It is well established that microglial form and function are inextricably linked. In recent years, the traditional view that microglial form ranges between "ramified resting" and "activated amoeboid" has been emphasized through advancing imaging techniques that point to microglial form being highly dynamic even within the currently accepted morphological categories. Moreover, microglia adopt meaningful intermediate forms between categories, with considerable crossover in function and varying morphologies as they cycle, migrate, wave, phagocytose, and extend and retract fine and gross processes. From a quantitative perspective, it is problematic to measure such variability using traditional methods, but one way of quantitating such detail is through fractal analysis. The techniques of fractal analysis have been used for quantitating microglial morphology, to categorize gross differences but also to differentiate subtle differences (e.g., amongst ramified cells). Multifractal analysis in particular is one technique of fractal analysis that may be useful for identifying intermediate forms. Here we review current trends and methods of fractal analysis, focusing on box counting analysis, including lacunarity and multifractal analysis, as applied to microglial morphology.

There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction. To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal). A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use. HRV was calculated from electrocardiography under a standardized short-term resting state condition. HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size. Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.

The natural complexity of the brain, its hierarchical structure, and the sophisticated topological architecture of the neurons organized in micronetworks and macronetworks are all factors contributing to the limits of the application of Euclidean geometry and linear dynamics to the neurosciences. The introduction of fractal geometry for the quantitative analysis and description of the geometric complexity of natural systems has been a major paradigm shift in the last decades. Nowadays, modern neurosciences admit the prevalence of fractal properties such as self-similarity in the brain at various levels of observation, from the microscale to the macroscale, in molecular, anatomic, functional, and pathological perspectives. Fractal geometry is a mathematical model that offers a universal language for the quantitative description of neurons and glial cells as well as the brain as a whole, with its complex three-dimensional structure, in all its physiopathological spectrums. For a holistic view of fractal geometry of the brain, we review here the basic concepts of fractal analysis and its main applications to the basic neurosciences.

This paper concerns the validation of automatic retinal image analysis (ARIA) algorithms. For reasons of space and consistency, we concentrate on the validation of algorithms processing color fundus camera images, currently the largest section of the ARIA literature. We sketch the context (imaging instruments and target tasks) of ARIA validation, summarizing the main image analysis and validation techniques. We then present a list of recommendations focusing on the creation of large repositories of test data created by international consortia, easily accessible via moderated Web sites, including multicenter annotations by multiple experts, specific to clinical tasks, and capable of running submitted software automatically on the data stored, with clear and widely agreed-on performance criteria, to provide a fair comparison.

Objective: This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls.Design and methods: Participants attended the School of Community Health, Diabetes Screening Clinic, Charles Sturt University, Australia, between February 2006 and June 2008. A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds.Results: Serum 8-hydroxy 2′-deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3±140 pg/ml) compared with controls (210.1±166 pg/ml; P<0.01). The diabetic group (1979.6±1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5±103 pg/ml; P<0.001) and overweight subjects (724±102 pg/ml; P=0.005) compared with the lean subjects (196.5±327 pg/ml).Conclusion: Our results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage.