Iodine chemistry in the troposphere and its effect on ozone

Despite the potential influence of iodine chemistry on the oxidizing capacity of the troposphere, reactive iodine distributions and their impact on tropospheric ozone remain almost unexplored aspects of the global atmosphere. Here we present a comprehensive global modelling experiment aimed at estimating lower and upper limits of the inorganic iodine burden and its impact on tropospheric ozone. Two sets of simulations without and with the photolysis of IxOy oxides (i.e. I2O2, I2O3 and I2O4) were conducted to define the range of inorganic iodine loading, partitioning and impact in the troposphere. Our results show that the most abundant daytime iodine species throughout the middle to upper troposphere is atomic iodine, with an annual average tropical abundance of (0.15-0.55) pptv. We propose the existence of a "tropical ring of atomic iodine" that peaks in the tropical upper troposphere (∼11-14 km) at the equator and extends to the sub-tropics (30°N-30°S). Annual average daytime I = IO ratios larger than 3 are modelled within the tropics, reaching ratios up to ∼20 during vigorous uplift events within strong convective regions. We calculate that the integrated contribution of catalytic iodine reactions to the total rate of tropospheric ozone loss (IOx Loss) is 2-5 times larger than the combined bromine and chlorine cycles. When IxOy photolysis is included, IOx Loss represents an upper limit of approximately 27, 14 and 27% of the tropical annual ozone loss for the marine boundary layer (MBL), free troposphere (FT) and upper troposphere (UT), respectively, while the lower limit throughout the tropical troposphere is ∼9 %. Our results indicate that iodine is the second strongest ozone-depleting family throughout the global marine UT and in the tropical MBL. We suggest that (i) iodine sources and its chemistry need to be included in global tropospheric chemistry models, (ii) experimental programs designed to quantify the iodine budget in the troposphere should include a strategy for the measurement of atomic I, and (iii) laboratory programs are needed to characterize the photochemistry of higher iodine oxides to determine their atmospheric fate since they can potentially dominate halogen-catalysed ozone destruction in the troposphere

Impact of metabolic comorbidity on the association between body mass index and heatlh-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants

<p/>Background: The prevalence of obesity is rising in Scotland and globally. Overall, obesity is associated with increased morbidity, mortality and reduced health-related quality of life. Studies suggest that "healthy obesity" (obesity without metabolic comorbidity) may not be associated with morbidity or mortality. Its impact on health-related quality of life is unknown. <p/>Methods: We extracted data from the Scottish Health Survey on self-reported health-related quality of life, body mass index (BMI), demographic information and comorbidity. SF-12 responses were converted into an overall health utility score. Linear regression analyses were used to explore the association between BMI and health utility, stratified by the presence or absence of metabolic comorbidity (diabetes, hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for potential confounders (age, sex and deprivation quintile). <p/>Results: Of the 5,608 individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had metabolic comorbidity. There was an inverted U-shaped relationship whereby health utility was highest among overweight individuals and fell with increasing BMI. There was a significant interaction with metabolic comorbidity (p = 0.007). Individuals with metabolic comorbidty had lower utility scores and a steeper decline in utility with increasing BMI (morbidly obese, adjusted coefficient: -0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042, 95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). <p/>Conclusions: The adverse impact of obesity on health-related quality of life is greater among individuals with metabolic comorbidity. However, increased BMI is associated with reduced health-related quality of life even in the absence of metabolic comorbidity, casting doubt on the notion of "healthy obesity"

Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

Marine biogenic emissions of benzene and toluene and their contribution to secondary organic aerosols over the polar oceans

Reactive trace gas emissions from the polar oceans are poorly characterized, even though their effects on atmospheric chemistry and aerosol formation are crucial for assessing current and preindustrial aerosol forcing on climate. Here, we present seawater and atmospheric measurements of benzene and toluene, two gases typically associated with pollution, in the remote Southern Ocean and the Arctic marginal ice zone. Their distribution suggests a marine biogenic source. Calculated emission fluxes were 0.023 ± 0.030 (benzene) and 0.039 ± 0.036 (toluene) and 0.023 ± 0.028 (benzene) and 0.034 ± 0.041 (toluene) μmol m−2 day−1 for the Southern Ocean and the Arctic, respectively. Including these average emissions in a chemistry-climate model increased secondary organic aerosol mass concentrations only by 0.1% over the Arctic but by 7.7% over the Southern Ocean, with transient episodes of up to 77.3%. Climate models should consider the hitherto overlooked emissions of benzene and toluene from the polar oceans

Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Safety, efficacy and survival of patients with primary malignant brain tumours (PMBT) in phase I (Ph1) trials: the 12-year Royal Marsden experience.

BACKGROUND:Primary malignant brain tumours (PMBT) constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment options at relapse are limited. First-in-human solid tumour studies have historically excluded patients with PMBT due to the poor prognosis, concomitant drug interactions and concerns regarding toxicities. METHODS:Retrospective data were collected on clinical and tumour characteristics of patients referred for consideration of Ph1 trials in the Royal Marsden Hospital between June 2004 and August 2016. Survival analyses were performed using the Kaplan-Meier method, Cox proportional hazards model. Chi squared test was used to measure bivariate associations between categorical variables. RESULTS:100pts with advanced PMBT were referred. At initial consultation, patients had a median ECOG PS 1, median age 48 years (range 18-70); 69% were men, 76% had glioblastoma; 68% were on AEDs, 63% required steroid therapy; median number of prior treatments was two. Median OS for patients treated on a Ph1 trials was 9.3 months (95% CI 5.9-12.9) versus 5.3 months (95% CI 4.1-6.1) for patients that did not proceed with a Ph1 trial, p = 0.0094. Steroid use, poor PS, neutrophil-to-lymphocyte ratio and treatment on a Ph1 trial were shown to independently influence OS. CONCLUSIONS:We report a survival benefit for patients with PMBT treated on Ph1 trials. Toxicity and efficacy outcomes were comparable to the general Ph1 population. In the absence of an internationally recognized standard second line treatment for patients with recurrent PMBT, more Ph1 trials should allow enrolment of patients with refractory PMBT and Ph1 trial participation should be considered at an earlier stage

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Endocytosis as a biological response in receptor pharmacology: evaluation by fluorescence microscopy

The activation of G-protein coupled receptors by agonist compounds results in diverse biological responses in cells, such as the endocytosis process consisting in the translocation of receptors from the plasma membrane to the cytoplasm within internalizing vesicles or endosomes. In order to functionally evaluate endocytosis events resulted from pharmacological responses, we have developed an image analysis method -the Q-Endosomes algorithm- that specifically discriminates the fluorescent signal originated at endosomes from that one observed at the plasma membrane in images obtained from living cells by fluorescence microscopy. Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent protein (YFP) and permanently expressed in HEK293 cells was used as experimental model to validate this methodology. Time-course experiments performed with several agonists resulted in different sigmoid curves depending on the drug used to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by morphine plus serotonin was significantly different, in kinetics as well as in maximal response parameters, from the one caused by DAMGO, sufentanyl or methadone. Therefore, this analytical tool permits the pharmacological characterization of receptor endocytosis in living cells with functional and temporal resolution

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients