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PubMed2003

Suppression of RelA/p65 transactivation activity by a lignoid manassantin isolated from Saururus chinensis.

In our search for NF-kappaB inhibitors from natural resources, we have previously identified two structurally related dilignans, manassantin A and B as specific inhibitors of NF-kappaB activation from Saururus chinensis. However, their molecular mechanism of action remains unclear. We here demonstrate that manassantins A and B are potent inhibitors of NF-kappaB activation by the suppression of transciptional activity of RelA/p65 subunit of NF-kappaB. These compounds significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or TNF-alpha in a dose-dependent manner. However, these compounds did not prevent the DNA-binding activity of NF-kappaB assessed by electrophoretic mobility shift assay as well as the induced-degradation of IkappaB-alpha protein by LPS or TNF-alpha. Further analysis revealed that manassantins A and B dose-dependently suppressed not only the induced NF-kappaB activation by overexpression of RelA/p65, but also transactivation activity of RelA/p65. Furthermore, treatment of cells with these compounds prevented the TNF-alpha-induced expression of anti-apoptotic NF-kappaB target genes Bfl-1/A1, a prosurvival Bcl-2 homologue, and resulted in sensitizing HT-1080 cells to TNF-alpha-induced cell death. Similarly, these compounds also suppressed the LPS-induced inducible nitric oxide synthase expression and nitric oxide production. Taken together, manassantins A and B could be valuable candidate for the intervention of NF-kappaB-dependent pathological condition such as inflammation and cancer.

Animals↗

PubMed2002

Unified algorithm for real-time detection of drug interaction and drug allergy.

This algorithm aims at unifying and generalizing the algorithm for detecting all types of documented drug interactions such as drug-drug interactions, drug-disease interactions, drug-patient interactions (drug allergy) from patient profile information and drug-laboratory test interactions in real-time prescribing system. Ideally, the system should conform to the following criteria: (1) data independence; (2) software interconnectability; (3) knowledge expandability; (4) flexibility; and (5) computation resource efficiency. We propose a robust Structured Query Language (SQL) algorithm to detect drug interactions and drug allergy according to such criteria. We believe that this is the first public domain algorithm in SQL that could be easily implemented into most open-system prescribing software which support SQL language. The algorithm comprises two major stages: 'expand' and 'extract'. The former expands all information in the prescription with their synonyms, groups, or components. The latter extracts the documented interactions by inner-joining knowledge-base with two independent copies of the expanded prescription list simultaneously. Simulation study for speed performance indicates that this algorithm is well behaved, for the speed of computation does not grow faster than the growth in prescription size.

Algorithms↗

PubMed2003

The burden of type 2 diabetes: are we doing enough?

Increasing levels of obesity, arising from energy-rich diets and sedentary lifestyles, are driving a global pandemic of type 2 diabetes. The prevalence of type 2 diabetes worldwide is set to increase from its present level of 150 million, to 225 million by the end of the decade and to as many as 300 million by 2025. Shocking as they are, these figures represent only clinically diagnosed diabetes, and many more cases of diabetes remain undiagnosed and untreated. In addition, up to one-quarter of western populations have impaired glucose tolerance or the dysmetabolic syndrome, which are considered to represent pre-diabetic states. Type 2 diabetes is appearing increasingly in children and adolescents, and the frequency of diagnosis of paediatric type 2 diabetes is outstripping that of type 1 diabetes in some areas. The long-term complications associated with type 2 diabetes carries a crushing burden of morbidity and mortality, and most type 2 diabetic patients die prematurely from a cardiovascular event. Diabetic patients are more than twice as costly to manage as non-diabetic patients, due mainly to the high costs associated with management of diabetic complications. Indeed, diabetes care already accounts for about 2-7% of the total national health care budgets of western European countries. Controlling the type 2 diabetes epidemic will require changes to the structure of healthcare delivery. Well-resourced interventions will be required, with effective co-ordination between all levels of government, health care agencies, multidisciplinary health care teams, professional organisations, and patient advocacy groups. Above all, intervention is needed today.

Adolescent↗

PubMed2005

Psychological and physical well-being during unemployment: a meta-analytic study.

The authors used theoretical models to organize the diverse unemployment literature, and meta-analytic techniques were used to examine the impact of unemployment on worker well-being across 104 empirical studies with 437 effect sizes. Unemployed individuals had lower psychological and physical well-being than did their employed counterparts. Unemployment duration and sample type (school leaver vs. mature unemployed) moderated the relationship between mental health and unemployment, but the current unemployment rate and the amount of unemployment benefits did not. Within unemployed samples, work-role centrality, coping resources (personal, social, financial, and time structure), cognitive appraisals, and coping strategies displayed stronger relationships with mental health than did human capital or demographic variables. The authors identify gaps in the literature and propose directions for future unemployment research.

Adaptation, Psychological↗

PubMed2003

Use of a novel outbred by inbred F1 cross to detect genetic markers for growth.

A unique outbred by inbred F1 resource population was established. The population structure facilitated the unique opportunity of examining gene by genetic background interaction through crossing two modern broiler sires with dams from two unrelated inbred lines, with no selection for growth rate, to produce about 600 F1 chicks. Pools of DNA were generated from the phenotypic extremes (20% high and low) for 8-week body weight for each of the four combinations of sire and dam line. For one sire family, pools were also separately generated for each sex. The pools were genoyped with 25 informative (segregating) microsatellites. This unique F1 cross between outbred and inbred populations allowed use of the inbred alleles as an 'internal control' for polymerase chain reaction amplification quality in DNA pools. Ten microsatellites showed marked differences (P < 0.05) in allele frequencies between high and low pools, suggesting an association between marker and quantitative trait loci (QTL). These differences were verified using selective genotyping. For many markers, differences in allele frequencies between the high and the low pools, or marker effect, varied between the two dam lines and the two sexes, suggesting an interaction between some genes and the genetic background as represented by different dam lines or sexes. The suggestive marker-QTL associations identified in this F1 population demonstrate the efficiency of this population design while different QTL effects in different genetic line crosses and sexes highlight the importance of gene by genetic background interaction in QTL detection.

Animals↗

PubMed2001

Patient reported quality of care before vs. after the implementation of a diagnosis related groups (DRG) classification and payment system in one Swedish county.

Patient reported quality of care before vs. after the implementation of a diagnosis related groups (DRG) classification and payment system in one Swedish county. The purpose was to evaluate the effects of a diagnosis related groups (DRG)-intervention on the quality of care as perceived by patients at two surgical clinics in the County Council of Gävleborg, Sweden. The study was planned as a nonequivalent control groups design, but external factors turned it into a prospective longitudinal design. Changes in patient experiences of received care were evaluated for the period 1992-1996. Of the 40 included consecutive patients per year from each hospital, > 85% completed the questionnaire. The selection of patients was defined by diagnoses and surgical treatments, and by geographical area. The results demonstrated a decrease of the quality of care as seen from the patient perspective, especially with respect to treatment by staff. Previously stated DRG goals were partially fulfilled and the DRG-intervention was gradually implemented. Other presumed causal variables were: other reforms, restrained resources, quality assurance activities, organizational and structural changes within the county council. Further studies of the effects of health care reforms would yield more distinct conclusions, provided it would be possible to evaluate interventions prior to full-scale implementation.

Adolescent↗

PubMed2005

Segmental duplications and copy-number variation in the human genome.

The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P < .000001), which suggests that segmental duplications are a major catalyst of large-scale variation in the human genome. Importantly, segmental duplications themselves were also significantly enriched >4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic disorders.

Chromosomes, Artificial, Bacterial↗

PubMed2026

The First Highly Contiguous Genome Assembly for the Western Bluebird (Sialia mexicana).

The western bluebird (Sialia mexicana) is a secondary cavity-nesting thrush that has experienced historical population declines, local extirpations, and more recent recoveries associated with nest box programs. Despite these regional successes, recent eBird estimates suggest continued range-wide declines and substantial geographic variation in population trajectories, making this species a useful system for future studies of demographic change, connectivity, and conservation genomics. However, genomic resources for western bluebirds remain limited, and no reference genome currently exists for any species in the genus Sialia. Here, we present the first high-quality de novo reference genome for S. mexicana. Using PacBio HiFi long-read sequencing from an adult female, we generated a highly contiguous, phased 1.3 Gb nuclear assembly with a contig N50 of 24.8 Mb and high BUSCO completeness of 98.3%. We annotated the nuclear genome using transcriptomic and protein evidence, identifying 16,656 protein-coding genes and 26,060 transcripts/protein isoforms. We also assembled a complete ∼16 kb mitochondrial genome from Illumina short-read data. This reference genome provides a foundational resource for future studies of population structure, genetic diversity, connectivity, demographic history, and adaptation in western bluebirds and related taxa.

Animals↗

PubMed1999

Zambia: the role of aid management in sustaining visionary reform.

As part of its ongoing reform of the health sector, Zambia has developed a number of systems and structures to coordinate and manage external resources. With increasing attention being given to the potential for sector-wide approaches (SWAps) to enhance the efficiency and effectiveness of health systems in low-income countries, Zambia provides an interesting case study of how this is emerging in practice over time. The paper outlines the different coordination mechanisms and assesses them in terms of selected criteria of effectiveness, finding that the potential to meet reform objectives is currently not being met. Factors influencing the effectiveness of these mechanisms are identified as falling into categories around personalities and human interaction, the nature of reform processes, and the impact of broader context. The need to maintain dialogue in the face of external constraints and uncertainties is stressed.

Developing Countries↗

PubMed2001

Interorganizational relationships among HIV/AIDS service organizations in Baltimore: a network analysis.

A wide variety of organizations has become involved in providing medical and social services to people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Although there is much interest among policymakers, service providers, and clients in coordination among HIV/AIDS service organizations, few studies have used network analytic tools to examine existing systems of HIV-related care. In an effort to fill this gap, this study used network analysis methods to describe several aspects of the interorganizational relationships among 30 HIV/AIDS service agencies in Baltimore, Maryland. Client referrals to other organizations, client referrals from other organizations, exchange of information about shared clients, formal written linkage agreements for client referrals, and joint programs were each examined as a distinct type of network tie, with each the basis of a separate network among these 30 organizations. All of the networks except the one based on joint programs were relatively well connected, with most organizations either directly or indirectly linked. Most of the interorganizational collaboration occurred on a rather ad hoc basis for the purposes of meeting the more immediate needs presented by clients. Highly structured coordination involving substantial investment of resources and ongoing interagency activities appeared to be less common. The findings from this study also suggest that the providers in Baltimore tend to work directly with others as client needs arise rather than negotiating through "clearinghouse" types of organizations. Of the 30 HIV/AIDS service organizations, 5 were highly central in at least four of the five different types of networks. These five organizations--each having a critical role in the continuum of care--may be considered the most central core of the HIV/AIDS service delivery network in Baltimore. These organizations tend to be those that have been created specifically to provide HIV-related services or that specialize in HIV/AIDS care. This research can help policymakers understand how an HIV-related service delivery network may function and delineate key features of a network. In all communities, this type of assessment is critical to designing interventions to promote collaboration that are feasible within the context of existing interorganizational relationships. This type of data also has implications for informing activities to build the capacity of HIV/AIDS service organizations.

Acquired Immunodeficiency Syndrome↗

PubMed1999

The tmRNA website.

tmRNA (10Sa RNA) has a central role in trans -translation, in which a peptide tag encoded in tmRNA is added to the abnormally short protein product of a broken mRNA, as a signal for proteolysis of the entire tagged protein. The tmRNA website was established in 1997 as a resource for phylogenetic considerations of tmRNA structure and function. Since then, three partial tmRNA sequences have been completed, and sequences from 13 more species have been identified. Forty-six species from 10 bacterial phyla and chloroplasts are now represented in the database. Provisional sequence alignments and predicted proteolysis tag sequences are provided, as well as a literature review and a guide to searching for new tmRNA sequences. The tmRNA website is accessible via WWW at a new URL: http://sunflower.bio.indiana.edu/kwilliam/tmRNA /home.html

Bacteria↗

PubMed2005

Disease modification and cardiovascular risk reduction: two sides of the same coin?

Inflammatory rheumatic diseases are associated with a substantial increase in accelerated atherosclerosis, with complex interactions between traditional and disease-related risk factors. Therefore, cardiovascular risk reduction should be considered as integral to the control of disease activity in the care plans of patients with RA, SLE and, arguably any chronic inflammatory disease. Shared care structures, already established for the monitoring of DMARDs, could be adapted to communicate and monitor cardiovascular risk reduction objectives. We review the evidence for the efficacy of a range of therapeutic strategies, the majority of which impact on both disease activity and cardiovascular risk. The algorithm proposed here attempts to distil the latest advice from specialist panels at the National Cholesterol Education Program and the British Hypertension Society, as well as incorporating the existing data on SLE and RA patients. The algorithm is structured to minimize clinic time and resources necessary to stratify patients into groups for ROUTINE, SUBSTANTIAL or INTENSIVE risk management; the associated table summarizes optimal therapeutic objectives in each of these groups. The implication of this algorithm is that management of cardiovascular risk should be much more aggressive than is currently the norm in patients with chronic inflammatory diseases, such as RA and SLE. Long-term studies of such interventions are needed to further clarify the benefits of intensive cardiovascular risk management in these patients.

Algorithms↗

PubMed2003

From past paradigms to future frontiers: unique care delivery models to facilitate nursing work and quality outcomes.

As healthcare processes were reengineered in response to managed care, traditional care delivery models were abandoned, resulting in nursing staff dissatisfaction, increased healthcare error, and eroding clinical outcomes. An aging patient population, chronicity of illness, the proliferation of new medical information and technology, severity of illness, and the focus of acute care to "stabilization and transition" necessitate the creation of systems that address changes in nursing work expectations while maximizing available resources. By evaluating unit-specific structure and process criteria and allocation of provider roles, unique, setting-specific care delivery models can be created to facilitate direct and nondirect patient care functions, resulting in improved financial and clinical outcomes.

Delivery of Health Care↗

PubMed2006

Staff nurse empowerment in line and staff organizational structures for chief nurse executives.

OBJECTIVE: The authors tested a model linking chief nurse executive (CNE) organizational structures (line and staff) to staff nurse perceptions of workplace empowerment in 2 large Canadian hospitals. BACKGROUND: Kanter's theoretical constructs of empowerment (ie, access to information, support, resources and opportunity, and formal and informal power) were used to explore this phenomena. No published studies were found linking organizational structure to staff nurse empowerment. METHODS: Staff nurses (n = 256) were surveyed in 2 large teaching hospitals, one with a CNE in a line structure, the other with a CNE in a staff structure. Multiple regression analysis was used to test the proposed model. RESULTS: Staff nurses with a CNE in a line structure felt significantly more empowered in their access to resources than nurses with a CNE in a staff structure. Kanter's empowerment structures explained 63% of the variance in nurses' global empowerment in a line structure and 42% in the staff structure. Access to information, resources, and formal power was an important predictor of nurses' global empowerment in the line hospital, whereas only access to support was a significant predictor in the staff hospital. CONCLUSION: Support for the model tested in this study highlights the importance of the CNE in creating and sustaining healthy work environments for nurses.

Analysis of Variance↗

PubMed2005

Development of a training curriculum for public health preparedness.

We describe the development of a 2-day training curriculum in emergency public health to improve the competency of public health personnel to prepare for, and respond to, both natural and human-caused disaster hazards. The training is conducted in a face-to-face setting and content is mapped to recognized emergency preparedness competencies for public health workers. The training materials are uniquely structured to the specific hazards, demographics, resources, and local emergency response agencies for each jurisdiction. This training program incorporates a series of challenging interactive scenarios that reinforce decision making in a public health emergency. Pretesting and posttesting are used to evaluate knowledge gained by participants. This interactive approach aligns with the principles of adult learning, and training evaluations indicate that this method is an effective integration of process and content.

Competency-Based Education↗

PubMedDate not supplied

The interrelationship of organizational characteristics of magnet hospitals, nursing leadership, and nursing job satisfaction.

This study examined whether magnet hospitals continue to provide higher levels of job satisfaction and empowerment among nurses when compared with non-magnet hospitals. Also studied at both types of hospitals was whether job satisfaction discrepancy was interlinked with leadership effectiveness and support of professional nursing practice. Nurses employed at magnet hospitals experienced higher levels of empowerment and job satisfaction due to greater access to work empowerment structures. The elements accounting for differences in empowerment and job satisfaction scores included: (1) greater accessibility of magnet nurse leaders, (2) better support of clinical nurse autonomous decision making by magnet nurse leaders, and (3) greater access to work empowerment structures such as opportunity, information, and resources at magnet hospitals.

Adult↗

PubMed2003

Measurement of quality of life IV. Use of the SEQOL, QOL5, QOL1, and other global and generic questionnaires.

Quality-of-life (QOL) rating scales can be used to measure and describe the quality of life of a specific population or patient group. Many decisions can be taken and policies implemented when we know more about a group or population. The global quality-of-life concept may help in expressing the objective of the initiatives taken to benefit specific groups. The objective may be that we hope the efforts will increase their quality of life by a certain percentage. This explicit expectation will force the decision makers to stand by their noble intentions. They are obliged to evaluate their efforts and will have to learn something from it. A questionnaire thus constitutes a useful scientific instrument, as databases based on comprehensive and thorough questionnaire surveys that seek to encompass all aspects of life can provide valuable and precise information. The value of such a database depends on the correct use of the questionnaires and this paper examines some examples of how quality-of-life rating scales can be used. We identified at least ten ways to use the quality-of-life questionnaire: describing the quality of life of a population or patient group; formulating an objective for support, treatment, or care; screening or identifying individuals who need treatment; evaluating treatment and care; facilitating communication between physician and patients; involving the patient in the decision-making process; allocating resources; investigating the causal relation between the quality of life and ill health in prospective studies; creating an awareness of the quality of life and health promotion; and helping the practitioner to accumulate knowledge. Enhancing the quality of life is therefore a determining factor in the process of increasing awareness and responsible conduct in relation to the environment, natural resources, the working environment, and the structure of society. Putting the quality of life on the agenda inherently has a constructive and positive effect on the life and functioning of the individual and society.

Health Status↗

PubMed2005

Restoring sanitation services after an earthquake: field experience in Bam, Iran.

A powerful earthquake hit the city of Bam in southeast Iran on 26 December 2003. In its aftermath, a number of international relief agencies, including Oxfam, assisted in providing emergency sanitation services. Oxfam's programme consisted of constructing and repairing toilets and showers in villages located outside of the city. In contrast with other organisations, Oxfam opted for brick-work structures, using local materials and human resources rather than prefabricated cubicles. The choice illustrates the dilemmas faced by agencies involved in emergency sanitation: responding to needs in a manner consistent with international standards and offering assistance in a timely fashion while involving beneficiaries. Following a preliminary survey, Oxfam concluded that the provision of showers and latrines, in addition to utilisation of local materials and human resources, was essential for ensuring well-being, empowerment and dignity among members of the affected population, thereby maximising the benefits.

Disaster Planning↗