Leg ulcers are indicators of systemic dysfunction in individuals with sickle cell disease.

Leg ulcers in individuals living with Sickle Cell Disease are evidence of systemic dysfunction. Data from a U.S. study link leg ulcers to wider pulse pressure and markers of chronic hemolysis, inflammation, renal, and liver dysfunction.

Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.

Specificity protein 1 (SP1), hypoxia-inducible factor 1 (HIF-1), and MYC are important transcription factors (TFs). SP1, a constitutively expressed housekeeping gene, regulates diverse yet distinct biological activities; MYC is a master regulator of all key cellular activities including cell metabolism and proliferation; and HIF-1, whose protein level is rapidly increased when the local tissue oxygen concentration decreases, functions as a mediator of hypoxic signals. Systems analyses of the regulatory networks in cancer have shown that SP1, HIF-1, and MYC belong to a group of TFs that function as master regulators of cancer. Therefore, the contributions of these TFs are crucial to the development of cancer. SP1, HIF-1, and MYC are often overexpressed in tumors, which indicates the importance of their roles in the development of cancer. Thus, proper manipulation of SP1, HIF-1, and MYC by appropriate agents could have a strong negative impact on cancer development. Under these circumstances, these TFs have naturally become major targets for anticancer drug development. Accordingly, there are currently many SP1 or HIF-1 inhibitors available; however, designing efficient MYC inhibitors has been extremely difficult. Studies have shown that SP1, HIF-1, and MYC modulate the expression of each other and collaborate to regulate the expression of numerous genes. In this review, we provide an overview of the interactions and collaborations of SP1, HIF1A, and MYC in the regulation of various cancer-related genes, and their potential implications in the development of anticancer therapy.

In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway.

Cancer progression is associated with the development of antitumor autoantibodies in patients' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan nordihydroguaiaretic acid (NDGA), enhanced the production of EAAs and inhibited tumor growth at low noncytotoxic concentrations via its immunoregulatory activity. Intratumoral injection of P4N improved the quantity and quality of EAAs, and passive transfer of P4N-induced EAAs dramatically suppressed lung metastasis formation and prolonged the survival of mice inoculated with metastatic CT26 tumor cells. P4N-induced EAAs specifically recognized two surface antigens, 78-kDa glucose-regulated protein (GRP78) and F1F0 ATP synthase, on the plasma membrane of cancer cells. Additionally, P4N treatment led to B-cell proliferation, differentiation to plasma cells, and high titers of autoantibody production. By serial induction of autocrine and paracrine signals in monocytes, P4N increased B-cell proliferation and antibody production via the leukotriene A4 hydrolase (LTA4H)/activin A/B-cell activating factor (BAFF) pathway. This mechanism provides a useful platform for studying and seeking a novel immunomodulator that can be applied in targeting therapy by improving the quantity and quality of the EAAs.

Simulation study comparing the effectiveness of the Gynecare Morcellex®, the MOREsolution™, and the Rotocut™ G1 tissue Morcellators.

Laparoscopic surgery has revolutionized the manner in which many operations are performed today. The volume of tissue to be removed during some operations can be a limiting factor for laparoscopy and is frequently a reason for converting from a minimally invasive laparoscopic surgical approach to the conventional open surgical approach. The introduction of the electronic morcellator has helped facilitate the removal of large specimens via minimally invasive surgery. The purpose of this study is to evaluate the effectiveness of the Gynecare Morcellex® morcellator (Ethicon, Inc., Somerville, NJ), the MOREsolution™ morcellator (Blue Endo, Lenexa, Kansas), and the Rotocut™ G1 morcellator (Karl Storz, Tuttlingen, Germany) tissue morcellators based upon their ease of use and efficacy in a simulation setting among an unbiased cohort of novice surgeons. University of Central Florida College of Medicine students were observed using the three different morcellators in a randomized order on 250 g beef tissue models and were surveyed on the ease of use of the morcellators. The MOREsolution™ tissue morcellator demonstrated significantly faster tissue morcellation times (544.6 ± 123.0 sec) and produced a higher number of long tissue fragments (7.44 ± 0.683) compared to the Rotocut™ G1 morcellators' time (609.7 ± 153.2 sec) and number of long tissue fragments (6.00 ± 0.638). No significant differences were found between the Gynecare Morcellex® and other morcellators in the total number of fragments obtained nor study participant opinion on the ease of use of the three morcellators. This study demonstrates that the MOREsolution™ morcellator is a faster morcellator and produces larger tissue fragments as compared to the Rotocut™ G1; however, more studies should be performed to confirm these findings in a clinical setting.

Tetra-O-methyl-nordihydroguaiaretic acid inhibits energy metabolism and synergistically induces anticancer effects with temozolomide on LN229 glioblastoma tumors implanted in mice while preventing obesity in normal mice that consume high-fat diets.

Tetra-O-methyl-nordihydroguaiaretic acid (terameprocol; M4N), a global transcription inhibitor, in combination with a second anticancer drug induces strong tumoricidal activity and has the ability to suppress energy metabolism in cultured cancer cells. In this study, we showed that after continuous oral consumption of high-fat (HF) diets containing M4N, the M4N concentration in most of the organs in mice reached ~1 µM (the M4N concentration in intestines and fat pads was as high as 20-40 µM) and treatment with the combination of M4N with temozolomide (TMZ) suppressed glycolysis and the tricarboxylic acid cycle in LN229 human glioblastoma implanted in xenograft mice. Combination treatment of M4N with TMZ also reduced the levels of lactate dehydrogenase A (LDHA), a key enzyme for glycolysis; lactate, a product of LDHA-mediated enzymatic activity; nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for nicotinamide adenine dinucleotide plus hydrogen (NADH)/NAD+ salvage pathway; and NAD+, a redox electron carrier essential for energy metabolism. It was also shown that M4N suppressed oxygen consumption in cultured LN229 cells, indicating that M4N inhibited oxidative phosphorylation. Treatment with M4N and TMZ also decreased the level of hypoxia-inducible factor 1A, a major regulator of LDHA, under hypoxic conditions. The ability of M4N to suppress energy metabolism resulted in induction of the stress-related proteins activating transcription factor 4 and cation transport regulator-like protein 1, and an increase in reactive oxygen species production. In addition, the combination treatment of M4N with TMZ reduced the levels of oncometabolites such as 2-hydroxyglutarate as well as the aforementioned lactate. M4N also induced methylidenesuccinic acid (itaconate), a macrophage-specific metabolite with anti-inflammatory activity, in tumor microenvironments. Meanwhile, the ability of M4N to suppress energy metabolism prevented obesity in mice consuming HF diets, indicating that M4N has beneficial effects on normal tissues. The dual ability of combination treatment with M4N to suppress both energy metabolism and oncometabolites shows that it is potentially an effective therapy for cancer.

Optimization strategies for colpotomizer technology during total laparoscopic hysterectomy.

As technology has evolved, so has the ability to perform a hysterectomy in a minimallly invasive fashion. Currently, total laparoscopic hysterectomy has been further advanced with the advent of uterine manipulation devices that incorporate the use of a cupped colpotomizer. Unfortunately, many gynecologic surgeons lack the understanding of how to fully utilize such a surgical guide to facilitate development of the vesico-uterine reflection, skeletonize uterine vasculature, gain entry into the vagina, and subsequently close the vaginal cuff. Safe completion of these steps has the potential to minimize complications such as ureteral and bladder injury in addition to vaginal cuff dehiscence. The following technical review will address methods for the safe and effective use of various cupped colpotomizer devices during total laparoscopic hysterectomy.

A Nurse-Led Population-Based Health Education Project to Improve Infant Care Knowledge for an Old Order Mennonite Community.

Population health is changing the focus of nursing practice as nurses are challenged to focus on health promotion and education for communities rather than limiting their practice to restorative care for individual acute care patients. This new focus is necessary to improve knowledge of maternal and infant health among vulnerable populations. One particularly vulnerable population is members of Old Order Mennonite communities, who frequently rely on self-trained local midwives in the community for home births and home remedies when caring for their infants. Providing evidence-based education to members of this isolated population can be a challenge because they do not typically access information outside of the community. The purpose of this article is to share the process of developing, publishing, and disseminating a culturally sensitive infant care manual for an Old Order Mennonite community using a community-based participatory model and to highlight the impact nursing outreach can have on improving health knowledge.

Real-time polymerase chain reaction detection of Bordetella pertussis DNA in acellular pertussis vaccines.

Using 2 real-time polymerase chain reaction (PCR) assays for Bordetella pertussis, 2 of 5 acellular pertussis vaccines were found to contain B. pertussis DNA. Because residual DNA in vaccines can cause environmental contamination, the administration of acellular pertussis vaccines to patients should be physically separated from the collection of patients' specimens for testing of B. pertussis DNA by real-time PCR.

The value of patient self-report for disease surveillance.

OBJECTIVE: To determine the accuracy of self-reported information from patients and families for use in a disease surveillance system. DESIGN: Patients and their parents presenting to the emergency department (ED) waiting room of an urban, tertiary care children's hospital were asked to use a Self-Report Tool, which consisted of a questionnaire asking questions related to the subjects' current illness. MEASUREMENTS: The sensitivity and specificity of three data sources for assigning patients to disease categories was measured: the ED chief complaint, physician diagnostic coding, and the completed Self-Report Tool. The gold standard metric for comparison was a medical record abstraction. RESULTS: A total of 936 subjects were enrolled. Compared to ED chief complaints, the Self-Report Tool was more than twice as sensitive in identifying respiratory illnesses (Rate ratio [RR]: 2.10, 95% confidence interval [CI] 1.81-2.44), and dermatological problems (RR: 2.23, 95% CI 1.56-3.17), as well as significantly more sensitive in detecting fever (RR: 1.90, 95% CI 1.67-2.17), gastrointestinal problems (RR: 1.10, 95% CI 1.00-1.20), and injuries (RR: 1.16, 95% CI 1.08-1.24). Sensitivities were also significantly higher when the Self-Report Tool performance was compared to diagnostic codes, with a sensitivity rate ratio of 4.42 (95% CI 3.45-5.68) for fever, 1.70 (95% CI 1.49-1.93) for respiratory problems, 1.15 (95% CI 1.04-1.27) for gastrointestinal problems, 2.02 (95% CI 1.42-2.87) for dermatologic problems, and 1.06 (95% CI 1.01-1.11) for injuries. CONCLUSIONS: Disease category assignment based on patient-reported information was significantly more sensitive in correctly identifying a disease category than data currently used by national and regional disease surveillance systems.

Obesity research and the forgotten African American child.

BACKGROUND/OBJECTIVES: Obesity/overweight is the most prevalent nutritional problem in adult and pediatric populations in the United States. We review up-to-date data on obesity in general, with emphasis on research findings in children. We also focus on non-Hispanic Blacks, an ethnic group that is relatively under-researched, despite having higher rates of obesity than Whites. METHODS: An electronic search of MEDLINE/ PubMed and several other bibliographic databases, including JSTOR, EBSCO, and Pro-Quest, was conducted, and all relevant articles in English were retrieved. RESULTS: Risk factors for childhood obesity are attributable to a combination of genetic and environmental factors. Literature has focused on the general population and genetic transmission from parents to children. Researchers agree that although genetics plays a major role, the risk of a child becoming obese is highly correlated with environment, as well. Relatively little research has been conducted to delineate obesity risk factors among Blacks, and virtually nothing is known on the determinants of obesity and obesity phenotype acquisition in the Black child. CONCLUSIONS: Genetic and environmental factors play a role in the development of childhood obesity. Despite the rich body of work on the topic, data that specifically address childhood obesity in Blacks are scanty. We need more information on childhood obesity in Blacks so that evidence-based prevention measures can be formulated to reduce the high prevalence of obesity in that population.

Cancer Prevention in the Survivorship Setting.

OBJECTIVES: To describe how nurses can use risk reduction and health promotion activities to facilitate surveillance of late effects and secondary cancers in long-term cancer survivors. DATA SOURCES: Literature review on survivorship, nursing practice, cancer prevention, and survivorship; articles published in peer-reviewed scientific journals; and Web-based or professional organization resources. CONCLUSION: Appropriate participation in screening activities, early detection of cancer, and further advances in treatment have contributed to the rise in cancer survivors. A demand for nurses with clinical experience and competence in survivorship care will follow. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses have an essential role in providing safe and high-quality care throughout the survivorship experience, which can contribute to better long-term outcomes.

Advancing the Use of Administrative Data for Emergency Department Diagnostic Imaging Research.

Administrative data are critical to describing patterns of use, cost, and appropriateness of imaging in emergency care. These data encompass a range of source materials that have been collected primarily for a nonresearch use: documenting clinical care (e.g., medical records), administering care (e.g., picture archiving and communication systems), or financial transactions (e.g., insurance claims). These data have served as the foundation for large, descriptive studies that have documented the rise and expanded role of diagnostic imaging in the emergency department (ED). This article summarizes the discussions of the breakout session on the use of administrative data for emergency imaging research at the May 2015 Academic Emergency Medicine consensus conference, "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The authors describe the areas where administrative data have been applied to research evaluating the use of diagnostic imaging in the ED, the common sources for these data, and the strengths and limitations of administrative data. Next, the future role of administrative data is examined for answering key research questions in an evolving health system increasingly focused on measuring appropriateness, ensuring quality, and improving value for health spending. This article specifically focuses on four thematic areas: data quality, appropriateness and value, special populations, and policy interventions.

Comparing the da Vinci si single console and dual console in teaching novice surgeons suturing techniques.

BACKGROUND AND OBJECTIVES: Robot-assisted laparoscopic surgery is often taught with the surgical mentor at the surgeon console and the trainee at the patient's bedside. The da Vinci dual console (Intuitive Surgical, Sunnyvale, California) allows a surgical mentor to teach with both the mentor and the trainee working at a surgeon console simultaneously. The purpose of this study is to evaluate the effectiveness of the dual console versus the single console for teaching medical students robotic tasks. METHODS: Forty novice medical students were randomized to either the da Vinci single-console or dual-console group and were taught 4 knot-tying techniques by a surgical mentor. The students were timed while performing the tasks. RESULTS: No statistically significant differences in mean task times were observed between the single- and dual-console groups: interrupted stitch with a 2-handed knot (300 seconds for single vs 294 seconds for dual, P=.59), interrupted stitch with a 1-handed knot (198 seconds for single vs 212 seconds for dual, P=.88), figure-of-8 stitch with a 2-handed knot (261 seconds for single vs 219 seconds for dual, P=.20), and figure-of-8 stitch with a 1-handed knot (200 seconds for single vs 199 seconds for dual, P=.53). CONCLUSION: No significant difference was observed in performance time when teaching knot-tying techniques to medical students using the da Vinci dual console compared with the single console. More research needs to be performed on the utility of the da Vinci dual console in surgical training.

Single-incision laparoscopic myomectomy.

Laparoscopic myomectomy is a minimally invasive surgical option for the treatment of uterine leiomyomas. Single-incision laparoscopy is a relatively new concept that has potential in gynaecological surgery although the technical challenges of single-incision access have limited the widespread use of the technique. The use of intracorporeal suturing is a significant component of the learning curve for laparoscopic myomectomy and presents an even greater challenge with single-incision laparoscopic myomectomy. This article describes a surgeon's approach to single-incision laparoscopic myomectomy.

Single-port gynecologic surgery.

Innovation in gynecologic surgery is constantly evolving toward making procedures less invasive. The benefits of laparoscopic surgery over conventional abdominal surgery have been well demonstrated in terms of reducing postoperative pain and decreasing postoperative morbidity, hospital stay duration, and postoperative recovery time. The minimally invasive single-port laparoscopic surgery is another innovation that may further improve gynecologic surgery outcomes. This article reviews the history and types of single-port procedures available, as well as the advantages and challenges that physicians face regarding the adoption of these procedures into general practice.