Assessment of distribution and evolution of mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance.

BACKGROUND: We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. METHODS: Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. RESULTS: Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). CONCLUSIONS: Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls.

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10(-11)). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.

Right coronary MR angiography at 7 T: a direct quantitative and qualitative comparison with 3 T in young healthy volunteers.

PURPOSE: To objectively compare quantitative parameters related to image quality attained at coronary magnetic resonance (MR) angiography of the right coronary artery (RCA) performed at 7 T and 3 T. MATERIALS AND METHODS: Institutional review board approval was obtained, and volunteers provided signed informed consent. Ten healthy adult volunteers (mean age ± standard deviation, 25 years ± 4; seven men, three women) underwent navigator-gated three-dimensional MR angiography of the RCA at 7 T and 3 T. For 7 T, a custom-built quadrature radiofrequency transmit-receive surface coil was used. At 3 T, a commercial body radiofrequency transmit coil and a cardiac coil array for signal reception were used. Segmented k-space gradient-echo imaging with spectrally selective adiabatic fat suppression was performed, and imaging parameters were similar at both field strengths. Contrast-to-noise ratio between blood and epicardial fat; signal-to-noise ratio of the blood pool; RCA vessel sharpness, diameter, and length; and navigator efficiency were quantified at both field strengths and compared by using a Mann-Whitney U test. RESULTS: The contrast-to-noise ratio between blood and epicardial fat was significantly improved at 7 T when compared with that at 3 T (87 ± 34 versus 52 ± 13; P = .01). Signal-to-noise ratio of the blood pool was increased at 7 T (109 ± 47 versus 67 ± 19; P = .02). Vessel sharpness obtained at 7 T was also higher (58% ± 9 versus 50% ± 5; P = .04). At the same time, RCA vessel diameter and length and navigator efficiency showed no significant field strength-dependent difference. CONCLUSION: In our quantitative and qualitative study comparing in vivo human imaging of the RCA at 7 T and 3 T in young healthy volunteers, parameters related to image quality attained at 7 T equal or surpass those from 3 T.

A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety.

AIMS: To investigate if vaginal application of dequalinium chloride (DQC, Fluomizin®) is as effective as vaginal clindamycin (CLM) in the treatment of bacterial vaginosis (BV). METHODS: This was a multinational, multicenter, single-blind, randomized trial in 15 centers, including 321 women. They were randomized to either vaginal DQC tablets or vaginal CLM cream. Follow-up visits were 1 week and 1 month after treatment. Clinical cure based on Amsel's criteria was the primary outcome. Secondary outcomes were rate of treatment failures and recurrences, incidence of post-treatment vulvovaginal candidosis (VVC), lactobacillary grade (LBG), total symptom score (TSC), and safety. RESULTS: Cure rates with DQC (C1: 81.5%, C2: 79.5%) were as high as with CLM (C1: 78.4%, C2: 77.6%). Thus, the treatment with DQC had equal efficacy as CLM cream. A trend to less common post-treatment VVC in the DQC-treated women was observed (DQC: 2.5%, CLM: 7.7%; p = 0.06). Both treatments were well tolerated with no serious adverse events occurring. CONCLUSION: Vaginal DQC has been shown to be equally effective as CLM cream, to be well tolerated with no systemic safety concerns, and is therefore a valid alternative therapy for women with BV [ClinicalTrials.gov, Med380104, NCT01125410].

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Climate change data and predictions for the Himalayas are very sparse and uncertain, characterized by a ?Himalayan data gap? and difficulties in predicting changes due to topographic complexity. A few reliable studies and climate change models for Nepal predict considerable changes: shorter monsoon seasons, more intensive rainfall patterns, higher temperatures, and drought. These predictions are confirmed by farmers who claim that temperatures have been increasing for the past decade and wonder why the rains have ?gone mad.? The number of hazard events, notably droughts, floods, and landslides are increasing and now account for approximately 100 deaths in Nepal annually. Other effects are drinking water shortages and shifting agricultural patterns, with many communities struggling to meet basic food security before climatic conditions started changing. The aim of this paper is to examine existing gaps between current climate models and the realities of local development planning through a case study on flood risk and drinking water management for the Municipality of Dharan in Eastern Nepal. This example highlights current challenges facing local-level governments, namely, flood and landslide mitigation, providing basic amenities ? especially an urgent lack of drinking water during the dry season ? poor local planning capacities, and limited resources. In this context, the challenge for Nepal will be to simultaneously address increasing risks caused by hazard events alongside the omnipresent food security and drinking water issues in both urban and rural areas. Local planning is needed that integrates rural development and disaster risk reduction (DRR) with knowledge about climate change considerations. The paper concludes with a critical analysis of climate change modeling and the gap between scientific data and low-tech and low capacities of local planners to access or implement adequate adaptation measures. Recommendations include the need to bridge gaps between scientific models, the local political reality and local information needs.

Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Utilité des biomarqueurs du sepsis en réanimation [Usefulness of biomarkers of sepsis in the ICU].

Despite some progress, the mortality of severe sepsis and septic shock remains high. Immunotherapy directed against inflammatory mediators failed, but new treatments more specifically tailored to individual situations are actively investigated. C-reactive protein (CRP) and procalcitonin (PCT) have not demonstrated to be useful for individual prognostic stratification. New biomarkers such as pancreatic stone protein (PSP) or growth arrest specific protein 6 (Gas6) could improve this prediction. Combined with the clinical course, "PCT" allows to tailor individually the duration of antibiotic therapy in ICU patients. This still contested innovative approach significantly reduces overall exposure to antibiotics.