Citations

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.

Abstract Background: NPC is endemic to Asia and over 40% of cases harbor PIK3CA amplification. MK2206 is an allosteric AKT inhibitor with activity in NPC in vitro. Methods: Pts who had progressed after palliative chemotherapy (chemo) for metastatic or recurrent NPC, received oral MK-2206 at 200 mg on Days 1, 8, 15 & 22 of each 28-day cycle until disease progression. Plasma samples were collected at serial time points during cycle 1 for EBV DNA analysis, archived tumor samples were collected where feasible. The primary dual endpoints (2-stage design) consisted of RECIST-defined tumor response rate (RR) and 6-month (m) progression-free survival (PFS) rate. Secondary endpoints were overall survival (OS), PFS and adverse events (AEs). Results: Of the 21 pts enrolled, the median age was 47 years (range: 32-67), 91% were male, 81% had prior radiotherapy and 81% had > 1 prior line of palliative chemo. At the time of analysis, 20 out of 21 pts have ended treatment. The best responses were: 1 partial response (PR, 5%) lasting 4 ms; 10 stable disease (SD, 50%), 9 progressive disease (PD, 45%). The 6-m PFS rate was 38.9% (95% CI: 18.1-59.3%) and median PFS was 2.7 ms (95% CI: 0.9-7.2 ms). The 6-m OS rate was 67.9% (95% CI: 41.8-84.1%) and median survival has not been reached. In 7 pts who had SD more than or equal to 6 ms, the duration of treatment ranged from 6.4-13.9 ms. Of the 21 pts evaluable for AEs, 12 pts (57%) had at least one grade 3 AE [[Unable to Display Character: –]] macular rash (6 pts - 29%), dysphagia (2 pts - 10%), hyperglycemia (2 pts - 10%) (see Table 1). The tumor samples of 7 pts were analyzed by FISH; 3 showed PIK3CA amplification, including 1 pt with chromosome 3 polysomy. Amongst these pts, 1 had SD more than 6ms, 1 had SD more than 12 ms, and 1 is still on treatment. Pts who had SD less than 6 m or PD did not have PIK3CA amplification. Conclusions: MK2206 is well tolerated and has signs of activity in unselected pts with NPC. Preliminary results suggest that PIK3CA amplification may be related to prolonged disease stabilization from MK2206, and analysis for other PIK3CA gene alterations in more samples will be undertaken. Result of the plasma EBV DNA result will be presented. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B273. Citation Format: Brigette B. Ma, Boon Cher Goh, Wan Teck Lim, Eng Huat Tan, Gilberto de Lima Lopes, Edwin P. Hui, Ann D. King, Kwok Wai Lo, Herbert Loong, Leung Li, Nathan Foster, Michael Kam, Sing Fai Leung, Charles Erlichman, Anthony TC Chan. Multicenter Phase II study of MK-2206 in previously treated patients (pts) with recurrent and metastatic nasopharyngeal carcinoma (NPC): Mayo Clinic Phase II Consortium (Protocol: MC1079). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B273.