Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications.

A small library of FAAH and dual FAAH/MAGL inhibitors designed for peripheral selectivity were targeted. Of these compounds, three were identified to have desirable FAAH inhibition and reduced permeability in a PAMPA assay. Those three compounds were advanced into a MAGL inhibitor assay and one was found to be a relative selective FAAH inhibitor, FAAH to MAGL IC ratio of 1:27, and one was found to be more characteristic of a true dual enzyme inhibitor, FAAH to MAGL IC ratio of 1:4.

The Versatility of Sirtuin-1 in Endocrinology and Immunology.

Sirtuins belong to the class III family of NAD-dependent histone deacetylases (HDAC) and are involved in diverse physiological processes that range from regulation of metabolism and endocrine function to coordination of immunity and cellular responses to stress. Sirtuin-1 (SIRT1) is the most well-studied family member and has been shown to be critically involved in epigenetics, immunology, and endocrinology. The versatile roles of SIRT1 include regulation of energy sensing metabolic homeostasis, deacetylation of histone and non-histone proteins in numerous tissues, neuro-endocrine regulation via stimulation of hypothalamus-pituitary axes, synthesis and maintenance of reproductive hormones via steroidogenesis, maintenance of innate and adaptive immune system via regulation of T- and B-cell maturation, chronic inflammation and autoimmune diseases.

Genomic, microbial and environmental standardization in animal experimentation limiting immunological discovery.

Background: The use of inbred mice housed under standardized environmental conditions has been critical in identifying immuno-pathological mechanisms in different infectious and inflammatory diseases as well as revealing new therapeutic targets for clinical trials. Unfortunately, only a small percentage of preclinical intervention studies using well-defined mouse models of disease have progressed to clinically-effective treatments in patients. The reasons for this lack of bench-to-bedside transition are not completely understood; however, emerging data suggest that genetic diversity and housing environment may greatly influence muring immunity and inflammation.

Adaptive sampling: recruiting a diverse community sample of survivors of sexual violence.

Accessing vulnerable and hard-to-reach populations is a significant challenge for nurse researchers. Adaptive sampling is a procedure that has been used effectively in community-based research to recruit rare or hidden populations. Structured community assessment, as practiced by community health nurses, can be used to enhance adaptive sampling procedures to recruit research participants.

Geriatric education in US schools of pharmacy: a snapshot.

Objective: The objective of this study was to assess the structure, resources, and activities of academic geriatrics courses in U.S. pharmacy schools.

Teenage pregnancy among African-Americans: a qualitative examination of maternal education, teenage pregnancy, family dynamics, and conflict resolution.

This qualitative study is derived from interviews conducted during a larger quantitative study that examined facilitators and barrier to communication and negotiations in African American families whose teen daughters had one or more unwed teen pregnancies. Based on the larger study's findings that the education of the teens mother was a statistically significant factor in teen pregnancy, 17 robust interviews were analyzed in this study and sorted on variables of maternal education and teen pregnancies. From the analysis of the data, seven themes emerged.

Two successful models for preparing competent critical care nurses. The Parkland Health and Hospital System Critical Care and Trauma Nurse Internship and Critical Care Residency.

Part of the mission statement of Parkland Health and Hospital System involves participating in educational programs dedicated to the art and science of caring for the sick and injured, the promotion of wellness, and the delivery of health services. The concept of the Nurse Internship and Nurse Residency fits well in the framework of this hospital. The continued support of these programs from the PHHS administration is visible evidence of the institution's commitment to excellence.

The challenges of recruiting African American subjects and entry strategies used in northeast Ohio.

This article focuses on the recruitment of African American subjects because there are wide gaps in health outcomes within African American communities. Historical occurrences have contributed to the distrust of the motives of researchers about the purposes and credibility of research studies. Commonly acknowledged challenges include researchers' lack of sensitivity and understanding of minority subjects (Fujimoto, 1989; El-Sadr & Capps, 1992; Pletsch, Howe & Tenney, 1995).

Organization, expression, and localization of the murine mdmx gene and pseudogene.

The mdmx gene is the first additional member of the mdm2 gene family to be isolated. It encodes a protein similar to MDM2 in several domains and also retains the ability to bind and inhibit p53 transactivation in vitro. However, mdmx does not appear to be transcriptionally regulated by p53.

p73 gene alterations and expression in primary oral and laryngeal squamous carcinomas.

p73, a recently identified gene, maps to chromosome region 1p36.3, which is frequently deleted in a variety of solid tumors. Although the gene shares sequence and functional homologies with p53, its suppressor function has not been proven.

High metastatic potential in mice inheriting a targeted p53 missense mutation.

To understand the relevance of p53 missense mutations in vivo, we generated a mouse containing an arg-to-his substitution at p53 amino acid 172, which corresponds to the R175H hot-spot mutation in human tumors by homologous recombination. Inadvertently, this mouse contains the additional deletion of a G nucleotide at a splice junction that attenuates levels of mutant p53 to near wild-type levels. Mice heterozygous for the mutant allele differed from p53(+/-) mice in tumor spectrum, with a significant increase in the number of carcinomas and a slight decrease in the number of lymphomas.

TP53 mutation and haplotype analysis of two large African American families.

Two large apparently unrelated African American families with a high incidence of breast cancer and other tumors characteristic of Li-Fraumeni breast sarcoma cancer family syndrome were studied. Mutation screening revealed that in both families the affected members carried a germline mutation of the TP53 gene at codon 133 (ATG--> ACG, M133T). In order to determine whether an ancestral haplotype was shared by these two families, polymorphic markers within and flanking the TP53 gene were studied.

Afrocentric perspective of adolescent pregnancy in African American families: a literature review.

This article gives a detailed overview of the literature on adolescent pregnancy in African American families. According to the latest data available from the National Center for Health Statistics (1998), the greatest decline in adolescent pregnancy was among African Americans. In spite of the decline of 21% from 1991-1996, African American adolescent's birth rate was still almost twice the rate of European Americans.

Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family.

Li-Fraumeni syndrome (LFS) is characterized by a high risk of sarcomas, early onset of breast cancer, and a diversity of other cancers occurring as multiple primary tumors in multiple family members. In many families with LFS, germline mutations within the tumor-suppressor gene p53 have been identified. However, mutations in p53 have not been detected in approximately 30% of LFS families.

Effect of pelvic muscle exercise on transient incontinence during pregnancy and after birth.

Objective: To test the effect of pelvic muscle exercise on postpartum symptoms of stress urinary incontinence and pelvic muscle strength in primigravidas during pregnancy and postpartum.

Methods: A prospective trial randomized women into treatment (standardized instruction in pelvic muscle exercise) or control (routine care with no systematic pelvic muscle exercise instruction). Urinary incontinence symptoms were measured by questionnaire.

Independent pathways of p53 induction by cisplatin and X-rays in a cisplatin-resistant ovarian tumor cell line.

The p53 tumor suppressor gene is critical in regulating cell proliferation following DNA damage, and disruption of p53 protein function by mutation has been implicated as a factor responsible for resistance of tumor cells to chemotherapeutic agents. Our studies were initiated by asking whether the translational product of the p53 gene is associated with cisplatin resistance in the 2780CP human ovarian tumor model. We have demonstrated by single-strand conformation polymorphism analysis and sequencing that p53 in parental cisplatin-sensitive A2780 cells was wild type.

Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis is a genetic disorder of unknown etiology. Scoliosis is a clinical feature of inherited connective-tissue disorders including Marfan syndrome. Mutations within the gene of FBN1 (fibrillin 15), a component of the extracellular matrix, are now linked to Marfan syndrome and similar clinical phenotypes.

Follow-up of comprehensive geriatric assessment in a family medicine residency clinic.

Background: The objective of this study was to evaluate the effect of outpatient geriatric consultation by referring academic physicians and to verify the results of a previous study.

Methods: We conducted a retrospective review of charts of 37 patients referred for geriatric consultation during a 7-month period of a university- and community-hospital-affiliated family practice residency clinic in urban northeast Washington, DC. The consultation involved team assessment, which led to formal recommendations to the attending physician.

The potential role of the elastic fiber system in adolescent idiopathic scoliosis.

To assess its possible role in the etiology of adolescent idiopathic scoliosis, the elastic fiber system of the ligamentum flavum was examined in twenty-three patients who had scoliosis and in five age-matched individuals who did not. Elastic fibers are composed of two components: the amorphous core of elastin and microfibrils, of which fibrillin is the primary element. Fresh-frozen histological specimens of ligamentum flavum removed at the time of an operation were examined by Verhoeff staining for elastic fibers and by immunohistochemical staining with use of a monoclonal antibody to fibrillin.

Third position base changes in codons 5' and 3' adjacent UGA codons affect UGA suppression in vivo.

The base sequence around nonsense codons affects the efficiency of nonsense codon suppression. Published data, comparing different nonsense sites in a mRNA, implicate the two bases downstream of the nonsense codon as major determinants of suppression efficiency. However, the results we report here indicate that the nature of the contiguous upstream codon can also affect nonsense suppression, as can the third (wobble) base of the contiguous downstream codon.

Glycine tRNA mutants with normal anticodon loop size cause -1 frameshifting.

Mutations in the acceptor stem, the 5-methyluridine-pseudouridine-cytidine (TFC) arm, and the anticodon of Salmonella tRNA2Gly can cause -1 frameshifting. The potential for standard base pairing between acceptor stem positions 1 and 72 is disrupted in the mutant sufS627. This disruption may interfere with the interaction of the tRNA with elongation factor-Tu.

Physiologic rationale of Sv-O2 monitoring.

Mixed venous oxygen saturation is a global indicator of the balance between oxygen transport and oxygen demand. In critically ill patients, the delivery of adequate quantities of oxygen to meet the cellular oxygen demands is paramount. While parameters such as SaO2, PaO2, and CO reveal important information about oxygen transport, the SvO2 indicates the adequacy of supply in relation to tissue oxygen demands.

Fat embolism syndrome: a variant of ARDS (continuing education credit).

Fat embolism syndrome (FES) is a relatively uncommon, life-threatening sequela of long-bone fractures. Occurring 24 to 48 hours postinjury, the syndrome manifests as hypoxemia, confusion, and petechiae. The pathophysiologic changes in the lung are consistent with those of ARDS.