Metals in the environment as risk factors for infectious diseases: gaps and opportunities

Many parts of the world in which common infectious diseases are endemic also have the highest prevalence of trace metal deficiencies or rising rates of trace metal pollution. Infectious diseases can increase human susceptibility to adverse effects of metal exposure (at suboptimal or toxic levels), and metal excess or deficiency can increase the incidence or severity of infectious diseases. The co-clustering of major infectious diseases with trace metal deficiency or toxicity has created a complex web of interactions with serious but poorly understood health repercussions, yet has been largely overlooked in animal and human studies. This book focuses on the distribution, trafficking, fate, and effects of trace metals in biological systems. Its goal is to enhance our understanding of the relationships between homeostatic mechanisms of trace metals and the pathogenesis of infectious diseases. Drawing on expertise from a range of fields, the book offers a comprehensive review of current knowledge on vertebrate metal-withholding mechanisms and the strategies employed by different microbes to avoid starvation (or poisoning). Chapters summarize current, state-of-the-art techniques for investigating pathogen-metal interactions and highlight open question to guide future research. The book makes clear that improving knowledge in this area will be instrumental to the development of novel therapeutic measures against infectious diseases. ContributorsM. Leigh Ackland, Vahid Fa Andisi, Angele L. Arrieta, Michael A. Bachman, J. Sabine Becker, Robert E. Black, Julia Bornhorst, Sascha Brunke, Joseph A. Caruso, Jennifer S. Cavet, Anson C. K. Chan, Christopher H. Contag, Heran Darwin, George V. Dedoussis, Rodney R. Dietert, Victor J. DiRita, Carol A. Fierke, Tamara Garcia-Barrera, David P. Giedroc, Peter-Leon Hagedoorn, James A. Imlay, Marek J. Kobylarz, Joseph Lemire, Wenwen Liu, Slade A. Loutet, Wolfgang Maret, Andreas Matusch, Trevor F. Moraes, Michael E. P. Murphy, Maribel Navarro, Jerome O. Nriagu, Ana-Maria Oros-Peusquens, Elisabeth G. Pacyna, Jozef M. Pacyna, Robert D. Perry, John M. Pettifor, Stephanie Pfaffen, Dieter Rehder, Lothar Rink, Anthony B. Schryvers, Ellen K. Silbergeld, Eric P. Skaar, Miguel C. P. Soares, Kyrre Sundseth, Dennis J. Thiele, Richard B. Thompson, Meghan M. Verstraete, Gonzalo Visbal, Fudi Wang, Mian Wang, Thomas J. Webster, Jeffrey N. Weiser, Günter Weiss, Inga Wessels, Bin Ye, Judith T. Zelikoff, Lihong Zhang

Process evaluation design and tools used in a kindergarten-based, family-involved intervention to prevent obesity in early childhood. The ToyBox-study

Process evaluation (PE) is used for the in-depth evaluation of the implementation process of health promotion programmes. The aim of the current paper was to present the PE design and tools used in the ToyBox-intervention. The PE design was based on a three-step approach, including the identification of ToyBox-specific PE elements (step 1), the development of PE tools and harmonization of procedures (step 2), and the implementation of PE using standardized protocol and tools across the intervention countries (step 3). Specifically, to evaluate the implementation of the intervention, teachers' monthly logbooks were recorded (dose delivered, fidelity, dose received); post-intervention questionnaires were completed by parents/caregivers and teachers (dose received); participation and attrition rates were recorded (recruitment, reach); and audit questionnaires and retrospective information on weather conditions were collected (physical and social environment within which the intervention was implemented). Regarding the teachers' training sessions, the researchers who performed the trainings completed evaluation forms and documented teachers' attendance after each training (dose delivered, fidelity, dose received) and teachers completed evaluation forms after each training (dose received). The PE performed in the ToyBox-intervention may contribute in the evaluation of its effectiveness, guide the revision of the intervention material and provide insights for future health promotion programmes and public health policy.

Automotive can network response time analysis with variable jitter

Many methods to calculate message latencies for Controller Area Network (CAN) have previously been presented based upon the static worst-case behaviour of the system. With the use of modern simulation tools however, the behaviour of CAN networks can be simulated dynamically in order to find the likely worst-case response times for CAN messages. This paper shows the development of an automotive body control network model to be used as the basis for further simulations. A method to simulate the Worst-Case Response Time of this model is then presented, taking into account random queuing jitter.

Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer

We and others have shown that the copper transporters ATP7A and ATP7B play a role in cellular resistance to cisdiaminedichloroplatinum (II) (CDDP).  In this study, we found that ATP7A transfection of Chinese hamster ovary  cells (CHOK1) and fibroblasts isolated from Menkes disease patients  enhanced resistance not only to CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7-ethyl-10- hydroxy-camptothecin (SN-38),  etoposide, doxorubicin, mitoxantron, and 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A preferentially localized
doxorubicin fluorescence to the Golgi apparatus in contrast to the more intense nuclear staining of doxorubicin in the parental cells. Brefeldin A   partially and monensin completely altered the distribution of doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the uptake of SN-38 in membrane vesicles. These findings strongly suggested that   ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi network has an important role of ATP7A-related drug resistance. ATP7A was expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the adjacent normal epithelium. Using the histoculture drug response assay that is useful for the prediction of drug sensitivity of clinical cancers, ATP7A-expressing colon cancer cells were significantly more  resistant to SN-38 than ATP7Anegative cells. Thus, ATP7A confers  resistance to various anticancer agents on cancer cells and might be a good index of drug resistance in clinical colon cancers.

ß- adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling

Hormone-sensitive lipase (HSL), an important regulatory enzyme for triacylglycerol hydrolysis within skeletal muscle, is controlled by β-adrenergic signaling as well as intrinsic factors related to contraction and energy turnover. In the current study, we tested the capacity of 5′AMP-activated protein kinase (AMPK) to suppress β-adrenergic stimulation of HSL activity. Eight male subjects completed 60 min of cycle exercise at 70% VO2 peak on two occasions: either with normal (CON) or low (LG) pre-exercise muscle glycogen content, which is known to enhance exercise-induced AMPK activity. Muscle samples were obtained before and immediately after exercise. Pre-exercise glycogen averaged 375 ± 35 and 163 ± 27 mmol·kg–1 dm for CON and LG, respectively. AMPK α-2 was not different between trials at rest and was increased (3.7-fold, P<0.05) by exercise during LG only. HSL activity did not differ between trials at rest and increased (0 min: 1.67 ± 0.13; 60 min: 2.60 ± 0.26 mmol·min–1·kg–1 dm) in CON. The exercise-induced increase in HSL activity was attenuated by AMPK α-2 activation in LG. The attenuated HSL activity during LG occurred despite higher plasma epinephrine levels (60 min: CON, 1.96 ± 0.29 vs LG, 4.25 ± 0.60 nM, P<0.05) compared with CON. Despite the attenuated HSL activity in LG, IMTG was decreased by exercise (0 min: 27.1 ± 2.0; 60 min: 22.5 ± 2.0 mmol.kg–1 dm, P<0.05), whereas no net reduction occurred in CON. To confirm the apparent effect of AMPK on HSL activity, we performed experiments in muscle cell culture. The epineprine-induced increase in HSL activity was totally attenuated (P<0.05) by AICAR administration in L6 myotubes. These data provide new evidence indicating that AMPK is a major regulator of skeletal muscle HSL activity that can override β-adrenergic stimulation. However, the increased IMTG degradation in LG suggests factors other than HSL activity are important for IMTG degradation.

Synthesis and reactivity of para-substituted benzoylmethyltellurium(II and IV) compounds: observation of intermolecular C-H-O hydrogen bonding in the crystal structure of (p-MeOC6H4COCH2)2TeBr2

Bis(p</i>-substituted benzoylmethyl)tellurium dibromides, (p</i>-YC₆H₄COCH₂)₂TeBr₂, (y=H (1a), Me (1b), MeO (1c)) can be prepared
either by direct insertion of elemental Te across CRf-Br bonds (where C_Rf refers to &alpha;-carbon of a functionalized organic moiety) or by the oxidative addition of bromine to (p</i>-YC₆H₄COCH₂)₂Te (y = H (2a), Me (2b), MeO (2c)). Bis(p</i>-substituted benzoylmethyl)tellurium dichlorides, (p</i>-YC₆H₄COCH₂)₂TeCh (y = H (3a), Me (3b), MeO (3c)), are prepared by the reaction of the bis(p</i>-substituted benzoylmethyl)tellurides 2a--c with S0₂Cl₂, whereas the corresponding diiodides (p</i>-YC₆H₄COCH₂)₂Teh (y = H
(4a), Me (4b), MeO (4c)) can be obtained by the metathetical reaction of la--c with KI, or alternatively, by the oxidative addition of
iodine to 2a--c. The reaction of 2a--c with allyl bromide affords the diorganotellurium dibrornides la--c, rather than the expected
triorganotelluronium bromides. Compounds 1-4 were characterized by elemental analyses, IR spectroscopy, p>1p>H, p>l3p>C and p>125p>Te
NMR spectroscopy (solution and solid-state) and in case of Ie also by X-ray crystallography. (p</i>-MeOC₆H₄COCH₂)₂TeBr₂ (1c) provides, a rare example, among organotellurium compounds, of a supramolecular architecture, where C-H-O hydrogen bonds appear to be the non-covalent intermolecular associative force that dominates the crystal packing.

A culturally appropriate diet and lifestyle intervention can successfully treat the components of metabolic syndrome in female Pakistani immigrants residing in Melbourne, Australia

This study was designed to test the effectiveness of a culturally appropriate diet and lifestyle intervention to treat metabolic syndrome in female Pakistani immigrants residing in Melbourne, Australia. Forty Pakistani women with metabolic syndrome (aged 20-50 years) completed a 12-week culturally appropriate diet and exercise program. Results indicate that, before intervention, participants were sedentary, taking 4000 &plusmn; 22.6 steps per day, and had an obese-classified body mass index (BMI) of 29.2 &plusmn; 0.46 kg/m2 (BMI was categorized in accordance with guidelines specifically designed for Asians) and high waist circumference of 132 &plusmn; 25.95 cm. Participants were hypertensive (systolic, 135 &plusmn; 1.3 mm Hg; diastolic, 86 &plusmn; 0.68 mm Hg), were dyslipidemic (total cholesterol, 6.8 &plusmn; 0.15 mmol/L; triglycerides, 2.9 &plusmn; 0.09 mmol/L), and had elevated blood glucose (6.4 &plusmn; 0.33 mmol/L) and fasting blood insulin (45 &plusmn; 6.3 μU/mL) levels. After the 12-week culturally appropriate intervention, activity increased (8600 &plusmn; 596.7 steps per day, P</i> < .05); and BMI (27.8 &plusmn; 0.45 kg/m2), blood pressure (systolic, 125 &plusmn; 1.4 mm Hg; diastolic, 80 &plusmn; 0.6 mm Hg), cholesterol (5.5 &plusmn; 0.1 mmol/L), blood glucose (5.9 &plusmn; 0.33 mmol/L), and blood insulin (24.14 &plusmn; 1.8 μU/mL) levels were all significantly reduced (P</i> < .05). This study revealed that the Pakistani female migrants who had metabolic syndrome and its components can successfully be treated via a culturally appropriate diet and lifestyle intervention. The success of the current program raises the possibility that other high-risk ethnic groups can also be treated with a culturally appropriate program.

Therapist-assisted, internet-based treatment for panic disorder: can general practitioners achieve comparable patient outcomes to psychologists

Background: Mental illness is an escalating concern worldwide. The management of disorders such as anxiety and depression largely falls to family doctors or general practitioners (GPs). However, GPs are often too time constrained and may lack the necessary training to adequately manage the needs of such patients. Evidence-based Internet interventions represent a potentially valuable resource to reduce the burden of care and the cost of managing mental health disorders within primary care settings and, at the same time, improve patient outcomes.
Objective: The present study sought to extend the efficacy of a therapist-assisted Internet treatment program for panic disorder, Panic Online, by determining whether comparable outcomes could be achieved and maintained when Panic Online was supported by either GPs or psychologists.
Methods: Via a natural groups design, 96 people with a primary diagnosis of panic disorder (with or without agoraphobia) completed the Panic Online program over 12 weeks with the therapeutic assistance of their GP (n = 53), who had received specialist training in cognitive behavioral therapy, or a clinical psychologist (n = 43). Participants completed a clinical diagnostic telephone interview, conducted by a psychologist, and a set of online questionnaires to assess panic-related symptoms at three time periods (pretreatment, posttreatment, and 6 month follow-up).
Results: Both treatments led to clinically significant improvements on measures of panic and panic-related symptomatology from pretreatment to posttreatment. Both groups were shown to significantly improve over time. Improvements for both groups were maintained at follow-up; however, the groups did differ significantly on two quality of life domains: physical (F₁,₈₂ = 9.13, P</i> = .00) and environmental (F₁,₈₂ = 4.41, P</i> = .04). The attrition rate was significantly higher among those being treated by their GP (χp>2p>₁ = 4.40, P</i> = .02, N = 96).
Conclusions: This study provides evidence that Internet-based interventions are an effective adjunct to existing mental health care systems. Consequently, this may facilitate and enhance the delivery of evidence-based mental health treatments to increasingly large segments of the population via primary care systems and through suitably trained health professionals.

How systematic reviews can foster evidence-based clinical decisions : part II

In the prior issue, we spoke about what a systematic review is and where a clinician can find this important evidence for decision making (Fineout-Overholt et al. 2008). In this column, we will address what is involved in conducting a systematic review, and how critically appraising a systematic review informs clinicians of the best evidence available to make decisions that impact outcomes.

Dispersion of information or market behaviour : general public trading in S & P 500 index futures

This paper considers 15 minute records of trading volume and traded prices coinciding with the reporting intervals required by the Commodity Futures Trading Commission. Records are extracted from trade records for two way trade between market makers (CTI1) and the general public (CTI4) from January 1994 to June 2004. Futures price records are matched with S&amp;P500 cash index price records. Simultaneous volatility models are specified and estimated to test trading volume to futures volatility lead/lag effects and also futures volatility to cash index volatility lead/lag effects. There is evidence that existing theoretical models of the general public trading behaviour do not explain such behaviour in these very actively traded markets. These effects can depend more on market conditions than what is suggested in theoretical models.

Can sand slugs in rivers deliver conservation benefits? The biodiversity value of tributary junction plug wetlands in the Glenelg River, Australia

Restoration works are carried out to alleviate human impacts and improve habitats within ecosystems. However, human impacts may also create new (anthropogenic) habitat for species to exploit.A dilemma arises when proposed restoration works would remove anthropogenic habitat and the assemblages it supports. Sediment input into the Glenelg River has formed tributary junction plug wetlands at confluences. Sand slug removal is proposed as part of river rehabilitation, but would also drain plug wetlands. We sampled four plug wetland, four river run and three river pool sites to determine whether plug wetlands influence water quality and add to the biodiversity of macroinvertebrates in the Glenelg River.Water quality and macroinvertebrate diversity were similar in plug wetlands, river runs and river pools.Assemblages were distinct among all sites, regardless of type, so there was no characteristic ‘plug-wetland fauna’. Therefore, although removal of plug wetlands would not cause a dramatic loss of invertebrate biodiversity, it would destroy anthropogenic habitat that supports a similar range of species to natural habitats in a river subject to multiple degrading processes. Gains from rehabilitation should be weighed against the value of anthropogenic habitat and the extent of similar habitat lost elsewhere in the ecosystem.

Variations in vascular access flows in haemodialysis can depend on needle orientation

Introduction: While using the Transonic Qc[TM] machine to assess access flow in arteriovenous fistulae (AVF), we observed that when compared to antegrade arterial needle insertion, retrograde arterial needle insertion could regularly produce lower access flow measurements. This study sought to explore this phenomenon.

Method: 23 patients entered and 20 finished the study. Patient selection criteria included: functioning AVF and an adequate AVF length for either retrograde or antegrade arterial needle insertion. After ensuring stable and similar blood pressures, 3 flow measurements were taken during the first 2 hours on the same dialysis day of 3 consecutive weeks using antegrade needle insertion then were repeated on 3 further consecutive weeks using retrograde insertion.

Results: Overall, access flows measured with retrograde insertion were significantly lower by a mean difference of 107.15 ml/min (57-484 ml/min) than the flows measured with antegrade needle placement. In 5/20, 3 recorded minimal difference and 2 had a higher access flows during retrograde insertion. No recirculation was observed during either antegrade or retrograde needle insertion. The paired t-test showed that there was significant difference between the antegrade versus retrograde mean measurements (p = 0.005).

Conclusion: Although the sample size is small and the number of measurements limited, we conclude that access flows may be greater with an antegrade arterial orientation compared to flows recorded with a retrograde orientation. The phenomenon behind this conclusion is yet to be investigated. We suggest that when using the Transonic Qc[TM] access measurement device the arterial needle should always be in the same direction for each measurement for each individual patient.