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At least 109 records · Page 6Linked to original sources

Reducing the knowledge-practice gap in the management of patients with cardiovascular disease.

Despite major progress in the development of effective therapy to reduce mortality and morbidity from cardiovascular disease, it remains the leading cause of mortality in this country. One aspect of this problem is represented by the lag in adoption of treatments with documented efficacy in large clinical trials. This "knowledge-practice gap" has been attributed to factors at multiple levels of the health care system that impede implementation of optimal therapy. Although there is evidence of progress in the use of recommended therapeutic modalities in the past decade, this has been modest. Recent approaches to assessment of patient care by physicians, health plans, and institutions through the tracking of clinical performance have been instituted to promote optimal patient care. They are being increasingly utilized for purposes of accreditation and will also provide guidance for consumer purchasing of health care. Such methods have the potential to promote increased adherence to current standards of care.

Cardiovascular Diseases↗

Characterization of human involucrin promoter distal regulatory region transcriptional activator elements-a role for Sp1 and AP1 binding sites.

Human involucrin (hINV) is an important precursor of the keratinocyte cornified envelope that is specifically expressed in the suprabasal layers of stratifying epithelia. Previous truncation and mutagenesis experiments have shown that an activator protein 1 (Ap1) site, AP1-5, located 2100bp upstream of the transcription start site, is required for optimal promoter activity. These previous studies suggest that AP1-5 is part of a distal regulatory region spanning nucleotides -2473 to -2088. In the present report, we study the distal regulatory region (DRR), which surrounds AP1-5. Our studies show that this region contains weak and strong activator elements spanning nucleotides -2473/-2216 and -2140/-2088, respectively. The strong activator element contains AP1-5 and an adjacent specificity protein 1 (Sp1) site. The AP1-5 site is absolutely required for DRR activity, as its mutation reduces transcription to basal levels. Mutagenesis studies of the AP1-5 and Sp1 sites in the presence or absence of the weak activator element indicate that the Sp1 site and the weak activator element synergistically activate the AP1-5 site-dependent transcription. The cooperation between the Sp1 and AP1-5 sites is also observed in the context of the full-length promoter. Gel mobility shift and supershift studies show that Sp1, but not Sp2, Sp3 or Sp4 binds to the Sp1 site. When the Sp1 site is mutated or the distance between the AP1-5 and Sp1 site is increased, the binding of AP1 factors to AP1-5 is markedly reduced. Surprisingly, gel shift studies suggest that activation does not require the formation of a stable AP1/Sp1/DNA ternary complex. These studies suggest that the AP1-5 site is absolutely required for transcriptional activation, that the weak activator element and Sp1 sites serve to enhance this activation, and that the Sp1 site is required for optimal AP1 factor binding at the AP1-5 site.

Base Sequence↗

Factors affecting food intake of women with Alzheimer's type dementia in long-term care.

This study assessed the nutrient intake and problems associated with the feeding of individuals who have advanced senile dementia of the Alzheimer's type (SDAT). The sample consisted of 19 non-ambulatory women, ranging in age from 67 to 105 years, with documented SDAT, who reside in a long-term-care facility. Dietary intake was recorded, and feeding practices were observed for a 3-day period. The mean daily energy intake was 1,558 kcal, with a mean protein intake of 65 gm during the study. Nutritional supplements, consisting of fortified beverages and/or puddings, provided 29% of the calories and 41.5% of the protein intake while contributing considerable amounts of vitamins and minerals. Maintenance of optimal caloric and protein intake is difficult for advanced SDAT patients who are at high risk for infection and skin breakdown related to poor swallowing ability, incontinence, and immobility. Four major factors emerged that promoted optimal intake: using skillful feeding techniques, selecting appropriate food consistency, providing adequate time in which to feed, and capitalizing on the midday meal when cognitive abilities were at their peak.

Aged↗

Well-being therapy in school settings: a pilot study.

BACKGROUND: There is increasing interest in the psychobiological mechanisms of resilience and psychological well-being. It is conceivable that activation of such mechanisms in the school setting may entail long-term benefits, both in terms of the developmental process and of prevention of distress. This study wants to apply and test the efficacy of a school-based intervention protocol derived from well-being therapy (WBT) compared to cognitive-behavioral strategies. METHODS: School interventions were performed in a population of 111 students randomly assigned to: (a) a protocol using theories and techniques derived from cognitive-behavioral therapy; (b) a protocol derived from WBT. Assessment before and after interventions was performed using two self-rating scales: Kellner's Symptom Questionnaire and Ryff's Psychological Well-Being Scales. RESULTS: Both school-based interventions resulted in a comparable improvement in symptoms and psychological well-being. CONCLUSIONS: This new well-being-enhancing strategy could play an important role in the prevention of psychological distress in school settings and in promoting optimal human functioning among children.

Adolescent↗

Genomic organization and transcriptional analysis of the human l-glutaminase gene.

In mammals, glutaminase (GA) is expressed in most tissues, but the regulation of organ-specific expression is largely unknown. Therefore, as an essential step towards studying the regulation of GA expression, the human liver-type GA (hLGA) gene has been characterized. LGA genomic sequences were isolated using the genome walking technique. Analysis and comparison of these sequences with two LGA cDNA clones and the Human Genome Project database, allowed the determination of the genomic organization of the LGA gene. The gene has 18 exons and is approx. 18 kb long. All exon/intron junction sequences conform to the GT/AG rule. Progressive deletion analysis of LGA promoter-luciferase constructs indicated that the core promoter is located between nt -141 and +410, with several potential regulatory elements: CAAT, GC, TATA-like, Ras-responsive element binding protein and specificity protein 1 (Sp1) sites. The minimal promoter was mapped within +107 and +410, where only an Sp1 binding site is present. Mutation experiments suggested that two CAAT recognition elements near the transcription-initiation site (-138 and -87), play a crucial role for optimal promoter activity. Electrophoretic mobility-shift assays confirmed the importance of CAAT- and TATA-like boxes to enhance basal transcription, and demonstrated that HNF-1 motif is a significant distal element for transcriptional regulation of the hLGA gene.

5' Flanking Region↗

Roles of an Ets motif and a novel CACGAC direct repeat in transcription of the murine dihydrolipoamide dehydrogenase (Dld) gene.

The 5'-flanking region of the murine dihydrolipoamide dehydrogenase (Dld) gene was characterized for its promoter activity. DNase I footprinting analysis of the promoter region (-545 bp to +41 bp) revealed six major protein-binding domains (termed P1 to P6) that were protected by NIH3T3 fibroblast nuclear extracts. Transient transfection assays, using a series of nested deletions of the 2.5 kb 5'-flanking region ligated to the chloramphenicol acetyltransferase reporter gene, identified that the -42-bp to +41-bp region, which harbours the P1, P2, and P3 domains, had minimal transcriptional activity. When the 5'-flanking region was extended from -42 bp to -82 bp, there was an approx. 5-fold increase in promoter activity. To identify further the cis elements involved in transcription of the Dld gene (-82 bp to +41 bp), a series of mutations were introduced into this region and evaluated for functional effects using transient transfection and electrophoretic mobility shift assays. Mutation or deletion of the CACGAC direct repeat, located from -61 bp to -46 bp, resulted in minimal promoter activity. Mutation of the Ets motif, located from -37 bp to -32 bp, reduced the minimal promoter activity by approx. 50%, whereas the deletion of this motif almost abolished the promoter activity. These results indicate that: (i) the Ets motif is required for the minimal promoter activity and (ii) the CACGAC direct repeat enhances promoter activity. Database searches failed to identify the direct repeat with the CACGAC motif and hence the CACGAC sequence may represent a novel motif. The requirement of both the Ets motif and the direct repeat element for optimal promoter activity represents a unique combination for gene transcription.

3T3 Cells↗

DNA elements recognizing NF-Y and Sp1 regulate the human multidrug-resistance gene promoter.

Regulation of the human multidrug resistance gene (hMDR1) was studied by mapping DNA elements in the proximal promoter necessary for efficient transcription. Transient transfection analysis in tumor cell lines (HCT116, HepG2, and Saos2) of promoter deletions identified several regulatory domains. These cell lines expressed hMDR1 mRNA. Removal of an element between +25 and +158 reduced promoter activity by 2-3-fold, whereas deletion of sequences from approximately -5000 to -138 base pairs gave a approximately 2-fold increase. The activity of the hMDR1 promoter (-137 to +25) was comparable in activity to the SV40 early promoter and enhancer combination. Deletion of the hMDR1 promoter between -86 and -44 reduced activity by 5-10-fold, identifying an important regulatory region. This minimal region (-88 to -37) activated transcription when inserted upstream of a synthetic promoter, suggesting that it acts independently of other regulatory sequences. Two DNA elements within 85 base pairs of the transcriptional start site were required to confer efficient gene expression. A double-point mutation in the Y box (inverted CCAAT box) between -70 and -80 reduced activity of the promoter by 5-10-fold, and a single-point mutation at -52 within a GC-rich element reduced activity by 3-fold. Thus, both the Y-box and GC elements must each remain intact for optimal promoter activity. DNA-binding analyses suggest that the transcription factor NF-Y, but not YB-1 or c/EBP, is most likely responsible for controlling the activity of the Y-box element in these tumor cell lines. DNA-binding analyses also suggest that Sp1, alone or in combination with other nuclear factors, likely controls the activity of the GC element.

Base Sequence↗

Psychosocial determinants of adherence to highly active antiretroviral therapy among injection drug users in Vancouver.

BACKGROUND: Sub-optimal adherence to highly active antiretroviral therapy (HAART) among injection drug users (IDUs) is a significant concern. As such, there is an urgent need to identify psychosocial determinants of adherence that can be incorporated into interventions designed to promote optimal adherence. OBJECTIVE: To identify psychosocial determinants of adherence to HAART, as well as self-reported reasons for missing doses of HAART among HIV-infected IDUs. METHODS: We developed an eight-item adherence self-efficacy scale comprised of two sub-scales: adherence efficacy and self-regulatory efficacy. We examined correlates between adherence self-efficacy, outcome expectations, socio-demographic characteristics, drug use and risk behaviours, social support and HAART adherence among 108 HIV-infected participants in the Vancouver Injection Drug Users Study (VIDUS). Pharmacy-based adherence to HAART was obtained through a confidential record linkage to the province of British Columbia's HIV/AIDS Drug Treatment Program. Participants were defined as adherent if they picked-up 95% of their HAART prescriptions. Participants were also asked to indicate reasons for missing doses of HAART. Logistic regression was used to identify the factors independently associated with adherence to HAART. RESULTS: Seventy-one (66%) HIV-infected IDUs were less than 95% adherent. Forgetting was the most frequently cited reason (27%) for missing doses of HAART. Factors independently associated with adherence to HAART included adherence efficacy expectations [OR=1.8 (95% CI: 1.0-3.1); P=0.039] and negative outcome expectations [OR=0.8 (95% CI: 0.7-0.9); P=0.027]. CONCLUSIONS: We found low rates of adherence to HAART among IDUs. Psychological constructs derived from self-efficacy theory are highly germane to the understanding of adherence behaviour, and interventions that address these constructs should be developed and tested among HIV-infected drug users.

Adult↗

Using metacognition to promote certification success: the Testing Health Promotion Plan.

Metacognition, the process of knowing one's personal learning behaviors, is a powerful force in the educational repertoire of nursing staff development faculty who seek to promote optimal learning outcomes for practicing nurses. Metacognition also supports major goals of educational evaluation which include improvements in learning, instruction, and performance. In this article, metacognition is scrutinized from the perspectives of learning theory and memory processing. Implications for promoting successful certification results are presented.

Certification↗

Glucocorticoid repression and basal regulation of the epoxide hydrolase promoter.

Through a series of promoter deletions and gene transfer experiments we have examined the basal regulation and glucocorticoid-mediated repression of the rat epoxide hydrolase gene. Three regions of the 5' flanking sequence were found to influence the basal level of promoter function in H4IIE hepatoma cells. Region A (-891 to -355 bp) contains an apparent repressor of epoxide hydrolase expression, while regions B (-271 to -171 bp) and C (-141 to -85) were found to contain important sequences required for optimal promoter activity. Previous work has demonstrated that dexamethasone represses epoxide hydrolase transcription by approximately 50% in isolated rat liver nuclei, and, in this study, we have demonstrated that the ability of the epoxide hydrolase promoter to drive CAT expression is similarly repressed in H4IIE cells treated with 1 microM dexamethasone. Furthermore, the level of endogenous epoxide hydrolase mRNA is decreased by 70-88% in nontransfected H4IIE cells treated with dexamethasone. Interestingly, promoter activity was not decreased by dexamethasone in COS cells, which lack glucocorticoid receptors. The current data show that sequences from -42 to +110 bp are sufficient to support the dexamethasone response, and, furthermore, they suggest that repression may not require direct interaction of the ligand-receptor complex with the promoter region.

Animals↗

The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes.

Adaptive immune responses begin after antigen-bearing dendritic cells (DCs) traffic from peripheral tissues to lymph nodes. Here, we show that DC migration from skin to lymph nodes utilizes the leukotriene C(4) (LTC(4)) transporter multidrug resistance-associated protein 1 (MRP1). DC mobilization from the epidermis and trafficking into lymphatic vessels was greatly reduced in MRP1(-/-) mice, but migration was restored by exogenous cysteinyl leukotrienes LTC(4) or LTD(4). In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to the chemokine CCL19, but not to other related chemokines. Antagonism of CCL19 in vivo prevented DC migration out of the epidermis. Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC(4), which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.

ATP-Binding Cassette Transporters↗

Raising the bar for health and safety in child care.

During the past few decades, this country has experienced many socio-economic changes including a rise in the number of dual-income families and single parent homes. Combined with a fluctuating economy and drastic reforms in welfare, one of the results has been an ever-increasing number of children being cared for in out-of-home settings. With almost 75% of all children under age 5 years and 50% of infants in some form of child care on a regular basis, opportunities abound for nurses to promote optimal health and safety in child care. To ensure quality child care for these children, health care professionals are uniquely positioned to provide consultation services to centers and family child care settings. With expertise in child development, infection control, disease prevention, and health promotion, pediatric and public health nurses can provide many types of child care health consultation services to impact the care of these children positively.

Child↗

Hypothermia and localized cold injuries.

Hypothermia and localized cold injuries are largely preventable with proper preparation for activities in cold environments. Proficient field management is crucial to the final outcome in terms of function and viability because proper care is vital to preventing exacerbation of the initial exposure and injury. Rapid rewarming is optimal when further cold exposure can be avoided reliably. Repetitive freeze-thaw cycles are associated with increased morbidity and tissue loss caused by progressive microvascular injury and thrombosis. The subsequent care is largely supportive and consists of wound care and physical and hydrotherapy to promote optimal functional recovery.

Body Temperature Regulation↗

Asthma adherence and the athlete.

Although much has been written on the topic of adherence (also known as compliance) in asthma, little is known about adherence in the asthmatic athlete. There are shared reasons for poor adherence to treatment among athletes of varying ages and levels of competition. The Shared Decision-Making model is considered to be the optimal approach to enhancing adherence among all patients with chronic disease but is particularly well applied to athletes with asthma. This article discusses athlete-related, physician-related, and treatment-related barriers to adherence, as well as how to overcome these barriers to promote optimal disease management. Special considerations for the elite or professional athlete are also addressed.

Adult↗

A novel association between clustered NF-kappaB and C/EBP binding sites is required for immune regulation of mosquito Defensin genes.

A comparative analysis identified key cis-acting regulatory elements responsible for the temporal control of mosquito Defensin gene expression. The promoters of Anopheles gambiae Defensin 1 and two isoforms of Aedes aegypti Defensin A are up-regulated by immune challenge. This stimulated activity depends upon a cluster of three NF-kappaB binding sites and closely associated C/EBP-like motifs, which function as a unit for optimal promoter activity. Binding of NF-kappaB and C/EBP like transcription factors is confirmed by electrophoretic mobility shift assay, including supershifts with antibodies to C/EBP. KappaB-like motifs are abundant within antimicrobial peptide gene promoters and most are very closely associated with putative C/EBP binding sites. This novel association between NF-kappaB and C/EBP binding sites may, therefore, be of widespread significance.

Aedes↗

EBNA-2 transactivates a lymphoid-specific enhancer in the BamHI C promoter of Epstein-Barr virus.

Among the few Epstein-Barr virus (EBV) genes expressed during latency are the Epstein-Barr nuclear antigens (EBNAs), at least one of which contributes to the ability of the virus to transform B lymphocytes. We have analyzed a promoter located in the BamHI-C fragment of EBV which is responsible for the expression of EBNA-1 in some cell lines. Deletion analysis of a 1.4-kb region 5' of the RNA start site has identified a 700-bp fragment that is required for optimal promoter activity in latently infected B lymphocytes, as shown by promoter constructs linked to the chloramphenicol acetyltransferase reporter gene. This fragment is also able to enhance activity, in an orientation-independent manner, of the simian virus 40 early promoter linked to the chloramphenicol acetyltransferase gene. The enhancer element has some constitutive activity in EBV-negative lymphoid cells, which is increased in the presence of the EBNA-2 gene product. Further deletions have shown that the EBNA-2-responsive region requires a 98-bp region that contains a degenerate octamer-binding motif. In epithelial cells there was no enhancer activity regardless of the presence of EBNA-2. These results demonstrate that BamHI-C promoter activity may be dependent not on an enhancer contained in the ori-P, as was previously assumed, but rather on EBNA-2 transactivation of this more proximal enhancer located in the upstream region of the BamHI C promoter itself.

Antigens, Viral↗

Developmental intervention in the newborn intensive care unit.

Developmental intervention for infants with perinatal asphyxia requires an individualized therapeutic plan. A team approach incorporating developmental goals and intervention strategies into the nursing care of these infants is essential for optimal developmental outcome. Therapeutic management must always be appropriate for the infant's health status, gestational age, and organizational capabilities. An understanding of the neurophysiologic basis for intervention and the therapeutic management techniques for infants who are sick, recuperating, or convalescing will help the nurse to promote optimal development when caring for the asphyxiated infant.

Asphyxia Neonatorum↗

U6 snRNA genes of Arabidopsis are transcribed by RNA polymerase III but contain the same two upstream promoter elements as RNA polymerase II-transcribed U-snRNA genes.

Previously we have demonstrated that the U2 snRNA genes from the higher plant Arabidopsis thaliana contain two upstream elements, the USE with sequence RTCCCACATCG and a -30 'TATA' box, which are essential for transcription by RNA polymerase II, and that the conserved spacing of about four helical DNA turns between these elements is important for optimal promoter function. We have now isolated three genes encoding U6 RNA in Arabidopsis. Transcription of these genes in transfected protoplasts of Nicotiana plumbaginifolia is resistant to alpha-amanitin indicating that they are transcribed by RNA polymerase III. The upstream regions of three Arabidopsis U6 genes contain USE and -30 TATA-like elements similar to those found to be important for transcription of U2 RNA genes but the spacing between the two elements is about 10 bp closer than in the U2 genes. Using synthetic U6 genes we demonstrate that the USE and TATA elements are indispensable for their transcription, the TATA boxes of U2 and U6 genes are interchangeable, and that the intragenic A box-like sequence of U6 gene is not essential. Increasing the distance between the USE and TATA by 10 bp inactivates U6 gene transcription, demonstrating that proper positioning of the elements is also important for transcription by RNA polymerase III. The data indicate that the structure of U-snRNA gene promoters and the determinants of polymerase specificity are completely different between vertebrates and plants.

Amanitins↗