CO2 surgical laser for treatment of stress urinary incontinence in women: a randomized controlled trial.

BACKGROUND: Stress urinary incontinence is a common condition that can be treated conservatively and/or surgically. Given the risks of surgery, developing effective nonsurgical treatment options would be beneficial. Some studies have suggested that laser therapy may improve or cure stress urinary incontinence. However, there is a lack of sham-controlled randomized controlled trials to judge treatment efficacy. OBJECTIVE: This study aimed to compare the effects of CO2 vaginal laser vs sham therapy for treating stress urinary incontinence. STUDY DESIGN: This was a multicenter, participant-blinded, sham-controlled, parallel group (1:1) superiority randomized controlled trial performed in outpatient clinics in 2 hospitals. We included women aged 18 to 80 years with objective and subjective stress urinary incontinence. Participants had undertaken or declined supervised pelvic floor muscle training. Intervention was performed using a CO2 fractionated vaginal laser. Participants underwent 3 treatments, 4 weeks apart, with increasing energy and density settings. Sham treatment was performed using an identical technique with a deactivated pedal. The primary outcome was the subjective stress urinary incontinence rate (proportion with leak with cough, sneeze, or laughter) at 3 months after completion of treatment. Secondary outcomes included objective stress urinary incontinence, change in the disease-specific patient-reported outcomes, health-related quality of life, and adverse effects. Categorical outcomes were compared using the chi square test and continuous outcomes using analysis of covariance, adjusting for the baseline score. RESULTS: There were 52 participants who received laser and 49 who received sham treatment. One participant in each group withdrew from the study before the endpoint, and 2 participants in the laser group did not participate in the follow-up visits. Participant mean age was 53 (34-79) years. Mean body mass index was 26.1 (18.1-49.6); 90% were vaginally parous. At 3 months, there was no difference between the sham and active treatment arm in subjective stress urinary incontinence (46 [96%] vs 48 [98%]; relative risk, 0.98 [95% confidence interval, 0.91-1.05]; P=.55) or in objective stress urinary incontinence (37 [80%] vs 33 [80%]; relative risk, 0.99 [95% confidence interval, 0.81-1.23]; P=.995). Patient-reported outcomes and health-related quality of life were also comparable between the groups. Vaginal bleeding occurred in 3 participants after laser and 1 participant after sham treatment. Pain during treatment did not differ between laser and sham treatment. CONCLUSION: We were unable to show an improvement in stress urinary incontinence after CO2 vaginal laser therapy compared with sham treatment.

Small lightning flashes from shallow electrical storms on Jupiter.

Lightning flashes have been observed by a number of missions that visited or flew by Jupiter over the past several decades. Imagery led to a flash rate estimate of about 4 × 10-3 flashes per square kilometre per year (refs. 1,2). The spatial extent of Voyager flashes was estimated to be about 30 kilometres (half-width at half-maximum intensity, HWHM), but the camera was unlikely to have detected the dim outer edges of the flashes, given its weak response to the brightest spectral line of Jovian lightning emission, the 656.3-nanometre Hα line of atomic hydrogen1,3-6. The spatial resolution of some cameras allowed investigators to confirm 22 flashes with HWHM greater than 42 kilometres, and to estimate one with an HWHM of 37 to 45 kilometres (refs. 1,7-9). These flashes, with optical energies comparable to terrestrial 'superbolts'-of (0.02-1.6) × 1010 joules-have been interpreted as tracers of moist convection originating near the 5-bar level of Jupiter's atmosphere (assuming photon scattering from points beneath the clouds)1-3,7,8,10-12. Previous observations of lightning have been limited by camera sensitivity, distance from Jupiter and long exposures (about 680 milliseconds to 85 seconds), meaning that some measurements were probably superimposed flashes reported as one1,2,7,9,10,13. Here we report optical observations of lightning flashes by the Juno spacecraft with energies of approximately 105-108 joules, flash durations as short as 5.4 milliseconds and inter-flash separations of tens of milliseconds, with typical terrestrial energies. The flash rate is about 6.1 × 10-2 flashes per square kilometre per year, more than an order of magnitude greater than hitherto seen. Several flashes are of such small spatial extent that they must originate above the 2-bar level, where there is no liquid water14,15. This implies that multiple mechanisms for generating lightning on Jupiter need to be considered for a full understanding of the planet's atmospheric convection and composition.

Imaging-Based Surrogate Markers of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma: A Local Perspective.

PURPOSE: To identify computed tomography (CT) features of epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma in Canadian population and whether imaging-based surrogate markers of EGFR mutation in our population were similar to those found in the Asian population. MATERIALS AND METHODS: Pretreatment CT scans of 223 patients with adenocarcinoma of the lung (112 with EGFR mutation and 111 without mutation) were retrospectively assessed for 20 specific CT features by 2 radiologists, who were blinded to the status of EGFR mutation. Univariate and multivariate logistic regression analyses as well as areas under the receiver operating characteristic curve were performed to discriminate characteristics of EGFR-activating mutation features. RESULTS: Epidermal growth factor receptor mutation-positive adenocarcinomas were more frequently found in female (P < .03), less than 20 pack-year smoking history (P < .001), smaller tumor (P < .01), spiculated margins (P < .05), without centrilobular emphysema (P < .001), and without lymphadenopathy (P < .05), similarly to the Asian population. Multivariate logistic regression analyses of combined clinical and radiological features identified less than 20 pack-year smoking history, smaller tumor diameter, fine or coarse spiculations, noncentral location of the tumor, and lack of centrilobular emphysema and pleural attachment as the strongest independent prognostic factors for the presence of an EGFR mutation. These combined features improved prognostic ability area under the curve to 0.879, compared to 0.788 for clinical features only. CONCLUSION: Several CT findings may help predict the presence of an activating mutation in EGFR in lung adenocarcinomas in our Canadian population. Combining clinical and radiological features improves prognostic ability to determine the EGFR mutation status compared to clinical features alone.

Patient attitude and acceptance towards episiotomy during pregnancy before and after information provision: a questionnaire.

INTRODUCTION AND HYPOTHESIS: Evidence regarding how women feel about episiotomies is not recorded in the literature. As the most common surgical procedure, there is a need to understand how women feel about episiotomy. METHODS: The primary outcome was to identify the percentage of women who would accept an episiotomy if required. A literature review was compiled to provide nulliparous women in their third trimester with evidence-based information about episiotomies and perineal tears. Questions eliciting demographics, pre-information level of anxiety and acceptance of episiotomy were asked. After reading the information sheets, anxiety and knowledge were assessed again. Changes in anxiety levels from pre- to post-information were investigated using paired samples t tests. Because anxiety was measured on a scale, we assessed potential departures from normality by using the Wilcoxon signed-rank test. Questions also assessed the value women placed on this form of education. RESULTS: There were 105 responses, with 88% accepting episiotomy, 2% declining and 10% seeking more information to decide. Eighty-one percent of women agreed that the information provided helped them to understand more about childbirth and 62% agreed that they felt more comfortable with the birthing process after reading the material. There was a reduction in anxiety levels regarding episiotomies after reading information (p = 0.002) and perineal tears (p = 0.02). CONCLUSIONS: Most women will accept an episiotomy if required. Antenatal education about episiotomies is important to women and helps them feel more comfortable with the birthing process. Written information increases acceptance and reduces anxiety levels regarding episiotomies.

Head and neck squamous cell carcinoma: prediction of cervical lymph node metastasis by dual-energy CT texture analysis with machine learning.

OBJECTIVES: This study was conducted in order to evaluate a novel risk stratification model using dual-energy CT (DECT) texture analysis of head and neck squamous cell carcinoma (HNSCC) with machine learning to (1) predict associated cervical lymphadenopathy and (2) compare the accuracy of spectral versus single-energy (65 keV) texture evaluation for endpoint prediction. METHODS: Eighty-seven patients with HNSCC were evaluated. Texture feature extraction was performed on virtual monochromatic images (VMIs) at 65 keV alone or different sets of multi-energy VMIs ranging from 40 to 140 keV, in addition to iodine material decomposition maps and other clinical information. Random forests (RF) models were constructed for outcome prediction with internal cross-validation in addition to the use of separate randomly selected training (70%) and testing (30%) sets. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for predicting positive versus negative nodal status in the neck. RESULTS: Depending on the model used and subset of patients evaluated, an accuracy, sensitivity, specificity, PPV, and NPV of up to 88, 100, 67, 83, and 100%, respectively, could be achieved using multi-energy texture analysis. Texture evaluation of VMIs at 65 keV alone or in combination with only iodine maps had a much lower accuracy. CONCLUSIONS: Multi-energy DECT texture analysis of HNSCC is superior to texture analysis of 65 keV VMIs and iodine maps alone and can be used to predict cervical nodal metastases with relatively high accuracy, providing information not currently available by expert evaluation of the primary tumor alone. KEY POINTS: • Texture features of HNSCC tumor are predictive of nodal status. • Multi-energy texture analysis is superior to analysis of datasets at a single energy. • Dual-energy CT texture analysis with machine learning can enhance noninvasive diagnostic tumor evaluation.

αNAC interacts with histone deacetylase corepressors to control Myogenin and Osteocalcin gene expression.

In the nucleus of differentiated osteoblasts, the DNA-binding αNAC protein acts as a transcriptional coactivator of the Osteocalcin gene. Chromatin immunoprecipitation-microarray assays (ChIP-chip) showed that αNAC binds the Osteocalcin promoter but also identified the Myogenin promoter as an αNAC target. Here, we confirm these array data using quantitative ChIP and further detected that αNAC binds to these promoters in myoblasts. Since these genes are differentially regulated during osteoblastogenesis or myogenesis, these results suggest cell- and promoter-context specific functions for αNAC. We hypothesized that αNAC dynamically recruits corepressors to inhibit Myogenin expression in cells committing to the osteoblastic lineage or to inhibit Osteocalcin transcription in differentiating myoblasts. Using co-immunoprecipitation assays, we detected complexes between αNAC and the corepressors HDAC1 and HDAC3, in myoblasts and osteoblasts. Sequential ChIP confirmed HDAC1 recruitment by αNAC at the Osteocalcin and Myogenin promoters. Interaction with the corepressors was detectable in pre-osteoblasts and in myoblasts but disappeared as the cells differentiate. Treatment with an HDAC inhibitor caused de-repression of Osteocalcin expression in myoblasts. Overexpression of αNAC in myoblasts inhibits expression of Myogenin and differentiation. However, overexpression of an N-terminus truncated αNAC mutant allowed myoblasts to express Myogenin and differentiate, and this mutant did not interact with HDAC1 or HDAC3. This study identified an additional DNA-binding target and novel protein-protein interactions for αNAC. We propose that αNAC plays a role in regulating gene transcription during mesenchymal cell differentiation by differentially recruiting corepressors at target promoters.