bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vagal stimulation mimics preconditioning and postconditioning of ischemic myocardium in mice by activating different protection mechanisms
Authors: Buchholz Bruno , Kelly Jazmín , Muñoz Marina , Bernatené Eduardo A. , Méndez Diodati Nahuel , González Maglio Daniel H. , Dominici Fernando P. , Gelpi Ricardo J. 
Published: April 2018

Vagal stimulation (VS) during myocardial ischemia and reperfusion has beneficial effects. However, it is not known whether short-term VS applied before ischemia or at the onset of reperfusion protects the ischemic myocardium. This study was designed to determine whether short-term VS applied before ischemia or at the onset of reperfusion reduces myocardial infarct size (IS), mimicking classic preconditioning and postconditioning. A second objective was to study the participation of muscarinic and nicotinic receptors in the protection of both preischemic and reperfusion stimulation. FVB mice were subjected to 30 min of regional myocardial ischemia followed by 2 h of reperfusion without VS, with 10-min preischemic VS (pVS), or with VS during the first 10 min of reperfusion (rVS). pVS reduced IS, and this effect was abolished by atropine and wortmannin. rVS also reduced IS in a similar manner, and this effect was abolished by the α7-nicotinic acetylcholine receptor blocker methyllycaconitine. pVS increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation. No changes in Akt and GSK-3β phosphorylation were observed in rVS. Stimulation-mediated IS protection was abolished with the JAK2 blocker AG490. rVS did not modify IL-6 and IL-10 levels in the plasma or myocardium. Splenic denervation and splenectomy did not abolish the protective effect of rVS. In conclusion, pVS and rVS reduced IS by different mechanisms: pVS activated the Akt/GSK-3β muscarinic pathway, whereas rVS activated α7-nicotinic acetylcholine receptors and JAK2, independently of the cholinergic anti-inflammatory pathway. NEW & NOTEWORTHY Our data suggest, for the first time, that vagal stimulation applied briefly either before ischemia or at the beginning of reperfusion mimics classic preconditioning and postconditioning and reduces myocardial infarction, activating different mechanisms. We also infer an important role of α7-nicotinic receptors for myocardial protection independent of the cholinergic anti-inflammatory pathway.
Spheroids of cardiomyocytes derived from human-induced pluripotent stem cells improve recovery from myocardial injury in mice
Authors: Mattapally Saidulu , Zhu Wuqiang , Fast Vladimir G. , Gao Ling , Worley Chelsea , Kannappan Ramaswamy , Borovjagin Anton V. , Zhang Jianyi 
Published: April 2018

The microenvironment of native heart tissue may be better replicated when cardiomyocytes are cultured in three-dimensional clusters (i.e., spheroids) than in monolayers or as individual cells. Thus, we differentiated human cardiac lineage-induced pluripotent stem cells in cardiomyocytes (hiPSC-CMs) and allowed them to form spheroids and spheroid fusions that were characterized in vitro and evaluated in mice after experimentally induced myocardial infarction (MI). Synchronized contractions were observed within 24 h of spheroid formation, and optical mapping experiments confirmed the presence of both Ca2+ transients and propagating action potentials. In spheroid fusions, the intraspheroid conduction velocity was 7.0 ± 3.8 cm/s on days 1– 2 after formation, whereas the conduction velocity between spheroids increased significantly ( P = 0.003) from 0.8 ± 1.1 cm/s on days 1– 2 to 3.3 ± 1.4 cm/s on day 7. For the murine MI model, five-spheroid fusions (200,000 hiPSC-CMs/spheroid) were embedded in a fibrin patch and the patch was transplanted over the site of infarction. Later (4 wk), echocardiographic measurements of left ventricular ejection fraction and fractional shortening were significantly greater in patch-treated animals than in animals that recovered without the patch, and the engraftment rate was 25.6% or 30% when evaluated histologically or via bioluminescence imaging, respectively. The exosomes released from the spheroid patch seemed to increase cardiac function. In conclusion, our results established the feasibility of using hiPSC-CM spheroids and spheroid fusions for cardiac tissue engineering, and, when fibrin patches containing hiPSC-CM spheroid fusions were evaluated in a murine MI model, the engraftment rate was much higher than the rates we have achieved via the direct intramyocardial injection. NEW & NOTEWORTHY Spheroids fuse in culture to produce structures with uniformly distributed cells. Furthermore, human cardiac lineage-induced pluripotent stem cells in cardiomyocytes in adjacent fused spheroids became electromechanically coupled as the fusions matured in vitro, and when the spheroids were combined with a biological matrix and administered as a patch over the infarcted region of mouse hearts, the engraftment rate exceeded 25%, and the treatment was associated with significant improvements in cardiac function via a paracrine mechanism, where exosomes released from the spheroid patch.
An Observational Study of the Association of Video- Versus Text-Based Informed Consent With Multicenter Trial Enrollment
Authors: Fanaroff Alexander C. , Li Shuang , Webb Laura E. , Miller Vincent , Navar Ann Marie , Peterson Eric D. , Wang Tracy Y. 
Published: April 2018

Background:
Patient participation in clinical research is low, in part because of the length and complexity of the informed consent process. Video informed consent may enhance the appeal of research and help break down barriers to participation.

Methods and Results:

The PALM study (Patient and Provider Assessment of Lipid Management) enrolled 7904 patients at cardiology, endocrinology, and primary care clinics across the United States to evaluate cholesterol management practices. Of 153 participating clinics, 67 (43.8%) secured institutional review board approval to use a tablet-based video informed consent tool that patients could select to navigate through the informed consent process instead of traditional text-based informed consent. At sites without institutional review board approval of video consent, all patients read a text-based informed consent document. Site activation times and enrollment volumes, as well as characteristics of enrolled patients, were compared between sites with and without video consent capability. Sites with video consent capability more often used a central institutional review board (89.6% versus 73.3%), were more often rural (16.7% versus 3.8%), and tended to have fewer providers. Compared with sites without video consent capability, sites with video consent capability had shorter times from site approach to first patient enrollment (median 178 versus 207 days;
P
=0.02). Sites with video consent capability enrolled similar numbers of patients as sites without video consent capability (
P
=0.48) but enrolled a greater proportion of patients who were ≥75 years old (27.5% versus 23.6%;
P
<0.001) and nonwhite (17.7% versus 14.2%;
P
<0.001).

Conclusions:
In this observational study of recruitment in a multicenter registry, sites approved for video consent use enrolled the same number of patients as sites with only traditional text-based informed consent but had faster speed to first patient enrolled and more often enrolled older and nonwhite patients. Future randomized trials are needed to assess the impact of video consent on enrollment mechanics and demographics.

CLINICAL TRIAL REGISTRATION:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02341664
Rac1 Modulates Endothelial Function and Platelet Aggregation in Diabetes Mellitus
Authors: Schiattarella Gabriele Giacomo , Carrizzo Albino , Ilardi Federica , Damato Antonio , Ambrosio Mariateresa , Madonna Michele , Trimarco Valentina , Marino Marina , De Angelis Elena , Settembrini Silvio , Perrino Cinzia , Trimarco Bruno , Esposito Giovanni , Vecchione Carmine 
Published: April 2018

Background

Vascular complications and abnormal platelet function contribute to morbidity and mortality in diabetes mellitus. We hypothesized that the Rho‐related
GTP
ase protein, Rac1, can influence both endothelial and platelet function and might represent a potential novel therapeutic target in diabetes mellitus.

Methods and Results

We used both in vitro and ex vivo approaches to test the effects of pharmacological inhibition of Rac1 during hyperglycemic condition. We evaluated the effect of
NSC
23766, a pharmacological inhibitor of Rac1, on vascular function in diabetic mice and platelet aggregation in diabetic subjects. We demonstrated that the administration of
NSC
23766 protects from hyperglycemia‐induced endothelial dysfunction, restoring NO levels, and reduces oxidative stress generated by nicotinamide adenine dinucleotide phosphate oxidase. Mechanistically, we identified Rho‐associated coiled‐coil serine/threonine kinase‐1 as a downstream target of Rac1. Moreover, we reported that during hyperglycemic conditions, human platelets showed hyperactivation of Rac1 and impaired
NO
release, which were both partially restored after
NSC
23766 treatment. Finally, we characterized the antiplatelet effect of
NSC
23766 during hyperglycemic conditions, demonstrating the additional role of Rac1 inhibition in reducing platelet aggregation in diabetic patients treated with common antiplatelet drugs.

Conclusions
Our data suggest that the pharmacological inhibition of Rac1 could represent a novel therapeutic strategy to reduce endothelial dysfunction and platelet hyperaggregation in diabetes mellitus.
Trends in Forecasting the Tracks of Atlantic Tropical Cyclones
Authors: Neumann Charles J. 
Published: April 2018

Errors in official 24 h forecasts of tropical cyclone motion over the Atlantic for the period 1954–80 are examined for the purpose of isolating any long-term trends in the data. It is shown that the magnitude of a forecast error has been primarily a function of forecast difficulty, i.e., how well storm motion adheres to climatology and persistence. Another contributing factor (in the negative partial correlation sense) is shown to be the storm's initial longitude—a measure of the adequacy of initial analyses.
After adjusting 24 h forecast error for these two factors, it is shown that errors have declined gradually over the 27 years from near 124 n mi in 1954 to near 107 n mi in 1980—a 13.7% reduction. Most of the decline since the mid-1960s is attributed to better specification of initial storm motion through satellite imagery.
Although the decline of forecast errors is encouraging, a disturbing aspect is that the rate of decline appears to have slowed in recent years. This leveling-off is attributed to a loss in the ability to assess environmental steering through mid-level analysis deficiencies that have been compounding since 1965 and, more recently, to a plateauing in the ability to obtain still better storm initial-motion vectors. To assure a continued monotonic decline in 24 h forecast errors, mid-level initial analysis (500 mb) over the essentially data-void tropical cyclone basins must be improved.
Interpretation of Some Terms and Phrases in Public Weather Forecasts
Authors: Murphy Allan H. , Brown Barbara G. 
Published: April 2018

This paper reports some results of a study in which two groups of individuals—undergraduate students and professional meteorologists at Oregon State University—completed a short questionnaire concerning their interpretations of terminology commonly used in public weather forecasts. The questions related to terms and phrases associated with three elements: 1) cloudiness—fraction of sky cover; 2) precipitation—spatial and/or temporal variations; and 3) temperature—specification of intervals.
The students' responses indicate that cloudiness terms are subject to wide and overlapping ranges of interpretation, although the interpretations of these terms correspond quite well to National Weather Service definitions. Their responses to the precipitation and temperature questions reveal that some confusion exists concerning the meaning of spatial and temporal modifiers in precipitation forecasts and that some individuals interpret temperature ranges in terms of asymmetric intervals. When compared to the students' responses, the meteorologists' responses exhibit narrower ranges of interpretation of the cloudiness terms and less confusion about the meaning of spatial/temporal precipitation modifiers.
The study was not intended to be a definitive analysis of public understanding of forecast terminology. Instead, it should be viewed as a primitive form of the type of forecast-terminology study that must be undertaken in the future. Some implications of this investigation for future work in the area are discussed briefly.
Corrections and Additions to Verification Study of Performance of 1976 University of Wisconsin Model2
Authors: Harnack Robert P. , Sammler William R. 
Published: April 2018

Revised and complete verification statistics for mainland United States long-range forecasts made for the period 1976–80 by the 1976 version of the University of Wisconsin model are presented. Corrections to earlier published values are given, as well as skill scores obtained using a much more complete set of stations for which forecasts were made.
The overall skill score for the pentad temperature forecasts made for January, April, July, and October is negative (−0.14), while those for pentad precipitation and individual year July precipitation forecasts are positive (0.12 and 0.04, respectively). The individual year January temperature forecast skill score was unchanged at −0.08 overall.
Do audit firm and audit costs/fees influence earnings management in Swedish municipalities?
Authors: Donatella Pierre , Haraldsson Mattias , Tagesson Torbjörn 
Published: April 2018

Previous research on the private sector shows that auditors and auditing firms are important actors in ensuring high-quality reporting based on accrual accounting. The aim of this study is to explore whether audit firms and audit costs/fees influence municipalities’ probability of applying earnings management in their annual accounts. The empirical data, which covered the financial years 2011–13, were handpicked from annual reports or retrieved from other sources. In general, our study shows that the probability of earnings management increased if audit costs/fees increased. However, there were differences regarding the probability of earnings management relating to which audit firm was engaged. This implies that audit quality is a factor that affects the probability of earnings management in Swedish municipalities. The study also indicates that different audit firms make different trade-offs between professional versus commercial logics, and that this is reflected in the clients’ propensity to engage in earnings management. Points for practitioners Today a majority of developed countries have adopted accrual-based accounting for municipalities. Along with accrual-based accounting follows the risk of earnings management. Problems regarding accounting quality imply an increased importance of the financial audit. However, our study shows that there is no obvious positive relationship between audit cost/fees and audit quality. The ability to constrain earnings management seems to vary between audit firms. The important implication for practitioners is that auditing must have quality standards that are subject to follow-up and control, which applies both on a system level and also when municipalities procure and contract audit firms for audit assignments.
Localized morphea after breast implant for breast cancer: A case report
Authors: Moretti A , Bianchi F , Abbate IV , Gherardi G , Bonavita M , Passoni E , Nazzaro G , Bramati A , Dazzani MC , Piva S , Paternò E , Frungillo N , Farina G , La Verde N 
Published: April 2018

Purpose: Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases. Case report: In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis. Conclusion: In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.
Metal Resurfacing Inlay Implant for Osteochondral Talar Defects After Failed Previous Surgery: A Midterm Prospective Follow-up Study
Authors: Vuurberg Gwendolyn , Reilingh Mikel L. , van Bergen Christiaan J.A. , van Eekeren Inge C.M. , Gerards Rogier M. , van Dijk C. Niek 
Published: April 2018

Background: Treatment of osteochondral talar defects (OCDs) after failed previous surgery is challenging. Promising short-term results have been reported with use of a metal resurfacing inlay implant. Purpose: To evaluate the midterm clinical effectiveness of the metal implant for OCDs of the medial talar dome after failed previous surgery. Study Design: Case series; Level of evidence, 4. Methods: We prospectively studied all patients who met the inclusion criteria and received a metal resurfacing inlay implant between 2007 and 2014. The primary outcome measure was implant survival, as measured by reoperation rate. Secondary outcome measures were numeric rating scales for pain at rest and during walking, running, and stair climbing; the Foot and Ankle Outcome Score (FAOS); the American Orthopaedic Foot and Ankle Society Ankle Hindfoot Scale; the 36-Item Short Form Health Survey (SF-36); return to work and sports; and radiographic evaluation. Results: This study included 38 patients with a mean age of 39 years (SD, ±13 years) and a mean follow-up of 5.1 years (SD, ±1.5 years). Two patients (5%) underwent revision surgery by means of an ankle arthrodesis (2 and 6 years postoperatively). In 8 patients, computed tomography scanning was conducted to assess postoperative complaints. These scans showed impression of the tibial plafond (n = 4), a small tibial cyst (<2.5 mm; n = 1), and cyst formation around the implant screw (n = 4). A total of 21 reoperations were performed, including medial malleolar screw removal (n = 12), arthroscopic removal of bony anterior impingement (n = 7), and calcaneal realignment osteotomy (n = 2). All secondary outcome measures improved significantly, apart from pain at rest, the FAOS symptoms subscale, and the SF-36 mental component scale. The mean time for return to sport was 4.1 months (SD, ±3 months), and 77% of patients resumed sporting activities postoperatively. Only 1 patient did not return to work postoperatively. Radiographs at final follow-up showed cyst formation (n = 2), subchondral periprosthetic radiolucency (n = 2), and non-preexisting joint space narrowing (n = 2). Conclusion: This study shows that the metal implant is an effective technique when assessed at midterm follow-up for OCDs of the medial talar dome after failed previous surgery.
Burden of Care of Various Infant Orthopedic Protocols for Improvement of Nasolabial Esthetics in Patients With CUCLP
Authors: Singer Emily , Daskalogiannakis John , Russell Kathy A. , Mercado Ana M. , Hathaway Ronald R. , Stoutland Alicia , Long Ross E. , Fessler Jennifer , Semb Gunvor , Shaw William C. 
Published: April 2018

Objectives: 1. To evaluate the orthodontic burden of care of nasoalveolar molding (NAM) and modified McNeil for the treatment of patients with complete unilateral cleft lip and palate (CUCLP). 2. To compare the esthetic outcomes of each with those of centers not utilizing infant orthopedics (IO). Design: Retrospective cohort study. Setting: Institutional. Participants: Four cohorts with repaired CUCLP (n = 149) from 3 centers. Interventions: Two cohorts were treated in the same center and had either traditional infant orthopedics (TIO) or NAM and 2 were treated in centers not employing IO. Main Outcome Measures: Burden of care data for the IO groups were compared using t tests. Frontal and profile photographs at approximately age 5 were collected for ratings of nasolabial esthetics, using a modification of the Asher-McDade method. Intrarater and interrater reliabilities were determined using weighted κ statistics. Median ratings were compared using a Kruskal-Wallis test. Results: The burden of care of NAM was significantly greater than TIO for both the number of visits (9.9 vs 6.6, [ P < .001]); and treatment duration (127 vs 112 days, [ P < .05]). Significant differences in nasolabial esthetic ratings were noted among the 3 centers. No significant differences were observed in the nasolabial esthetic outcomes between the NAM and TIO groups. Conclusions: 1. NAM required more visits and longer overall duration compared with TIO. 2. The center employing IO showed favorable nasolabial esthetics compared to those not utilizing IO. 3. No significant differences were found in the nasolabial esthetics of patients who have received NAM compared with TIO.
Impact of Vancomycin Treatment on Human Mesenchymal Stromal Cells During Osteogenic Differentiation
Authors: Bariteau Jason T. , Kadakia Rishin J. , Traub Brian C. , Viggeswarapu Manjula , Willett Nick J. 
Published: April 2018

Background: Vancomycin is frequently applied locally to the operative site during foot and ankle procedures to help prevent infection. Although the efficacy of locally applied vancomycin has been demonstrated in spine surgery, there is no consensus on dosing and indication within foot and ankle surgery. Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) is key to healing of both fractures and arthrodesis. The purpose of this research was to determine the impact of vancomycin on human hMSCs during the process of osteogenic differentiation. Methods: hMSCs were cultured in osteogenic differentiation media to promote osteogenic differentiation. Cells were treated with vancomycin at differing concentrations of 0, 50, 500, and 5000 µg/mL. Viability and cell growth were assessed via LIVE/DEAD viability/cytotoxicity kit (Invitrogen, Waltham, MA) after 1, 3, and 7 days of vancomycin treatment. Differentiation and mineralization was assessed via alizarin red staining after 21 days of treatment. Mean cell viability, cell number, and mineralization were compared between treatment groups using 1-way analysis of variance and the Tukey-Kramer method for post hoc pairwise comparisons. Results: At the highest concentrations of vancomycin, there was a significant reduction in cell viability and proliferation after 3 days compared with all other treatment groups. Mineralization was also significantly decreased with higher doses of vancomycin. Conclusion: At high concentrations, vancomycin may impair hMSC viability and osteogenic differentiation. Clinical Relevance: Surgeons should exercise caution and consider the limited soft tissue envelope when applying vancomycin locally during foot and ankle surgery, especially during arthrodesis procedures.