1 was also an independent predictor of outcomes in unadjusted and adjusted outcomes analyses (hazard ratio 3.99, p<0.001 and hazard ratio 3.35, p=0.002, respectively).A PA:A ratio >1 is associated with worse outcomes in patients with IPF. HRCT PA: A ratio measurement may assist in risk stratification and prognostication of IPF patients.

Inflammatory Diseases of the Lung Induced by Conventional Cigarette Smoke: A Review.

Smoking-induced lung diseases were extremely rare prior to the 20th century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs-depending on the signaling pathway (nuclear factor-κB, adenosine monophosphate-activated protein kinase, c-Jun N-terminal kinase, p38, and signal transducer and activator of transcription 3) activated. Multiple proteins are upregulated and secreted in response to CS exposure, and many of these have immunomodulatory activities that contribute to disease pathogenesis. In particular, metalloproteases 9 and 12, surfactant protein D, antimicrobial peptides (LL-37 and human ß defensin 2), and IL-1, IL-6, IL-8, and IL-17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking-induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS-induced diseases, including COPD, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by secondhand and thirdhand smoke exposure and the pulmonary diseases that result. New targeted antiinflammatory therapeutic options are currently under investigation and hopefully will yield promising results for the treatment of these highly prevalent smoking-induced diseases.

Pulmonary artery size as a predictor of pulmonary hypertension and outcomes in patients with chronic obstructive pulmonary disease.

RATIONALE: The relationship between pulmonary artery size with underlying pulmonary hypertension and mortality remains to be determined in COPD. We sought to evaluate the relationships in a cohort of patients with advanced COPD. METHODS: A retrospective study of advanced COPD patients evaluated between 1998 and 2012 was conducted at a tertiary care center. Patients with chest computed tomography images and right heart catheterizations formed the study cohort. The diameters of the pulmonary artery and ascending aorta were measured by independent observers and compared to pulmonary artery pressures. Intermediate-term mortality was evaluated for the 24-month period subsequent to the respective studies. Cox proportional hazards model was used to determine independent effects of variables on survival. RESULTS: There were 65 subjects identified, of whom 38 (58%) had pulmonary hypertension. Patients with and without pulmonary hypertension had mean pulmonary artery diameters of 34.4 mm and 29.1 mm, respectively (p = 0.0003). The mean PA:A ratio for those with and without pulmonary hypertension was 1.05 and 0.87, respectively (p = 0.0003). The PA:A ratio was an independent predictor of mortality with a reduced survival in those with a PA:A >1 (p = 0.008). CONCLUSIONS: The PA:A ratio is associated with underlying pulmonary hypertension in patients with COPD and is an independent predictor of mortality. This readily available measurement may be a valuable non-invasive screening tool for underlying pulmonary hypertension in COPD patients and appears to impart important independent prognostic information.

Student understanding of type 2 diabetes mellitus.

BACKGROUND: An estimated 25.8 million people in the United States have type 2 diabetes, including seven million people who have the disease but are undiagnosed. These numbers indicate that education about diabetes is needed. METHODS: To evaluate university students' knowledge about diabetes (risk factors, signs and symptoms and complications) we utilized a survey. Specifically, we determined: (1) knowledge of type 2 diabetes; (2) if participants' academic field of study affected their knowledge of type 2 diabetes; (3) if participants who had a family member with type 2 diabetes had a greater knowledge of the disease; and (4) if age affected students' knowledge of the disease. RESULTS: A questionnaire was completed by 469 students from The University of South Dakota. Students' knowledge of type 2 diabetes was poor: 30.1 percent of the students scored higher than 70 percent (with only 6.8 percent of the students scoring higher than 80 percent). No significant differences in knowledge scores were found between students who pursued health-related fields of study versus students who did not. Participants who had a family member with type 2 diabetes had a greater knowledge of the disease and felt that they had a higher risk for getting the disease. Significant differences in knowledge were only found between the youngest and oldest age groups. CONCLUSIONS: USD students' knowledge of type 2 diabetes is limited. Solutions need to communicate the risk factors and severity of the disease. Possible ways for improving diabetes education is to include health fairs as well as to integrate diabetes modules into K-12 education courses.

Cyanine dye conjugates as probes for live cell imaging.

A series of fluorescent compounds suitable for live cell imaging is described. Functionalized forms of four different asymmetric cyanine dyes are reported that are amenable to peptide conjugation. The photophysical properties of the modified dyes and conjugates and the use of the compounds as cellular imaging agents are described. The results obtained indicate that these spectrally versatile compounds, which have absorption and emission profiles spanning the visible spectrum, are useful probes for cellular imaging.

Tunable DNA cleavage by intercalating peptidoconjugates.

The properties of a novel family of peptide-based DNA-cleavage agents are described. Examination of the DNA-cleavage activities of a systematic series of peptide-intercalator conjugates revealed trends that show a strong dependence on peptide sequence. Conjugates differing by a single residue displayed reactivities that varied over a wide range. The cleavage activity was modulated by the electrostatic or steric qualities of individual amino acids. Isomeric conjugates that differed in the position of the tether also exhibited different reactivities. The mechanism of DNA cleavage for these compounds was also probed and was determined to involve hydrogen-atom abstraction from the DNA backbone. Previous studies of these compounds indicated that amino acid peroxides were the active agents in the cleavage reaction; in this report, the chemistry underlying the reaction is characterized. The results reported provide insight into how peptide sequences can be manipulated to produce biomimetic compounds.