Effects of Oral Saline Consumption on Heart Rate Variability Measurements During Postural Change

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Hydration Status Effect on Anaerobic Power and Fatigue in Collegiate Female Soccer Players

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Successful Use of Squeezed-Fat Grafts to Correct a Breast Affected by Poland Syndrome

This study attempted to reconstruct deformities of a Poland syndrome patient using autologous fat tissues. All injected fat tissues were condensed by squeezing centrifugation. Operations were performed four times with intervals over 6 months. The total injection volume was 972 ml, and the maintained volume of 628 ml was measured by means of a magnetic resonance image (MRI). The entire follow-up period was 4.5 years. After surgery, several small cysts and minimal calcifications were present but no significant complications. The cosmetic outcomes and volume maintenance rates were excellent despite the overlapped large-volume injections. In conclusion, higher condensation of fat tissues through squeezing centrifugation would help to achieve better results in volume maintenance and reduce complications. It is necessary, however, to perform more comparative studies with many clinical cases for a more scientific analysis. The study experiments with squeezed fat simply suggest a hypothesis that squeezing centrifugation could select healthier cells through pressure disruption of relatively thinner membranes of larger, more vulnerable and more mature fat cells

Power losses in thick steel laminations with hysteresis

Magnetic power losses have been experimentally investigated and theoretically predicted over a range of frequencies (direct current—1.5 kHz) and peak inductions (0.5-1.5 T) in 1‐mm‐thick FeSi 2 wt. % laminations. The direct current hysteresis properties of the system are described by the Preisach model, with the Preisach distribution function reconstructed from the measurement of the recoil magnetization curve (Bp=1.7 T). On this basis, the time behavior of the magnetic induction vs frequency at different lamination depths is calculated by a finite element method numerical solution of Maxwell equations, which takes explicitly into account the Preisach model hysteretic B(H) relationship. The computed loop shapes are, in general, in good agreement with the measured ones. The power loss dependence on frequency is predicted and experimentally found to change from a ∼f3/2 to a ∼f2 law with increasing peak induction

Dynamic interaction of PTP mu with multiple cadherins in vivo

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTP mu associates with the cadherin-catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977-986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTP mu interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTP mu, and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTP mu and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTP mu from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTP mu in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513-1517) have asserted that the association we observed between PTP mu and the cadherin-catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTP mu, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTP mu. obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTP mu antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTP mu, and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function

Empowerment and satisfaction in a multinational study of routine clinical practice

Objective: Decision-making between mental health clinicians and patients is under-researched. We tested whether mental health patients are more satisfied with a decision made (i) using their preferred decision-making style and (ii) with a clinician with the same decision-making style preference. Method: As part of the CEDAR Study (ISRCTN75841675), a convenience sample of 445 patients with severe mental illness from six European countries were assessed for desired clinical decision-making style (rated by patients and paired clinicians), decision-specific experienced style and satisfaction. Results: Patients who experienced more involvement in decision-making than they desired rated higher satisfaction (OR = 2.47, P = 0.005, 95% CI 1.32–4.63). Decisions made with clinicians whose decision-making style preference was for more active involvement than the patient preference were rated with higher satisfaction (OR = 3.17, P = 0.003, 95% CI 1.48–6.82). Conclusion: More active involvement in decision-making than the patient stated as desired was associated with higher satisfaction. A clinical orientation towards empowering, rather than shared, decision-making may maximise satisfaction

Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific.Results: Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly.Methods: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples.Conclusions: We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery

Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma

Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies

Participation in medical decision-making across Europe: an international longitudinal multicenter study

Background: The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries. Methods: The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations. Results: We found large cross-national differences in patients’ desire to participate in decision-making, with the center explaining 40% of total variance in the desire for participation (p<0.001). Averaged over time and independent of patient characteristics, London (mean=2.27), Ulm (mean=2.13) and Zurich (mean=2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean=1.97), where scores were in turn significantly higher than in Debrecen (mean=1.56). The lowest scores were reported in Naples (mean=1.14). Over time, desire for participation in decision-making increased significantly in Zurich (b=0.23) and decreased in Naples (b=-0.14). In all other centers, values remained stable. Conclusions: This study demonstrates that patients’ desire for participation in decisionmaking varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe

KEYNOTE-022 part 3: A randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

Background In the KEYNOTE-022 study, pembrolizumab with dabrafenib and trametinib (triplet) improved progression-free survival (PFS) versus placebo with dabrafenib and trametinib (doublet) without reaching statistical significance. Mature results on PFS, duration of response (DOR), and overall survival (OS) are reported. Methods The double-blind, phase 2 part of KEYNOTE-022 enrolled patients with previously untreated BRAF V600E/K-mutated advanced melanoma from 22 sites in seven countries. Patients were randomly assigned 1:1 to intravenous pembrolizumab (200 mg every 3 weeks) or placebo plus dabrafenib (150 mg orally two times per day) and trametinib (2 mg orally one time a day). Primary endpoint was PFS. Secondary endpoints were objective response rate, DOR, and OS. Efficacy was assessed in the intention-to-treat population, and safety was assessed in all patients who received at least one dose of study drug. This analysis was not specified in the protocol. Results Between November 30, 2015 and April 24, 2017, 120 patients were randomly assigned to triplet (n=60) or doublet (n=60) therapy. With 36.6 months of follow-up, median PFS was 16.9 months (95% CI 11.3 to 27.9) with triplet and 10.7 months (95% CI 7.2 to 16.8) with doublet (HR 0.53; 95% CI 0.34 to 0.83). With triplet and doublet, respectively, PFS at 24 months was 41.0% (95% CI 27.4% to 54.2%) and 16.3% (95% CI 8.1% to 27.1%); median DOR was 25.1 months (95% CI 14.1 to not reached) and 12.1 months (95% CI 6.0 to 15.7), respectively. Median OS was not reached with triplet and was 26.3 months with doublet (HR 0.64; 95% CI 0.38 to 1.06). With triplet and doublet, respectively, OS at 24 months was 63.0% (95% CI 49.4% to 73.9%) and 51.7% (95% CI 38.4% to 63.4%). Grade 3-5 treatment-related adverse events (TRAEs) occurred in 35 patients (58%, including one death) receiving triplet and 15 patients (25%) receiving doublet. Conclusion In BRAF V600E/K-mutant advanced melanoma, pembrolizumab plus dabrafenib and trametinib substantially improved PFS, DOR, and OS with a higher incidence of TRAEs. Interpretation of these results is limited by the post hoc nature of the analysis