Compliance with growth hormone treatment - is it a problem?

Treatments fail for a number of reasons. These include the failure of medicines at a molecular level, failure to achieve the correct diagnosis and therefore use of the correct medication, problems surrounding the doctor-patient relationship, and failure of the service to meet patients' expectations. Compliance is characteristically viewed as the major cause of treatment failures but implicit in the use of the term compliance is the reliance on an imbalance of power where the patient follows what is ordered. Such an approach is likely to lead to failure. A better model is concerned with promoting the full participation of the patient to generate a therapeutic alliance. Despite the need for parental administration and a daily therapeutic regimen there appears to be little evidence to suggest that concordance is a major problem in growth hormone therapy. This is probably because treatment administration relies on the presence of a carer and there are tangible effects. However, concordance is likely to be an issue where there is mismatch between the patient's expectations and those of the doctor. Such a situation may arise when the therapeutic margin is narrow or the therapeutic effect minimal. To resolve this situation, adequate pre-intervention discussion is essential, which should include a clear statement of short- and long-term treatment targets and the likelihood of these being achieved or not. Carefully constructed health care plans are the key and should include educational programmes, home support and regular reinforcement. When concordance problems are suspected, careful consideration needs to be given as to whether the diagnosis is correct, is the treatment really effective and appropriate and does the patient really want the treatment.     

Natural selection on floral traits of Lobelia (Lobeliaceae): spatial and temporal variation

The strength and direction of natural selection on floral traits can vary spatially and temporally because of variation in the biotic and abiotic environment. High spatial variation in selection should lead to differentiation of floral traits among populations. In contrast, high temporal variation in selection should retard the evolution of population-specific floral phenotypes. To determine the relative importance of spatial vs. temporal variation in natural selection, we measured phenotypic selection on seven floral traits of the wildflowers Lobelia cardinalis and L. siphilitica in 1999 and 2000. Lobelia cardinalis experienced significant temporal variation in selection, whereas L. siphilitica experienced spatial variation in selection on the same traits. This variation in selection on floral traits was associated with spatial and temporal differences in the soil microenvironment. Although few studies of natural selection include spatial or temporal replicates, our results suggest that such replication is critical for understanding the distribution of phenotypes in nature.     

Maximum-likelihood estimation of relatedness

Relatedness between individuals is central to many studies in genetics and population biology. A variety of estimators have been developed to enable molecular marker data to quantify relatedness. Despite this, no effort has been given to characterize the traditional maximum-likelihood estimator in relation to the remainder. This article quantifies its statistical performance under a range of biologically relevant sampling conditions. Under the same range of conditions, the statistical performance of five other commonly used estimators of relatedness is quantified. Comparison among these estimators indicates that the traditional maximum-likelihood estimator exhibits a lower standard error under essentially all conditions. Only for very large amounts of genetic information do most of the other estimators approach the likelihood estimator. However, the likelihood estimator is more biased than any of the others, especially when the amount of genetic information is low or the actual relationship being estimated is near the boundary of the parameter space. Even under these conditions, the amount of bias can be greatly reduced, potentially to biologically irrelevant levels, with suitable genetic sampling. Additionally, the likelihood estimator generally exhibits the lowest root mean-square error, an indication that the bias in fact is quite small. Alternative estimators restricted to yield only biologically interpretable estimates exhibit lower standard errors and greater bias than do unrestricted ones, but generally do not improve over the maximum-likelihood estimator and in some cases exhibit even greater bias. Although some nonlikelihood estimators exhibit better performance with respect to specific metrics under some conditions, none approach the high level of performance exhibited by the likelihood estimator across all conditions and all metrics of performance.     

Accelerating the rate of disassembly of karyopherin.cargo complexes

Transport of macromolecules across the nuclear pore complex (NPC) occurs in seconds and involves assembly of a karyopherin.cargo complex and docking to the NPC, translocation of the complex across the NPC via interaction with nucleoporins (Nups), and dissociation of the complex in the nucleoplasm. To identify rate-limiting steps in the Kap95p.Kap60p-mediated nuclear import pathway of Saccharomyces cerevisiae, we reconstituted key intermediate complexes and measured their rates of dissociation and affinities of interaction. We found that a nuclear localization signal-containing protein (NLS-cargo) dissociates slowly from Kap60p monomers and Kap60p.Kap95p heterodimers with half-lives (t(12)) of 7 and 73 min, respectively; that Kap60p and Kap60p.NLS-cargo complexes dissociate slowly from Kap95p (t(12) = 36 and 73 min, respectively); and that Kap95p.Kap60p.NLS-cargo complexes and Kap95p.Kap60p heterodimers dissociate rapidly from the nucleoporin Nup1p (t(12) < or = 21 s) and other Nups. A search for factors that accelerate disassembly of the long-lived intermediates revealed that Nup1p and Nup2p accelerate 16- and 19-fold the rate of dissociation of NLS-cargo from Kap60p.Kap95p heterodimers; that Gsp1p-GTP accelerates > or = 447-fold the rate of dissociation of Kap60p.NLS-cargo from Kap95p; and that Nup2p and the Cse1p.Gsp1p-GTP complex independently accelerate > or = 22- and > or = 39-fold the rate of dissociation of NLS-cargo from Kap60p. We suggest that Nup1p, Nup2p, Cse1p, and Gsp1p accelerate disassembly of Kap95p.Kap60p.NLS-cargo complexes by triggering allosteric mechanisms within Kaps that cause rapid release of binding partners. In that way, Nup1p, Nup2p, Cse1p, and Gsp1p may function as karyopherin release factors (or KaRFs) in the nuclear basket structure of the S. cerevisiae NPC.     

Evidence consistent with human L1 retrotransposition in maternal meiosis I

We have used a unique polymorphic 3' transduction to show that a human L1, or LINE-1 (long interspersed nucleotide element-1), retrotransposition event most likely occurred in the maternal primary oocyte during meiosis I. We characterized a truncated L1 retrotransposon with a 3' transduction that was inserted, in a Dutch male patient, into the X-linked gene CYBB, thereby causing chronic granulomatous disease. We used the unique flanking sequence to localize the precursor L1 locus, LRE3, to chromosome 2q24.1. In a cell culture assay, the retrotransposition frequency of LRE3 is greater than that for any other element that has been tested to date. The patient's mother had two LRE3 alleles that differed slightly in the 3'-flanking genomic DNA. The patient had a single LRE3 allele that was identical to one of the maternal alleles; however, the patient's insertion matched the maternal LRE3 allele that he did not inherit. Other data indicate that there is only a small chance that the father (unavailable for analysis) carries the precursor LRE3 allele. In addition, paternal origin of the insertion would have required that an LRE3 mRNA transcribed before meiosis II be carried separately from its precursor LRE3 allele in the fertilizing sperm. Since the mother carries a potential precursor allele and the insertion was on the patient's maternal X chromosome, it is highly likely that the insertion originated during maternal meiosis I.     

Anaerobic infections in children

Anaerobic bacteria can cause a variety of endogenous infections in children. Because of their fastidious nature, they are difficult to isolate from infectious sites, and are often overlooked. Anaerobic infections can occur in all body sites, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues. They colonize the newborn after delivery and have been recovered from several types of neonatal infections. These include cellulitis of the site of fetal monitoring, neonatal aspiration pneumonia, bacteremia, conjunctivitis, omphalitis, and infant botulism. The lack of adequate therapy may lead to clinical failures. Their isolation requires appropriate methods of collection, transportation and cultivation of specimens. Treatment is complicated by their slow growth, their polymicrobial nature and their growing resistance to antimicrobials. Antimicrobial therapy is often the only form of therapy required, whereas in others it is an important adjunct to a surgical approach. Because anaerobes are generally recovered mixed with aerobic organisms, the choice of antimicrobial agents should provide coverage of both types of pathogens.     

Moderation of oral bacterial adhesion on saliva-coated hydroxyapatite by polyaspartate

AIMS: Synthetic sodium alpha,beta-polyaspartate (PA) has been investigated as a moderator of adhesion and the subsequent biofilm formation by oral bacteria. METHODS AND RESULTS: The inhibition of bacterial adhesion by PA was assessed by (i) a 30-min incubation with Streptococcus sanguis in a microtitre assay with the wells coated with hydroxyapatite (HAP) and (ii) an 18-h challenge with human salivary microflora in a HAP disc assay. In contrast to HAP-coated surfaces, clean polystyrene surfaces in the microtitre assay exhibited no anti-adhesion properties. It has been found that PA significantly and similarly adsorbs onto HAP surfaces in the presence and absence of salivary coating. The HAP disc assay also showed that PA, both in aqueous solutions and in toothpaste, reduced the level of adhered microflora and this effect was enhanced by added propylene oxide-ethylene oxide copolymers. CONCLUSION: The principal finding from this work is the potential role for PA as an inhibitor of dental plaque formation. PA may significantly modify the salivary pellicle. SIGNIFICANCE AND IMPACT OF THE STUDY: This work indicates the use of PA in controlling the development of dental plaque and the formation of bacterial biofilm in general.     

Combined histomorphometric and gene-expression profiling applied to toxicology

We have developed a unique methodology for the combined analysis of histomorphometric and gene-expression profiles amenable to intensive data mining and multisample comparison for a comprehensive approach to toxicology. This hybrid technology, termed extensible morphometric relational gene-expression analysis (EMeRGE), is applied in a toxicological study of time-varied vehicle- and carbon-tetrachloride (CCl₄)-treated rats, and demonstrates correlations between specific genes and tissue structures that can augment interpretation of biological observations and diagnosis.     

The state and conservation of Southeast Asian biodiversity

Southeast Asia is a region of conservation concern due to heavy losses of its native habitats. In this overview, we highlight the conservation importance of Southeast Asia by comparing its degree of species endemism and endangerment, and its rate of deforestation with other tropical regions (i.e., Meso-America, South America, and Sub-Saharan Africa). Southeast Asia contains the highest mean proportion of country-endemic bird (9%) and mammal species (11%). This region also has the highest proportion of threatened vascular plant, reptile, bird, and mammal species. Furthermore, not only is Southeast Asia’s annual deforestation rate the highest in the tropics, but it has also increased between the periods 1990–2000 and 2000–2005. This could result in projected losses of 13–85% of biodiversity in the region by 2100. Secondary habitat restoration, at least in certain countries, would allow for some amelioration of biodiversity loss and thus potentially lower the currently predicted extinction rates. Nonetheless, urgent conservation actions are needed. Conservation initiatives should include public education, sustaining livelihoods, and ways to enhance the sustainability of agriculture and increase the capacity of conservation institutions. Furthermore, these actions should be country-specific and not ignore areas heavily populated by humans, as they can also harbour high numbers of threatened species. We urge that cooperative conservation initiatives be undertaken and support (e.g., capacity-building) be given by more developed countries in the region and beyond.