bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of phosphotyrosyl phosphatase activator induces apoptosis via mitochondrial pathway and the attenuation by simultaneous tau hyperphosphorylation
Authors: Luo Dan‐Ju , Feng Qiong , Wang Zhi‐Hao , Sun Dong‐Sheng , Wang Qun , Wang Jian‐Zhi , Liu Gong‐Ping
Published: May 2014

Phosphotyrosyl phosphatase activator (PTPA) is decreased in the brains of Alzheimer's disease (AD) and the AD transgenic mouse models. Here, we investigated whether down‐regulation of PTPA affects cell viability and the underlying mechanisms. We found that PTPA was located in the integral membrane of mitochondria, and knockdown of PTPA induced cell apoptosis in HEK293 and N2a cell lines. PTPA knockdown decreased mitochondrial membrane potential and induced Bax translocation into the mitochondria with a simultaneous release of Cyt C, activation of caspase‐3, cleavage of poly (DNA ribose) polymerase (PARP), and decrease in Bcl‐xl and Bcl‐2 protein levels. Over‐expression of Protein phosphatase 2A (PP2A) catalytic subunit (PP2AC) did not rescue the apoptosis induced by PTPA knockdown, and PTPA knockdown did not affect the level of and their phosphorylation of mitogen‐activated protein kinases (MAPKs), indicating that PP2A and MAPKs were not involved in the apoptosis induced by PTPA knockdown. In the cells with over‐expression of tau, PTPA knockdown induced PP2A inhibition and tau hyperphosphorylation but did not cause significant cell death. These data suggest that PTPA deficit causes apoptotic cell death through mitochondrial pathway and simultaneous tau hyperphosphorylation attenuates the PTPA‐induced cell death.

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Phosphotyrosyl phosphatase activator (PTPA) is decreased in the brains of Alzheimer's disease (AD) and AD transgenic mouse models. Here, we investigated whether down‐regulation of PTPA affects cell viability. We found that PTPA located in the integral membrane of mitochondria, and knockdown of PTPA induced cell apoptosis in HEK293 and N2a cell lines by decreasing mitochondrial membrane potential, which leads to translocation of Bax and a simultaneous release of Cyt C. In the cells with tau over‐expression, PTPA knockdown inactivated PP2A to phosphorylate tau to avoid cell apoptosis which induced by PTPA knockdown.
Non‐invasive and Invasive Predictors of Paravalvular Regurgitation Post CoreValve® Stent Prosthesis Implantation in Aortic Valves
Authors: ANGER THOMAS , BAUER VERENA , PLACHTZIK CLAUDIA , GEISLER TOBIAS , GAWAZ MEINRAD , OBERHOFF MARTIN , HÖHER MARTIN
Published: May 2014

Objectives

The long‐term success of CoreValve® stent prosthesis (Medtronic) implantation for severe aortic valve stenosis is limited by postprocedural paravalvular regurgitation (PVR).

Methods

We have retrospectively investigated preinterventional cardiac 256‐slice computed tomography (CT) scans and aortography to define predictors for mild, moderate, or severe PVR, in a blinded fashion.

Results

We investigated 100 consecutive patients with a mean aortic valve area (AVA) of 0.69 cm2 and a mean age of 79.4 years. PVR was defined by echocardiography as mild (63), moderate (18), or severe (19). We found no differences according to AVA, left ventricular function, deployed stent size, calcification rate of the aortic valve, and stent position. Anatomically, the annular size and the angle between the left ventricular outflow tract (LVOT) and the ascending aorta demonstrated significant (P < 0.05) differences in the severity of the PVR: an LVOT: ascending aorta angle >12.6°, annulus area >8.9 cm2, and annulus diameter difference >3.9 mm. The multivariate analysis demonstrated that deviation angle, difference of aortic annulus (longitudinal–orthogonal), and CoreValve size were independent predictors of PVR.

Conclusion

Our data demonstrate the feasibility of cardiac CT to evaluate predictors of PVR post‐CoreValve placement. We support the aortic annulus (the area as well as the diameter differences) and the deviation of the linear slope from LVOT to ascending aorta as predictors of severe paravalvular regurgitations poststent implantation. (J Interven Cardiol 2014;27:275–283)
Drug‐Eluting Balloon in the Treatment of In‐Stent Restenosis and Diffuse Coronary Artery Disease: Real‐World Experience from Our Registry
Authors: BASAVARAJAIAH SANDEEP , LATIB AZEEM , SHANNON JOANNE , NAGANUMA TORU , STICCHI ALESSANDRO , BERTOLDI LETIZIA , COSTOPOULOS CHARIS , FIGINI FILIPPO , CARLINO MAURO , CHIEFFO ALAIDE , MONTORFANO MATTEO , COLOMBO ANTONIO
Published: May 2014

Objectives

To report a single‐center experience of drug‐eluting balloons (DEB) in the treatment of in‐stent restenosis (ISR) and de novo coronary artery disease.

Background

DEB are emerging as an alternative treatment for coronary stenosis especially when metal scaffolding is undesirable (in‐stent restenosis and small‐vessel de novo disease). Although there are various randomized trials and registry studies, the data from real‐world cohorts are lacking.

Methods

Consecutive patients treated with the In.Pact Falcon™ (Medtronic Inc., Minneapolis, MN, USA) paclitaxel‐eluting balloon between January 2009 and December 2011 were retrospectively studied. The measured end‐points were cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE) defined as combination of cardiac death, MI, and TVR.

Results

A total of 275 lesions were successfully treated in 184 patients. The mean age was 66.2 ± 9.6 years, and 87% were males. The predominant indication for DEB use was ISR (62%), with de novo lesions accounting for the remainder (38%). A mean of 1.48 ± 0.9 DEB were used per patient. Bailout stenting was required in 24% of lesions. The median clinical follow‐up was 14.6 months (IQR 12–23). The overall rates of cardiac death, MI, TLR, TVR, and MACE were 3.8%, 1.6%, 16.8%, 17.9%, and 21.7%, respectively. The overall rate of stent thrombosis was 0.5% (n = 1).

Conclusion

Our results suggests that DEB can be considered in lesions where the use of stents is not desirable, especially restenotic lesions. Further long‐term follow‐up of these patients will provide us more insights on the long‐term outcomes. (J Interven Cardiol 2014;27:348–355)
LIVING KIDNEY DONATION: CONSIDERATIONS AND DECISION‐MAKING
Authors: Agerskov Hanne , Bistrup Claus , Ludvigsen Mette Spliid , Pedersen Birthe D.
Published: May 2014

Background

When possible, renal transplantation is the treatment of choice for patients with end‐stage kidney disease. Technological developments in immunology have made it possible to perform kidney transplants between donors and recipients despite antibodies against the donor organ. This allows for a wider range of relationships between recipient and donor. We investigated experiences of, and reflections on, kidney donation among genetic and non‐genetic living donors before first consultation at the transplant centre.

Objective

The aim was to investigate early experiences in the process of becoming a living kidney donor (LKD).

Materials and Methods

The study was conducted within a phenomenological‐hermeneutic theoretical framework. Data were generated through semi‐structured interviews with 18 potential donors. Data were interpreted and discussed in accordance with the Ricoeur's text interpretation theory on the three levels of naïve reading, structural analysis and critical interpretation and discussion.

Results

Two themes emerged: the decision‐making process and dilemmas in decision‐making. The study identifies that the decision about donation was made in relation to one's own life, family situation and in relation to the recipient—considerations that demonstrate that a range of dilemmas can occur during the decision‐making process. The desire to help was prominent and was of significance in decision‐making.

Conclusion

The study provides insight and knowledge for the health care professionals to meet and involve donors' narratives in reflections about and modifications to clinical nursing practice. It is essential that health care professionals have an understanding and appreciation of the experiences and concerns among LKDs, and this can help in planning and providing individual nursing care and support to donors.
Salutary effects of melatonin combined with treadmill exercise on cartilage damage
Authors: Hong Yunkyung , Kim Hyunsoo , Lee Youngjeon , Lee Seunghoon , Kim Koo , Jin Yunho , Lee Sang‐Rae , Chang Kyu‐Tae , Hong Yonggeun
Published: May 2014

Osteoarthritis (OA) is a major cause of disability in the adult population. The purpose of this study was to evaluate the effects of melatonin with graded dosage on extracellular matrix synthesis and cellular death in response to cartilage damage in vitro and in vivo. TNF‐α reduced the viability of primary cultured chondrocytes and extracellular matrix protein, but melatonin at concentrations of 1 μm and 1 nm restored them. Rats with knee instability induced by intra‐articular collagenase were used for the in vivo study. Joint parameters were significantly augmented in the collagenase injection‐only group but not in the melatonin‐alone or melatonin+exercise groups, as cartilage degeneration progressed. Serum TNF‐α and IL‐6 were upregulated by collagenase injection, which was attenuated by melatonin with and without exercise in the early phase. TGF‐β1 mRNA was either conserved or enhanced by melatonin with and without exercise at the early phase. In particular, melatonin combined with exercise dramatically decreased the expression of not only catabolic mediators but also cellular death markers with lower mineralization. At the advanced phase, prolonged melatonin treatment promoted mineralization through caspase‐3‐mediated chondrocyte apoptosis. However, co‐intervention induced extracellular matrix remodeling through increases in IL‐6, EPAS‐1, and MMP‐13. Reconstructed micro‐CT images showed that collagenase injection induced subchondral bone erosion, formation of parameniscal osteophytes, and reduction of trabecular bone thickness regardless of the intervention, which was minimized by combined intervention. In conclusion, we suggest that melatonin with treadmill exercise may have both preventive and synergistic effects on rescue from cartilage degeneration and is more effective in the initial phase.
Synergistic cytotoxicity of the poly (ADP‐ribose) polymerase inhibitor ABT‐888 and temozolomide in dual‐drug targeted magnetic nanoparticles
Authors: Muñoz‐Gámez José A , López Viota Julián , Barrientos Andrés , Carazo Ángel , Sanjuán‐Nuñez Laura , Quiles‐Perez Rosa , Muñoz‐de‐Rueda Paloma , Delgado Ángel , Ruiz‐Extremera Ángeles , Salmerón Javier
Published: May 2014

Background & Aims

Hepatocellular carcinoma (HCC) is associated with a poor prognosis because of a lack of effective treatment options. The objective of this study was to examine a new strategy for HCC treatment, namely the use of poly (ADP‐ribose) polymerase 1 (PARP‐1) inhibitor (ABT‐888) together with Temozolomide (TMZ) incorporated onto magnetic nanoparticles.

Methods

Magnetic Fe3O4/Fe cores were encapsulated within a silica shell to facilitate the simultaneous incorporation of ABT‐888 and TMZ. In vitro tests were performed with HepG2, Hep3B and PLC‐PRF‐5 liver tumoural cell lines and with WRL‐68 liver non‐tumoural cells.

Results

The magnetic nanocarriers were loaded simultaneously with ABT‐888 and TMZ. High stability and extended release were achieved in culture medium. Confocal microscopy images showed that drug‐loaded particles were uptaken and accumulated into the cytoplasm of liver tumoural cells, inducing the following effects: G2/M cell cycle arrest (P < 0.05), accumulation of DNA damage (P < 0.05), mitochondrial depolarization (P < 0.01), reduction in BCL‐xL, FOS, JUND gene expression (P < 0.05), PARP‐1 fragmentation, Caspase‐3 activation and apoptotic cell death (P < 0.05). Interestingly, drugs loaded onto nanoparticles exhibited better efficiency than free drugs (cell death triggered by drug delivery nanosystem: 53.5% vs. 34.5% by free drugs, P = 0.01).

Conclusions

These magnetic nanocompounds are able to incorporate both drugs simultaneously, enter the tumour cells and release them. ABT‐888/TMZ/NPs decrease the transcription of key genes involved in tumour survival and induce apoptotic cell death in a more effective manner than is achieved by free drugs.
Alteration of Urothelial Inflammation, Apoptosis, and Junction Protein in Patients with Various Bladder Conditions and Storage Bladder Symptoms Suggest Common Pathway Involved in Underlying Pathophysiology
Authors: LIU Hsin‐Tzu , JIANG Yuan‐Hong , KUO Hann‐Chorng
Published: May 2014

Objective

Lower urinary tract symptoms (LUTS) are common in various bladder disorders. This study investigated urothelial dysfunction and chronic inflammation in the urothelium in different types of lower urinary tract dysfunction (LUTD), which causes bladder storage symptoms.

Methods

Bladder tissues were obtained from patients with LUTD including 17 with interstitial cystitis/bladder pain syndrome (IC/BPS), 15 with bladder outlet obstruction (BOO), 12 with spinal cord injury (SCI), 12 with recurrent urinary tract infection (UTI), 13 with ketamine related cystitis (KC) and 10 controls. The bladder specimens were investigated using immunofluorescence (IF) staining of the urothelial junction protein E‐cadherin and the TUNEL assay for urothelial apoptosis. Mast cell activation was also measured by IF using tryptase for mucosal inflammation. Statistical analysis was performed using the Kruskal–Wallis and Wilcoxon rank‐sum test and P‐values less than 0.05 were considered significant.

Results

Highly significant increases of mast cell infiltration were observed in patients with KC (7.8 ± 3.7), IC/BPS (4.6 ± 3.0), recurrent UTI (2.4 ± 1.2), SCI (3.7 ± 2.7), and BOO (5.1 ± 2.0) compared with controls (1.3 ± 1.2) (all p < 0.05). Statistically significant increases of apoptotic cells were observed in patients with KC (4.2 ± 1.5), IC/BPS (2.4 ± 1.7), SCI (2.4 ± 1.4), recurrent UTI (1.9 ± 2.4), and BOO (1.2 ± 1.1) compared with controls (0.08 ± 0.3) (all p < 0.05). Significantly decreased expression of E‐cadherin in patients with IC/BPS (25.1 ± 16.3), KC (11.0 ± 11.3), and recurrent UTI (26.2 ± 5.0) was found compared to controls (42.4 ± 16.7) and patients with SCI (44.4 ± 18.8) or BOO (42.8 ± 14.3) (all P < 0.05).

Conclusion

Increased urothelial inflammation and urothelial cell apoptosis seem to share common pathophysiologies of various LUTDs that cause similar bladder symptoms.
Modelling, substrate docking and mutational analysis identify residues essential for function and specificity of the major fungal purine transporter AzgA
Authors: Krypotou Emilia , Lambrinidis George , Evangelidis Thomas , Mikros Emmanuel , Diallinas George
Published: May 2014

The AzgA purine/H+ symporter of Aspergillus nidulans is the founding member of a functionally and phylogenetically distinct transporter family present in fungi, bacteria and plants. Here a valid AzgA topological model is built based on the crystal structure of the Escherichia coli uracil transporter UraA, a member of the nucleobase‐ascorbate transporter (NAT/NCS2) family. The model consists of 14 transmembrane, mostly α‐helical, segments (TMSs) and cytoplasmic N‐ and C‐tails. A distinct compact core of 8 TMSs, made of two intertwined inverted repeats (TMSs 1–4 and 8–11), is topologically distinct from a flexible domain (TMSs 5–7 and 12–14). A putative substrate binding cavity is visible between the core and the gate domains. Substrate docking, molecular dynamics and mutational analysis identified several residues critical for purine binding and/or transport in TMS3, TMS8 and TMS10. Among these, Asn131 (TMS3), Asp339 (TMS8) and Glu394 (TMS10) are proposed to directly interact with substrates, while Asp342 (TMS8) might be involved in subsequent substrate translocation, through H+ binding and symport. Thus, AzgA and other NAT transporters use topologically similar TMSs and amino acid residues for substrate binding and transport, which in turn implies that AzgA‐like proteins constitute a distant subgroup of the ubiquitous NAT family.
Translational potential of a mouse in vitro bioassay in predicting gastrointestinal adverse drug reactions in Phase I clinical trials
Authors: Keating C. , Ewart L. , Grundy L. , Valentin J.P. , Grundy D.
Published: May 2014

Background

Motility‐related gastrointestinal (GI) adverse drug reactions (GADRs) such as diarrhea and constipation are a common and deleterious feature associated with drug development. Novel biomarkers of GI function are therefore required to aid decision making on the GI liability of compounds in development.

Methods

Fifteen compounds associated with or without clinical GADRs were used to assess the ability of an in vitro colonic motility bioassay to predict motility‐related GADRs. Compounds were examined in a blinded fashion for their effects on mouse colonic peristaltic motor complexes in vitro. For each compound concentration‐response relationships were determined and the results compared to clinical data. Compounds were also assessed using GI transit measurements obtained using an in vivo rat charcoal meal model.

Key Results

Within a clinically relevant dosing range, the in vitro assay identified five true and three false positives, four true and three false negatives, which gave a predictive capacity of 60%. The in vivo assay detected four true and four false positives, four false and three true negatives, giving rise to a predictive capacity for this model of 47%.

Conclusions & Inferences

Overall these results imply that both assays are poor predictors of GADRs. Further analysis would benefit from a larger compound set, but the data show a clear need for improved models for use in safety pharmacology assessment of GI motility.
A case–control study of childhood trauma in the development of irritable bowel syndrome
Authors: Halland M. , Almazar A. , Lee R. , Atkinson E. , Larson J. , Talley N. J. , Saito Y. A.
Published: May 2014

Background

The etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain–gut axis and therefore be important. Thus, we conducted a family based case–control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS).

Methods

Outpatients with IBS, matched controls, and their first‐degree relatives completed a self‐report version of Bremner' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi‐squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations.

Key Results

Data were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13–2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma.

Conclusions & Inferences

IBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS.
Cell therapy to remove excess copper in Wilson's disease
Authors: Gupta Sanjeev
Published: May 2014

To achieve permanent correction of Wilson's disease by a cell therapy approach, replacement of diseased hepatocytes with healthy hepatocytes is desirable. There is a physiological requirement for hepatic ATP7B‐dependent copper (Cu) transport in bile, which is deficient in Wilson's disease, producing progressive Cu accumulation in the liver or brain with organ damage. The ability to repopulate the liver with healthy hepatocytes raises the possibility of cell therapy in Wilson's disease. Therapeutic principles included reconstitution of bile canalicular network as well as proliferation in transplanted hepatocytes, despite toxic amounts of Cu in the liver. Nonetheless, cell therapy studies in animal models elicited major differences in the mechanisms driving liver repopulation with transplanted hepatocytes in Wilson's disease versus nondiseased settings. Recently, noninvasive imaging was developed to demonstrate Cu removal from the liver, including after cell therapy in Wilson's disease. Such developments will help advance cell/gene therapy approaches, particularly by offering roadmaps for clinical trials in people with Wilson's disease.
Is there a relationship between red or processed meat intake and obesity? A systematic review and meta‐analysis of observational studies
Authors: Rouhani M. H. , Salehi‐Abargouei A. , Surkan P. J. , Azadbakht L.
Published: May 2014

A body of literature exists regarding the association of red and processed meats with obesity; however, the nature and extent of this relation has not been clearly established. The aim of this study is to conduct a systematic review and meta‐analysis of the relationship between red and processed meat intake and obesity. We searched multiple electronic databases for observational studies on the relationship between red and processed meat intake and obesity published until July 2013. Odds ratios (ORs) and means for obesity‐related indices and for variables that may contribute to heterogeneity were calculated. A systematic review and a meta‐analysis were conducted with 21 and 18 studies, respectively (n = 1,135,661). The meta‐analysis (n = 113,477) showed that consumption of higher quantities of red and processed meats was a risk factor for obesity (OR: 1.37; 95% CI: 1.14–1.64). Pooled mean body mass index (BMI) and waist circumference (WC) trends showed that in comparison to those in the lowest ntile, subjects in the highest ntile of red and processed meat consumption had higher BMI (mean difference: 1.37; 95% CI: 0.90–1.84 for red meat; mean difference: 1.32; 95% CI: 0.64–2.00 for processed meat) and WC (mean difference: 2.79; 95% CI: 1.86–3.70 for red meat; mean difference: 2.77; 95% CI: 1.87–2.66 for processed meat). The current analysis revealed that red and processed meat intake is directly associated with risk of obesity, and higher BMI and WC. However, the heterogeneity among studies is significant. These findings suggest a decrease in red and processed meat intake.
Comparison of propofol and dexmedetomedine techniques in children undergoing magnetic resonance imaging
Authors: Wu Junzheng , Mahmoud Mohamed , Schmitt Megan , Hossain Md , Kurth Dean
Published: May 2014

Background

Propofol (PRO) and dexmedetomidine (DEX) are commonly used to produce anesthesia and sedation for routine MRI procedures. Children with complex conditions often require much lengthy MRI for multi‐body‐part scans with frequent scanner coil changes and patient body reposition. This study compared PRO and DEX techniques on outcomes for the particular MRI setting with longer than 1 h duration.

Methods

95 children, aged from 1 to 7 years, scheduled for MRI >75 min were randomly assigned to PRO or DEX group. After induced with sevoflurane, a loading dose of PRO (2 mg·kg−1) was administrated and followed by continuous infusion (200 μg·kg−1·min−1); a loading dose of DEX (2 μg·kg−1) was administrated and followed by continuous infusion (2 μg·kg−1·h−1). Patients received O2 by nasal cannula. The observed outcomes were times for induction, MRI, emergence, and recovery, and total time (induction to discharge); MRI pauses from patient movement; incidence of technique failure and critical events; emergence and behavior in postanesthesia care unit (PACU); parental satisfaction; and arterial pressure (BP) and heart rate (HR) during anesthesia.

Results

PRO compared with DEX showed significantly less time for anesthesia induction (16.3 versus 24.2 min), emergence (21.2 versus 39.9 min), PACU (35.7 versus 62.5 min), and total time (135 versus 173 min) (all P < 0.001). There were significantly fewer pauses during MRI and lower failure rate to complete MRI in PRO versus DEX (0.22 versus 0.81, P = 0.01 and 1 versus 15, P < 0.001), less behavioral disturbances in PACU, and higher parental satisfaction in PRO versus DEX (P < 0.01). There were no critical events in either group: In PRO, mean BP during MRI (from 52 ± 8 to 58 ± mmHg) was significantly less than before anesthesia (80 ± 12 mmHg), while HR remained relatively constant (range of 97–103) at its baseline of 108 ± 21, but in DEX, mean BP remained unchanged (from 76 ± 12 to 78 ± 15) during anesthesia compared with before anesthesia (79 ± 14 mmHg), while HR decreased (74 ± 16 to 78 ± 15) during anesthesia from its baseline (102 ± 17) .

Conclusion

For children undergoing lengthy multicomponent MRI, the propofol technique yielded overall better outcomes than the dexmedetomedine technique in terms of timeliness, PACU emergence characteristics, and parental satisfaction.
Update on the 2012 guidelines for the management of pediatric traumatic brain injury – information for the anesthesiologist
Authors: Hardcastle Nina , Benzon Hubert A. , Vavilala Monica S.
Published: May 2014

Traumatic brain injury (TBI) is a significant contributor to death and disability in children. Considering the prevalence of pediatric TBI, it is important for the clinician to be aware of evidence‐based recommendations for the care of these patients. The first edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents was published in 2003. The Guidelines were updated in 2012, with significant changes in the recommendations for hyperosmolar therapy, temperature control, hyperventilation, corticosteroids, glucose therapy, and seizure prophylaxis. Many of these interventions have implications in the perioperative period, and it is the responsibility of the anesthesiologist to be familiar with these guidelines.
Bleeding management for pediatric craniotomies and craniofacial surgery
Authors: Goobie Susan M. , Haas Thorsten
Published: May 2014

Pediatric patients when undergoing craniotomies and craniofacial surgery may potentially have significant blood loss. The amount and extent will be dictated by the nature of the surgical procedure, the proximity to major blood vessels, and the age, and weight of the patient. The goals should be to maintain hemodynamic stability and oxygen carrying capacity and to prevent and treat hyperfibrinolysis and dilutional coagulopathy. Over transfusion and transfusion‐related side effects should be minimized. This article will highlight the pertinent considerations for managing massive blood loss in pediatric patients undergoing craniotomies and craniofacial surgery. North American and European guidelines for intraoperative administration of fluid and blood products will be discussed.
Outpatient analgesia via paravertebral peripheral nerve block catheter and On‐Q pump—a case series
Authors: Visoiu Mihaela
Published: May 2014

Outpatient pain management after iliac crest bone harvesting can be challenging. We report the use of home L2 paravertebral nerve block catheter (L2PVBC) in a series of five children. The pain scores were low, and analgesic medication consumption was minimal. No complications were reported related with these catheters, and the patients reported very high pain control satisfaction scores. Outpatient L2PVBC can be beneficial as part of a multimodal analgesia strategy in selected pediatric patients.
When Accomplishments Come Back to Haunt You: The Negative Effect of Competence Signals on Women's Performance Evaluations
Authors: Inesi M. Ena , Cable Daniel M.
Published: May 2014

This research explores the possibility that the very accomplishments that are critical to success during the hiring process (e.g., educational attainment, promotion history) can lead to a drop in future performance evaluations for women. We theorized that evaluators may see such competence signals as a threat to the traditional gender hierarchy, which leads to a negative bias when evaluating women's on‐the‐job performance. In Study 1, we examined this hypothesis among commanding officers in the U.S. military, who gave lower performance ratings to female subordinates whose pay grade approached their own. The same was not true for male subordinates. Studies 2, 3a, and 3b experimentally tested the boundary conditions of this effect using two additional competence signals (educational attainment and past career successes) and 2 different populations. Across these studies, we replicated the negative relationship between competence signal strength and performance evaluations for female subordinates but only under conditions in which the evaluator would be particularly likely to experience gender hierarchy threat. Specifically, it emerged when the evaluator was male and high social‐dominance oriented and when the female subordinate's objective on‐the‐job performance was high. Finally, Study 3a demonstrated how organizations can mitigate this negative bias by using objective (rather than subjective) performance evaluations.
Transition from hospital to home following pediatric solid organ transplant: Qualitative findings of parent experience
Authors: Lerret Stacee M. , Weiss Marianne E. , Stendahl Gail , Chapman Shelley , Neighbors Katie , Amsden Katie , Lokar Joan , Voit Ashley , Menendez Jerome , Alonso Estella M.
Published: May 2014

Transplant providers are challenged to determine appropriate interventions for patients and families due to limited published research regarding the context of the post‐discharge experience from the perspective of parents of transplanted children. The purpose of this study is to describe the parent perspective of the transition from hospital to home following their child's solid organ transplant. Within a mixed‐methods design, 37 parents of pediatric heart, kidney, and liver transplant recipients from three pediatric hospitals responded to qualitative interview questions on the day of hospital discharge and three wk following hospital discharge. Insight to the discharge preparation process revealed necessary education components. Post‐discharge themes were identified for coping, knowledge, and adherence. The parents' responses provide awareness as to specific stressors and concerns parents are faced with when their child is discharged from the hospital after solid organ transplant and opportunities for ways the transplant team can provide support.
The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I‐MIBG accompanied by ASCT for high‐risk and relapsed neuroblastoma: A pilot study
Authors: Hamidieh Amir Ali , Beiki Davood , Paragomi Pedram , Fallahi Babak , Behfar Maryam , Fard‐Esfahani Armaghan , Hosseini Ashraf Sadat , Shamshiri Ahmadreza , Eftekhari Mohammad , Ghavamzadeh Ardeshir
Published: May 2014

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant 131I‐MIBG scintigraphy. Twenty high‐risk patients were enrolled. On day −30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG‐avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m2), carboplatin (1500 mg/m2), and melphalan (210 mg/m2). Non‐MIBG‐avid subgroup received etoposide (600 mg/m2), carboplatin (1200 mg/m2), and melphalan (150 mg/m2). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17–65) in MIBG‐avid and 38.9 months (range, 18–65) in non‐MIBG‐avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG‐avid patients, the three‐yr OS was 66 ± 21%. In MIBG‐non‐avid subgroup, the three‐yr OS was 53 ± 20%. In MIBG‐avid and non‐MIBG‐avid subgroups, the three‐yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre‐ASCT MIBG scintigraphy in high‐risk neuroblastoma. MIBG‐avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.
Efficacy of bortezomib for reducing donor‐specific antibodies in children and adolescents on a steroid minimization regimen
Authors: Nguyen Stephanie , Gallay Brian , Butani Lavjay
Published: May 2014

AMR is increasingly being recognized as an important cause of renal allograft injury, contributing to significant morbidity and graft loss. There are few controlled trials and no well‐established treatment guidelines for AMR in renal transplant recipients. We retrospectively reviewed the outcome of four pediatric renal transplant recipients on a steroid minimization immunosuppression protocol treated with bortezomib for elevated DSA and acute AMR from 2012 to 2013. All patients received four doses of bortezomib 1.3 mg/m2 given on days one, four, eight, and 11. All patients also received other treatments prior to bortezomib, which may have included rituximab, methylprednisolone, plasmapheresis, and/or IVIg. While bortezomib in addition to other therapies significantly decreased DSA titers, DSA remained very elevated months after treatment. All four patients had immediate improvement or stabilization of renal function but one eventually lost her graft. There were no adverse events related to bortezomib six months after treatment.
An endobronchial inflammatory myofibroblastic tumor in a 10‐yr‐old child after allogeneic hematopoietic cell transplantation
Authors: Fujino Hisanori , Park Young‐Dong , Uemura Suguru , Tanaka Shinzo , Kawabe Masakazu , Maeda Sayaka , Kato Itaru , Watanabe Ken‐Ichiro , Umeda Katsutsugu , Hiramatsu Hidefumi , Adachi Souichi , Sato Toshihiko , Date Hiroshi , Haga Hironori , Sumimoto Shinichi
Published: May 2014

IMTs belong to the group of soft tissue tumor and could occur at any anatomical site; however, the causes and growth feature remain unclear. This case report documents a 10‐yr‐old male suffering from slowly developing dyspnea on exertion and cough around seven months post‐HCT. He was diagnosed with an endobronchial tumor based on imaging, and histology confirmed ALK‐positive submucosal spindle‐shaped cells with infiltrative cells, compatible with IMT. We should be aware that IMT is a potential complication of pediatric allogeneic HCT and can cause sudden airway obstruction.
Scurvy: A new problem for patients with chronic GVHD involving mucous membranes; an easy problem to resolve
Authors: Kletzel Morris , Powers Kim , Hayes Meghan
Published: May 2014

Vitamin C deficiency in developed countries is typically observed in patients with unique clinical conditions such as cystic fibrosis or anorexia nervosa, or in patients on long‐term tube feeds. We report here a clinical observation in six pediatric and adolescent patients (median age 17.5 yr, range 9.8–23.5 yr) with chronic GVHD with mucous membrane involvement found to be vitamin C deficient. These patients' baseline serum vitamin C levels ranged from <0.12 to 0.94 mg/dL (normal value 0.20–1.90 mg/dL), with a mean level 0.56 ± 0.36 mg/dL and a median level 0.6 mg/dL. Among these patients, signs and symptoms of mucositis failed to respond to standard chronic GVHD therapy. After receiving treatment with 2000 mg of ascorbic acid by mouth, daily patients displayed increased serum vitamin C levels. Clinically, this correlated with a remarkable improvement in patients' mucositis and ability to eat.
Physiological responses of spring rapeseed (Brassica napus) to red/far‐red ratios and irradiance during pre‐ and post‐flowering stages
Authors: Rondanini Deborah P. , del Pilar Vilariño Maria , Roberts Marcos E. , Polosa Marina A. , Botto Javier F.
Published: May 2014

Early shade signals promote the shade avoidance syndrome (SAS) which causes, among others, petiole and shoot elongation and upward leaf position. In spite of its relevance, these photomorphogenic responses have not been deeply studied in rapeseed (Brassica napus). In contrast to other crops like maize and wheat, rapeseed has a complex developmental phenotypic pattern as it evolves from an initial rosette to the main stem elongation and an indeterminate growth of floral raceme. In this work, we analyzed (1) morphological and physiological responses at individual level due to low red/far‐red (R/FR) ratio during plant development, and (2) changes in biomass allocation, grain yield and composition at crop level in response to high R/FRratio and low irradiance in two modern spring rapeseed genotypes. We carried out pot and field experiments modifying R/FRratios and irradiance at vegetative or reproductive stages. In pot experiments, low R/FRratio increased the petiole and lamina length, upward leaf position and also accelerated leaf senescence. Furthermore, low R/FRratio reduced main floral raceme and increased floral branching with higher remobilization of soluble carbohydrates from the stems. In field experiments, low irradiance during post‐flowering reduced grain yield, harvest index and grain oil content, and high R/FRratio reaching the crop partially alleviated such effects. We conclude that photomorphogenic signals are integrated early during the vegetative growth, and irradiance has stronger effects than R/FRsignals at rapeseed crop level.
The Effects of Project‐Based Learning on Students' Academic Achievement, Attitude, and Retention of Knowledge: The Subject of “Electricity in Our Lives”
Authors: Karaçalli Saide , Korur Fikret
Published: May 2014

The aim of this study is to analyze the effects of project‐based learning on students' academic achievement, attitude, and retention of knowledge in relation to the subject of “Electricity in Our Lives” in a fourth‐grade science course. The study was conducted in a quasi‐experimental design as a “pre‐test, post‐test with control group.” In the experimental group, the unit was taught through the project‐based learning method. The measuring tools were administered to both groups before and after the applications. To perfectly analyze the “process” of the method, seven different learning assessment “forms” were administered to the students. The findings of the forms indicated that the students learn to construct their own learning and to evaluate changes in their own behavior through the application of the method.

The application of different methods between both groups had a statistically significant effect in terms of academic achievement, (F(1,112) = 46.78, p = .000) and of retention of knowledge (F(1,112) = 35.24, p = .000). However, there were no statistically significant effects from being in different groups for the attitudes of students (F(1,112) = .99, p = .321). For the students, being in the project‐based learning groups resulted in better academic achievement and retention of knowledge than being in the traditional teaching group.
The Science Teaching Self‐Efficacy of Prospective Elementary Education Majors Enrolled in Introductory Geology Lab Sections
Authors: Baldwin Kathryn A.
Published: May 2014

This study examined prospective elementary education majors' science teaching self‐efficacy while they were enrolled in an introductory geology lab course for elementary education majors. The Science Teaching Efficacy Belief Instrument Form B (STEBI‐B) was administered during the first and last lab class sessions. Additionally, students were asked an open‐ended question to describe their experience in the education majors' geology lab. The results of the STEBI‐B were analyzed using paired t‐tests to determine whether the students changed their personal science teaching efficacy (PSTE) and science teaching outcome expectancy (STOE). Results of this study indicate a significant increase in PSTE. No significant differences were found in STOE. This study suggests that science content courses designed for education majors may lead to a positive change in science teaching self‐efficacy and has implications for teacher educators in preparing science content courses for their teacher preparation program.
The Effectiveness of Process‐Oriented Guided Inquiry Learning to Reduce Alternative Conceptions in Secondary Chemistry
Authors: Barthlow Michelle J. , Watson Scott B.
Published: May 2014

A nonequivalent, control group design was used to investigate student achievement in secondary chemistry. This study investigated the effect of process‐oriented guided inquiry learning (POGIL) in high school chemistry to reduce alternate conceptions related to the particulate nature of matter versus traditional lecture pedagogy. Data were collected from chemistry students in four large high schools and were analyzed using analysis of covariance. The results show that POGIL pedagogy, as opposed to traditional lecture pedagogy, resulted in fewer alternate conceptions related to the particulate nature of matter. Male and female students in the POGIL group posted better posttest scores than their traditional group peers. African‐American and Hispanic students in the POGIL group exhibited achievement gains consistent with Caucasian and Asian students. Further studies are needed to determine the value of POGIL to address achievement gap concerns in chemistry.
Neither silverfish nor fowl: the enigmatic Carboniferous Carbotriplura kukalovaeKluge, 1996 (Insecta: Carbotriplurida) is the putative fossil sister group of winged insects (Insecta: Pterygota)
Authors: STANICZEK ARNOLD H. , SROKA PAVEL , BECHLY GÜNTER
Published: May 2014

We revise the type material of the enigmatic fossil insect Carbotriplura kukalovae Kluge, 1996 from the Pennsylvanian of the Czech Republic. Multiple errors in the original description are documented and corrected. C. kukalovae is regarded as a possible transitional fossil link between Zygentoma and Pterygota. Carbotriplurida is therefore elevated to ordinal rank and considered as putative fossil sister group of Pterygota. The paranotal theory of the origin of insect wings and the parachute theory of origin of insect flight are briefly discussed and further corroborated. Testajapyx thomasi from the Pennsylvanian of Mazon Creek is tentatively considered as Dermaptera rather than Diplura.
An Uplifting Experience: A Course Sequence Designed to Facilitate Proficiency Development
Authors: Lindseth Martina , Brown Joshua R.
Published: May 2014

This article discusses a three‐course sequence which has been designed to aid students' attainment of Advanced Low proficiency according to ACTFL guidelines. A cycle of iterative tasks (with increasing learner autonomy) within and between the courses in the sequence are highlighted and their implementation discussed. Additionally, metalinguistic activities which bolster development of tools necessary for proficiency development are described. In exposing students to these tasks and activities, instructors of such sequences can facilitate the learning process, engage students in the course and its assessments, and help develop cognitive skills applicable beyond the classroom.
From Visual Literacy to Literary Proficiency: An Instructional and Assessment Model for the Graphic Novel Version of Kafka'sDie Verwandlung
Authors: Kutch Lynn Marie
Published: May 2014

This article argues that instructors can effectively implement visual and multi‐modal methods often used in beginner and intermediate courses as effective building blocks to develop skills of literary analysis. The article presents aspects of a mini‐curriculum based onDie Verwandlung, the graphic novel, and examples of student work and feedback from a 200‐level graphic‐novel course. Corresponding to the format of a graphic novel that combines pictorial and visual information, items in the curriculum consistently incorporate methods to build visual literacy to move students toward verbal literacy. The article contributes to language pedagogy in explaining the use of graphic novels in the language classroom to develop literary analytical proficiency. Field‐tested examples demonstrate ways students learn to use illustrations and literary products to support higher‐level analysis. The article suggests that carefully crafted questions can emphasize the visual exploration that has typically gone into reading graphic texts, but has less frequently been associated with building skills of literary exploration.
Imprinting in rice: the role of DNA and histone methylation in modulating parent‐of‐origin specific expression and determining transcript start sites
Authors: Du Miru , Luo Ming , Zhang Ruofang , Finnegan E. Jean , Koltunow Anna M. G.
Published: May 2014

Over 200 imprinted genes in rice endosperm are known, but the mechanisms modulating their parental allele‐specific expression are poorly understood. Here we use three imprinted genes, OsYUCCA11, yellow2‐like and ubiquitin hydrolase, to show that differential DNA methylation and tri‐methylation of histone H3 lysine 27 (H3K27me3) in the promoter and/or gene body influences allele‐specific expression or the site of transcript initiation. Paternal expression of OsYUCCA11 required DNA methylation in the gene body whereas the gene body of the silenced maternal allele was hypomethylated and marked with H3K27me3. These differential markings mirror those proposed to modulate paternal expression of two Arabidopsis genes, PHERES1 and a YUCCA homolog, indicating conservation of imprinting mechanisms. At yellow2‐like, DNA hypomethylation in the upstream flanking region resulted in maternal transcripts that were longer than paternal transcripts; the maternal transcript initiation site was marked by DNA methylation in the paternal allele, and transcription initiated ~700 bp downstream. The paternal allele of an ubiquitin hydrolase gene exhibited gene body DNA methylation and produced full‐length transcripts, while the maternal allele was hypomethylated in the 5′ gene body and transcripts initiated from a downstream promoter. Inhibition of DNA methylation by 5‐azacytidine or zebularine activated the long transcripts from yellow2‐like and enhanced expression of the short transcripts from the ubiquitin hydrolase in seedlings, indicating that DNA methylation prevents transcript initiation from cryptic promoters. These observations suggest a paradigm whereby maternal genome hypomethylation is associated with the production of distinct transcripts, potentially diversifying the gene products from the two alleles.