Background-The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. Methods and Results-We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger's syndrome; New York Heart Association class II to III). Functional class improved by Ն1 class in all patients. Pretreatment versus posttreatment values (meanϮSEM) were as follows: 6-minute walk, 376Ϯ30 versus 504Ϯ27 m, PϽ0.0001; mean PA pressure, 70Ϯ3 versus 52Ϯ3 mm Hg, PϽ0.007; pulmonary vascular resistance index 1702Ϯ151 versus 996Ϯ92 dyne · s · cm Ϫ5 · m Ϫ2, PϽ0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. Figure 1. Short-term inhaled nitric oxide (iNO) reduces pulmonary vascular resistance in PAH, 4,5 but ambulatory delivery in humans is cumbersome. Another strategy is to prolong the survival of cGMP in PASMCs by inhibiting type-5 phosphodiesterase (PD-5), an isoform that is primarily located in the penis and lungs, which rapidly degrades cGMP. Because of PD-5's tissue distribution (pulmonaryϾsystemic vasculature), PD-5 inhibitors are attractive candidate pulmonary vasodilators that minimally decrease systemic blood pressure. (75 mg) is an effective and relatively selective pulmonary vasodilator. 4,5 We hypothesized that PD-5 inhibition acutely causes human PA dilatation, in part by opening of BK Ca channels, and that it chronically improves hemodynamics and functional capacity in moderately severe PAH. Conclusion-This MethodsWe studied 5 consecutive patients with PAH (nϭ4 New York Heart Association [NYHA] class III; patient 3 class II). All subjects provided informed consent. Patients with class IV PAH were excluded because they often require epoprostenol, which could confound the assessment of sildenafil's effects. All the patients had been stable for Ͼ3 months, and their standard therapy was not altered before initiation of sildenafil. All were on diuretics and coumadin, and patients 2 and 4 were on Ca 2ϩ channel blockers because they had been shown to respond to iNO with Ͼ20% decrease in pulmonary vascular resistance (Figure 2). No patient was taking nitrates. All patients had primary pulmonary hypertension (PPH) except patient 2, w...

Automatic Non-rigid Histological Image Registration (ANHIR) challenge was organized to compare the performance of image registration algorithms on several kinds of microscopy histology images in a fair and independent manner. We have assembled 8 datasets, containing 355 images with 18 different stains, resulting in 481 image pairs to be registered. Registration accuracy was evaluated using manually placed landmarks. In total, 256 teams registered for the challenge, 10 submitted the results, and 6 participated in the workshop. Here, we present the results of 7 wellperforming methods from the challenge together with 6 well-known existing methods. The best methods used coarse but robust initial alignment, followed by non-rigid registration, used multiresolution, and were carefully tuned for the data at hand. They outperformed off-the-shelf methods, mostly by being more robust. The best methods could successfully register over 98% of all landmarks and their mean landmark registration accuracy (TRE) was 0.44% of the image diagonal. The challenge remains open to submissions and all images are available for download.

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Color Doppler ultrasound is accurate and sensitive for diagnosis of torsion in the setting of acute scrotum. Despite heterogeneity on preoperative ultrasound, many testes were considered to be salvageable at surgery. The salvage rate of torsed testes was high.

This study presents the novel vascular application of rapid prototyping to pediatric congenital heart disease. Anatomic models are an intuitive means of communicating complex imaging data, such as the pulmonary vascular tree, which can be referenced intraoperatively.

BackgroundPortable oxygen concentrators (POCs) typically include pulse flow (PF) modes to conserve oxygen. The primary aims of this study were to develop a predictive in vitro model for inhaled oxygen delivery using a set of realistic airway replicas, and to compare PF for a commercial POC with steady flow (SF) from a compressed oxygen cylinder.MethodsExperiments were carried out using a stationary compressed oxygen cylinder, a POC, and 15 adult nasal airway replicas based on airway geometries derived from medical images. Oxygen delivery via nasal cannula was tested at PF settings of 2.0 and 6.0, and SF rates of 2.0 and 6.0 L/min. A test lung simulated three breathing patterns representative of a chronic obstructive pulmonary disease patient at rest, during exercise, and while asleep. Volume-averaged fraction of inhaled oxygen (FiO2) was calculated by analyzing oxygen concentrations sampled at the exit of each replica and inhalation flow rates over time. POC pulse volumes were also measured using a commercial O2 conserver test system to attempt to predict FiO2 for PF.ResultsRelative volume-averaged FiO2 using PF ranged from 68% to 94% of SF values, increasing with breathing frequency and tidal volume. Three of 15 replicas failed to trigger the POC when used with the sleep breathing pattern at the 2.0 setting, and four of 15 replicas failed to trigger at the 6.0 setting. FiO2 values estimated from POC pulse characteristics followed similar trends but were lower than those derived from airway replica experiments.ConclusionFor the POC tested, PF delivered similar, though consistently lower, volume-averaged FiO2 than SF rates equivalent to nominal PF settings. Assessment of PF oxygen delivery using POC pulse characteristics alone may be insufficient; testing using airway replicas is useful in identifying possible cases of failure and may provide a better assessment of FiO2.

The use of intraoral ultrasound imaging has received great attention recently due to the benefits of being a portable and low-cost imaging solution for initial and continuing care that is noninvasive and free of ionizing radiation. Alveolar bone is an important structure in the periodontal apparatus to support the tooth. Accurate assessment of alveolar bone level is essential for periodontal diagnosis. However, interpretation of alveolar bone structure in ultrasound images is a challenge for clinicians. This work is aimed at automatically segmenting alveolar bone and locating the alveolar crest via a machine learning (ML) approach for intraoral ultrasound images. Three convolutional neural network–based ML methods were trained, validated, and tested with 700, 200, and 200 images, respectively. To improve the robustness of the ML algorithms, a data augmentation approach was introduced, where 2100 additional images were synthesized through vertical and horizontal shifting as well as horizontal flipping during the training process. Quantitative evaluations of 200 images, as compared with an expert clinician, showed that the best ML approach yielded an average Dice score of 85.3%, sensitivity of 88.5%, and specificity of 99.8%, and identified the alveolar crest with a mean difference of 0.20 mm and excellent reliability (intraclass correlation coefficient ≥0.98) in less than a second. This work demonstrated the potential use of ML to assist general dentists and specialists in the visualization of alveolar bone in ultrasound images.