Candida pneumonia: What we know and what we don’t

The diagnosis of Candida pneumonia is a difficult one to make, and some experts often question whether the entity truly exists. This article assimilates the information currently available regarding Candida pulmonary infection to elucidate the presentation of the disease and the hosts in which it occurs. It also describes how to interpret the presence of Candida in respiratory secretions from both immunocompetent and immunocompromised patients. Finally, it describes how the diagnosis of Candida pneumonia can be made, which patients with suspected disease should be treated, and which antifungal agents should be used.     

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual’s blood pressure, the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection, and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases.

Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. While there are only few proteomic studies specifically addressing human primary hypertension, there are more data available in hypertensive disorders in pregnancy, such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches.

Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardized large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases.     

UV radiation: what we know and do we protect ourselves adequately?

Chronic sun exposure causes degenerative changes in the skin that are recognized as photoaging, immunosuppression and photocarcinogenesis. Sun is necessary for life, so total sun avoidance is impossible. Sun exposure during the first 15 years of life and blistering sunburns before age 20 have been linked to an increased risk of melanoma. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. In our study, performed four years ago, we have shown the knowledge of more than 4000 people about the effects of UV rays on the skin. The results show us that sun exposure is still exaggerated and uncontrolled due to the lack of knowledge about this topic. Encouraging photoprotection and improving the awareness of the general public about the harmful effects of too much sun exposure must be the leading preventative health strategy.     

Prostate cancer gene therapy-what have we learned and where are we going?

With recent advances in genetic engineering, tumor biology, and immunology, gene therapy has been recognized as a promising new treatment option for various cancers, including prostate cancer. Several clinical trials of prostate cancer gene therapy, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes, and anti-oncogenes, are under way and preliminary reports have emerged. Although gene therapy for prostate cancer is still at an early stage and requires additional technological breakthroughs, new insights obtained from recent clinical trials indicate a promising potential for prostate cancer gene therapy. In this report, general concepts, current progress, and future prospects in prostate cancer gene therapy are summarized.     

Community genetics: what have we accomplished and where should we be going?

Research in community genetics seeks to understand how the dynamic interplay between ecology and evolution shapes simple and complex communities and ecosystems. A community genetics perspective, however, may not be necessary or informative for all studies and systems. To better understand when and how intraspecific genetic variation and microevolution are important in community and ecosystem ecology, we suggest future research should focus on three areas: (i) determining the relative importance of intraspecific genetic variation compared with other ecological factors in mediating community and ecosystem properties; (ii) understanding the importance of microevolution in shaping ecological dynamics in multi-trophic communities; and (iii) deciphering the phenotypic and associated genetic mechanisms that drive community and ecosystem processes. Here, we identify key areas of research that will increase our understanding of the ecology and evolution of complex communities but that are currently missing in community genetics. We then suggest experiments designed to meet these current gaps.     

Leptin in farm animals: where are we and where can we go?

Fat affects meat quality, value and production efficiency as well as providing energy reserves for pregnancy and lactation in farm livestock. Leptin, the adipocyte product of the obese (ob) gene, was quickly seen as a predictor of body fat content in animals approaching slaughter and an aid to assessing reproductive readiness in females. Its participation in inflammation and immune responses that help animals survive infection and trauma has clear additional relevance to meat and milk production. Furthermore, almost a decade of discoveries of nucleotide polymorphisms in the leptin and leptin receptor genes has suggested useful applications relating to feed intake regulation, the efficiency of feed use, the composition of growth, the timing of puberty, mammogenesis and mammary gland function and fertility in cattle, pigs and poultry. The current review attempts to summarise where research has taken us in each of these aspects and speculates on where future research might lead.     

Joint analysis of demography and selection in population genetics: where do we stand and where could we go?

Teasing apart the effects of selection and demography on genetic polymorphism remains one of the major challenges in the analysis of population genomic data. The traditional approach has been to assume that demography would leave a genome-wide signature, whereas the effect of selection would be local. In the light of recent genomic surveys of sequence polymorphism, several authors have argued that this approach is questionable based on the evidence of the pervasive role of positive selection and that new approaches are needed. In the first part of this review, we give a few empirical and theoretical examples illustrating the difficulty in teasing apart the effects of selection and demography on genomic polymorphism patterns. In the second part, we review recent efforts to detect recent positive selection. Most available methods still rely on an a priori classification of sites in the genome but there are many promising new approaches. These new methods make use of the latest developments in statistics, explore aspects of the data that had been neglected hitherto or take advantage of the emerging population genomic data. A current and promising approach is based on first estimating demographic and genetic parameters, using, e.g., a likelihood or approximate Bayesian computation framework, focusing on extreme outlier regions, and then using an independent method to confirm these. Finally, especially for species where evidence of natural selection has been limited, more experimental and versatile approaches that contrast populations under varied environmental constraints might be more successful compared with species-wide genome scans in search of specific signatures.     

Moderate ischemic mitral regurgitation (IMR) and metabolic syndrome: where are we now and where are we going?

Background

The metabolic syndrome appears to affect 10% to 25% of adult population worldwide. Several studies have described the association between metabolic syndrome and ischaemic heart disease, however, none linked metabolic syndrome to ischemic mitral regurgitation, a serious clinical problem facing both the cardiologists and cardiac surgeons. Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. The myocardial ischemia can result in altered ventricular geometry, leading to mitral insufficiency. Interestingly metabolic syndrome showed more pronounced alteration of left ventricular geometry and function especially in obese subjects.

Presentation of the hypothesis

We have recently proposed that there is link between metabolic syndrome and ischemic mitral regurgitation and associated complications. Operative strategy for moderate ischaemic mitral regurgitation continues to be debated between revascularisation alone and concomitant valve repair at the time of coronary artery bypass surgery. Each of the above group has published studies, with results supporting each argument.

Testing the hypothesis

Generally speaking the treatments available for metabolic syndrome are based in both life style modification (dietary advice and advice to increase physical activity) and medical treatment to enhance insulin sensitivity. Randomised controlled trials may show whether the current available treatment of metabolic syndrome may have an impact on moderate ischemic mitral regurgitation.

Implications of the hypothesis

Metabolic syndrome was shown to alter left ventricular geometry and therefore it is possible to postulate that the variation in the response of different patients with moderate ischemic mitral regurgitation to current management may be attributed to the absence and presence of metabolic syndrome. Research testing of this hypothesis in the future may reveal whether concomitant treatment of metabolic syndrome will play part in the management of moderate ischemic mitral regurgitation.     

Why and how do we model circadian rhythms?

In our attempts to understand the circadian system, we unavoidably rely on abstractions. Instead of describing the behavior of the circadian system in all its complexity, we try to derive basic features from which we form a global concept on how the system works. Such a basic concept is a model of reality. The author discusses why it is advantageous or even necessary to transform conceptual models into mathematical formulations. As examples to demonstrate those advantages, the author reviews 4 types of mathematical models: negative feedback models thought to operate within pacemaker cells, models on coupling between pacemaker cells to generate pacemaker output, oscillator models describing the behavior of the composite circadian pacemaker, and models describing how the circadian pacemaker influences behavior.     

Examining the developing bone: What do we measure and how do we do it?

The clinical tools available to evaluate bone development in children are often ambiguous, and difficult to interpret. Unfortunately bone densitometry methods (i.e., dual energy X-ray absorptiometry, DXA) which have a relatively straightforward application in adult osteoporosis, are far more difficult to evaluate in the growing skeleton. Even with adequate "adjustment" for bone size or maturity, bone "density" (areal or volumetric) alone often gives an inaccurate assessment of bone strength--especially in children. Ideally, we would like to measure both material and geometric properties of bone to accurately estimate "strength". Mechanically meaningful measures of bone geometry (bone cross-sectional area, cortical thickness) and estimates of bending strength (section modulus, or SSI) are available with non-invasive techniques such as (p)QCT and some DXA software. With new technology it might be possible to also measure bone material properties, which will be especially important in some pediatric disorders. In children, we also need to know something about the loads imposed on a child's bone and consider not only absolute bone strength, but also the strength of bone relative to the physiologic loads. Interpreting bone strength in light of the loads imposed (particularly muscle force) is critical for an accurate diagnosis of the developing bone.     

Antibiotic use in animal agriculture: what have we learned and where are we going?

Antibiotics are enormously important for the humane and efficient production of food animals. These benefits are somewhat offset by the human and animal health antibiotic resistance risks posed by their use in animals. This article provides an overview of what we have learned about antibiotic resistance as an issue in animal agriculture and where that knowledge could lead us in the future. To preserve the effectiveness of antibiotics, more action is needed to ensure their prudent use, particularly in the case of antibiotic growth promoters and antibiotics deemed critically important for human and animal health.     

Pim kinases in hematological malignancies: where are we now and where are we going?

The proviral insertion in murine (PIM) lymphoma proteins are a serine/threonine kinase family composed of three isoformes: Pim-1, Pim-2 and Pim-3. They play a critical role in the control of cell proliferation, survival, homing and migration. Recently, overexpression of Pim kinases has been reported in human tumors, mainly in hematologic malignancies. In vitro and in vivo studies have confirmed their oncogenic potential. Indeed, PIM kinases have shown to be involved in tumorgenesis, to enhance tumor growth and to induce chemo-resistance, which is why they have become an attractive therapeutic target for cancer therapy. Novel molecules inhibiting Pim kinases have been evaluated in preclinical studies, demonstrating to be effective and with a favorable toxicity profile. Given the promising results, some of these compounds are currently under investigation in clinical trials. Herein, we provide an overview of the biological activity of PIM-kinases, their role in hematologic malignancies and future therapeutic opportunities.     

Hippocampus and memory. Can we have our place and fear it too?

Theories of hippocampal function are often split into cognitive map theories and relational/episodic memory theories. In this issue of Neuron, show that hippocampal cells respond to the combination of spatial location and conditioned stimuli in a nonspatial fear conditioning task, suggesting a potential bridge between the competing theories of hippocampal function.     

Oxidative stress and cancer: have we moved forward?

'Reactive species' (RS) of various types are formed in vivo and many are powerful oxidizing agents, capable of damaging DNA and other biomolecules. Increased formation of RS can promote the development of malignancy, and the 'normal' rates of RS generation may account for the increased risk of cancer development in the aged. Indeed, knockout of various antioxidant defence enzymes raises oxidative damage levels and promotes age-related cancer development in animals. In explaining this, most attention has been paid to direct oxidative damage to DNA by certain RS, such as hydroxyl radical (OH*). However, increased levels of DNA base oxidation products such as 8OHdg (8-hydroxy-2'-deoxyguanosine) do not always lead to malignancy, although malignant tumours often show increased levels of DNA base oxidation. Hence additional actions of RS must be important, possibly their effects on p53, cell proliferation, invasiveness and metastasis. Chronic inflammation predisposes to malignancy, but the role of RS in this is likely to be complex because RS can sometimes act as anti-inflammatory agents.