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PubMed2005

Population-level assessment of risks of pesticides to birds and mammals in the UK.

It is generally acknowledged that population-level assessments provide a better measure of response to toxicants than assessments of individual-level effects. Population-level assessments generally require the use of models to integrate potentially complex data about the effects of toxicants on life-history traits, and to provide a relevant measure of ecological impact. Building on excellent earlier reviews we here briefly outline the modelling options in population-level risk assessment. Modelling is used to calculate population endpoints from available data, which is often about individual life histories, the ways that individuals interact with each other, the environment and other species, and the ways individuals are affected by pesticides. As population endpoints, we recommend the use of population abundance, population growth rate, and the chance of population persistence. We recommend two types of model: simple life-history models distinguishing two life-history stages, juveniles and adults; and spatially-explicit individual-based landscape models. Life-history models are very quick to set up and run, and they provide a great deal of insight. At the other extreme, individual-based landscape models provide the greatest verisimilitude, albeit at the cost of greatly increased complexity. We conclude with a discussion of the implications of the severe problems of parameterising models.

Animals↗
PubMed2026

Scalable medium-density genotyping platforms for cultivar identification, pedigree authentication, marker-assisted and genomic selection, and other applications in strawberry.

A broad spectrum of high-density genotyping approaches, including single-nucleotide polymorphism (SNP) arrays, genotyping-by-sequencing, and whole-genome reduced-representation sequencing, have been shown to perform well in strawberry (Fragaria × ananassa), despite the inherent complexity of the octoploid genome. While these approaches are effective, their routine deployment in breeding programs can be constrained by cost, computational requirements, and workflow complexity. In parallel, many breeding programs continue to rely on locus-specific assays for marker-assisted selection, resulting in fragmented and inefficient genotyping strategies. Here, we describe medium-density amplicon-based genotyping platforms for strawberry designed to provide cost-effective, turnkey solutions that integrate markers used for marker-assisted selection with genome-wide markers suitable for genomic prediction in a single laboratory assay. These platforms were developed by targeting 1,650 or 4,811 target SNPs via amplicon sequencing, and are interoperable with existing high-density genotyping resources, including a widely used 50K SNP array, thereby facilitating data integration across platforms. We benchmarked their performance relative to the 50K SNP array across breeding-relevant applications, including identity and purity testing, pedigree authentication, marker-assisted selection, and genomic selection, and further evaluated the feasibility of genotype imputation to enhance genome-wide information content. Across analyses, the 1,650- and 4,811-amplicon platforms produced results comparable to higher-density platforms while substantially reducing genotyping cost and analytical overhead. This work demonstrates that targeted amplicon-based genotyping can support efficient, scalable, and integrated genome-informed breeding, enabling the routine application of both marker-assisted and genomic selection within strawberry breeding workflows. Open-source R workflows are provided to support streamlined analyses in breeding contexts.

Fragaria↗
PubMed2006

A simplified QTL mapping approach for screening and mapping of novel AFLP markers associated with beef marbling.

Genome screening of quantitative trait loci (QTL) for a complex trait is usually costly and highly laborious, as it requires a large number of markers spanning the whole genome. Here we present a simplified approach for screening and mapping of QTL-linked markers for beef marbling using a WagyuxLimousin F(2) reference population. This simplified approach involves integration of the amplified fragment length polymorphism (AFLP) with DNA pooling and selective genotyping and comparative bioinformatics tools. AFLP analysis on two high and two low marbling DNA pools yielded ten visually different markers. Among them, four were confirmed based on individual AFLP validation. Sequencing and in silico characterization assigned two of these AFLP markers to bovine chromosomes 1 (BTA1) and 13 (BTA13), which are orthologous to human chromosomes HSA21q22.2 and HSA10p11.23 with both regions harboring QTL for obesity-related phenotypes. Both AFLP markers showed significantly large additive genetic effects (0.28+/-0.11 on BTA1 and 0.54+/-0.21 on BTA13) on beef-marbling score (BMS) (P<0.05). Overall, this approach is less time consuming, inexpensive and in particular, suitable for screening and mapping QTL-linked markers when targeting one or a few complex traits.

Animals↗
PubMedDate not supplied

Does population management of chronic disease lead to lower costs of care?

The paper by Bruce Fireman and colleagues is an important contribution to the dialogue about the role of chronic disease management in quality improvement and health care cost mitigation. There is much enthusiasm for the potential impact of disease management techniques on the costs associated with chronic and complex health conditions. This Perspective describes several considerations that are important to the interpretation of studies of the cost impact of disease management and to assessments of the future usefulness of these interventions.

Chronic Disease↗
PubMed2025

Development of a plant-based vaccine against brucellosis: stable expression of Brucella abortus OMP25 in transgenic tobacco.

Brucellosis, caused by Brucella species, is a global threat to livestock farming, resulting in economic losses and socio-economic challenges, particularly in rural areas. Despite its impact, no licensed human vaccines are available. Animal vaccination remains the most cost-effective control method, but traditional vaccine production is expensive. Edible vaccines, using plants as bioreactors to produce immunogenic antigens, offer a low-cost alternative by eliminating complex purification processes. This study developed a transgenic plant by expressing the Brucella abortus outer membrane protein OMP25 in tobacco plants. OMP25, a conserved transmembrane protein with high immunogenicity, was cloned into a Gateway pDONR vector via a Boundary Pairing reaction and transferred to a binary destination vector via a Left-Right reaction. The destination vector was introduced into Agrobacterium tumefaciens and subsequently used for Agrobacterium-mediated transformation of tobacco plants. Transgenic plants were selected on media containing kanamycin, and the expression of the transgene was verified through the fluorescence of green fluorescent protein. Microcallus formation and shoot development on selective media confirmed kanamycin resistance and the successful integration of the transgene. After phenotypic selection, genomic DNA was extracted from transgenic plants and analyzed by PCR (Polymerase Chain Reaction) using primers specific to the OMP25 gene. Positive PCR results validated the successful integration of the OMP25 gene into the plant genome. Gene expression was further confirmed at the RNA level through real-time quantitative PCR (qRT-PCR) and at the protein level via Western blot analysis. Future studies will evaluate immune responses in animal models. This approach demonstrates the potential for low-cost, effective vaccines to combat brucellosis, addressing critical economic and public health challenges.

Plants, Genetically Modified↗
PubMed2003

Amphotericin B lipid complex for the treatment of invasive fungal infections.

Amphotericin B lipid complex (ABLC; Abelcet, Enzon Pharmaceuticals) has become the dominant marketed lipid amphotericin B compound to emerge since the approval of these agents from the mid-1990s onwards. This agent is a 1:1 combination of amphotericin B and a lipid moiety consisting of dimyristoyl phosphatidylcholine and dimyrisoyl phosphatidylcholine, which exists in a ribbon-like molecular structure. ABLC undergoes rapid reticuloendothelial uptake from the circulation and achieves significantly higher tissue concentrations in the liver, spleen and lung compared to comparably dosed conventional amphotericin B. ABLC is approved by the FDA for all mycoses in amphotericin B-intolerant or -refractory infection. Randomised, controlled trials of amphotericin B have shown comparable efficacy in candidiasis and an improved outcome in invasive aspergillosis versus historical controls. ABLC has demonstrated a reduced incidence of nephrotoxicity and infusion reactions versus amphotericin B. Comparative studies against other lipid formulations are quite limited and have shown variable differences in infusion toxicity, nephrotoxicity, hepatotoxicity and clinical efficacy. Postapproval experience has shown substantial efficacy for less common mycotic pathogens including zygomycosis. The precise position of ABLC versus both other lipid formulations and expanding formulary of new antifungal agents is in flux. Future studies which examine its clinical efficacy, role in combination therapy, toxicity and cost-effectiveness in these complex patients are needed.

Amphotericin B↗
PubMed1993

Cost-effectiveness of endoscopic surgery.

Endoscopic surgery is a rapidly defusing treatment approach subject to continual technological advance. It offers great potential for economic benefits as well as health gains, but as shown in the article in this issue by Kesteloot and Penninckx, the relative cost of open versus endoscopic surgery is a quite complex issue. The main factors influencing the costs and effectiveness of endoscopic surgery are reviewed and the need for more and better evaluation studies highlighted.

Cholecystectomy, Laparoscopic↗
PubMed1992

Medical office buildings--the challenges and the rewards.

Hospitals considering the development of on-campus medical office complexes may find the process challenging and costly. But when developed and leased appropriately, medical office complexes can provide significant benefits to hospitals. Leasing on-campus medical office space to physicians serves to improve relationships with the physician community, and thereby can increase hospital utilization and revenue. The expanded facilities also allow the hospital to offer a greater scope of medical services to the local community. Authors Sands and Rendina examine the advantages of participation in medical office building development.

Economics, Medical↗
PubMed2006

Upper lip reconstruction with the alar crescent flap: A new approach.

PURPOSE: The alar crescent advancement flap technique has been widely used for repair of large central defects of the upper lip and base of the nose because of its 1-stage procedural simplicity and good results. Several more complicated and multiple staged procedures that respect either structure or function, often compromising one to achieve the other, have become popular and have recently taken its place. However, these procedures are more complex and in many cases require a staged approach. In this study, we present a series of 33 patients who underwent reconstruction of large upper lip defects utilizing alar crescent flaps between 1992 and 2002. PATIENTS AND METHODS: A series of 20 patients underwent reconstruction of large upper lip defects using alar crescent flaps between 1992 and 2002. Malignant etiologies were responsible for the defect in all patients. Reconstruction was performed as a 1-staged procedure in 19 cases. In 1 patient with a total upper lip defect, bilateral alar crescent flaps were used in conjunction with a cross lip flap that was later divided in a second stage procedure. RESULTS: All patients tolerated the procedure well with no major complications. Minor complications not requiring surgical intervention occurred in 5 patients. During the 12- to 60-month follow-up, all patients were found to be satisfied with the functional result. However, 7 patients underwent minor surgical procedures for esthetic improvement. There was no recurrence of disease in the 20 patients who underwent resection of malignancy. CONCLUSIONS: In these 20 cases, we have shown the utility of the alar crescent flap for varying length partial and full-thickness reconstruction of upper lip defects. This simple and straightforward technique provided good functional and esthetic results. The disadvantage of this procedure is the loss of philtral anatomic detail. Its primary advantage is that it is a single-stage procedure with a relatively low morbidity and patient inconvenience. As a single-stage technique it satisfies concerns over cost containment over more complex and staged procedures while still providing a good functional and cosmetic result. Furthermore, for those same reasons, this procedure is a good first choice in the elderly.

Adult↗
PubMedDate not supplied

Site-specific PEGylation of protein disulfide bonds using a three-carbon bridge.

The covalent conjugation of a functionalized poly(ethylene glycol) (PEG) to multiple nucleophilic amine residues results in a heterogeneous mixture of PEG positional isomers. Their physicochemical, biological, and pharmaceutical properties vary with the site of conjugation of PEG. Yields are low because of inefficient conjugation chemistry and production costs high because of complex purification procedures. Our solution to these fundamental problems in PEGylating proteins has been to exploit the latent conjugation selectivity of the two sulfur atoms that are derived from the ubiquitous disulfide bonds of proteins. This approach to PEGylation involves two steps: (1) disulfide reduction to release the two cysteine thiols and (2) re-forming the disulfide by bis-alkylation via a three-carbon bridge to which PEG was covalently attached. During this process, irreversible denaturation of the protein did not occur. Mechanistically, the conjugation is conducted by a sequential, interactive bis-alkylation using alpha,beta-unsaturated beta'-monosulfone functionalized PEG reagents. The combination of (a) maintaining the protein's tertiary structure after disulfide reduction, (b) the mechanism for bis-thiol selectivity of the PEG reagent, and (c) the steric shielding of PEG ensure that only one PEG molecule is conjugated at each disulfide bond. PEG was site-specifically conjugated via a three-carbon bridge to 2 equiv of the tripeptide glutathione, the cyclic peptide hormone somatostatin, the tetrameric protein l-asparaginase, and to the disulfides in interferon alpha-2b (IFN). SDS-PAGE, mass spectral, and NMR analyses were used to confirm conjugation, thiol selectivity, and connectivity. The biological activity of the l-asparaginase did not change after the attachment of four PEG molecules. In the case of IFN, a small reduction in biological activity was seen with the single-bridged IFN (without PEG attached). A significantly larger reduction in biological activity was seen with the three-carbon disulfide single-bridged PEG-IFNs and with the double-bridged IFN (without PEG attached). The reduction of the PEG-IFN's in vitro biological activity was a consequence of the steric shielding caused by PEG, and it was comparable to that seen with all other forms of PEG-IFNs reported. However, when a three-carbon bridge was used to attach PEG, our PEG-IFN's biological activity was found to be independent of the length of the PEG. This property has not previously been described for PEG-IFNs. Our studies therefore suggest that peptides, proteins, enzymes, and antibody fragments can be site-specifically PEGylated across a native disulfide bond using three-carbon bridges without destroying their tertiary structure or abolishing their biological activity. The stoichiometric efficiency of this approach also enables recycling of any unreacted protein. It therefore offers the potential to make PEGylated biopharmaceuticals as cost-effective medicines for global use.

Alkylation↗
PubMed2003

Coupling of chemical extraction and expanded-bed adsorption for simplified inclusion-body processing: optimization using surface plasmon resonance.

Integration of the chemical extraction of recombinant inclusion-body protein from Escherichia coli, and its recovery by metal-affinity expanded-bed adsorption (IMAC-EBA) under denaturing conditions, was investigated. The viral coat protein L1 with a hexa-histidine tag was expressed in Escherichia coli HMS174(DE3) as a model protein. Interference of released host DNA with adsorbent fluidization in the EBA step was solved by selective precipitation using spermine and low-speed centrifugation. However, the capacity and selectivity of the adsorbent for L1 remained lower than anticipated. The binding of L1 to immobilized Ni(2+) was therefore studied in detail using surface plasmon resonance (SPR). The Tris buffer and ethylene-diamine tetraacetic acid (EDTA) used in the extraction mixture were found to interfere significantly with the L1-Ni(2+) interaction. The SPR studies suggest that L1 binding could be improved by replacing the Tris buffer with HEPES and by adding CaCl(2) to inactivate the EDTA. The modified chemical extraction conditions resulted in effective L1 extraction from cytoplasmic inclusion bodies, at high cell density (OD(600 )= 80) and without the use of reducing agent, into a medium optimized for subsequent IMAC recovery. The modified buffer conditions resulted in an improved binding capacity and a good L1 purification factor (12.7) and recovery yield (71%). This work demonstrates that it is possible to reduce the complexity and hence the cost associated with traditional processes used to prepare purified denatured protein, ready for refolding, from cytoplasmic inclusion bodies.

Adsorption↗
PubMed1991

Two explanations of nurse practitioner interactions and participatory decision making with physicians.

The purpose of this study was to test a theoretical model that integrated two explanations of nurse practitioner interaction and participatory decision making with physicians. The two explanations were derived from technology theory and social exchange theory. Nurse practitioners (N = 38) responded to a four-scale magnitude estimation instrument measuring each of four concepts in the model: complexity, expected benefit-cost ratio of interaction, interaction, and participatory decision making. Predictions derived from both theories were supported. Nurse practitioner decisions about interaction with physicians were influenced by the dynamics of social exchange with physicians, as well as the technological requirements of primary care. The findings offer nurse practitioners new strategies for managing professional exchanges on behalf of their patients.

Adult↗
PubMed2006

Physicians, pharmacists and patients' compliance with chronic treatment in Bulgaria.

PURPOSE: To study the patient-physician and patient-pharmacist interrelation in order to reveal the systematic factors that influence patients' compliance. METHODS: Standard individual questionnaires were developed and used to assess compliance and non-compliance among different categories of patients suffering from chronic diseases. RESULTS: There is a relatively good communication between the patients and the health-care givers but in order to improve compliance (adherence) further, this level of communication has to be improved. The main reasons for non-adherence were: the high cost of drugs, the complexity of the daily regimen, negligence, and distrust of treatment. Insufficient information in the patient information leaflet, together with an inappropriate drug formulation also appear to be important factors that cause non-compliance. This is especially so, when patients have to receive more than one drug, or medications in different dosage forms, and it is particularly marked when elderly people are involved. CONCLUSION: Despite the comparatively high level of compliance found in this study (50-92%), there are possibilities for individualization of treatment that merit attention in order that the level of compliance can be improved.

Adult↗
PubMed2006

Nanomachining by colloidal lithography.

Colloidal lithography is a recently emerging field; the evolution of this simple technique is still in progress. Recent advances in this area have developed a variety of practical routes of colloidal lithography, which have great potential to replace, at least partially, complex and high-cost advanced lithographic techniques. This Review presents the state of the art of colloidal lithography and consists of three main parts, beginning with synthetic routes to monodisperse colloids and their self-assembly with low defect concentrations, which are used as lithographic masks. Then, we will introduce the modification of the colloidal masks using reactive ion etching (RIE), which produces a variety of nanoscopic features and multifaceted particles. Finally, a few prospective applications of colloidal lithography will be discussed.

Colloids↗
PubMed1998

Mechanisms of uptake of gallium by human neuroblastoma cells and effects of gallium and aluminum on cell growth, lysosomal protease, and choline acetyl transferase activity.

We have studied the uptake and removal of gallium, used as an analogue of aluminum, and the effects of aluminum itself on cultured human neuroblastoma cells treated with soluble metal complexes. The prohibitively high cost of measurement of the only available radioisotope of aluminum (26Al) precluded its usage, and so we considered that gallium, which is chemically extremely similar, would be the most suitable model. Gallium has been used thus in a number of previous biological studies and has been found to behave like aluminum in many respects. We have previously shown that Al-EDTA treatment results in uptake of aluminum and expression of hyperphosphorylated tau, a key component of Alzheimer's disease paired helical filaments. Here we demonstrate that gallium uptake can occur by two separate methods, both leading to physiologically relevant intracellular metal concentrations. Uptake from medium containing bovine transferrin occurred mainly by pinocytosis, but in the presence of human transferrin (hTf), uptake by transferrin-mediated endocytosis occurred also, despite a very low level of hTf saturation, indicating that Tf-mediated uptake is a very effective method of Ga internalization. The intracellular gallium is relatively stable, though partially removable by (1 mM) EDTA, desferrioxamine, or 1,2-dimethyl-3-hydroxypyrid-4-one. Aluminum and gallium treatment were found to increase the overall activity of lysosomal proteases, enzymes implicated in amyloid precursor protein cleavage. No effects were detected on choline acetyl transferase activity, cell growth, or tritiated thymidine incorporation or on the structure of the cells, as judged by light or electron microscopy.

Aluminum↗
PubMed2003

In situ product removal (ISPR) in whole cell biotechnology during the last twenty years.

This review sums up the activity in the field of in situ product removal in whole cell bioprocesses over the last 20 years. It gives a complete summary of ISPR operations with microbial cells and cites a series of interesting ISPR applications in plant and animal cell technology. All the ISPR projects with microbial cells are categorized according to their products, their ISPR techniques, and their applied configurations of the ISPR set-up. Research on ISPR application has primarily increased in the field of microbial production of aromas and organic acids such lactic acid over the last ten years. Apart from the field of de novo formation of bioproducts, ISPR is increasingly applied to microbial bioconversion processes. However, despite of the large number of microbial whole cell ISPR projects (approximately 250), very few processes have been transferred to an industrial scale. The proposed processes have mostly been too complex and consequently not cost effective. Therefore, this review emphasizes that the planning of a successful whole cell ISPR process should not only consider the choice of ISPR technique according to the physicochemical properties of the product, but also the potential configuration of the whole process set-up. Furthermore, additional process aspects, biological and legal constraint need to be considered from the very beginning for the design of an ISPR project. Finally, future trends of new, modified or improved ISPR techniques are given.

Biological Products↗
PubMed1989

Evaluation of care for the disabled mentally ill: theoretical issues.

A precondition for the discharge from an institution of the chronically disabled mentally ill is the availability of adequate alternative facilities and services, optimally meeting their social and mental health needs and allowing as much quality of life as possible at the lowest possible cost. Only a few studies have found alternative care to lead to better outcomes than treatment in good-quality hospitals with respect to illness course and social disablement. Therefore, it is an important question whether extramural care and of what type is better and possibly less expensive than traditional inpatient treatment and for which patients. Health data collected at the national and regional levels provide a basis for continuous monitoring of utilization of services. Such data, however, usually have the limitation of being aggregate in nature and not including contacts with social services. These deficits can be avoided by using cumulative case registers, recording if possible all contacts of the socially disabled mentally ill with intramural and extramural mental health and social services and covering a define catchment area. Because the disabled mentally ill, depending on their own resources and those of their family and the community at large, have basic needs differing in each individual case, as well as various specific needs determined by the illness which they cannot meet on their own, it is necessary to provide a variety of facilities and services and to coordinate their work. Evaluation and cost-effectiveness investigations of complex packages of care yield generalizable results only if the forms of care under study are defined precisely enough.(ABSTRACT TRUNCATED AT 250 WORDS)

Aftercare↗
PubMed2026

Harnessing Probiotic LAB and Bacteriocins for Clean-Label Food Processing and Biopreservation: Omics, Molecular Innovations and Industrial Applications.

The persistence of microbial agents in foods, especially spore forming bacteria is one of the most significant challenges to food preservation and safety, undermining product quality, shelf life, and consumer health. The use of traditional control methods, including thermal processing and chemical preservatives, are increasingly limited by consumer demands for minimally processed foods, and the emergence of resistant microbial strains. Advances have been made in the use of probiotics like lactic acid bacteria (LAB) and their biometabolites like bacteriocins in food processing and preservation, particularly to control biofilm and endospore forming pathogens including Bacillus sp., Listeria sp., Staphylococcus sp., Clostridium sp., E. coli etc. in foods and food processing plants/surfaces. Given the ability of these organisms to cause foodborne illness and form resilient biofilms in the food processing ecosystem and their resistance to the conventional method of their elimination, the antimicrobial peptides (bacteriocins) are gaining increasing prominence as useful alternatives to synthetic antimicrobials in enhancing food safety and combating the threats of these pathogens. This review addresses current information on the inhibition of persistent microbial spoilage contaminants, biofilm-forming pathogens, and spore formers of interest to the food industry using LAB and their bacteriocins. Current developments in isolation, characterization, and mode of action of bacteriocins are explored, including synergistic activity with other preservative hurdle techniques such as encapsulation, and nanobiotechnology. Importantly, there is a focus on the utilization of molecular and omics-based approaches to enable a better understanding of bacteriocin biosynthesis, gene regulation, host-microbe interactions and gut microbiome regulation potential of probiotic LABs, permitting the rational development of targeted and strain-specific interventions. Developments in the incorporation of bacteriocin-producing LAB into functional starter cultures and bio-protective products, and challenges in stability, regulatory approval, and scalability for industrial use, are also discussed in the paper. Despite their considerable potential, broader translation remains constrained by regulatory requirements, production and formulation costs, variable efficacy in complex food matrices, and the limited validation of many candidate bacteriocins beyond laboratory and model-food systems. Collectively, these advances position LAB and their bacteriocins at the leading edge of developing sustainable, clean-label, and efficacious functional foods and food preservation systems. Their functionality can be expanded by integrating genomics, synthetic biology, and predictive modeling for the maximization of their biopreservative potential in diverse food matrices and in gut microbiota modulation.

Bioactive Peptides↗