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AbstractBackgroundThis study compared prucalopride, a selective, prokinetic, 5‐HT4 receptor agonist, with polyethylene glycol 3350 + electrolytes (PEG3350), an osmotic laxative, on colonic motility parameters, primarily high‐amplitude propagating contractions (HAPCs) in patients with chronic constipation.MethodsThis randomized, cross‐over, reader‐blinded study was conducted at a single site in the USA. The study was open to men and women aged 18–75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 × 13.8 g PEG3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude ≥100 mmHg, propagation ≥20 cm [HAPC1]) in the 12 h after treatment administration. Analyses were also conducted at two co‐primary thresholds: mean amplitude ≥75 mmHg, propagation ≥20 cm (HAPC2); and mean amplitude ≥75 mmHg, propagation ≥10 cm (HAPC3). Secondary endpoints included HAPC area under the curve (AUC), contraction force, amplitude, duration, and propagation velocity.Key ResultsThirteen women were enrolled, with 12 completing the study. Significantly more HAPC1 (8.7 ± 2.06 vs 2.9 ± 2.06; p = 0.012) and HAPC2 (9.0 ± 2.11 vs 3.3 ± 2.11; p = 0.017) were observed in the 12‐h periods with prucalopride than with PEG3350. Prucalopride significantly increased mean propagation distance and velocity (HAPC2) and mean AUC, force, and amplitude (HAPC3) compared with PEG3350. Adverse events were mild or moderate.Conclusions & InferencesPrucalopride was superior to PEG3350 in inducing HAPCs in patients with chronic constipation.ClinicalTrials.gov number NCT01707667.

In this work, an ultrasound-guided remote measurement technique is proposed for bone demineralization assessment. Utilizing an acoustic radiation force (ARF) beam as our excitation source and a receiving hydrophone, the mechanical properties of a bone can be noninvasively assessed. Focusing the ARF beam on the bone surface acts as point force generating vibrational waves. Coupling the bone surface and hydrophone, the ensuing radiating acoustic pressure from these vibrational waves are captured for analysis. Of particular interest, are the features best related to the bone’s mechanical properties. Conducting ex-vivo experiments demonstrated that the velocity feature best delineates intact and demineralized bones. The typical velocity of an intact bone (3000 m/s) is higher in comparison to a 72 h demineralized bone (1600 m/s). According to the receiver operating characteristic (ROC) curve, the optimal velocity cut-off value of 3096 m/s yields 80% sensitivity and 82.61% specificity between the intact and demineralized bones. Other features, such as the spectra of the demineralized bones’ acoustic response, exhibited higher attenuation for frequencies below 200 kHz in comparison to the intact bones. A time-frequency analysis demonstrated a frequency shift with demineralization. These results demonstrate the potential application of our proposed technique for monitoring bone demineralization.

Summary Background and Purpose Sprawling ( Swl ) is a radiation‐induced mutation which has been identified to have a nine base pair deletion in dynein heavy chain 1 (DYNC1H1: encoded by a single gene Dync1h1 ). This study is to investigate the phenotype and the underlying mechanism of the Dync1h1 mutant. Methods and Results To display the phenotype of Swl mutant mice, we examined the embryos of homozygous ( Swl/Swl ) and heterozygous ( Swl /+) mice and their postnatal dorsal root ganglion (DRG) of surviving Swl /+ mice. The Swl /+ mice could survive for a normal life span, while Swl/Swl could only survive till embryonic (E) 8.5 days. Excessive apoptosis of Swl/ + DRG neurons was revealed during E11.5–E15.5 days, and the peak rate was at E13.5 days. In vitro study of mutated DRG neurons showed impaired retrograde transport of dynein‐driven nerve growth factor (NGF). Mitochondria, another dynein‐driven cargo, demonstrated much slower retrograde transport velocity in Swl/+ neurons than in wild‐type (WT) neurons. Nevertheless, the Swl , Loa, and Cra mutations did not affect homodimerization of DYNC1H1. Conclusion The Swl/Swl mutation of Dync1h1 gene led to embryonic mal‐development and lethality, whereas the Swl/+ DRG neurons demonstrated deficient retrograde transport in dynein‐driven cargos and excessive apoptosis during mid‐ to late‐developmental stages. The underlying mechanism of the mutation may not be due to impaired homodimerization of DYNC1H1.

Polarity protein complexes are crucial for epithelial apical-basal polarity and directed cell migration. Since alterations of these processes are common in cancer, polarity proteins have been proposed to function as tumor suppressors or oncogenic promoters. Here, we review the current understanding of polarity protein functions in epithelial homeostasis, as well as tumor formation and progression. As most previous studies focused on the function of single polarity proteins in simplified model systems, we used a genomics approach to systematically examine and identify the expression profiles of polarity genes in human cancer. The expression profiles of polarity genes were distinct in different human tissues and classified cancer types. Additionally, polarity expression profiles correlated with disease progression and aggressiveness, as well as with identified cancer types, where specific polarity genes were commonly altered. In the case of Scribble, gene expression analysis indicated its common amplification and upregulation in human cancer, suggesting a tumor promoting function.

Though congenital pericardial absence is often asymptomatic, complications can be life threatening. To date, few short case reports, primarily from the pre-CT and MR era, describe congenital absence of the right pericardium. We present a more comprehensive discussion of the embryologic derangements causing such defects and offer an up-to-date review of characteristic radiologic findings. Recognition of characteristic imaging findings of congenital pericardial absence is crucial in guiding diagnosis and management.

ObjectivesTo determine the frequency and predictors of pericardial effusion following epicardial sheath removal.BackgroundPericardial effusion can occur following cardiac surgical or interventional procedures including percutaneous epicardial access (EpiAcc), which is increasingly used as part of electrophysiology ablation procedures.MethodsA retrospective analysis of the Mayo Clinic comprehensive electronic medical record was performed from all patients who underwent planned EpiAcc as part of an electrophysiology ablation procedure between January 1, 2004 and June 30, 2013.ResultsOf 144 patients (mean age 51.3 ± 15.5 years, 68% male) who underwent planned EpiAcc as part of an electrophysiology ablation (95.8% pericardial access success rate), seven (4.9%) developed a postoperative pericardial effusion requiring repeat EpiAcc. Inferior access was utilized in 74 (51.4%) patients. Patients with pericardial effusion tended to be younger (41.1 years vs 51.8 years, P = 0.08) and were more likely to have undergone inferior approach access (85.7% vs 49.6%, P = 0.06) than those who did not develop postoperative pericardial effusion. Seventy‐one percent of patients with postoperative pericardial effusion versus 32.1% of patients without postoperative pericardial effusion had a preprocedure ejection fraction ≥55% (P = 0.03). There were no procedural‐related deaths, and no difference in mortality between groups.ConclusionsPostoperative pericardial effusion requiring repeat access/drainage was relatively infrequent, occurring in 4.9% of patients shortly after epicardial procedures. While the majority occur early and therefore require close observation, some patients may present in a delayed manner.