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Background: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours., Methods: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials., Results: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001)., Conclusion: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours., Clinical Trial Registration: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

Unlike biologically available nitrogen and phosphorus, which are often at limiting concentrations in surface seawater, sulfur in the form of sulfate is plentiful and not considered to constrain marine microbial activity. Nonetheless, in a model system in which a marine bacterium obtains all of its carbon from co-cultured phytoplankton, bacterial gene expression suggests that at least seven dissolved organic sulfur (DOS) metabolites support bacterial heterotrophy. These labile exometabolites of marine dinoflagellates and diatoms include taurine, N-acetyltaurine, isethionate, choline-O-sulfate, cysteate, 2,3-dihydroxypropane-1-sulfonate (DHPS), and dimethylsulfoniopropionate (DMSP). Leveraging from the compounds identified in this model system, we assessed the role of sulfur metabolites in the ocean carbon cycle by mining the Tara Oceans dataset for diagnostic genes. In the 1.4 million bacterial genome equivalents surveyed, estimates of the frequency of genomes harboring the capability for DOS metabolite utilization ranged broadly, from only 1 out of every 190 genomes (for the C2 sulfonate isethionate) to 1 out of every 5 (for the sulfonium compound DMSP). Bacteria able to participate in DOS transformations are dominated by Alphaproteobacteria in the surface ocean, but by SAR324, Acidimicrobiia, and Gammaproteobacteria at mesopelagic depths, where the capability for utilization occurs in higher frequency than in surface bacteria for more than half the sulfur metabolites. The discovery of an abundant and diverse suite of marine bacteria with the genetic capacity for DOS transformation argues for an important role for sulfur metabolites in the pelagic ocean carbon cycle.

Assessment of right ventricular (RV) structure and function by echocardiography has largely been qualitative in the past. More recent approaches emphasise the quantification of RV structure from multiple echocardiographic views and quantification of multiple parameters of RV function. Current echocardiographic examinations should include at least two quantitative measures of RV function. This paper will highlight commonly used measures along with their strengths and weaknesses. With further technical developments in three-dimensional and myocardial deformation imaging and as more outcome data become available it is likely that further quantitative assessment will become routine and be used to guide diagnosis and treatment choices., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Exercise capacity is frequently reduced in people with diabetes mellitus (DM), and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semisupine exercise echocardiography 1 h after placebo or sildenafil ingestion in a double-blind randomized crossover design. The primary efficacy end point was exercise capacity (V̇o 2peak ) while secondary measures included pulmonary vascular resistance, cardiac output, and change in PTAC. DM subjects were aged 44 ± 13 yr, 73% male, with 16 ± 10 yr DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4 ±1.2 beats/min, P = 0.04) and cardiac output (+322 ± 21 ml, P = 0.03) improved. However, the degree of PTAC did not change ( P = 0.93) and V̇o 2peak did not increase following sildenafil as compared with placebo (V̇o 2peak : 31.8 ± 9.7 vs. 32.1 ± 9.5 ml·min -1 ·kg -1 , P = 0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction. NEW & NOTEWORTHY This is one of the largest and most comprehensive studies of cardiopulmonary exercise performance in people with diabetes mellitus and to our knowledge the first to assess the effect of sildenafil using detailed echocardiographic measures during incremental exercise. Sildenafil attenuated the rise in pulmonary vascular resistance while augmenting cardiac output and intriguingly heart rate, without conferring any improvement in exercise capacity. The enhanced central hemodynamic indexes may have been offset by reduced peripheral O 2 extraction.

Background: Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular changes, leads to elevated pulmonary artery pressures, dyspnoea, a reduction in exercise tolerance, right heart failure, and ultimately death.Prostacyclin analogue drugs mimic endogenous prostacyclin which leads to vasodilation, inhibition of platelet aggregation, and reversal of vascular remodelling. Prostacyclin's short half-life theoretically enhances selectivity for the pulmonary vascular bed by direct (via central venous catheter) administration. Initial continuous infusion prostacyclins were efficacious, but use of intravenous access increases the risk of adverse events. Newer and safer subcutaneous, oral and inhaled preparations are now available, though possibly less potent.Selexipag is an oral selective prostacyclin receptor (IP receptor) agonist that works similarly to prostacyclin, potentially more stable, with less complex administration and titration., Objectives: To determine the efficacy and safety of prostacyclin, prostacyclin analogues or prostacyclin receptor agonists for PAH in adults and children., Search Methods: We performed searches on CENTRAL, MEDLINE, and Embase up to 16 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles., Selection Criteria: We included any randomised controlled trials (RCTs) which compared prostacyclin, prostacyclin analogues or prostacyclin receptor agonists to control (placebo, any other treatment or usual care) for at least six weeks., Data Collection and Analysis: We used standard methods specified by Cochrane. Primary outcomes included change in World Health Organization (WHO) functional class, six-minute walk distance (6MWD), and mortality., Main Results: Seventeen trials with 3765 mostly adult participants were included; median trial duration was 12 weeks. Fifteen trials used prostacyclin analogues: intravenous (N = 4); subcutaneous (N = 1); oral (N = 5); inhaled (N = 5); two used oral prostacyclin receptor agonists. Three intravenous and two inhaled trials were open-label.Participants using prostacyclin had 2.39 times greater odds of improving by at least one WHO functional class (95% confidence interval (CI) 1.72 to 3.32; 24 per 100 (95% CI 18.5 to 30.4) with prostacyclin compared to 12 per 100 with control; 8 trials, 1066 participants; moderate-certainty evidence). Improvement occurred with intravenous (odds ratio (OR) 14.96, 95% CI 4.76 to 47.04), and inhaled (OR 2.94, 95% CI 1.53 to 5.66), but not with oral preparations. Participants using prostacyclin increased their 6MWD by 19.50 metres (95% CI 14.82 to 24.19; 13 trials, 2283 participants; low-certainty evidence), which was clinically significant with intravenous (mean difference (MD) 91.76 metres; 95% CI 58.97 to 124.55), but not with non-intravenous preparations (subcutaneous: MD 16.00 metres, 95% CI 7.38 to 24.62; oral: MD 14.76 metres, 95% CI 7.81 to 21.70; inhaled: MD 26.97 metres, 95% CI 17.21 to 36.73). Mortality was reduced in the intravenous (OR 0.29, 95% CI 0.12 to 0.69; risk of death 6 per 100 (95% CI 2.38 to 12.31) with prostacyclin compared to 17 per 100 with control; 4 trials, 255 participants), but not in the non-intravenous studies (OR 0.82, 95% CI 0.48 to 1.40; risk of death 21 per 1000 (95% CI 12.00 to 34.20) with prostacyclin compared to 25 per 1000 with control; moderate-certainty evidence; 12 trials, 2299 participants). We reduced the certainty of evidence due to few studies per subgroup and use of open-label trials.Prostacyclins improved cardiopulmonary haemodynamics (reduction in mean pulmonary artery pressure by 3.60 mmHg (95% CI -4.73 to -2.48); pulmonary vascular resistance by 2.81 WU (95% CI -3.80 to -1.82); right atrial pressure by 1.90 mmHg (95% CI -2.58 to -1.22), and increase in cardiac index by 0.31 L/min/m 2 (95% CI 0.23 to 0.38); low-certainty evidence), improved dyspnoea (low-certainty evidence, and improved quality of life (moderate-certainty evidence), when compared to control. When only subcutaneous/inhaled trials were included the effect was still significant, but the magnitude was smaller. There was no difference across oral trials.Adverse events were increased in all prostacyclin preparations, including vasodilation (OR 5.03, 95% CI 3.84 to 6.58), headache (OR 3.16, 95% CI 2.62 to 3.80), jaw pain (OR 5.25, 95% CI 3.96 to 6.98), diarrhoea (OR 2.81, 95% CI 2.29 to 3.46), nausea/vomiting (OR 2.39, 95% CI 1.98 to 2.88), myalgias (OR 2.75, 95% CI 1.65 to 4.58), upper respiratory tract events (OR 1.61, 95% CI 1.22 to 2.13), extremity pain (OR 3.36, 95% CI 2.32 to 4.85), and infusion site reactions (OR 14.41, 95% CI 9.16 to 22.66). In the intravenous trials, there was a 12%-25% risk of serious non-fatal events including sepsis, haemorrhage, pneumothorax and pulmonary embolism.Two trials (1199 participants) compared oral selexipag to placebo; no trials compared selexipag with prostacyclin. There was a small 12.62 metre improvement in 6MWD (95% CI 1.90 to 23.34; high-certainty evidence), and weak evidence for haemodynamics. The effect was uncertain for WHO functional class. The risk of death with selexipag was five per 100 compared to three per 100 with placebo, though the CI crossed zero so the true effect is uncertain (risk difference (RD) 0.02 (95% CI -0.00 to 0.04). There was less clinical worsening with selexipag (OR 0.47, 95% CI 0.37 to 0.60), though more side effects, including vasodilation (OR 2.67, 95% CI 1.72 to 4.17), headache (OR 3.91, 95% CI 3.07 to 4.98), jaw pain (OR 5.33, 95% CI 3.64 to 7.81), diarrhoea (OR 3.11, 95% CI 2.39 to 4.05), nausea/vomiting (OR 2.92, 95% CI 2.29 to 3.73), pain in the extremities (OR 2.44, 95% CI 1.69 to 3.52), and myalgias (OR 3.05, 95% CI 2.02 to 4.58)., Authors' Conclusions: This review demonstrates clinical and statistical benefit for intravenous prostacyclin (compared to control) with improved functional class, 6MWD, mortality, symptoms scores, and cardiopulmonary haemodynamics, but at a cost of adverse events. This may be due to a true effect, or may be overestimated due to the inclusion of small, short or open-label studies. There was a statistical and small clinical benefit in function and haemodynamics for inhaled prostacyclin, but the effect is uncertain for mortality. The effect of oral prostacyclins are less certain. Selexipag demonstrated less clinical worsening without discernable impact on survival, increased adverse events; and the effect on other outcomes is less certain. Real-world registry data may provide further information about clinical effect.

Background: Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heart disease (PH-LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders. Phosphodiesterase type 5 (PDE5) inhibitors increase vasodilation and inhibit proliferation., Objectives: To determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults and children., Search Methods: We performed searches of CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 26 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles., Selection Criteria: We included randomised controlled trials that compared any PDE5 inhibitor versus placebo, or any other PAH disease-specific therapies, for at least 12 weeks. We include separate analyses for each PH group., Data Collection and Analysis: We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were: change in WHO functional class, six-minute walk distance (6MWD), and mortality. Secondary outcomes were haemodynamic parameters, quality of life/health status, dyspnoea, clinical worsening (hospitalisation/intervention), and adverse events. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the GRADE approach and created 'Summary of findings' tables., Main Results: We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children.Nineteen trials included group 1 PAH participants. PAH participants treated with PDE5 inhibitors were more likely to improve their WHO functional class (odds ratio (OR) 8.59, 95% confidence interval (CI) 3.95 to 18.72; 4 trials, 282 participants), to walk 48 metres further in 6MWD (95% CI 40 to 56; 8 trials, 880 participants), and were 22% less likely to die over a mean duration of 14 weeks (95% CI 0.07 to 0.68; 8 trials, 1119 participants) compared to placebo (high-certainty evidence). The number needed to treat to prevent one additional death was 32 participants. There was an increased risk of adverse events with PDE5 inhibitors, especially headache (OR 1.97, 95% CI 1.33 to 2.92; 5 trials, 848 participants), gastrointestinal upset (OR 1.63, 95% CI 1.07 to 2.48; 5 trials, 848 participants), flushing (OR 4.12, 95% CI 1.83 to 9.26; 3 trials, 748 participants), and muscle aches and joint pains (OR 2.52, 95% CI 1.59 to 3.99; 4 trials, 792 participants).Data comparing PDE5 inhibitors to placebo whilst on other PAH-specific therapy were limited by the small number of included trials. Those PAH participants on PDE5 inhibitors plus combination therapy walked 19.66 metres further in six minutes (95% CI 9 to 30; 4 trials, 509 participants) compared to placebo (moderate-certainty evidence). There were limited trials comparing PDE5 inhibitors directly with other PAH-specific therapy (endothelin receptor antagonists (ERAs)). Those on PDE5 inhibitors walked 49 metres further than on ERAs (95% CI 4 to 95; 2 trials, 36 participants) (low-certainty evidence). There was no evidence of a difference in WHO functional class or mortality across both treatments.Five trials compared PDE5 inhibitors to placebo in PH secondary to left-heart disease (PH-LHD). The quality of data were low due to imprecision and inconsistency across trials. In those with PH-LHD there were reduced odds of an improvement in WHO functional class using PDE5 inhibitors compared to placebo (OR 0.53, 95% CI 0.32 to 0.87; 3 trials, 285 participants), and those using PDE5 inhibitors walked 34 metres further compared to placebo (95% CI 23 to 46; 3 trials, 284 participants). There was no evidence of a difference in mortality. Five trials compared PDE5 inhibitors to placebo in PH secondary to lung disease/hypoxia, mostly in COPD. Data were of low quality due to imprecision of effect and inconsistency across trials. There was a small improvement of 27 metres in 6MWD using PDE5 inhibitors compared to placebo in those with PH due to lung disease. There was no evidence of worsening hypoxia using PDE5 inhibitors, although data were limited. Three studies compared PDE5 inhibitors to placebo or other PAH-specific therapy in chronic thromboembolic disease. There was no significant difference in any outcomes. Data quality was low due to imprecision of effect and heterogeneity across trials., Authors' Conclusions: PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side-effect profile for each individual when choosing which PDE5 inhibitor to prescribe.While there appears to be some benefit for the use of PDE5 inhibitors in PH-left-heart disease, it is not clear based on the mostly small, short-term studies, which type of left-heart disease stands to benefit. These data suggest possible harm in valvular heart disease. There is no clear benefit for PDE5 inhibitors in pulmonary hypertension secondary to lung disease or chronic thromboembolic disease. Further research is required into the mechanisms of pulmonary hypertension secondary to left-heart disease, and cautious consideration of which subset of these patients may benefit from PDE5 inhibitors. Future trials in PH-LHD should be sufficiently powered, with long-term follow-up, and should include invasive haemodynamic data, WHO functional class, six-minute walk distance, and clinical worsening.

Denitrification by sulfur-oxidizing bacteria is an effective nitrate removal strategy in engineered aquatic systems. However, the community taxonomic and metabolic diversity of sulfur-driven denitrification (SDN) systems, as well as the relationship between nitrate removal and SDN community structure, remains underexplored. This is particularly true for SDN reactors applied to marine aquaria, despite the increasing use of this technology to supplement filtration. We applied 16S rRNA gene, metagenomic, and metatranscriptomic analyses to explore the microbial basis of SDN reactors operating on Georgia Aquarium's Ocean Voyager, the largest indoor closed-system seawater exhibit in the United States. The exhibit's two SDN systems vary in water retention time and nitrate removal efficiency. The systems also support significantly different microbial communities. These communities contain canonical SDN bacteria, including a strain related to Thiobacillus thioparus that dominates the system with the higher water retention time and nitrate removal but is effectively absent from the other system. Both systems contain a wide diversity of other microbes whose metagenome-assembled genomes contain genes of SDN metabolism. These include hundreds of strains of the epsilonproteobacterium Sulfurimonas , as well as gammaproteobacterial sulfur oxidizers of the Thiotrichales and Chromatiales , and a relative of Sedimenticola thiotaurini with complete denitrification potential. The SDN genes are transcribed and the taxonomic richness of the transcript pool varies markedly among the enzymatic steps, with some steps dominated by transcripts from noncanonical SDN taxa. These results indicate complex and variable SDN communities that may involve chemical dependencies among taxa as well as the potential for altering community structure to optimize nitrate removal. IMPORTANCE Engineered aquatic systems such as aquaria and aquaculture facilities have large societal value. Ensuring the health of animals in these systems requires understanding how microorganisms contribute to chemical cycling and waste removal. Focusing on the largest seawater aquarium in the United States, we explore the microbial communities in specialized reactors designed to remove excess nitrogen through the metabolic activity of sulfur-consuming microbes. We show that the diversity of microbes in these reactors is both high and highly variable, with distinct community types associated with significant differences in nitrogen removal rate. We also show that the genes encoding the metabolic steps of nitrogen removal are distributed broadly throughout community members, suggesting that the chemical transformations in this system are likely a result of microbes relying on other microbes. These results provide a framework for future studies exploring the contributions of different community members, both in waste removal and in structuring microbial biodiversity., (Copyright © 2018 American Society for Microbiology.)

Implementation of wearable sweat sensors for continuous measurement of fluid based biomarkers (including electrolytes, metabolites and proteins) is an attractive alternative to common, yet intrusive and invasive, practices such as urine or blood analysis. Recent years have witnessed several key demonstrations of sweat based electrochemical sensing in wearable formats, however, there are still significant challenges and opportunities in this space for clinical acceptance, and thus mass implementation of these devices. For instance, there are inherent challenges in establishing direct correlations between sweat-based and gold-standard plasma-based biomarker concentrations for clinical decision-making. In addition, the wearable sweat monitoring devices themselves may exacerbate these challenges, as they can significantly alter sweat physiology (example, sweat rate and composition). Reported here is the demonstration of a fully integrated, wireless, wearable and flexible sweat sensing device for non-obtrusive and continuous monitoring of electrolytes during moderate to intense exertion as a metric for hydration status. The focus of this work is twofold: 1- design of a conformable fluidics systems to suit conditions of operation for sweat collection (to minimize sensor lag) with rapid removal of sweat from the sensing site (to minimize effects on sweat physiology). 2- integration of Na+ and K+ ion-selective electrodes (ISEs) with flexible microfluidics and low noise small footprint electronics components to enable wireless, wearable sweat monitoring. While this device is specific to electrolyte analysis during intense perspiration, the lessons in microfluidics and overall system design are likely applicable across a broad range of analytes.

The analytical identification of positional isomers (e.g., 3-, N 4 -, 5-methylcytidine) within the > 160 different post-transcriptional modifications found in RNA can be challenging. Conventional liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) approaches rely on chromatographic separation for accurate identification because the collision-induced dissociation (CID) mass spectra of these isomers nearly exclusively yield identical nucleobase ions (BH 2 + ) from the same molecular ion (MH + ). Here, we have explored higher-energy collisional dissociation (HCD) as an alternative fragmentation technique to generate more informative product ions that can be used to differentiate positional isomers. LC-MS/MS of modified nucleosides characterized using HCD led to the creation of structure- and HCD energy-specific fragmentation patterns that generated unique fingerprints, which can be used to identify individual positional isomers even when they cannot be separated chromatographically. While particularly useful for identifying positional isomers, the fingerprinting capabilities enabled by HCD also offer the potential to generate HPLC-independent spectral libraries for the rapid analysis of modified ribonucleosides. Graphical Abstract ᅟ.

Objective: To determine whether pulmonary microvascular disease is detectable in subjects with diabetes and associated with diminished exercise capacity using a novel echocardiographic marker quantifying the pulmonary transit of agitated contrast bubbles (PTAC)., Research Design and Methods: Sixty participants (40 with diabetes and 20 control subjects) performed cardiopulmonary (maximal oxygen consumption [VO 2 peak]) and semisupine bicycle echocardiography exercise tests within a 1-week period. Pulmonary microvascular disease was assessed using PTAC (the number of bubbles traversing the pulmonary circulation to reach the left ventricle, categorized as low PTAC or high PTAC). Echocardiographic measures of cardiac output, pulmonary artery pressures, and biventricular function were obtained during exercise., Results: Subjects with diabetes and control subjects were of similar age (44 ± 13 vs. 43 ± 13 years, P = 0.87) and sex composition (70% vs. 65% male, P = 0.7). At peak exercise, low PTAC was present in more participants with diabetes than control subjects (41% vs. 12.5%, χ 2 P = 0.041) and, in particular, in more subjects with diabetes with microvascular complications compared with both those without complications and control subjects (55% vs. 26% vs. 13%, χ 2 P = 0.02). When compared with high PTAC, low PTAC was associated with a 24% lower VO 2 peak ( P = 0.006), reduced right ventricular function ( P = 0.015), and greater pulmonary artery pressures during exercise ( P = 0.02)., Conclusions: PTAC is reduced in diabetes, particularly in the presence of microvascular pathology in other vascular beds, suggesting that it may be a meaningful indicator of pulmonary microvascular disease with important consequences for cardiovascular function and exercise capacity., (© 2018 by the American Diabetes Association.)

Background: Inflammation and microvascular dysfunction (MVD) are independently associated with adverse cardiovascular outcomes in patients with ischemic heart disease. This study aimed to assess the relationship between inflammation, MVD, and myocardial injury., Methods: Coronary microvascular function was assessed in 74 patients undergoing percutaneous coronary intervention (PCI) using the index of microvascular resistance (IMR) by a pressure-temperature sensor-tipped wire. Serum high-sensitivity C-reactive protein (hsCRP) level was quantified by rate turbidimetry. Severe MVD was defined as IMR ≥ 30. Pearson correlation was computed to assess the relationships between hsCRP, troponin, and IMR of culprit vessel. Predictors of severe MVD were assessed by regression analysis., Results: Acute coronary syndromes (ACSs) represented 49% of the total cohort. Study cohort was divided into low C-reactive protein (CRP) (hsCRP < 3 mg/L) and high CRP (hsCRP ≥ 3 mg/L) groups. There was higher representation of smokers (78 vs. 52%), diabetics (39 vs. 18%), and ACS (61 vs. 33%), as well as higher body mass index (29.4 ± 4.6 vs. 27.2 ± 4.1) in the high CRP group. Pre-PCI and post-PCI IMR were significantly elevated in the high CRP group compared to the low CRP group (pre-PCI IMR: 29.0 ± 13.9 vs. 17.4 ± 11.1, p  < 0.0001; post-PCI IMR: 23.0 ± 16.8 vs. 15.5 ± 8.4, p  = 0.02). Peak troponin levels were significantly raised in the high CRP group (9.96 ± 17.19 vs. 1.17 ± 3.00 μg/L, p  = 0.002). There was a strong positive correlation between hsCRP and pre-PCI IMR ( r  = 0.85, p  < 0.0001). Pre- and post-PCI IMR levels were correlated with peak troponin level ( r  = 0.45, p  < 0.0001; r  = 0.33, p  = 0.005, respectively). Predictors of severe MVD include male gender (OR 3.0), diabetes (OR 3.7), smoking history (OR 4.0), ACS presentation (OR 8.5), and hsCRP ≥ 3 mg/L (OR 5.6)., Conclusion: hsCRP is a significant predictor of MVD while MVD is associated with myocardial injury, supporting the central role of inflammation and MVD in the pathophysiology and complications of coronary artery disease., Clinical Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN): 12617000648325. Universal Trial Number (UTN): U1111-1196-2246.

In their role as primary producers, marine phytoplankton modulate heterotrophic bacterial activities through differences in the types and amounts of organic matter they release. This study investigates the transcriptional response of bacterium Ruegeria pomeroyi, a member of the Roseobacter clade known to affiliate with diverse phytoplankton groups in the ocean, during a shift in phytoplankton taxonomy. The bacterium was initially introduced into a culture of the dinoflagellate Alexandrium tamarense, and then experienced a change in phytoplankton community composition as the diatom Thalassiosira pseudonana gradually outcompeted the dinoflagellate. Samples were taken throughout the 30-day experiment to track shifts in bacterial gene expression informative of metabolic and ecological interactions. Transcriptome data indicate fundamental differences in the exometabolites released by the two phytoplankton. During growth with the dinoflagellate, gene expression patterns indicated that the main sources of carbon and energy for R. pomeroyi were dimethysulfoniopropionate (DMSP), taurine, methylated amines, and polyamines. During growth with the diatom, dihydroxypropanesulfonate (DHPS), xylose, ectoine, and glycolate instead appeared to fuel the bulk of bacterial metabolism. Expression patterns of genes for quorum sensing, gene transfer agent, and motility suggest that bacterial processes related to cell communication and signaling differed depending on which phytoplankton species dominated the co-culture. A remodeling of the R. pomeroyi transcriptome implicating more than a quarter of the genome occurred through the change in phytoplankton regime.

Parasitic nematodes negatively impact human and animal health worldwide. The market withdrawal of nematicidal agents due to unfavourable toxicities has limited the available treatment options. In principle, co-administering nematicides at lower doses along with molecules that potentiate their activity could mitigate adverse toxicities without compromising efficacy. Here, we screened for new small molecules that interact with aldicarb, which is a highly effective treatment for plant-parasitic nematodes whose toxicity hampers its utility. From our collection of 638 worm-bioactive compounds, we identified 20 molecules that interact positively with aldicarb to either kill or arrest the growth of the model nematode Caenorhabditis elegans. We investigated the mechanism of interaction between aldicarb and one of these novel nematicides called wact-86. We found that the carboxylesterase enzyme GES-1 hydrolyzes wact-86, and that the interaction is manifested by aldicarb's inhibition of wact-86's metabolism by GES-1. This work demonstrates the utility of C. elegans as a platform to search for new molecules that can positively interact with industrial nematicides, and provides proof-of-concept for prospective discovery efforts.

The fate of the sulfur moiety of dimethylsulfoniopropionate (DMSP) depends on the 'bacterial switch', a regulatory point between two metabolic pathways with different biogeochemical endpoints. Studies have focused on transcriptional patterns of known genes to determine physiological and environmental factors affecting this switch, but post-transcriptional regulation has been under-studied. Here we use a model bacterium containing both pathways to look for transcription of non-coding regulatory small RNAs (sRNAs) during DMSP metabolism. RNA-seq analysis of Ruegeria pomeroyi DSS-3 grown with DMSP, metabolic intermediates of DMSP degradation (MMPA or acetate), or methionine revealed 182 putative sRNAs, with 46 showing differential expression during growth on DMSP. A knockout mutant constructed for an upregulated sRNA had a phenotype that differed in its use of the two degradation pathways. Because transcription patterns of many differentially expressed sRNAs were not correlated with the transcription of their putative target gene, their effects on DMSP degradation would not be observable in the transcriptome. Overall, our results indicate that sRNAs are crucial but largely cryptic actors in regulating DMSP metabolism in this model marine bacterium and potentially other bacterial groups involved in the surface ocean sulfur cycle., (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

To establish a gold standard for the information given to patients about the risks associated with third molar extractions, we surveyed 79 oral and maxillofacial surgeons (OMFS) to find out what information they gave to patients during the consent process. We also surveyed 62 medicolegal solicitors to find out what information they thought patients should be given before the procedure, and in what form. A total of 20/76 OMFS (26%) used a two-stage process to obtain consent; 13 (17%) included paraesthesia on the consent form and also gave out an information leaflet. All the lawyers agreed that patients should give their consent in writing and thought that the risk of paraesthesia should be included on the form. Three-quarters thought that they should also be given an information leaflet that includes paraesthesia. We encourage surgeons to do this as part of the two-stage consent process., (Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group., Competing Interests: The authors declare no competing financial interests in association with this study.

In oligotrophic ocean waters where bacteria are often subjected to chronic nutrient limitation, community transcriptome sequencing has pointed to the presence of highly abundant small RNAs (sRNAs). The role of sRNAs in regulating response to nutrient stress was investigated in a model heterotrophic marine bacterium Ruegeria pomeroyi grown in continuous culture under carbon (C) and nitrogen (N) limitation. RNAseq analysis identified 99 putative sRNAs. Sixty-nine were cis-encoded and located antisense to a presumed target gene. Thirty were trans-encoded and initial target prediction was performed computationally. The most prevalent functional roles of genes anti-sense to the cis-sRNAs were transport, cell-cell interactions, signal transduction, and transcriptional regulation. Most sRNAs were transcribed equally under both C and N limitation, and may be involved in a general stress response. However, 14 were regulated differentially between the C and N treatments and may respond to specific nutrient limitations. A network analysis of the predicted target genes of the R. pomeroyi cis-sRNAs indicated that they average fewer connections than typical protein-encoding genes, and appear to be more important in peripheral or niche-defining functions encoded in the pan genome.

Left ventricular diastolic dysfunction is a well-described complication of systemic hypertension. However, less is known regarding the effect of chronic pressure overload on right ventricular (RV) diastolic function. We hypothesized that pulmonary hypertension (PHT) is associated with abnormal RV early relaxation and that this would be best shown by invasive pressure measurement. Twenty-five patients undergoing right heart catheterization for investigation of breathlessness and/or suspected PHT were studied. In addition to standard measurements, RV pressure was sampled with a high-fidelity micromanometer, and RV pressure/time curves were analyzed. Patients were divided into a PHT group and a non-PHT group on the basis of a derived mean pulmonary artery systolic pressure of 25 mmHg. Eleven patients were classified to the PHT group. This group had significantly higher RV minimum diastolic pressure ([Formula: see text] vs. [Formula: see text] mmHg, [Formula: see text]) and RV end-diastolic pressure (RVEDP; [Formula: see text] vs. [Formula: see text] mmHg, [Formula: see text]), and RV τ was significantly prolonged ([Formula: see text] vs. [Formula: see text] ms, [Formula: see text]). There were strong correlations between RV τ and RV minimum diastolic pressure ([Formula: see text], [Formula: see text]) and between RV τ and RVEDP ([Formula: see text], [Formula: see text]). There was a trend toward increased RV contractility (end-systolic elastance) in the PHT group ([Formula: see text] vs. [Formula: see text] mmHg/mL, [Formula: see text]) and a correlation between RV systolic pressure and first derivative of maximum pressure change ([Formula: see text], [Formula: see text]). Stroke volumes were similar. Invasive measures of RV early relaxation are abnormal in patients with PHT, whereas measured contractility is static or increasing, which suggests that diastolic dysfunction may precede systolic dysfunction. Furthermore, there is a strong association between measures of RV relaxation and RV filling pressures.

Ingested foreign bodies can prove a significant and potentially fatal threat. A case is reviewed where a patient swallowed his upper Kennedy Class I removable partial denture, highlighting the potential problems of this prosthesis design and the management of this scenario.

Antisense oligonucleotide therapy is a growing field in cardiac, metabolic, and muscular diseases. This precision therapy allows for treatment of diseases due to specific genetic defects. Antisense has few side effects and is relatively long lasting. Some major targets for antisense therapy include hyperglycemia, hyperlipidemia, and hypercholesterolemia. ISIS Pharmaceuticals recently commercialized antisense therapy with Kynamro (Mipomersen) for homozygous familial hypercholesterolemia, opening the door for other antisense oligonucleotides for lowering proteins. Antisense can also be used to increase proteins that are inhibited by mutant exons. Sarepta is testing exon 51 skipping in the mutated dystrophin gene, which if successful will help affected individuals walk, and may help restore some cardiac function. These antisense techniques also could be applied as antisense therapies to overcome gene defects in hypertension, heart disease, muscular defects and metabolic syndrome.

Right heart catheterization has been described via the arm but previous reports have been retrospective, performed for limited indications, and may not give an accurate assessment of the success rate or safety of this technique. We sought to prospectively examine the feasibility and safety of left and right heart catheterization entirely via the arm using the radial artery and an antecubital fossa vein for a broad range of indications. Fifty-eight consecutive procedures were included. Transradial arterial access was successful in 57 patients (98%), right heart catheterization via the antecubital fossa vein was successful in 54 patients (93%) and bilateral catheterization from the arm was achieved in 53 patients (91%). Standard diagnostic catheterization was the most frequent procedure (59%), although thermodilution (6.9%), percutaneous coronary intervention (33%), and coronary sinus sampling (16%) were also performed in selected cases. Compared to a historical cohort of patients undergoing right and left heart catheterization via femoral access, mean procedural time (38 vs 47 minutes; P=.03) and screening time (8.1 vs 11.2 minutes; P<.001) were significantly reduced. There was 1 venous forearm hematoma that was managed conservatively. Right and left heart catheterization can be performed routinely via the arm in a broad range of patients and is associated with reduced procedural and fluoroscopy time as compared to femoral access. This approach can be considered for all patients in whom right and left heart catheterization is planned.

Angelman syndrome (AS) is a severe neurodevelopmental disorder associated with disruption of maternally inherited UBE3A (ubiquitin protein ligase E3A) expression. At the present time, there is no effective treatment for AS. Mouse lines with loss of maternal Ube3a (Ube3a(m-/p+)) recapitulate multiple aspects of the clinical AS profile, including impaired motor coordination, learning deficits, and seizures. Thus, these genetic mouse models could serve as behavioral screens for preclinical efficacy testing, a critical component of drug discovery for AS intervention. However, the severity and consistency of abnormal phenotypes reported in Ube3a(m-/p+) mice can vary, dependent upon age and background strain, which is problematic for the detection of beneficial drug effects. As part of an ongoing AS drug discovery initiative, we characterized Ube3a(m-/p+) mice on either a 129S7/SvEvBrd-Hprt(b-m2) (129) or C57BL/6J (B6) background across a range of functional domains and ages to identify reproducible and sufficiently large phenotypes suitable for screening therapeutic compounds. The results from the study showed that Ube3a(m-/p+) mice have significant deficits in acquisition and reversal learning in the Morris water maze. The findings also demonstrated that Ube3a(m-/p+) mice exhibit motor impairment in a rotarod task, hypoactivity, reduced rearing and marble-burying, and deficient fear conditioning. Overall, these profiles of abnormal phenotypes can provide behavioral targets for evaluating effects of novel therapeutic strategies relevant to AS., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: This single-subject design study evaluated the feasibility and efficacy of passive and interactive videogame distraction on behavioral distress for a preschool-aged child receiving repeated burn dressing changes., Method: A 4-year-old girl underwent 3 baseline and 10 videogame distraction sessions (5 passive and 5 interactive) using a restricted alternating treatments design. Observed behavioral distress was coded, and parents and nurses rated the child's distress and cooperative behavior., Results: Relative to baseline, behavioral distress decreased and cooperative behavior increased immediately after the onset of videogame distraction. Single Case Randomization Tests revealed significantly lower behavioral distress and greater cooperation during interactive videogame distraction relative to passive videogame distraction., Conclusions: Interactive videogame distraction appears to be a feasible and effective pain management strategy for a preschool-aged child undergoing repeated painful medical procedures.

The metabotropic glutamate receptors (mGluRs) are evolutionarily conserved from nematodes to vertebrates. The Caenorhabditis elegans (C. elegans) genome contains three mGluR genes referred to as mgl-1, mgl-2, and mgl-3. The aim of this study was to characterize the pharmacological profiles of orthosteric and allosteric mGluR ligands on mgl-2. A phylogenetic analysis revealed that mgl-2 is closely associated with the mammalian Group 1 mGluRs (mGluR1 and mGluR5) and is distinct from Group 2 and 3 mGluRs. The ligand binding domain of mgl-2 displayed higher homology to the rat Group 1 mGluRs binding domains compared to the level of homology in the heptahelical transmembrane domain regions. We found that, when transiently expressed in human embryonic kidney 293 cells, mgl-2 can be activated by glutamate and couples to human G-proteins to induce the release of intracellular calcium. Dose-response analyses revealed that mgl-2 has approximately a 15-20-fold lower affinity for glutamate and quisqualate compared to rat mGluR5. In contrast to orthosteric agonists, Group 1 negative allosteric modulators that target the transmembrane domain were ineffective at mgl-2. Surprisingly, CDPPB, an mGluR5 positive allosteric modulator, potentiated glutamate mediated activation of mgl-2, although MPEP and fenobam, two mGluR5 antagonists that share similar binding residues with CDPPB were ineffective at mgl-2. These findings indicate that selective pressures on mGluR protein structures have resulted in conservation of the glutamate binding site, whereas the allosteric modulator sites have been subjected to greater divergent evolutionary changes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We demonstrate roll-to-roll (R2R) fabrication of highly selective, battery-free radio frequency identification (RFID) sensors on a flexible polyethylene terephthalate (PET) polymeric substrate. Selectivity of our developed RFID sensors is provided by measurements of their resonance impedance spectra, followed by the multivariate analysis of spectral features, and correlation of these spectral features to the concentrations of vapors of interest. The multivariate analysis of spectral features also provides the ability for the rejection of ambient interferences. As a demonstration of our R2R fabrication process, we employed polyetherurethane (PEUT) as a "classic" sensing material, extruded this sensing material as 25, 75, and 125-μm thick films, and thermally laminated the films onto RFID inlays, rapidly producing approximately 5000 vapor sensors. We further tested these RFID vapor sensors for their response selectivity toward several model vapors such as toluene, acetone, and ethanol as well as water vapor as an abundant interferent. Our RFID sensing concept features 16-bit resolution provided by the sensor reader, granting a highly desired independence from costly proprietary RFID memory chips with a low-resolution analog input. Future steps are being planned for field-testing of these sensors in numerous conditions.

The effectiveness of a passive flow sulfate-reducing bioreactor processing acid mine drainage (AMD) generated from an abandoned coal mine in Southern Illinois was evaluated using geochemical and microbial community analysis 10 months post bioreactor construction. The results indicated that the treatment system was successful in both raising the pH of the AMD from 3.09 to 6.56 and in lowering the total iron level by 95.9%. While sulfate levels did decrease by 67.4%, the level post treatment (1153 mg/l) remained above recommended drinking water levels. Stimulation of biological sulfate reduction was indicated by a +2.60‰ increase in δ(34)S content of the remaining sulfate in the water post-treatment. Bacterial community analysis targeting 16S rRNA and dsrAB genes indicated that the pre-treated samples were dominated by bacteria related to iron-oxidizing Betaproteobacteria, while the post-treated water directly from the reactor outflow was dominated by sequences related to sulfur-oxidizing Epsilonproteobacteria and complex carbon degrading Bacteroidetes and Firmicutes phylums. Analysis of the post-treated water, prior to environmental release, revealed that the community shifted back to predominantly iron-oxidizing Betaproteobacteria. DsrA analysis implied limited diversity in the sulfate-reducing population present in both the bioreactor outflow and oxidation pond samples. These results support the use of passive flow bioreactors to lower the acidity, metal, and sulfate levels present in the AMD at the Tab-Simco mine, but suggest modifications of the system are necessary to both stimulate sulfate-reducing bacteria and inhibit sulfur-oxidizing bacteria.

Training induces changes in cardiac structure and function which improves cardiac output (CO) and oxygen delivery during exercise. It is unclear whether it is cardiac structure or function which is of greatest importance in determining maximal oxygen consumption (VO(2max)). In 55 subjects (15 non-athletes, 32 amateur and 8 elite athletes), left and right ventricular (LV and RV) volumes and mass were assessed by magnetic resonance imaging (CMR). Comprehensive traditional and novel echocardiographic measures included colour-coded Doppler echocardiography to assess myocardial velocities, strain and strain rate at rest and maximal exercise in both ventricles. Measures of cardiac size and function were assessed as univariate and multivariate predictors of VO(2max). LV and RV mass correlated strongly with VO(2max) (r = 0.79 and r = 0.65, respectively, p < 0.0001), as did LV and RV end-diastolic volumes (r = 0.68 and r = 0.75, p < 0.0001) and heart rate reserve (r = 0.60, p < 0.0001). Measures of myocardial function were not predictive of VO(2max) with the exception of RV diastolic velocities (r = 0.32 and r = 0.36 for rest and exercise, respectively, p < 0.05). On multivariate analysis, only RV end-diastolic volume, LV mass and heart rate reserve were independent predictors (beta = 0.28, 0.45 and 0.27 respectively, p < 0.0001) and together explained 73% of the variance in VO(2max). Measures of cardiac morphology are strongly associated with VO(2max) in healthy adults and well-trained athletes. A combination of ventricular volume, mass and heart rate reserve explains much of the variance in VO(2max), whilst measures of myocardial function do not further strengthen predictive models.

Aims: Endurance training may be associated with arrhythmogenic cardiac remodelling of the right ventricle (RV). We examined whether myocardial dysfunction following intense endurance exercise affects the RV more than the left ventricle (LV) and whether cumulative exposure to endurance competition influences cardiac remodelling (including fibrosis) in well-trained athletes., Methods and Results: Forty athletes were studied at baseline, immediately following an endurance race (3-11 h duration) and 1-week post-race. Evaluation included cardiac troponin (cTnI), B-type natriuretic peptide, and echocardiography [including three-dimensional volumes, ejection fraction (EF), and systolic strain rate]. Delayed gadolinium enhancement (DGE) on cardiac magnetic resonance imaging (CMR) was assessed as a marker of myocardial fibrosis. Relative to baseline, RV volumes increased and all functional measures decreased post-race, whereas LV volumes reduced and function was preserved. B-type natriuretic peptide (13.1 ± 14.0 vs. 25.4 ± 21.4 ng/L, P = 0.003) and cTnI (0.01 ± .03 vs. 0.14 ± .17 μg/L, P < 0.0001) increased post-race and correlated with reductions in RVEF (r = 0.52, P = 0.001 and r = 0.49, P = 0.002, respectively), but not LVEF. Right ventricular ejection fraction decreased with increasing race duration (r = -0.501, P < 0.0001) and VO(2)max (r = -0.359, P = 0.011). Right ventricular function mostly recovered by 1 week. On CMR, DGE localized to the interventricular septum was identified in 5 of 39 athletes who had greater cumulative exercise exposure and lower RVEF (47.1 ± 5.9 vs. 51.1 ± 3.7%, P = 0.042) than those with normal CMR., Conclusion: Intense endurance exercise causes acute dysfunction of the RV, but not the LV. Although short-term recovery appears complete, chronic structural changes and reduced RV function are evident in some of the most practiced athletes, the long-term clinical significance of which warrants further study.

Background: The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis., Methods and Results: Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68±2.06, nonculprit sIMR 18.37±1.89, P=0.002; post percutaneous intervention sIMR 18.5±1.94 versus culprit sIMR 26.68±2.06, P<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96±1.78 versus nonculprit sIMR 18.37±1.89, P=0.52; post percutaneous intervention sIMR 18.5±1.94 versus cIMR 16.96±1.78, P=0.42)., Conclusions: When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina.

We present a case of an intermediate right coronary artery lesion with a fractional flow reserve (FFR) of 0.93 despite a myocardial perfusion scan demonstrating reversible ischemia in the inferior wall. An assessment of microvascular resistance was performed using the index of microcirculatory resistance (IMR). This was consistent with elevated resistance and may explain the discordance between the high FFR result, the positive perfusion study, and the lesion appearance on angiography. FFR assumes stable and minimal resistance at hyperemia; however, there may be situations where this does not occur, contributing to discrepant values. An understanding of the underlying physiological principles that underpin FFR is required for all physicians using this increasingly utilized technique., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aim: This study was undertaken to determine the cost of healthcare-associated bloodstream infections (HA-BSI) in adult patients admitted to an Auckland City Hospital., Method: A matched cohort study was performed with a 1:2 or 1:1 match in which all patients admitted between January and June 2005 who had HA-BSI were included. Controls were selected from patients admitted between July 2004 and December 2006. Patients with haemodialysis central line-related HA-BSI were not matched with controls as the admission was related purely to that episode of infection., Results: There were 106 episodes of HA-BSI in 99 patients. Fifty-five patients were able to be matched 1:1 or 1:2 with controls, group 1. Nineteen BSI episodes were in patients undergoing renal replacement therapy by haemodialysis and the patients were admitted as a consequence of this episode of infection, group 2. An episode of HA-BSI increased the length of the hospital admission by 9.7 days and 7.9 days in group 1 and group 2, respectively. The excess cost associated with an episode of HA- BSI was $20,394 in group 1 and $11,139 in group 2., Conclusion: There are substantial costs associated with HA-BSI. A proportion of these infections can be reduced by effective infection control measures.

Background: Quantification of left ventricular torsion may provide new indices of systolic and diastolic function. We sought to characterize the effect of acute manipulation of load on cardiac torsion, plecotropy in human subjects., Methods: Simultaneous Millar LV pressure, micromanometry, and echocardiograms were performed on 18 patients (10 male, mean age 66 years) with normal systolic function. Loading was altered sequentially by the administration of glyceryl trinitrate (GTN) and saline fluid loading. Echocardiographic speckle tracking imaging was used to quantify LV torsion and event timing was recorded relative to mitral valve opening (MVO)., Results: GTN administration decreased preload (LV end diastolic pressure: 15.7 vs 8.4 mmHg, P < 0.001), and afterload (wall stress: 140 vs 84 x10(3)dyn/cm(2), P < 0.02). Administration of fluid increased preload (LVEDP 11.3 vs 18.1 mmHg, P < 0.001) and increased wall stress, but to a lesser extent (102 vs 117 x10(3)dyn/cm(2), P < 0.003). GTN administration augmented peak torsion (8.4 vs 11.0 deg, P < 0.05), increased systolic torsion velocity (46.6 vs 65.3deg/sec, P < 0.01) and resulted in earlier onset of untwisting (-105 vs -127ms, P < 0.05). Fluid loading decreased the proportion of untwisting prior to MVO (39.0 vs 31.0%, P < 0.05), untwisting acceleration (-750 vs -592deg/sec/sec, P < 0.05) and delayed the timing of peak untwisting (-37.0 vs 9.1ms, P < 0.01), but did not affect systolic torsion parameters., Conclusions: Left ventricular torsion parameters are sensitive to acute changes in load and therefore need to be interpreted in the context of current loading conditions.

Aims: Left ventricular (LV) strain and strain rate have been proposed as novel indices of systolic function; however, there are limited data about the effect of acute changes on these parameters., Methods and Results: Simultaneous Millar micromanometer LV pressure and echocardiographic assessment were performed on 18 patients. Loading was altered sequentially by the administration of glyceryl trinitrate (GTN) and saline fluid loading. Echocardiographic speckle tracking imaging was used to quantify the peak systolic strain (S) and peak systolic strain rate (SR S) and dp/dt max was recorded from the micromanometer data. GTN administration decreased preload (LV end diastolic pressure [LVEDP]: 15.7 vs. 8.4 mmHg, P < 0.001) and afterload (end systolic wall stress: 74 vs. 43 x 10(3)dyn/cm(2), P < 0.001). Administration of fluid increased preload (LVEDP: 11.3 vs. 18.1 mmHg, P < 0.001) and increased wall stress (53 vs. 62 x 10(3)dyn/cm(2), P < 0.003). Administration of GTN resulted in increased circumferential SR S (-1.2 vs. -1.7s(-1), P < 0.01) and longitudinal SR S (-0.9 vs. -1.0 s(-1), P < 0.001). The administration of fluid resulted in decreased circumferential SR S (-1.5 vs. -1.3s(-1), P < 0.01) and longitudinal SR S (-1.0 vs. -0.9s(-1), P < 0.01). As preload and afterload increased, decrease in circumferential SR S (r = 0.63, P < 0.001; r = 0.56, P<0.001) and longitudinal SR S were observed (r = 0.42, P < 0.003; r = 0.49 P < 0.001)., Conclusion: Circumferential and longitudinal peak strain and systolic strain rate are sensitive to acute changes in load, an important factor that needs to be considered in their application as indices of systolic function.

An LAD/D1 bifurcation intervention was complicated by side-branch wire entrapment and unravelling requiring goose-neck snare removal. Residual microfilaments were retrieved from the main branch after further balloon inflations with a satisfactory final angiographic result and one-year follow-up. Various methods are available to avoid and deal with this complication.

Attached bacterial communities can generate three-dimensional (3D) physicochemical gradients that create microenvironments where local conditions are substantially different from those in the surrounding solution. Given their ubiquity in nature and their impacts on issues ranging from water quality to human health, better tools for understanding biofilms and the gradients they create are needed. Here we demonstrate the use of functional tomographic imaging via confocal fluorescence microscopy of ratiometric core-shell silica nanoparticle sensors (C dot sensors) to study the morphology and temporal evolution of pH microenvironments in axenic Escherichia coli PHL628 and mixed-culture wastewater biofilms. Testing of 70-, 30-, and 10-nm-diameter sensor particles reveals a critical size for homogeneous biofilm staining, with only the 10-nm-diameter particles capable of successfully generating high-resolution maps of biofilm pH and distinct local heterogeneities. Our measurements revealed pH values that ranged from 5 to >7, confirming the heterogeneity of the pH profiles within these biofilms. pH was also analyzed following glucose addition to both suspended and attached cultures. In both cases, the pH became more acidic, likely due to glucose metabolism causing the release of tricarboxylic acid cycle acids and CO(2). These studies demonstrate that the combination of 3D functional fluorescence imaging with well-designed nanoparticle sensors provides a powerful tool for in situ characterization of chemical microenvironments in complex biofilms.

Background: Left ventricular torsion, resulting from the rotation of the base and apex of the ventricle in opposite directions, may be an important component of normal cardiac function both at rest and with exercise. The effect of exercise on torsion in the general population and the influence of aging on changes in torsion with exercise are not known., Methods: Analysis of torsion, positive and negative torsion velocities, and negative torsion acceleration was performed using speckle tracking imaging on 33 stress echocardiograms using supine bicycle stress., Results: Resting and postexercise torsion could be assessed in 14 patients (42%). A total of 19 patients who were significantly older and larger (mean age 57 years, mean body mass index 28.2, both P < .03) were excluded as a result of inadequate frame rate and image quality after exercise. After exercise, significant increases in peak torsion (10.3 +/- 0.8 vs 13.3 +/- 1.3 degrees, P < .04), peak positive torsion (54.2 +/- 5.6 vs 113.6 +/- 12.3 degrees/s, P < .0001), and peak negative torsion (-56.3 +/- 7.9 vs -100.8 +/- 14.8 degrees/s, P < .03) velocities were observed. Ejection fraction correlated with torsion both at rest and after exercise (r = 0.63, P < .0004). At rest, torsion was greater in older individuals (8.9 +/- 0.6 vs 11.6 +/- 1.2 degrees, P < .04). With increasing age, exercise resulted in less augmentation of torsion (r = 0.59, P < .02) and positive torsion velocity (r = -0.79, P < .003), and decreased negative torsional acceleration (r = 0.60, P < .035)., Conclusions: Exercise results in increased cardiac plecotropy (the augmentation of torsion parameters in response to load or stimulus) but this effect is attenuated with aging. Further investigation is required to determine whether impairment of plecotropy contributes to the reduced exercise capacity associated with aging.

We describe the case of a 54-year-old male with recurrent chest pain, ST segment elevation, and bradycardia. Coronary vasospasm was confirmed by acetylcholine challenge. After failing medical therapy, stenting of an extensive segment of the right coronary artery has been clinically successful after 24-months follow-up., ((c) 2007 Wiley-Liss, Inc.)

Background: Our aim was to study the independent effect of heart rate (HR) on parameters of diastolic function, particularly mitral annular velocities measured by tissue Doppler imaging (TDI), an effect which is not well understood., Methods: Sixteen patients with dual chamber pacemakers attending for routine pacemaker review underwent detailed echocardiographic assessment during atrial pacing with intact atrioventricular conduction at baseline and accelerated HRs. Mitral inflow and annular tissue Doppler velocities and systolic strain parameters were compared., Results: Parameters of systolic function were unaffected by increased HR. When these parameters were compared at baseline (mean 67 bpm) and accelerated HR (mean 80 bpm), the following was observed: a significant decrease in early mitral inflow (E) wave (70.5 +/- 5.5 cm/s vs 63.5 +/- 4.9 cm/s, P < 0.02) and early mitral annular (E') velocities (7.0 +/- 0.5 cm/s vs 6.3 +/- 0.6 cm/s, P < 0.003) and a significant increase in mitral inflow A wave (70.3 +/- 4.5 cm/s vs 77.3 +/- 4.4 cm/s, P < 0.05) and late mitral annular (A') velocities (9.3 +/- 0.6 cm/s vs 10.8 +/- 0.5, P < 0.00004)., Conclusion: Changes in HR have previously unrecognized significant effects on tissue Doppler parameters of diastolic function. Further study is required to determine if tissue Doppler derived annular velocities should be corrected for HR.

Background and Objective: This study's aims were to identify the diagnoses, the public hospital costs and payments for non-New Zealand (non-NZ) patients referred because of possible tuberculosis (TB). There have been no previous financial studies in this area. Funding arrangements for these patients were also reviewed., Methods: A systematic, retrospective review was performed to identify the costs of investigating and managing non-NZ patients referred to the adult TB unit of a large, teaching hospital in Auckland, NZ. Patients were enrolled between 1 July 2002 and 30 June 2003., Results: Forty-five non-NZ patients were studied. The mean age was 33.8 (+/-13.4) years. Thirty-four (75.5%) were managed under compulsion through Section 9 of the NZ TB Act. Thirty-two (71%) patients received TB treatment: 11 (24%) had infectious pulmonary TB and four had active extra-pulmonary TB. There were no multi-drug-resistant isolates. Three TB cases accounted for 250 (39%) inpatient days. One patient with rifampicin-resistant TB was responsible for 117 (29%) day-patient ward visits. Four (13%) infectious TB cases were managed as inpatients for more than 6 weeks. The total cost of services (US dollars) for the 45 patients was 350,236 dollars. The cost range was 544-43,513 dollars per patient. Four patients incurred costs over 25,000 dollars., Conclusions: TB in non-residents is a costly problem in NZ. Current policy applying to this area and the ability to determine its cost-effectiveness are in need of review.

Insulinomas are the most common islet cell tumors and are located almost exclusively in the pancreas. Most of these tumors are sporadic, but they may also be associated with the multiple endocrine neoplasia type I syndrome. More than 90% of insulinomas are benign. Preoperative radiographic localization may prove difficult. Intraoperative palpation and ultrasound remain the gold standard for detection and appropriately planned resection. Although many options are available to treat the patient with malignant and metastatic disease, the mainstay of treatment remains surgery. Laparoscopic ultrasound and enucleation/resection may be increasingly used in the management of patients with insulinoma.