The value of susceptibility weighted imaging for immediate assessing the hyperacute outcome of MRgFUS ablation for uterine fibroids: a preliminary study.

PURPOSE: To investigate the value of susceptibility weighted imaging (SWI) for assessing the hyperacute outcome of ablation of uterine fibroids immediately after magnetic resonance-guided focused ultrasound (MRgFUS) treatment. METHODS: This retrospective imaging study included patients who underwent SWI and contrast-enhanced (CE) MR within 15 min of MRgFUS ablation for uterine fibroids. Two readers independently assessed the SWI features of ablative lesions and their association with the non-perfused volume (NPV) ratio. The intraclass correlation coefficient (ICC) and diagnostic value of SWI findings were calculated. RESULTS: A total of 27 uterine fibroids from 21 participants (mean age 40.1 ± 7.2 years) were analyzed. 51.9% (14/27) leiomyomas had NPV ratio ≥90%. In post-ablation SWI images, the interobserver ICC for the relative signal intensity and hypointense peripheral rim were 0.613 and 0.843, respectively (both p < .001). There was a significant difference in the prevalence of hypointense peripheral rim in leiomyomas with NPV ratio ≥90% and < 90% (p < .01), while the prevalence of relative signal intensity showed no significant difference (p > .05). When using the complete hypointense peripheral rim as a diagnostic criterion to identify NPV ratio ≥ 90%, readers 1 and 2 showed diagnostic sensitivity, specificity, and accuracy of 85.7%, 76.9%, 81.5%, and 78.6%, 76.9%, 77.8%, respectively. CONCLUSION: Identifying a complete hypointense peripheral rim on SWI may be a potential imaging marker for assessing the hyperacute outcome of uterine fibroids ablation by MRgFUS, specifically in determining whether the NPV ratio is ≥90%.

Diffusion-weighted imaging as a potential non-gadolinium alternative for immediate assessing the hyperacute outcome of MRgFUS ablation for uterine fibroids.

The aim of this study was to investigate the value of diffusion-weighted imaging (DWI) as a potential non-gadolinium alternative for promptly assessing the hyperacute outcome of magnetic resonance-guided focused ultrasound (MRgFUS) treatment for uterine fibroids. In this retrospective study we included 65 uterine fibroids from 44 women, who underwent axial DWI (b-value: 800 s/mm2) and contrast-enhanced (CE) MR within 15 min post-ablation. Two blinded observers independently reviewed the DWI findings of ablated necrotic lesions and measured their volumes on DWI and CE images. The post-ablation DWI images revealed clear depiction of ablative necrotic lesions in all fibroids, which were classified into two types: the bull's eye sign (type 1) and the bright patch sign (type 2). The inter-observer intraclass correlation coefficient for classifying DWI signal types was 0.804 (p < 0.001). Volumetric analysis of ablated necrosis using DWI and CE T1-weighted imaging showed no significant variance, nor did the non-perfused volume ratios (all p > 0.05). Bland-Altman analysis revealed a mean difference of 2.38% and 1.71% in non-perfused volume ratios between DWI and CE, with 95% limits of agreement from - 19.06 to 23.82% and - 18.40 to 21.82%, respectively. The findings of this study support the potential of DWI as a viable non-gadolinium alternative for evaluating the hyperacute outcomes of MRgFUS ablation in uterine fibroids.

microRNAs, the Link Between Dengue Virus and the Host Genome.

Dengue virus (DENV) is a small envelope virus of Flaviviridae that is mainly transmitted by Aedes aegypti and Aedes albopictus. It can cause dengue fever with mild clinical symptoms or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). At present, there are no specific drugs or mature vaccine products to treat DENV. microRNAs (miRNAs) are a class of important non-coding small molecular RNAs that regulate gene expression at the post-transcriptional level. It is involved in and regulates a series of important life processes, such as growth and development, cell differentiation, cell apoptosis, anti-virus, and anti-tumor. miRNAs also play important roles in interactions between host and viral genome transcriptomes. Host miRNAs can directly target the genome of the virus or regulate host factors to promote or inhibit virus replication. Understanding the expression and function of miRNAs during infection with DENV and the related signal molecules of the miRNA-mediated regulatory network will provide new insights for the development of miRNA-based therapies.

Involvement of Arabidopsis phospholipase D δ in regulation of ROS-mediated microtubule organization and stomatal movement upon heat shock.

Reactive oxygen species (ROS) are plant metabolic and signaling molecules involved in responses to various external stresses, but the existence of ROS receptors and how plants respond to ROS remain largely unknown. Here we report that the plasma membrane-localized phospholipase D δ (PLDδ) protein is crucial for sensing heat shock-induced ROS to initiate reorganization of guard cell microtubules in Arabidopsis cotyledons. Heat shock of wild-type Arabidopsis cotyledons stimulated ROS production which disrupted microtubule organization and induced stomatal closure, whereas this process was markedly impaired in pldδ mutants. Moreover, wild-type PLDδ, but not the Arg622-mutated PLDδ, complemented the pldδ phenotypes in heat shock-treated plants. ROS activated PLDδ by oxidizing cysteine residues, an action that was required for its functions in ROS-induced depolymerization of guard cell microtubules, stomatal closure, and plant thermotolerance. Additionally, lipid profiling reveals involvement of microtubule organization in the feedback regulation of glycerolipid metabolism upon heat stress. Together, our findings highlight a potential mechanosensory role for PLDδ in regulating the dynamic organization of microtubules and stomatal movement, as part of the ROS-sensing pathway, during the response to external stresses.

An investigation of the relationship between cataract surgery wait times and rates of surgery.

OBJECTIVE: The relationship between cataract surgery wait times and rates of surgery was investigated to determine whether wait times correlate with rates of surgery. DESIGN: Cross-sectional study. PARTICIPANTS: We collected 2 Ontario registries for cataract surgeries: (i) Cancer Care Ontario wait time registry; and (ii) The Ontario Health Insurance Plan billing records. METHODS: Both registries were used to determine whether wait times correlated with rates of surgery, and the data were then stratified by region of the province, priority (severity) of cases, age, and sex. RESULTS: The total number of surgeries performed between April 2, 2007, and March 31, 2008, was 65,520. The overall mean number of wait days was 69.8 days; the mean patient age was 72.5 years; and the surgery rate was 540.3 per 100,000 members of the population. For high-priority cases (priorities 1 and 2), there was a very weak inverse correlation (p = -0.27 and -0.21) between wait time and surgery rate, whereas the overall correlation between wait time and surgical rate was close to zero in both databases, regardless of the region, the patients' ages, and the patients' genders. CONCLUSIONS: This study demonstrates a very weak correlation between wait times for and rates of cataract surgery, and this should be a concern for policy makers. Further study is needed to see whether this null relationship persists over time and whether it exists for other monitored wait time procedures. Reasons for this null relationship will have to be determined and remedied as the use of wait times becomes a more widespread outcome in Canadian Healthcare.

VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: results of the NORTHERN trial.

Despite the promise of proangiogenic gene therapy most clinical trials have failed to show benefit for the primary end point analysis. The NOGA angiogenesis Revascularization Therapy: assessment by RadioNuclide imaging (NORTHERN) trial was a double-blind, placebo-controlled study of intramyocardial vascular endothelial growth factor (VEGF165) gene therapy versus placebo, involving seven sites across Canada, designed to overcome major limitations of previous proangiogenic gene therapy trials. A total of 93 patients with refractory Canadian Cardiovascular Society (CCS) class 3 or 4 anginal symptoms were randomized to receive 2,000 microg of VEGF plasmid DNA or placebo (buffered saline) delivered via the endocardial route using an electroanatomical NOGA guidance catheter. There was no difference between the VEGF-treated and the placebo groups in the primary end point of change in myocardial perfusion from baseline to 3 or 6 months, assessed by single photon emission tomography (SPECT) imaging, although a significant reduction in the ischemic area was seen in both groups. Also, similar improvements in exercise treadmill time and anginal symptoms were seen in the VEGF and the placebo groups at 3 and 6 months, although again there were no differences between these groups. Despite the intramyocardial administration of a high "dose" of plasmid DNA using a percutaneous guidance catheter system, there was no benefit of VEGF gene therapy at 3 or 6 months for any of the end points studied.

The safety of targeted antibiotic therapy for ventilator-associated pneumonia: a multicenter observational study.

PURPOSE: The aim of this study was to determine the safety of targeted antibiotic therapy (TT) in ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: This was a secondary analysis from a multicenter trial of 740 patients with suspected VAP randomized to bronchoscopy or endotracheal aspirate cultures; all received empirical broad-spectrum antibiotics. Patients were grouped by whether they received TT, defined as tailoring or discontinuing antibiotics in response to enrolment culture results. RESULTS: For patients with a positive culture (n = 412), baseline demographics, clinical progression of infection and multiple organ dysfunction scores (MODS), and mortality were similar for those on TT (n = 320) or those who did not receive TT (NoTT) (n = 92). The TT group had more days alive and off broad-spectrum antibiotics (14.5 vs 13.2, P = .04). In patients with a negative culture (n = 327), those on TT (n = 230) had similar baseline demographics, less frequent final adjudicated diagnosis of VAP (63.0% vs 76.3%, P = .02), and less severe clinical progression of infection and MODS compared with NoTT (n = 97). The TT group had more days alive and off broad-spectrum antibiotics (15.9 vs 13.1, P < .001), lower delta MODS (2.0 vs 3.0, P = .01), fewer mechanical ventilation days (9.8 vs 14.7, P = .03), and similar mortality compared to NoTT. CONCLUSIONS: Targeted therapy is associated with less antibiotic use and no evidence of harm in the management of patients with VAP.

Incidence of cutaneous malignant melanoma in the Ottawa region: 1996 to 2006.

BACKGROUND: The incidence rates of invasive primary cutaneous malignant melanoma in Canada have shown a gradual tapering in recent years, after decades of increases. This trend suggests that the incidence of melanoma in Canada is stabilizing; however, knowledge of the recent trend for both in situ and invasive tumors was lacking. OBJECTIVE: The purpose of this study was to examine the temporal trend of both in situ and invasive melanoma within the Ottawa region over a 10-year period. METHODS: The histopathology of cutaneous melanomas diagnosed in the Ottawa region was obtained for the years 1996, 2001, and 2006 from the main diagnostic centers servicing the area; however, not all melanomas have been accounted for. All rates are expressed per 100,000 population per year. RESULTS: Melanoma incidence decreased between 1996 and 2001 (-3.83) and increased between 2001 and 2006 (+7.46; p < or = .05). This increase is mainly attributable to in situ melanoma (+5.49; p < or = .05). There has been no statistically significant change in invasive melanoma. CONCLUSIONS: Invasive melanoma incidence in the Ottawa region remained stable, whereas in situ melanoma incidence increased.