February Issue Research Articles

Central catheter-related infections

I read with major interest the In Our Unit article in the February issue of Critical Care Nurse, “Central Catheter Infections: Use of a Multidisciplinary Team to Find Simple Solutions,” by Marian Racco and Kathleen Horn. As recently stated by the Centers for Disease Control, infections related to central catheters are among the most preventable nosocomial infections.1 Measures to control the rising incidence of this dreaded complication are frequently associated with significant hospital costs. However, as successfully demonstrated by Racco and Horn, low-tech and low-cost interventions such as educating and reinforcing intensive care unit staff to comply with current guidelines can significantly reduce hospital expenditures (approximate cost of $40000 per infection or $240000 per year), and more importantly save lives.In Belgium, in an effort to keep medical care payable, cost matters in medicine are becoming a key issue for the federal government, insurance institutions, hospitals, and patients. Consequently, in our unit similar initiatives as those performed by Racco and Horn are being organized. I would like to congratulate the authors on their remarkable efforts to reduce the number of central catheter infections in their unit. However, regarding the economic consequences of such a quality improvement process, I wonder if they could further elaborate on which parameters they included in their cost analysis aiming to estimate the real economic impact of their intervention.In 2005, before our team’s interventions, we incurred 6 central catheter-related infections. Using the cost estimation of $40000 per infection from the Centers for Disease Control, in 2005 our central catheter infections cost our hospital approximately $240000. In 2006, after our interventions were implemented, we had only 1 catheter-related infection. By reducing the number of central catheter infections by 5, our hospital saved approximately $200000.

Minority Microbiologists and ASM

Congratulations on Marion Johnson-Thompson's excellent article “Contribution of African-American Scientists to ASM” in the February issue of Microbe (p. 82). The emergence of minority microbiologists, from Wilton Taylor and Gerald Stokes to Clifford Houston, the first African-American President of ASM, occurred only during the last 30% of the history of SAB/ASM. As Marion Johnson-Thompson so rightly points out, “Times have changed and environments are more supportive of the presence of blacks in the discipline of microbiology and in ASM.”

Does resveratrol activate yeast Sir2 in vivo?

In the February issue of Aging Cell, Yang et al. (2007) describe resveratrol derivatives with improved stability and report that they increase yeast replicative lifespan. The authors refer to these drugs as ‘sirtuin activating compounds’, implying that lifespan is increased due to activation of the Sir2 histone deacetylase. We applaud the development of more stable and potent resveratrol analogs. We wish to point out, however, that whether resveratrol and related compounds activate Sir2 in vivo remains unknown and further experimental validation is necessary. The Yang et al. (2007) study as well as a prior report (Howitz et al., 2003) are complicated by the use of the PSY316AT yeast strain background. Among the strains commonly used in yeast aging research, PSY316AT is the only known case where overexpression of Sir2 fails to increase lifespan (Kaeberlein et al., 2004, 2005b). While it is possible that a sirtuin agonist could increase Sir2 activity in a manner not achieved by overexpression of the enzyme, it also needs to be considered that resveratrol (and its analogs) could affect longevity in a Sir2-independent manner. Resveratrol is known to interact with a variety of proteins that have yeast homologs, such adenosine monophosphate (AMP) kinase, protein kinase C and mitochondrial adenosine triphosphate (ATP) synthase, among others (Kaeberlein & Rabinovitch, 2006). Any of these proteins could potentially mediate effects of resveratrol on yeast cells or in other organisms. Another complicating factor is the use of replicative lifespan as the sole measure of drug activity. While longevity is of clear interest, increased lifespan does not imply increased Sir2 activity, as several single-gene mutations are known to increase lifespan in a Sir2-independent manner (Kaeberlein et al., 2004, 2005c). Sir2 activity can be measured more directly, for example, by monitoring transcription of marker genes at telomeres, silent mating loci and rDNA (Smith & Boeke, 1997; Roy & Runge, 2000; Sandmeier et al., 2002; Kaeberlein et al., 2005a). In fact, the PSY316AT strain used by Yang et al. was engineered for such a purpose and contains a subtelomerically integrated ADE2 marker. Activation of Sir2 by overexpression of the enzyme results in decreased ADE2 transcription, which in turn causes accumulation of a red pigment in this strain (Kaeberlein et al., 2005b). Visual inspection of the colonies in the lifespan assays would reveal this pigmentation and it would have been of interest for Yang et al. to comment whether the resveratrol derivatives increased Sir2 activity by this assay. It would also be of great interest to assess the effect of resveratrol and related compounds on Sir2-dependent silencing and histone acetylation at each of the loci Sir2 is known to silence. If locus-specific effects are observed, they could be compared between drug treatments and Sir2 overexpression, which would provide additional evidence of whether Sir2 enzymatic activity is enhanced in vivo by these compounds. The utility of these experiments extends beyond simple verification of these compounds as Sir2 agonists. In a prior study (Howitz et al., 2003), it was suggested that resveratrol activated Sir2 in a selective fashion, decreasing rDNA recombination without increasing rDNA silencing. Increased expression of Sir2, in contrast, enhances rDNA silencing (Fritze et al., 1997; Gallo et al., 2004). Thus, the reported locus-specific activity of resveratrol remains unexplained, but is of great interest when considering potential therapeutic applications in humans. In vitro assays have, however, also produced ambiguous results: while resveratrol activates Sir2 to deacetylate a fluorescent peptide substrate, it does not activate either Sir2 or the human ortholog SIRT1 towards more native peptide substrates (Borra et al., 2005; Kaeberlein et al., 2005b). We greet the development of more stable resveratrol analogs with optimism. Thus far, attempts to replicate the reported effects of resveratrol on yeast replicative lifespan (Howitz et al., 2003) or rDNA recombination have been unsuccessful (Kaeberlein et al., 2005b). One possible explanation is that resveratrol may be unstable over the time course required to carry out these assays. Fortunately, if resveratrol and related compounds do activate Sir2 in vivo, this activation should be easily detected and independently verified using the more stable derivatives, and most importantly, more specific assays for Sir2 activity. It is our hope that a more thorough examination of the in vivo effects of resveratrol and related compounds in yeast will resolve these interesting questions.

Does the Sun affect the Earth's climate?

From Eric Priest, Mike Lockwood, Sami Solanki and Arnold Wolfendale Svensmark’s article in the February issue (AG according to Svensmark’s ideas, this produces fewer clouds and thereby heats the Earth. This raises two key questions: firstly, is this mechanism viable and, secondly, can George Bush gain comfort from it in terms of the origins of present-day climate change? It is now well established that, at least before 1970, there was indeed a correlation between the Earth’s climate and solar activity. This can be seen in the papers by e.g. Solanki and Krivova (2003), for the last 150 years and Bond et al. (2001) over longer timescales. For instance, in the 17th century (dubbed the “little ice age”) the temperature of northern Europe was lower than normal and the river Thames froze over, and this was also a time of very low solar activity (called the “Maunder minimum”) when there appear to have been very few sunspots at all for 70 years. Also, the concentration of CO2 has been measured for the past 650 000 years from ice cores: it decreases during each ice age and goes up in between, to a maximum value that is generally 280 parts per million. Although these correlations do exist, there is as yet no generally agreed mechanism to explain them. The white-light solar emission does vary, but by only 0.1% over a solar cycle, and the century-scale drift appears to be also of this magnitude, which is too small to explain the variation in the Earth’s temperature. One suggestion (not yet proved) is that the UV or EUV emission of the Sun, which varies much more than the white-light emission and which is absorbed high in the atmosphere, could somehow be influencing the lowatmosphere climate and amplifying the solar effect. Another plausible suggestion is the one offered by Svensmark: but it is also not yet proved, since it is at present not clear that the cosmic ray-induced aerosols are in practice strong enough to affect climate. A puzzling feature of the suggestion is that there is no correlation of cosmic-ray flux with high-level clouds – which is where the ionization is highest – and yet an apparent correlation at low levels (below 3.2 km) where the ionization is low. Another difficulty concerns the averaging that is needed, since both cosmic rays and cloud cover vary with latitude in different ways. So, even if it works, does Svensmark’s mechanism give any support to George Bush’s attitude that the current global warming is not caused by human activity? Not at all! The observed correlations between the Sun’s behaviour and the Earth’s climate have completely failed since the 1970s. In the past 30 or 40 years the Earth’s temperature has gone up much more rapidly than you would expect from the Sun – indeed there is strong evidence that since 1985 all the changes in the Sun have been in the opposite direction to that required to warm the Earth. Also, the amount of CO2 in the atmosphere is now 380 parts per million – very much larger than it has been for the past 650 000 years. This was highlighted at a recent meeting in the Royal Society on the science of climate change following on from the IPCC’s (Intergovernmental Panel on Climate Change) report reviewing the latest scientific data on global warming. The mechanism proposed by Svensmark and any influences that the Sun has had on our past climate are valid and interesting fields of study that may well give us valuable new understanding of our climate system. But, in our view, there is no doubt at all that the ongoing global warming is not being caused by the Sun but mainly by the greenhouse gases such as CO2 that we are emitting. We all, therefore, have a part to play in reducing the greenhouse effect in future – we must not fail to respond to the rapid and unprecedented changes that are taking place today because of debate over the much slower changes that occurred in the past. Eric Priest, University of St Andrews; and Mike Lockwood, Sami Solanki and Arnold Wolfendale References Bond et al. 2001 Science 294 2130. Solanki and Krivova 2003 J. Geophys. Res. 108 7.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

The advent of the cytokine storm

The term 'cytokine storm' is now used in popular culture as an explanation for the distinctly unpleasant feeling we all sense at the onset of flu. The expression certainly has common currency, with 21 000 Google hits 12 months ago and 55 000 at the time of writing this article. The two-part Special Feature in the January and February issues of Immunology and Cell Biology acknowledges that the sense of this term, with the added complexity of knowing that the mediators involved are also necessary, at lower concentrations, for innate immunity to function, has finally come of age. While the articles on HIV, hepatitis, flaviviruses, tuberculosis, toxoplasmosis, shigellosis, schistosomiasis and visceral leishmaniasis essentially concern local pathological events from these cytokines, those on poxviruses, dengue, influenza and malaria describe variants of the consequences of a systemic response. Salmonella, because of its range of serovars, has a foot in each camp. The interesting omission is sepsis. Research into this condition has never managed to gain a foothold in some countries, despite it being the major cause of death in intensive care units in all first world countries and a part of the cytokine storm literature since 1981.

Letters

In the February issue Steenvoorde et al. reported the findings of a pilot study on the use of Dermacyn (Occulus Innovative Systems) on the infected foot ulcers of 10 patients. Four patients discontinued the treatment due to pain during immersion and Staphylococcus aureus was eliminated in only one of the six patients tested.

The New BMW four and six-cylinder spark-ignition engines with stratified combustion

Following the introduction of the six-cylinder twin-turbo engine with homogeneous combustion — presented in the February issue of MTZ —, with the new six-cylinder and four-cylinder naturally aspirated engines with stratified combustion, BMW now presents two further engines featuring a 2nd generation direct injection system (high-precision injection). The spray-guided combustion process opens up new dimensions for achieving significant benefits in fuel consumption both in the European driving cycle as well as in real customer-related operation. BMW is therefore pursuing a consistent strategy aimed at realising “efficient dynamics”.

Clinical Implications of the DREAM Study

The following points should be taken into consideration when determining “what circumstances TZDs [thiazolidinediones] should be used in people without documented diabetes,” as questioned by the commentary published in the February issue of Diabetes Care (1). The DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication) study (2) has limitations that prevent generalizations for individuals with impaired fasting …

Observing the sick child: Part 2c Respiratory auscultation

Nursing continues to extend its practice base as the acuity of children in general wards often with complex illnesses and treatment increases. There is a need for ongoing development of the physical assessment skills of nurses who care for children and young people in order to facilitate early recognition of clinical problems. Respiratory dysfunction is the common precursor to adverse events. The skill of auscultation adds another dimension that augments the respiratory assessment repertoire of the nurse. This article builds on the palpation skills presented in February issue and provides a practical step-by-step introduction to auscultation.

High-precision injection in combination with the new BMW twin-turbo petrol engine

The design highlights of the new engine that went into series production in mid-2006 with the 335i Coupe have already been described in the February issue of the MTZ. Continuing with this report, this article deals with the functional aspects of piezo-fuel injection technology used for the first time by BMW in connection with turbocharging which BMW is again reintroducing in petrol engine construction after an absence of more than 20 years.

A Dose of Dust That Quieted an Entire Hurricane Season?

In the 27 February issue of Eos, two climatologists suggest that dust blown across the Atlantic from the Sahara caused the 2006 hurricane season to be far less active than had been forecasted. (Read more.)

The U.S. Financial Sanctions against North Korea

In September 2005, the U.S. imposed financial restrictions on North Korea after blaming the North for illicit financial activities, including counterfeiting and money‐laundering. The U.S. financial sanctions against the North had direct and immediate impact on the ongoing six‐party negotiations on North Korea's nuclear issue. North Korea insisted on the lifting of U.S. financial sanctions as the precondition for returning to the negotiating table and consequently the six‐party talks on North Korea's nuclear issue stalled. The third session of the fifth round of six‐party talks in February 2007 produced an important accord on North Korea's nuclear question. This agreement was made possible after the U.S. and the DPRK reached a compromise on the financial sanctions issue. This article discusses the U.S. financial sanctions against North Korea and their implications for North Korea's nuclear question. It begins with an overview of the U.S. financial restrictions. This study then examines the nexus between the financial sanctions and the impasse at the six‐party talks on North Korea's nuclear issue. This is followed by a discussion of the breakthrough on the financial restrictions issue and the landmark agreement on North Korea's nuclear issue in February 2007. In this study, the authors argue that a mutually satisfactory resolution of the BDA dispute holds the key to a peaceful settlement of the second North Korean nuclear crisis. With the BDA dispute behind, the six‐party talks should gain momentum and prepare a road map for implementing the denuclearization of the Korean peninsula. Both the U.S. and North Korea should not miss this golden opportunity and make earnest efforts to build a firm foundation for peace and stability on the Korean peninsula and in Northeast Asia.

Letters

I have just read your article in the Practical Professional Child Care February issue, about My Job childminder – Jai Patel.

TLR signalling and phagosome maturation: an alternative viewpoint

TLR signalling and phagosome maturation: an alternative viewpoint

Toward a Mouse Model of Diabetic Nephropathy

Two articles in the October and February issues of JASN reported that diabetic mice that lack the eNOS gene develop accelerated kidney disease with features that resemble human diabetic nephropathy (DN). These articles are significant given the lack of good mouse models to study this important

Selected Abstracts from the February issue of the Journal of Vascular Surgery

Selected Abstracts from the February issue of the Journal of Vascular Surgery

Money for Nothing and Checks for Free: Recent Developments in U.S. Subprime Mortgage Markets

After a number of warning signs, the U.S. mortgage crisis became a headline issue in February 2007. Notwithstanding the bankruptcy of numerous mortgage companies, historically high delinquencies and foreclosures, and a significant tightening in subprime lending standards, the impact thus far on core U.S. financial institutions has been limited. This paper reviews the history and structure of the subprime market. The results suggest that new origination and funding technology appear to have made the financial system more stable at the expense of undermining the effectiveness of consumer protection regulation. Potential solutions to the management of this trade-off are then explored.

Money for Nothing and Checks for Free: Recent Developments in U.S. Subprime Mortgage Markets

After a number of warning signs, the U.S. mortgage crisis became a headline issue in February 2007. Notwithstanding the bankruptcy of numerous mortgage companies, historically high delinquencies and foreclosures, and a significant tightening in subprime lending standards, the impact thus far on core U.S. financial institutions has been limited. This paper reviews the history and structure of the subprime market. The results suggest that new origination and funding technology appear to have made the financial system more stable at the expense of undermining the effectiveness of consumer protection regulation. Potential solutions to the management of this trade-off are then explored.

Exciting Advances forJOSPTin Print, Online, and Internationally

This new year brings significant enhancements to the Journal of Orthopaedic & Sports Physical Therapy that are intended to increase JOSPT's usefulness to you as readers and authors, clinicians and researchers. With this print issue and beginning in February 2007 on the Journal's website, we offer you improved design and functionality that build on the JOSPT's 28-year tradition of publishing the best available research and clinical literature in the field. J Orthop Sports Phys Ther 2007:37(1):1–2. doi:10.2519/jospt.2007.0100