How to be naive

The transcription factor KLF2 directs expression of receptors involved in trafficking of naive T cells. In this issue of Immunity, Weinreich et al. (2009) demonstrate that KLF2 additionally represses IL-4 production, which otherwise induces CXCR3 expression.

Septic shock resuscitation: what goals and how to achieve them?

The need to achieve adequate tissue oxygen delivery early in patients with septic shock is well established. However, it is less well recognized that tissue hypoperfusion can exist despite normalization of systemic hemodynamics. Efforts to resuscitate septic patients until adequate tissue perfusion has been achieved can potentially improve outcome. In a multicenter study, 130 patients with septic shock were resuscitated within 12 hours of diagnosis using a protocol including goals for mean arterial and pulmonary artery occluded pressures, urinary output, arterial pH, and hemoglobin goals. They were then randomly assigned to further resuscitation with either a cardiac index (>or= 3 l/minute per m2) or a gastric mucosal pH (>or= 7.32) target. The intensive care unit length of stay and 28-day mortality did not differ between groups, but more patients in the cardiac index group were in the target range, both at baseline and after resuscitation, as compared with the gastric mucosal pH group. In contrast to cardiac index, gastric mucosal pH at baseline and at 24 and 48 hours predicted mortality. Whether other targets for the chosen variables, or different and--in particular--earlier resuscitation efforts would have favored one group cannot be concluded from the data provided.

Subclinical hypothyroidism and cardiovascular risk: how to end the controversy

The indications for screening and TSH threshold levels for treatment of subclinical hypothyroidism have remained a clinical controversy for over 20 years. Subclinical thyroid dysfunction is a common finding in the growing population of older adults, occurring in 10–15% among those age 65 and older, and may contribute to multiple common problems of older age, including cardiovascular disease, muscular impairment, mood problems, and cognitive dysfunction (1). In 2004, both the U.S. Preventive Services Task Force (2) and a clinical consensus group of experts (3) concluded that the existing evidence about the association between subclinical hypothyroidism and cardiovascular risks, primarily cross-sectional or case-control studies (4), was insufficient. For example, a frequently cited analysis from the Rotterdam study found a cross-sectional association between subclinical hypothyroidism and atherosclerosis, as measured by abdominal aortic calcification (odds ratio, 1.7; 95% confidence interval [CI], 1.1–2.6) and prevalent myocardial infarction (MI) (odds ratio, 2.3; 95% CI, 1.3–4.0) (5). Conversely, the prospective part of this study included only 16 incident MIs; the hazard ratio (HR) for subclinical hypothyroidism was 2.50, with broad 95% CIs (0.70–9.10). Potential mechanisms for the associations with cardiovascular diseases among adults with subclinical hypothyroidism include elevated cholesterol levels, inflammatory markers, raised homocysteine, increased oxidative stress, insulin resistance, increased systemic vascular resistance, arterial stiffness, altered endothelial function, and activation of thrombosis and hypercoagulability that have all been reported to be associated with subclinical hypothyroidism (1, 6).

Secondary arterial hypertension: when, who, and how to screen?

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs.

Using virtual reality to teach special populations how to cope in crisis: the case of a virtual earthquake

The unique characteristics of special populations such as pre-school children and Down syndrome kids in crisis and their distorted self-image were never studied before, because of the difficulty of crisis reproduction. This study proposes a VR setting that tries to model some special population's behaviour in the time of crises and offers them a training scenario. The sample population consisted of 30 pre-school children and 20 children with Down syndrome. The VR setting involved a high-speed PC, a VPL EyePhone 1, a MR toolkit, a vibrations plate, a motion capture system and other sensors. The system measured and modelled the typical behaviour of these special populations in a Virtual Earthquake scenario with sight and sound and calculated a VR anthropomorphic model that reproduced their behaviour and emotional state. Afterwards one group received an emotionally enhanced VR self-image as feedback for their training, one group received a plain VR self-image and another group received verbal instructions. The findings strongly suggest that the training was a lot more biased by the emotionally enhanced VR self-image than the other approaches. These findings could highlight the special role of the self-image to therapy and training and the interesting role of imagination to emotions, motives and learning. Further studies could be done with various scenarios in order to measure the best-biased behaviour and establish the most natural and affective VR model. This presentation is going to highlight the main findings and some theories behind them.