Hope for a broken heart?

Heart failure affects 23 million people worldwide and results from cardiac dysfunction characterized by decreased responsiveness to beta-adrenergic stimulation. A recent publication by W.J. Koch and colleagues highlights evidence for targeted beta-adrenergic receptor kinase (betaARK1) inhibition by gene transfer to improve contractile function and beta-adrenergic responsiveness in failing human myocardium. This proof-of-concept study has great importance for future heart failure therapy because it provides evidence for the therapeutic effectiveness of betaARK1 inhibition in failing human myocardium.     

Hope for a broken heart?

Heated debate has surrounded the issue of whether adult stem cells can differentiate into cardiac myocytes and contribute to the function of the heart. In this issue of Cell, demonstrate stem cells in the adult rat heart that differentiate into cardiac myocytes in vitro and, when injected into the adult rat heart, can reconstitute the injured myocardium and improve function. These findings should weigh heavily in future debates about the existence of stem cells in the adult heart and their capacity for functional repair after injury.     

Cognitive Performance of G?ttingen Minipigs Is Affected by Diet in a Spatial Hole-Board Discrimination Test

Consumption of a high energy diet, containing high amounts of saturated fat and refined sugar has been associated with impairment of cognitive function in rodents and humans. We sought to contrast the effect of a high fat/cholesterol, low carbohydrate diet and a low fat, high carbohydrate/sucrose diet, relative to a standard low fat, high carbohydrate minipig diet on spatial cognition with regards to working memory and reference memory in 24 male Göttingen minipigs performing in a spatial hole-board discrimination test. We found that both working memory and reference memory were impaired by both diets relative to a standard minipig diet high in carbohydrate, low in fat and sugar. The different diets did not impact levels of brain-derived neurotrophic factor in brain tissue and neither did they affect circulatory inflammation measured by concentrations of C-reactive protein and haptoglobin in serum. However, higher levels of triglycerides were observed for minipigs fed the diets with high fat/cholesterol, low carbohydrate and low fat, high carbohydrate/sucrose compared to minipigs fed a standard minipig diet. This might explain the observed impairments in spatial cognition. These findings suggest that high dietary intake of both fat and sugar may impair spatial cognition which could be relevant for mental functioning in humans.     

Is Antrum or Corpus the Best Site for Culture of Helicobacter pylori?

Background Isolating Helicobacter pylori on culture media and performing antibiotic susceptibility testing is potentially the most useful tool for guiding antibiotic therapy, especially when antimicrobial resistance is suspected. The aim of this study was to determine whether the yield of H. pylori culture was related to the site from which the gastric specimen was obtained either before or after therapy.
Methods. Gastric mucosal biopsies from the antrum and the corpus of the stomach were cultured. H. pylori status was determined by histological assessment using the Genta stain.
Results. Fifty-two patients with documented H. pylori infection were studied: Twenty-three were tested before antibiotic therapy and 29 after therapy had failed. In 47 patients (90%), both antral and corpus culture specimens were positive. In 5 patients (10%), only one site was positive, with three false-negative antral and two false negative corpus cultures. The overall sensitivity of culture in detecting H. pylori infection was 95% (95% confidence interval = 89–98%) and was not significantly different for the antrum or corpus, either before or after therapy.
Conclusion. Culture of gastric biopsies from either the antrum or the corpus has an excellent diagnostic yield even in patients who failed antimicrobial therapy.     

Pharmacological Cognitive Enhancement in Healthy Individuals: A Compensation for Cognitive Deficits or a Question of Personality?

The ongoing bioethical debate on pharmacological cognitive enhancement (PCE) in healthy individuals is often legitimated by the assumption that PCE will widely spread and become desirable for the general public in the near future. This assumption was questioned as PCE is not equally save and effective in everyone. Additionally, it was supposed that the willingness to use PCE is strongly personality-dependent likely preventing a broad PCE epidemic. Thus, we investigated whether the cognitive performance and personality of healthy individuals with regular nonmedical methylphenidate (MPH) use for PCE differ from stimulant-naïve controls. Twenty-five healthy individuals using MPH for PCE were compared with 39 age-, sex-, and education-matched healthy controls regarding cognitive performance and personality assessed by a comprehensive neuropsychological test battery including social cognition, prosocial behavior, decision-making, impulsivity, and personality questionnaires. Substance use was assessed through self-report in an interview and quantitative hair and urine analyses. Recently abstinent PCE users showed no cognitive impairment but superior strategic thinking and decision-making. Furthermore, PCE users displayed higher levels of trait impulsivity, novelty seeking, and Machiavellianism combined with lower levels of social reward dependence and cognitive empathy. Finally, PCE users reported a smaller social network and exhibited less prosocial behavior in social interaction tasks. In conclusion, the assumption that PCE use will soon become epidemic is not supported by the present findings as PCE users showed a highly specific personality profile that shares a number of features with illegal stimulant users. Lastly, regular MPH use for PCE is not necessarily associated with cognitive deficits.     

Continuum or discrete patch landscape models for savanna birds? Towards a pluralistic approach

Conceptualising landscapes as a mosaic of discrete habitat patches is fundamental to landscape ecology, metapopulation theory and conservation biology. An emerging question in ecology is: when is the discrete patch model more appropriate than alternative and conceptually appealing models such as the continuum model? There is limited empirical testing of the utility of alternative landscape models compared to the discrete patch model for a range of species. In this paper, we constructed three alternative sets of models for testing the effect of landscape structure on diversity and abundance of a suite of woodland birds in a savanna landscape of northern Australia: the null model (only site‐scale habitat variables, landscape context not important), the continuum model, and the discrete patch model. We utilised high‐spatial resolution satellite images to quantify spatial gradients in tree cover density (the continuum model), and to then aggregate the fine‐scale heterogeneity in tree cover into discrete patches of trees, with grass cover forming the “matrix” (the discrete patch‐model). We then evaluated the relative importance of the alternative models using generalised linear models and an information theoretic approach. We found that the importance of the models varied among species, with no single model dominant. Species that move between open grassy areas and woody shelter responded well to the continuum model, reflecting the importance of gradients in density of forage (grasses) and cover (trees), while the discrete model performed best for species that forage in all vegetation strata, and nest predominantly in dense woody vegetation. This finding supports a pluralistic approach, highlighting the need for adopting and testing more than one landscape model in savanna landscapes, and in other landscapes that do not have a well defined patch structure.     

Is a Persistent Global Bias Necessary for the Establishment of Planar Cell Polarity?

Planar cell polarity (PCP)–the coordinated polarisation of a whole field of cells within the plane of a tissue–relies on the interaction of three modules: a global module that couples individual cellular polarity to the tissue axis, a local module that aligns the axis of polarisation of neighbouring cells, and a readout module that directs the correct outgrowth of PCP-regulated structures such as hairs and bristles. While much is known about the molecular components that are required for PCP, the functional details of–and interactions between–the modules remain unclear. In this work, we perform a mathematical and computational analysis of two previously proposed computational models of the local module (Amonlirdviman et al., Science, 307, 2005; Le Garrec et al., Dev. Dyn., 235, 2006). Both models can reproduce wild-type and mutant phenotypes of PCP observed in the Drosophila wing under the assumption that a tissue-wide polarity cue from the global module persists throughout the development of PCP. We demonstrate that both models can also generate tissue-level PCP when provided with only a transient initial polarity cue. However, in these models such transient cues are not sufficient to ensure robustness of the resulting cellular polarisation.     

Diagnosing Adrenal Insufficiency: Which Test is Best—The 1-μG or the 250-μG Cosyntropin Stimulation Test?

ObjectiveTo review the available literature on the low-dose cosyntropin stimulation test (CST) for the diagnosis of primary and secondary adrenal insufficiency in both nonstressed and acutely ill patients.MethodsWe performed a MEDLINE search of all English-language literature, published between 1965 and 2007, in which the 1-μg and the 250-μg CSTs were compared in patients with primary and secondary adrenal insufficiency.ResultsThe majority of published evidence suggests that the 1-μg CST is more sensitive than the 250-μg CST for the diagnosis of secondary adrenal insufficiency in nonstressed patients. In patients with primary adrenal insufficiency, the low-dose CST is unlikely to add any diagnostic sensitivity to the high-dose CST. In critically ill patients, the 1-μg test is also likely to be more sensitive than the 250-μg test when an appropriate cutoff value is used (25 μg/dL).ConclusionThe 1-μg CST with a cortisol level determined at 30 minutes after stimulation, with use of a cutoff level of 18 to 20 μg/dL in nonstressed patients and less than 25 μg/dL or an increment of less than 9 μg/dL from baseline in critically ill patients, is the best test that is currently available for establishing the diagnosis of secondary adrenal insufficiency. (Endocr Pract. 2008;14: 233-238)     

Towards a blood-stage vaccine for malaria: are we following all the leads?

Although the malaria parasite was discovered more than 120 years ago, it is only during the past 20 years, following the cloning of malaria genes, that we have been able to think rationally about vaccine design and development. Effective vaccines for malaria could interrupt the life cycle of the parasite at different stages in the human host or in the mosquito. The purpose of this review is to outline the challenges we face in developing a vaccine that will limit growth of the parasite during the stage within red blood cells--the stage responsible for all the symptoms and pathology of malaria. More than 15 vaccine trials have either been completed or are in progress, and many more are planned. Success in current trials could lead to a vaccine capable of saving more than 2 million lives per year.     

Loop-Mediated Isothermal Amplification for Laboratory Confirmation of Buruli Ulcer Disease—Towards a Point-of-Care Test

Background

As the major burden of Buruli ulcer disease (BUD) occurs in remote rural areas, development of point-of-care (POC) tests is considered a research priority to bring diagnostic services closer to the patients. Loop-mediated isothermal amplification (LAMP), a simple, robust and cost-effective technology, has been selected as a promising POC test candidate. Three BUD-specific LAMP assays are available to date, but various technical challenges still hamper decentralized application. To overcome the requirement of cold-chains for transport and storage of reagents, the aim of this study was to establish a dry-reagent-based LAMP assay (DRB-LAMP) employing lyophilized reagents.

Methodology/Principal Findings

Following the design of an IS2404 based conventional LAMP (cLAMP) assay suitable to apply lyophilized reagents, a lyophylization protocol for the DRB-LAMP format was developed. Clinical performance of cLAMP was validated through testing of 140 clinical samples from 91 suspected BUD cases by routine assays, i.e. IS2404 dry-reagent-based (DRB) PCR, conventional IS2404 PCR (cPCR), IS2404 qPCR, compared to cLAMP. Whereas qPCR rendered an additional 10% of confirmed cases and samples respectively, case confirmation and positivity rates of DRB-PCR or cPCR (64.84% and 56.43%; 100% concordant results in both assays) and cLAMP (62.64% and 52.86%) were comparable and there was no significant difference between the sensitivity of the assays (DRB PCR and cPCR, 86.76%; cLAMP, 83.82%). Likewise, sensitivity of cLAMP (95.83%) and DRB-LAMP (91.67%) were comparable as determined on a set of 24 samples tested positive in all routine assays.

Conclusions/Significance

Both LAMP formats constitute equivalent alternatives to conventional PCR techniques. Provided the envisaged availability of field friendly DNA extraction formats, both assays are suitable for decentralized laboratory confirmation of BUD, whereby DRB-LAMP scores with the additional advantage of not requiring cold-chains. As validation of the assays was conducted in a third-level laboratory environment, field based evaluation trials are necessary to determine the clinical performance at peripheral health care level.     

Tsetse Salivary Gland Hypertrophy Virus: Hope or Hindrance for Tsetse Control?

MANY SPECIES OF TSETSE FLIES (DIPTERA: Glossinidae) are infected with a virus that causes salivary gland hypertrophy (SGH), and flies with SGH symptoms have a reduced fecundity and fertility. The prevalence of SGH in wild tsetse populations is usually very low (0.2%-5%), but higher prevalence rates (15.2%) have been observed occasionally. The successful eradication of a Glossina austeni population from Unguja Island (Zanzibar) using an area-wide integrated pest management approach with a sterile insect technique (SIT) component (1994-1997) encouraged several African countries, including Ethiopia, to incorporate the SIT in their national tsetse control programs. A large facility to produce tsetse flies for SIT application in Ethiopia was inaugurated in 2007. To support this project, a Glossina pallidipes colony originating from Ethiopia was successfully established in 1996, but later up to 85% of adult flies displayed symptoms of SGH. As a result, the colony declined and became extinct by 2002. The difficulties experienced with the rearing of G. pallidipes, epitomized by the collapse of the G. pallidipes colony originating from Ethiopia, prompted the urgent need to develop management strategies for the salivary gland hypertrophy virus (SGHV) for this species. As a first step to identify suitable management strategies, the virus isolated from G. pallidipes (GpSGHV) was recently sequenced and research was initiated on virus transmission and pathology. Different approaches to prevent virus replication and its horizontal transmission during blood feeding have been proposed. These include the use of antiviral drugs such as acyclovir and valacyclovir added to the blood for feeding or the use of antibodies against SGHV virion proteins. In addition, preliminary attempts to silence the expression of an essential viral protein using RNA interference will be discussed.     

What is the Best Elective Operation for Duodenal Ulcer?

During the past 40 years, after gastroenterostomy and pyloroplasty for duodenal ulcer had been replaced by partial gastrectomy in many centres, partial gastrectomy itself gave way to combinations of vagotomy with gastroenterostomy, pyloroplasty or antrectomy. Opinions differ concerning the procedure of choice and in this paper the author examines the causes of this diversity of opinion and assesses the reliability of conclusions that can be drawn about the elective treatment of duodenal ulcer today. Most reports of results from various operations have come from retrospective studies, and the causes of variability among such reports are analyzed to point out the great difficulty in making a valid judgment about the relative worth of the various operations used to treat duodenal ulcer. Results of some of the few prospective studies with randomized operations assessed blindly are then presented and note is taken of the surprising observation that greatly different operations appear to give remarkably similar results. From the data available the author develops a logical way of approaching the choice of operation for the various problems related to duodenal ulcer that require elective surgical treatment.