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Find video protocols related to scientific articles indexed in Pubmed.
A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology.
Nucleic Acids Res.
PUBLISHED: 11-19-2014
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Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined.
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Arthroscopic debridement for ankle haemophilic arthropathy.
Blood Coagul. Fibrinolysis
PUBLISHED: 11-18-2014
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The purpose of this study is to describe the results of arthroscopic ankle debridement (AAD) with the aim of determining whether it is possible to avoid or delay ankle fusion or total ankle replacement for advanced haemophilic arthropathy of the ankle in young patients. In a 12-year period (2000-2011), 24 AADs (one bilateral in two stages) were performed for advanced haemophilic arthropathy of the ankle in 23 patients (22 had haemophilia A, 1 haemophilia B, 0 with inhibitors against the deficient factor). Their average age at operation was 25.3 years (range 21-36). Inclusion criteria were: more than 50% of ankle motion, good axial alignment of the ankle (increased varus or valgus angulation was a contraindication for AAD) and pain greater than 6 points on a visual analogue scale (0-no pain to 10 points). Follow-up was for an average of 5.4 years (range 2-14 years). The results were evaluated retrospectively by the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale. The clinical results were excellent in 13 (54.2%), good in nine (37.5%) and fair in two (8.3%). There were two (8.3%) postoperative complications (haemarthroses resolved by join aspiration). Three patients (12.5%) required an ankle fusion. AAD should be considered in the young haemophiliac to delay ankle fusion or total ankle replacement. The operation may give the patient years of life without intense pain.
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An Optimized Mouse Thigh Infection Model for Enterococci and its Impact on Antimicrobial Pharmacodynamics.
Antimicrob. Agents Chemother.
PUBLISHED: 10-29-2014
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Negligible in vivo growth of enterococci and high dispersion of data has led to inaccurate estimation of antibiotic pharmacodynamics (PD). Here, we improved an in vivo model apt for PD studies by optimizing the in vitro culture conditions of enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM) and piperacillin-tazobactam (TZP) was determined in vivo against enterococci, comparing different conditions of inoculum preparation: aerobiosis, aerobiosis+mucin or anaerobiosis+mucin. Drug exposure was expressed as fAUC/MIC (VAN) or fT>MIC (SAM and TZP) and linked to the change in log10 CFU/thigh. Only anaerobiosis+mucin enhanced the in vivo growth yielding significant PD parameters with all antibiotics. In conclusion, robust in vivo growth of enterococci was crucial to determine better the PD of tested antibacterial agents; this was achieved by optimizing the procedure for preparing the inoculum.
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Minimally invasive therapy for epiphrenic diverticula: Systematic review of literature and report of six cases.
J Minim Access Surg
PUBLISHED: 10-23-2014
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Epiphrenic diverticula (ED) are infrequent and conventional surgical treatment entails aggressive open or transthoracic surgery. Minimally invasive treatment has changed the surgical approach but some surgical controversies are not resolved.
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Preliminary Results of a Phase II Trial of Proton Radiotherapy for Pediatric Rhabdomyosarcoma.
J. Clin. Oncol.
PUBLISHED: 10-20-2014
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This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS).
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Inhibiting CARD11 translation during BCR activation by targeting the eIF4A RNA helicase.
Blood
PUBLISHED: 10-17-2014
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Human diffuse large B-cell lymphomas (DLBCLs) often aberrantly express oncogenes that generally contain complex secondary structures in their 5' untranslated region (UTR). Oncogenes with complex 5'UTRs require enhanced eIF4A RNA helicase activity for translation. PDCD4 inhibits eIF4A and PDCD4 knockout mice have a high penetrance for B-cell lymphomas. Here, we show that upon B-cell receptor (BCR) mediated p70s6K activation, PDCD4 is degraded and eIF4A activity is greatly enhanced. We have identified a subset of genes involved in BCR signaling, including CARD11, BCL10 and MALT1, which have complex 5'UTRs and encode proteins with short half-lives. Expression of these known oncogenic proteins is enhanced upon BCR activation, and is attenuated by the eIF4A inhibitor, Silvestrol. Antigen-experienced IgG(+) splenic B-cells, from which most DLBCLs are derived, have higher levels of eIF4A cap-binding activity and protein translation than IgM(+) B-cells. Our results suggest that eIF4A-mediated enhancement of oncogene translation may be a critical component for lymphoma progression and specific targeting of eIF4A may be an attractive therapeutic approach in the management of human B-cell lymphomas.
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Impact on resistance of the use of therapeutically equivalent generics: the case of ciprofloxacin.
Antimicrob. Agents Chemother.
PUBLISHED: 10-15-2014
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Therapeutic nonequivalence of generic antibiotics may lead to treatment failure and resistance enrichment. However, there is no demonstration that an equivalent generic displays the same resistance selection profile of the innovator drug. We aimed to test this hypothesis with five generics of ciprofloxacin by assessing their pharmaceutical equivalence by microbiological assay and their efficacy in the neutropenic murine thigh infection model against Pseudomonas aeruginosa PA01. One equivalent generic was selected for analysis by tandem liquid-chromatography/mass spectrometry (LC/MS(2)) to confirm chemical identity and resistance selection experiments in a hollow fiber system (HF) simulating two clinical dosing regimens. Total and resistant populations were measured and the MIC of the resistant cells with and without an efflux pump inhibitor were determined. LC/MS found no differences between products and after seven days of treatment in the HF, both innovator and generic selected resistance with the same magnitude and mechanism, supporting the fact that a generic with demonstrated equivalence in vivo, is also equivalent regarding resistance selection.
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Suppression of Deacetylase SIRT1 Mediates Tumor-Suppressive NOTCH Response and Offers a Novel Treatment Option in Metastatic Ewing Sarcoma.
Cancer Res.
PUBLISHED: 10-03-2014
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The developmental receptor NOTCH plays an important role in various human cancers as a consequence of oncogenic mutations. Here we describe a novel mechanism of NOTCH-induced tumor suppression involving modulation of the deacetylase SIRT1, providing a rationale for the use of SIRT1 inhibitors to treat cancers where this mechanism is inactivated because of SIRT1 overexpression. In Ewing sarcoma cells, NOTCH signaling is abrogated by the driver oncogene EWS-FLI1. Restoration of NOTCH signaling caused growth arrest due to activation of the NOTCH effector HEY1, directly suppressing SIRT1 and thereby activating p53. This mechanism of tumor suppression was validated in Ewing sarcoma cells, B-cell tumors, and human keratinocytes where NOTCH dysregulation has been implicated pathogenically. Notably, the SIRT1/2 inhibitor Tenovin-6 killed Ewing sarcoma cells in vitro and prohibited tumor growth and spread in an established xenograft model in zebrafish. Using immunohistochemistry to analyze primary tissue specimens, we found that high SIRT1 expression was associated with Ewing sarcoma metastasis and poor prognosis. Our findings suggest a mechanistic rationale for the use of SIRT1 inhibitors being developed to treat metastatic disease in patients with Ewing sarcoma. Cancer Res; 74(22); 6578-88. ©2014 AACR.
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The genomic landscape of pediatric ewing sarcoma.
Cancer Discov
PUBLISHED: 09-03-2014
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Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date, with only EWS-ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS-ETS fusions in this disease.
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Direct comparison of electrochemical and spectrochemical kinetics for catalytic oxygen reduction.
J. Am. Chem. Soc.
PUBLISHED: 08-28-2014
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We describe here a direct comparison of electrochemical and spectrochemical experiments to determine rates and selectivity of oxygen reduction catalyzed by iron 5,10,15,20-meso-tetraphenylporphyrin chloride. Good agreement was found between the two methods, suggesting the same mechanism is occurring under both conditions, with the same third-order rate law, similar selectivity, and the derived rate constants agreeing within a factor of at most 4, with k(cat) ? 2 × 10(6) M(-2) s(-1). This Communication provides a rare example of a redox catalytic process characterized by two common but very different methods.
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Validation of a multi-modal treatment protocol for Ewing sarcoma-A report from the polish pediatric oncology group.
Pediatr Blood Cancer
PUBLISHED: 08-27-2014
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Ewing sarcoma (ES) is the second most common paediatric malignant bone tumor. Advances in multi-disciplinary care have resulted in significant improvement in cure rates over the last decades. However, the generalization of those results in countries traditionally excluded from large cooperative trials has yet to be demonstrated. We report the results of modern multi-disciplinary care for patients with ES in Poland.
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Pathologic changes associated with suspected hypovitaminosis A in amphibians under managed care.
Zoo Biol.
PUBLISHED: 08-19-2014
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Vitamin A deficiency is a recently recognized nutritional disease in amphibians fed insect-based diets. The classic pathologic lesion that has been associated with hypovitaminosis A in amphibians is squamous metaplasia of the lingual and oral mucosa. In an attempt to further characterize the range of lesions that may be associated with vitamin A deficiency, we reviewed archived amphibian necropsy reports from three facilities. As previously reported, the tongue was the most commonly affected site in animals presenting with squamous metaplasia. However, metaplastic changes were also observed in a variety of locations that included the oral cavity, nasal cavity, pharynx, esophagus, stomach, cloaca, skin, urinary bladder, ureter, and reproductive tract. In addition, species and age-specific differences were noted in the development of squamous metaplasia. This review highlights the need to establish standardized guidelines for optimal postmortem tissue sampling of amphibians in order to maximize the accurate diagnosis of pathologic lesions that may be associated with hypovitaminosis A. Zoo Biol. XX:XX-XX, 2014. © 2014 Wiley Periodicals Inc.
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Prevalence of methicillin-resistant Staphylococcus aureus : effect of different criteria for elimination of duplicates.
Chemotherapy
PUBLISHED: 08-14-2014
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The purpose of this study is to compare the effect of different systems for eliminating duplicates in order to optimize the calculation of the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection.
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Damage control resuscitation protocol and the management of open abdomens in trauma patients.
Am Surg
PUBLISHED: 08-09-2014
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Although the use of damage control laparotomy (DCL) is well established, the effect of damage control resuscitation (DCR) on the management of open abdomens is relatively poorly studied. The aim of the present study was to determine the predictors for failure to achieve primary fascial closure (PFC) after DCL in the setting of a massive transfusion (MT) and DCR. This is a retrospective review over a 12-year period of all patients that underwent MT and DCL. Patients who achieved PFC were compared with those who did not (NPFC). Student's t tests were used to compare the two groups. A multiple logistic regression model was performed to identify independent risk factors for failure to attain PFC. Of 174 patients, 101 achieved PFC. Mean (± standard deviation) age was 35.6 ± 14.9 years for PFC and 36.3 ± 14.0 years for NPFC (P = 0.75). Admission Glasgow Coma Scale score was 11.4 ± 4.6 for PFC and 10.6 ± 5.0 for NPFC (P = 0.25). Initial lactate (7.3 ± 3.8 vs 7.7 ± 4.1, P = 0.50), hemoglobin (11.3 ± 1.9 vs 11.0 ± 2.2, P = 0.43), systolic blood pressure (108 ± 44 vs 107 ± 35, P = 0.82), Injury Severity Score (34 ± 14 vs 36 ± 15, P = 0.32), and abdominal Abbreviated Injury Score (3.6 ± 1.1 vs 3.9 ± 1.0, P = 0.13) were similar between the two groups. There was no difference in total blood products administered at 24 hours (46 ± 26 vs 49 ± 29 units, P = 0.45). Logistic regression identified increasing volume of crystalloid at 24 hours (odds ratio, 0.86; 95% confidence interval, 0.74 to 0.99; P = 0.047), earlier operative year (2.1; 1.52 to 2.91; P < 0.001), and increased number of procedures (0.32, 0.18 to 0.58; P < 0.001) as independent predictors for failure to obtain PFC. Injury severity is not associated with failure to achieve PFC, whereas administration of large-volume crystalloid resuscitation, increasing number procedures, and earlier year of DCL are independent predictors for failure to achieve PFC. Application of DCR to DCL techniques results in an improvement in ability to achieve PFC.
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Patterns and Predictors of Sleep Quality Before, During, and After Hospitalization in Older Adults.
J Clin Sleep Med
PUBLISHED: 08-01-2014
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The impact of hospitalization on sleep in late-life is underexplored. The current study examined patterns of sleep quality before, during, and following hospitalization, investigated predictors of sleep quality patterns, and examined predictors of classification discordance between two suggested clinical cutoffs used to demarcate poor/good sleep.
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Developmental and adaptive functioning in children with retinoblastoma: a longitudinal investigation.
J. Clin. Oncol.
PUBLISHED: 07-14-2014
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To determine the developmental trajectory of early cognitive and adaptive skills in young children with retinoblastoma from diagnosis to 5 years of age.
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Effectiveness of three different alveolar ridge preservation techniques: a pilot randomized controlled trial.
Int J Periodontics Restorative Dent
PUBLISHED: 07-10-2014
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The aim of this pilot study was to obtain preliminary data regarding the effectiveness of three different alveolar ridge preservation modalities as compared with a control. Subjects in need of single-rooted tooth extraction were recruited and randomly allocated to one of four treatment groups: group 1 (control)--collagen plug; group 2--socket grafting and polytetrafluoroethylene (PTFE) barrier; group 3--socket grafting, buccal overbuilding, and PTFE barrier; group 4--socket grafting, collagen barrier, and PTFE barrier. The grafting material used in all groups was an allograft. At 16 weeks, surgical reentry was performed, and a bone core biopsy was harvested for histomorphometric analysis. A cone beam computed tomography scan was obtained at baseline and before surgical reentry. Clinical (keratinized mucosa [KM] and buccolingual ridge width [RW] changes) and volumetric outcomes were statistically analyzed. A total of 20 patients were recruited (5 patients per group). KM and buccolingual RW changes were minimal during the 16-week healing period for all groups, with no statistically significant differences. Volumetric analyses revealed comparable alveolar ridge resorption values for groups 1, 2, and 4 (3%, 7%, and 5%, respectively), while group 3 exhibited more reduction (16%). Histomorphometric analysis revealed the presence of adequate average values of mineralized tissue (group 1, 46.4%; group 2, 28.88%; group 3, 48.81%; group 4, 41.13%). Based on the clinical and volumetric outcomes, none of the ridge preservation modalities was superior to the control. The combination allograft (freeze-dried bone allograft and demineralized freeze-dried bone allograft) employed in this study appears to be a safe and adequate biomaterial for intraoral grafting.
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Ligand effect on the size, valence state and red/near infrared photoluminescence of bidentate thiol gold nanoclusters.
Nanoscale
PUBLISHED: 06-12-2014
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Synthesis and characterization of gold nanoclusters (Au NCs) stabilized by a zwitterion ligand (Zw) at different Au?:?Zw ratios are demonstrated. Au NCs exhibit photoluminescence (PL) emission which is tunable from the near infrared (805 nm) to the red spectral window (640 nm) and strongly influenced by the ligand shell size. Optical and chemical investigations suggest the presence of gold polymeric species and large nanoclusters for a molar ratio of Au?:?Zw = 1?:?1. For 1?:?5 < Au?:?Zw < 1?:?1, Zw induces etching of the large clusters and the formation of a monolayer of the bidentate ligands on the Au NCs (cluster size ?7 to 10 kDa) accompanied by red PL emission at ? = 710 nm. A second organic layer starts to form for larger Zw fractions (Au?:?Zw < 1?:?5) as a result of electrostatic and covalent interactions of the zwitterion leading to an enhancement and a blue-shift of the PL emission. The effect of temperature and pH on the optical properties of gold clusters is strongly dependent on the ligand shell and demonstrates the importance of defining gold nanoclusters as supramolecular assemblies with a complex environment.
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[Survival of patients with biopsy-proven idiopathic pulmonary fibrosis: Chilean National Thorax Institute experience].
Rev Med Chil
PUBLISHED: 05-28-2014
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Idiopathic Pulmonary Fibrosis (IPF) is the most prevalent of all interstitial lung diseases. The usual underlying pathological picture is an interstitial pneumonia (UIP). Aim: To describe the evolution of a Chilean cohort of patients with IPF.
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Arthroscopic BPTB graft reconstruction in ACL ruptures: 15-year results and survival.
Knee
PUBLISHED: 05-24-2014
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The aim of this study is to investigate the 15-year results and survival of arthroscopic ACL reconstruction using the central-third patellar bone-tendon-bone (BPTB) autograft.
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Medial Unicompartmental Osteoarthritis (MUO) of the Knee: Unicompartmental Knee Replacement (UKR) or Total Knee Replacement (TKR).
Arch Bone Jt Surg
PUBLISHED: 05-17-2014
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The aim of this review article is to analyze the clinical effectiveness of total knee replacement (TKR) compared to unicompartmental knee replacement (UKR) in patients with medial unicompartmental osteoarthritis (MUO) in terms of survival rates, revision rates and postoperative complications. The search engine was MedLine. The keywords used were: medial knee osteoarthritis. Three thousand and ninety-six articles were found on 28 April 2014. Of those, only twenty-eight were selected and reviewed because they were strictly focused on the topic of this article. Compared with those who have TKR, patients who undergo UKR have higher revision rates and lower survival rates at 5, 10 and 15 years. The reported overall risk of postoperative complications for patients undergoing TKR is 11%, compared with 4.3% for patients undergoing UKR. In conclusion, UKR have higher revision rates and lower survival rates than TKR. There is, however, an increased risk of postoperative complications after TKR.
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Delayed diagnosis and false relapse due to paternal testosterone use in adrenocortical carcinoma.
Pediatrics
PUBLISHED: 05-05-2014
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The prognosis of pediatric adrenocortical carcinoma often depends on prompt diagnosis to begin treatment before metastatic progression. We discuss a girl who presented at 8 months of age with virilization, which was thought to be due to exposure to a topical testosterone preparation being used by her father. Her testosterone level did not decrease promptly after her father discontinued the medication, however, and when she followed up with signs of Cushing syndrome 5 months later, metastatic adrenocortical carcinoma was diagnosed. The patient was successfully treated with surgery and multiagent chemotherapy. Nine months after the end of treatment, her testosterone level was again found to be elevated. Testosterone precursors were now absent, however, and there were no imaging signs of recurrence. Further history showed that her father had restarted topical testosterone, and this time, exogenous exposure was correctly diagnosed. As use of topical testosterone becomes more prevalent, exogenous exposure must be considered in the differential diagnosis of childhood virilization. Any persistent testosterone elevation after exposure ceases or signs of hypercortisolism, however, are inconsistent with this diagnosis. We believe that the risk-benefit ratio favors abdominal ultrasound to rule out malignancy in all children presenting with virilization.
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Thromboprophylaxis in haemophilia patients undergoing orthopaedic surgery.
Blood Coagul. Fibrinolysis
PUBLISHED: 05-01-2014
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The review of literature on thromboprophylaxis in nonhaemophilia patients undergoing orthopaedic surgery and on thromboprophylaxis in people with haemophilia undergoing orthopaedic surgery leads us to the conclusion that we cannot currently recommend thromboprophylaxis extensively in haemophilia patients undergoing orthopaedic surgery. This sharply contrasts with what the literature recommends for nonhaemophilia patients, that is to say mixed pharmacological and mechanical thromboprophylaxis. However, if we detect several risk factors for thromboembolism in a haemophiliac patient who is to undergo orthopaedic surgery, we should carry out the same type of thromboprophylaxis recommended for nonhaemophilia patients. Such risk factors are the following: orthopaedic surgery, increased age, previous thromboembolism, varicose veins, general anaesthesia, malignancy (cancer), factor V (Leiden) mutation, obesity, and the oral contraceptive pill (in women with von Willebrand disease).
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Siamese twins with craniofacial duplication and bilateral cleft lip/palate in a ceramic representation of the Chimú culture (Peru): a comparative analysis with a current case.
Twin Res Hum Genet
PUBLISHED: 04-28-2014
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Craniofacial duplication or diprosopus is a very rare malformation that is present in approximately 0.4% of conjoined twins. Here is presented a case of craniofacial duplication in association with bilateral cleft lip/palate in both heads found in a ceramic representation from the early Chimú culture from Peru. A comparative analysis is made with a current case of a 28-week-old fetus with similar characteristics. After reviewing the medical literature on conjoined twins, very few reports of facial cleft in both twins were found, with no reports at all of bilateral cleft lip/palate. This ceramic crock is considered one of the first representations suggestive of craniofacial duplication, and probably the first reporting it in association with facial cleft.
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Can a minimal replicating construct be identified as the embodiment of cancer?
Bioessays
PUBLISHED: 04-12-2014
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Genomic instability is a hallmark of cancer. Cancer cells that exhibit abnormal chromosomes are characteristic of most advanced tumours, despite the potential threat represented by accumulated genetic damage. Carcinogenesis involves a loss of key components of the genetic and signalling molecular networks; hence some authors have suggested that this is part of a trend of cancer cells to behave as simple, minimal replicators. In this study, we explore this conjecture and suggest that, in the case of cancer, genomic instability has an upper limit that is associated with a minimal cancer cell network. Such a network would include (for a given microenvironment) the basic molecular components that allow cells to replicate and respond to selective pressures. However, it would also exhibit internal fragilities that could be exploited by appropriate therapies targeting the DNA repair machinery. The implications of this hypothesis are discussed.
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The link between rhinitis and rapid-eye-movement sleep breathing disturbances in children with obstructive sleep apnea.
Am J Rhinol Allergy
PUBLISHED: 04-11-2014
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Rhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities.
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Ovarian function in female survivors after multimodal Ewing sarcoma therapy.
Pediatr Blood Cancer
PUBLISHED: 03-25-2014
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With advances in cancer care, more young women with Ewing sarcoma (ES) survive after treatment. Thus, we sought to analyze the ovarian function in prepubertal, pubertal and postpubertal females and young women receiving multimodal therapy for ES, and to identify patients at risk of infertility on whom fertility preservation would be indicated.
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Internal hemipelvectomy in the management of pelvic Ewing sarcoma - are outcomes better than with radiation therapy?
J. Pediatr. Surg.
PUBLISHED: 03-10-2014
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Pelvic Ewing sarcoma (ES) is commonly associated with a worse prognosis. Large size and location limit local control options to radiation therapy, and local recurrences are common. We evaluated the impact of hemipelvectomy and radiation on outcomes, including function.
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Repeal of the Michigan helmet law: early clinical impacts.
Am. J. Surg.
PUBLISHED: 03-04-2014
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Michigan repealed a 35-year mandatory helmet law on April 13, 2012. We examined the early clinical impacts at a level 1 trauma center in West Michigan.
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Pathologic risk-based adjuvant chemotherapy for unilateral retinoblastoma following enucleation.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 03-01-2014
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There are no standardized diagnostic or treatment guidelines for patients with advanced unilateral retinoblastoma.
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Nutrition and health in amphibian husbandry.
Zoo Biol.
PUBLISHED: 02-14-2014
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Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas. Zoo Biol. XX:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
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Hypothalamic PGC-1? Protects Against High-Fat Diet Exposure by Regulating ER?.
Cell Rep
PUBLISHED: 02-13-2014
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High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor ? (ER?) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1? regulates ER? and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1? and ER? in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1? depletion with ER? overexpression significantly inhibited PA-induced inflammation, confirming that ER? is a critical determinant of the anti-inflammatory response. Physiologic relevance of ER?-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1? and ER?, promoting inflammation and decrements in myocardial function in a sex-specific way.
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Myogenic Tumors in Nevoid Basal Cell Carcinoma Syndrome.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 02-13-2014
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In mice, activated Hedgehog (Hh) signaling induces tumors with myogenic differentiation. In humans, hyperactive Hh signaling due to germline PATCHED1 (PTCH1) mutations has been linked to nevoid basal cell carcinoma syndrome (NBCCS). We report an embryonal rhabdomyosarcoma in a 16-month-old girl with NBCCS and review the literature on myogenic neoplasms in NBCCS, including 8 fetal rhabdomyomas and 3 rhabdomyosarcomas. Of note, 3 population studies, including 255 individuals with NBCCS aged 4 months to 87 years, did not identify any myogenic tumors. Thus, myogenic tumors in NBCCS are rare and include both rhabdomyosarcomas and fetal rhabdomyomas.
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The Influence of Obesity on the Outcome of TKR: Can the Impact of Obesity be justified from the Viewpoint of the Overall Health Care System?
HSS J
PUBLISHED: 02-01-2014
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There is controversy in the literature regarding the justification of performing total knee replacement (TKR) in obese patients in view of their increased risk of poor outcomes and how those poorer outcomes impact the health care system overall.
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Surgical treatment of isolated patellofemoral osteoarthritis.
HSS J
PUBLISHED: 02-01-2014
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Isolated patellofemoral (PF) osteoarthritis (OA) affects 9% of persons older than 40 years. Nonoperative treatment should be exhausted fully before surgical treatment.
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Thromboprophylaxis in haemophilia patients undergoing orthopaedic surgery.
Blood Coagul. Fibrinolysis
PUBLISHED: 01-29-2014
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The review of literature on thromboprophylaxis in nonhaemophilia patients undergoing orthopaedic surgery and on thromboprophylaxis in people with haemophilia undergoing orthopaedic surgery leads us to the conclusion that we cannot currently recommend thromboprophylaxis extensively in haemophilia patients undergoing orthopaedic surgery. This sharply contrasts with what the literature recommends for nonhaemophilia patients, that is to say mixed pharmacological and mechanical thromboprophylaxis. However, if we detect several risk factors for thromboembolism in a haemophiliac patient who is to undergo orthopaedic surgery, we should carry out the same type of thromboprophylaxis recommended for nonhaemophilia patients. Such risk factors are the following: orthopaedic surgery, increased age, previous thromboembolism, varicose veins, general anaesthesia, malignancy (cancer), factor V (Leiden) mutation, obesity, and the oral contraceptive pill (in women with von Willebrand disease).
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Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study.
J. Pediatr.
PUBLISHED: 01-28-2014
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To investigate trends in incidence of differentiated thyroid carcinomas among children and adolescents and young adults.
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Evidence Based Conservative Management of Patello-femoral Syndrome.
Arch Bone Jt Surg
PUBLISHED: 01-20-2014
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Patellofemoral pain syndrome (PFPS) is defined as pain surrounding the patella when sitting with bent knees for prolonged periods of time or when performing activities like ascending or descending stairs, squatting or athletic activities. Patella dislocation is not included in PFPS. This review analyzes the evidence based conservative management of PFPS. A Cochrane Library search related to PFPS was performed until 18 January 2014. The key words were: patellofemoral pain syndrome. Eight papers were found, of which three were reviewed because they were focused on the topic of the article. We also searched the PubMed using the following keywords: evidence based conservative management of patellofemoral pain syndrome. Twelve articles were found, of which seven were reviewed because they were focused on the topic of the article. Overall ten articles were analyzed. Different treatments can be tried for PFPS, including pharmacotherapy, therapeutic ultrasound, exercise therapy, and taping and braces. Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce pain in the short term, but pain does not improve after three months. Therapeutic ultrasound appears not to have a clinically important effect on pain relief for patients with PFPS. The evidence that exercise therapy is more effective in treating PFPS than no exercise is limited with respect to pain reduction, and conflicting with respect to functional improvement. No significant difference has been found between taping and non-taping. The role of knee braces is still controversial. More well-designed studies are needed.
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Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group.
J. Clin. Oncol.
PUBLISHED: 01-06-2014
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To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection.
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Covalent modification of a ten-residue cationic antimicrobial peptide with levofloxacin.
Front Chem
PUBLISHED: 01-01-2014
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The rampant spread of antibiotic resistant bacteria has spurred interest in alternative strategies for developing next-generation antibacterial therapies. As such, there has been growing interest in cationic antimicrobial peptides (CAMPs) and their therapeutic applications. Modification of CAMPs via conjugation to auxiliary compounds, including small molecule drugs, is a new approach to developing effective, broad-spectrum antibacterial agents with novel physicochemical properties and versatile antibacterial mechanisms. Here, we've explored design parameters for engineering CAMPs conjugated to small molecules with favorable physicochemical and antibacterial properties by covalently affixing a fluoroquinolone antibiotic, levofloxacin, to the ten-residue CAMP Pep-4. Relative to the unmodified Pep-4, the conjugate was found to demonstrate substantially increased antibacterial potency under high salt concentrations. Historically, it has been observed that most CAMPs lose antibacterial effectiveness in such high ionic strength environments, a fact that has presented a challenge to their development as therapeutics. Physicochemical studies revealed that P4LC was more hydrophobic than Pep-4, while mechanistic findings indicated that the conjugate was more effective at disrupting bacterial membrane integrity. Although the inherent antibacterial effect of the incorporated levofloxacin molecules did not appear to be substantially realized in this conjugate, these findings nevertheless suggest that covalent attachment of small molecule antibiotics with favorable physicochemical properties to CAMPs could be a promising strategy for enhancing peptide performance and overall therapeutic potential. These results have broader applicability to the development of future CAMP-antibiotic conjugates for potential therapeutic applications.
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Searching for efficient Markov chain Monte Carlo proposal kernels.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-11-2013
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Markov chain Monte Carlo (MCMC) or the Metropolis-Hastings algorithm is a simulation algorithm that has made modern Bayesian statistical inference possible. Nevertheless, the efficiency of different Metropolis-Hastings proposal kernels has rarely been studied except for the Gaussian proposal. Here we propose a unique class of Bactrian kernels, which avoid proposing values that are very close to the current value, and compare their efficiency with a number of proposals for simulating different target distributions, with efficiency measured by the asymptotic variance of a parameter estimate. The uniform kernel is found to be more efficient than the Gaussian kernel, whereas the Bactrian kernel is even better. When optimal scales are used for both, the Bactrian kernel is at least 50% more efficient than the Gaussian. Implementation in a Bayesian program for molecular clock dating confirms the general applicability of our results to generic MCMC algorithms. Our results refute a previous claim that all proposals had nearly identical performance and will prompt further research into efficient MCMC proposals.
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Acute compartment syndrome in haemophilia.
Blood Coagul. Fibrinolysis
PUBLISHED: 09-26-2013
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Acute compartment syndrome (ACS) is characterized by an increase in pressure (intramuscular pressure) within a muscle compartment, which reduces capillary perfusion threatening tissue survival. Persistence of this increased pressure for a few hours will result in necrosis of muscle and nerve tissue, with contracture in the affected limb and permanent loss of function. For that reason, early treatment and diagnosis of ACS is fundamental. Diagnosis should be based on physical examination (pain on stretching the involved muscles) and on an objective measurement of the limb perfusion pressure (DBP minus intramuscular pressure) within the affected compartment. To obtain a reliable clinical diagnosis, the patient must be evaluated every 1-2 ?h. In children and in unconscious patients, where the level of pain cannot be appropriately determined, an accurate clinical diagnosis is unfeasible, hence the importance of measuring compartment pressure. A fasciotomy should be performed when the limb perfusion pressure is less than 30 ?mmHg when averaged over a 12-h period (monitored every 1-2? h). Only 16 studies have been published on haemophilic patients with ACS, which report on a total of 34 cases. If symptoms or pressure measurements are suggestive of ACS, an extensive fasciotomy will be required. Unfortunately, fasciotomy is not exempt from complications such as the need of subsequent surgery because of a delay in wound healing, the need of a skin graft, pain, cosmetic problems, nerve injury, permanent muscle weakness and chronic venous insufficiency. Overlooked compartment syndrome remains one of most common causes of malpractice lawsuits. In haemophilia, adequate substitution of coagulation factor must be the first step. The main principle of surgical treatment is an extensive fasciotomy.
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Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers.
Cancer
PUBLISHED: 09-09-2013
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Rhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline TP53 mutations correlates with certain RMS histologies.
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[Chemotherapy in patients with refractory Ewing sarcoma].
Med Wieku Rozwoj
PUBLISHED: 08-31-2013
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Patients with metastatic, progressive or recurrent Ewing sarcoma have a poor prognosis. In addition to increasing the intensity of conventional chemotherapy, the combination of irinotecan and temozolomide has been proposed as an effective salvage regimen for some pediatric malignancies.
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Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia.
J. Biol. Inorg. Chem.
PUBLISHED: 08-27-2013
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The oxidation of oxyhemoglobin to methemoglobin has been found to be facilitated by low molecular weight iron(III) thiosemicarbazone complexes. This deleterious reaction, which produces hemoglobin protein units unable to bind dioxygen and occurs during the administration of iron chelators such as the well-known 3-aminopyridine-2-pyridinecarbaldehyde thiosemicarbazone (3-AP; Triapine), has been observed in the reaction with Fe(III) complexes of some members of the 3-AP structurally-related thiosemicarbazone ligands derived from di-2-pyridyl ketone (HDpxxT series). We have studied the kinetics of this oxidation reaction in vitro using human hemoglobin and found that the reaction proceeds with two distinct time-resolved steps. These have been associated with sequential oxidation of the two different oxyheme cofactors in the ? and ? protein chains. Unexpected steric and hydrogen-bonding effects on the Fe(III) complexes appear to be the responsible for the observed differences in the reaction rate across the series of HDpxxT ligand complexes used in this study.
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On the origins of hierarchy in complex networks.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-29-2013
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Hierarchy seems to pervade complexity in both living and artificial systems. Despite its relevance, no general theory that captures all features of hierarchy and its origins has been proposed yet. Here we present a formal approach resulting from the convergence of theoretical morphology and network theory that allows constructing a 3D morphospace of hierarchies and hence comparing the hierarchical organization of ecological, cellular, technological, and social networks. Embedded within large voids in the morphospace of all possible hierarchies, four major groups are identified. Two of them match the expected from random networks with similar connectivity, thus suggesting that nonadaptive factors are at work. Ecological and gene networks define the other two, indicating that their topological order is the result of functional constraints. These results are consistent with an exploration of the morphospace, using in silico evolved networks.
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Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy.
Cancer
PUBLISHED: 07-10-2013
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The leading cause of death among patients with hereditary retinoblastoma is second malignancy. Despite its high rate of efficacy, radiotherapy (RT) is often avoided due to fear of inducing a secondary tumor. Proton RT allows for significant sparing of nontarget tissue. The current study compared the risk of second malignancy in patients with retinoblastoma who were treated with photon and proton RT.
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Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA): A model for sustainable development in pediatric oncology.
Pediatr Blood Cancer
PUBLISHED: 07-08-2013
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Bridging the survival gap for children with cancer, between those (the great majority) in low and middle income countries (LMIC) and their economically advantaged counterparts, is a challenge that has been addressed by twinning institutions in high income countries with centers in LMIC. The long-established partnership between a Central American consortium-Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA)-and institutions in Europe and North America provides a striking example of such a twinning program. The demonstrable success of this endeavor offers a model for improving the health outcomes of children with cancer worldwide. As this remarkable enterprise celebrates its 15th anniversary, it is appropriate to reflect on its origin, subsequent growth and development, and the lessons it provides for others embarking on or already engaged in similar journeys. Many challenges have been encountered and not all yet overcome. Commitment to the endeavor, collaboration in its achievements and determination to overcome obstacles collectively are the hallmarks that stamp AHOPCA as a particularly successful partnership in advancing pediatric oncology in the developing world. Pediatr Blood Cancer 2014;61:345-354. © 2013 Wiley Periodicals, Inc.
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The role of physical medicine and rehabilitation in haemophiliac patients.
Blood Coagul. Fibrinolysis
PUBLISHED: 05-29-2013
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Physical medicine and rehabilitation aim to evaluate, diagnose and treat disability in haemophiliac patients, while preventing injury or deterioration. They also aim to maintain the greatest degree of functional capacity and independence in patients with haemophilia, or to return them to that state. Rehabilitation, together with clotting factor replacement therapy, has revolutionized the management of these patients in developed countries and reduced their morbidity/mortality rates. A knowledge of the musculoskeletal signs and symptoms of haemophilia is essential for providing a treatment which is suitable and customized. Physical medicine and rehabilitation techniques, which are based on physical means, are intended to reduce the impact which these injuries and their consequences or sequelae can have on the quality of life of patients with haemophilia. Under ideal haemostatic control conditions (primary prophylaxis), people with haemophilia could achieve good physical condition which will allow them to enjoy both physical activity and a daily life without limitations. Currently, children undergoing primary prophylaxis are quite close to this ideal situation. For these physical activities to be carried out, the safest possible situations must be sought.
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Trends in incidence of primary cutaneous malignancies in children, adolescents, and young adults: A population-based study.
Pediatr Blood Cancer
PUBLISHED: 05-09-2013
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Skin cancer incidence among young adults is rising; however, the epidemiological characteristics of primary cutaneous lymphomas and cutaneous soft tissue sarcomas (CSTS) in individuals <30 years old has not been investigated. We analyzed the incidence and time-trends of primary cutaneous malignancies in children and adolescents/young adults (AYA).
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Mutations in Hedgehog pathway genes in fetal rhabdomyomas.
J. Pathol.
PUBLISHED: 05-04-2013
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Ligand-independent, constitutive activation of Hedgehog signalling in mice expressing a mutant, activated SmoM2 allele results in the development of multifocal, highly differentiated tumours that express myogenic markers (including desmin, actin, MyoD and myogenin). The histopathology of these tumours, commonly classified as rhabdomyosarcomas, more closely resembles human fetal rhabdomyoma (FRM), a benign tumour that can be difficult to distinguish from highly differentiated rhabdomyosarcomas. We evaluated the spectrum of Hedgehog (HH) pathway gene mutations in a cohort of human FRM tumours by targeted Illumina sequencing and fluorescence in situ hybridization testing for PTCH1. Our studies identified functionally relevant aberrations at the PTCH1 locus in three of five FRM tumours surveyed, including a PTCH1 frameshift mutation in one tumour and homozygous deletions of PTCH1 in two tumours. These data suggest that activated Hedgehog signalling contributes to the biology of human FRM.
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Barriers to effective treatment of pediatric solid tumors in middle-income countries: Can we make sense of the spectrum of nonbiologic factors that influence outcomes?
Cancer
PUBLISHED: 05-01-2013
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The delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MICs) that already are vigorously addressing pediatric cancer. The objective of this study was to improve the current understanding of barriers to effective treatment of pediatric solid tumors in MICs.
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Incidence of childhood and adolescent melanoma in the United States: 1973-2009.
Pediatrics
PUBLISHED: 04-15-2013
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Childhood and adolescent melanoma is rare but has been increasing. To gain insight into possible reasons underlying this observation, we analyzed trends in melanoma incidence diagnosed between the ages of 0 and 19 years among US whites by gender, stage, age at diagnosis, and primary site. We also investigated incidence trends by UV-B exposure levels.
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Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory Ewing sarcoma.
Pediatr Blood Cancer
PUBLISHED: 04-02-2013
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Patients with metastatic, progressive or recurrent Ewing sarcoma (ES) have a dismal outcome. The combination of irinotecan and temozolomide has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination with vincristine for patients with relapsed and refractory ES.
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Haemophilic synovitis of the elbow: radiosynovectomy, open synovectomy or arthroscopic synovectomy?
Thromb. Res.
PUBLISHED: 03-31-2013
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Arthroscopic synovectomy (AS) of the elbow, while providing similar pain relief to open synovectomy (OS), may place patients at higher risk for recurrence. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. Regarding haemophilia patients, radiosynovectomy (RS) is the best choice for patients with persistent synovitis of the elbow. In the elbow we recommend a dose of 30-40 megabecquerels (mBq) in children and a dose of 56-74 mBq in adults. If three consecutive RSs with 6 months intervals are ineffective, an AS or OS must be indicated. Synovectomy (by any method) significantly reduces bleeding episodes. Although the dose of radiation of RS is minimal, 0.32 millisieverts (mSv) in children, 0.54 mSv in adults, and neither articular nor systemic neoplastic changes related to RS have been reported so far, all patients must be given opportunity to consider risk/benefit ratios. Radiation dose due to natural sources is 2 mSv per year and the recommended limit for patients (apart from natural sources is 1 mSv per year). My current recommendation is to use RS in children older than 12 years of age. Therefore, in children younger than 12 years of age an AS should be indicated. OS should be reserved for adults requiring radial head excision (due to a severe limitation of pronation-supination) and synovectomy in the same surgical session.
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Radiosynovectomy: review of the literature and report from two haemophilia treatment centers.
Blood Coagul. Fibrinolysis
PUBLISHED: 03-16-2013
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Haemophilic arthropathy occurs due to recurrent bleeding into joints leading to swelling, inflammation, destruction of cartilage and bone, and development of arthritis. Although prophylactic replacement therapy assists in preventing arthropathy, it is not always adequate or affordable. Radiosynovectomy is a minimally invasive intervention for treatment of synovitis in haemophilic joints. The procedure utilises locally injected radioisotopes (Y, P, Rh) to ablate abnormal synovium with the goal of decreasing bleeding, slowing progression of cartilage and bone damage and preventing arthropathy. The objective of this review is to summarize the radiosynovectomy literature and to present patient outcomes associated with radiosynovectomy over the past 17 years from two haemophilia treatment centers (HTCs), one in the United States and one in Spain. Articles from these two centers support the current literature. A retrospective medical records review was performed by the two reporting HTCs on patients who underwent radiosynovectomy prior to 2009. Data review included: site of procedure, isotope utilized, bleeding frequency, and procedure complications. Radiosynovectomy is a cost-effective, minimally invasive, well tolerated procedure. As the paradigm for care in haemophilia shifts towards prevention of joint disease, the number of target joints with synovitis will likely decrease, except in patients who develop inhibitors. We propose early consideration of radiosynovectomy for patients with haemophilic synovitis prior to appearance of articular cartilage damage.
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Expression of the marA, soxS, acrB and ramA genes related to the AcrAB/TolC efflux pump in Salmonella enterica strains with and without quinolone resistance-determining regions gyrA gene mutations.
Braz J Infect Dis
PUBLISHED: 02-28-2013
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Several studies have been conducted in recent years to elucidate the structure, function and significance of AcrB, MarA, SoxS and RamA in Salmonella enterica. In this study, the relative quantification of acrB, soxS, marA and ramA genes expression was evaluated in 14 strains of S. enterica, with or without accompanying mutations in the quinolone resistance-determining regions of the gyrA gene, that were exposed to ciprofloxacin during the exponential growth phase. The presence of ciprofloxacin during the log phase of bacterial growth activated the genes marA, soxS, ramA and acrB in all S. enterica strains analyzed in this study. The highest expression levels for acrB were observed in strains with gyrA mutation, and marA showed the highest expression in the strains without mutation. Considering only the strains with ciprofloxacin minimum inhibitory concentration values<0.125 ?g/mL (sensitive to ciprofloxacin), the most expressed gene in the strains both with and without mutations was acrB. In the strains with ciprofloxacin minimum inhibitory concentration values ? 0.125 ?g/mL (low susceptibility), with and without mutations in gyrA, the most expressed gene was marA. In this study, we observed that strains resistant to nalidixic acid may express genes associated with the efflux pump and the expression of the AcrAB-TolC pump genes seems to occur independently of mutations in gyrA.
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Establishment and characterization of the first pediatric adrenocortical carcinoma xenograft model identifies topotecan as a potential chemotherapeutic agent.
Clin. Cancer Res.
PUBLISHED: 02-13-2013
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Pediatric adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Conventional chemotherapeutic agents have shown limited utility and are largely ineffective in treating children with advanced ACC. The lack of cell lines and animal models of pediatric ACC has hampered the development of new therapies. Here we report the establishment of the first pediatric ACC xenograft model and the characterization of its sensitivity to selected chemotherapeutic agents.
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Pediatric anophthalmic sockets and orbital implants: outcomes with polymer-coated implants.
Ophthalmology
PUBLISHED: 02-08-2013
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To compare wrapped and polymer-coated hydroxyapatite implants in children undergoing primary enucleation with no adjuvant therapies.
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Can cell mortality determine division of labor in tissue organization?
J. Theor. Biol.
PUBLISHED: 01-25-2013
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Tissue organization comes from the emergence of cell cooperation where cell homeostasis and function are performed as a trade-off of two excluding proliferative and differentiated cellular states. By introducing function in a population dynamics approach, I study the role of division of labor in tissue optimality when cell turn-over and limitation of space and resources are imposed as natural restrictions of a living tissue. The results indicate that although cell turn-over imposes a inevitable reduction in function abilities, the penalty is smaller when division of labor is at work, especially when a rapid cell-turnover and high cell density is a requirement for the tissue, as occurred in epithelia hierarchical tissues. Analytic results are in agreement with the experimental data available in literature. The study provides an explanation about why homogeneous tissues for which proliferative and functional tasks are performed by a same cell type are unlikely to be observed under high cell-renewal requirements.
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Pseudoaneurysms in haemophilia.
Blood Coagul. Fibrinolysis
PUBLISHED: 01-23-2013
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The incidence of bleeding as a result of a pseudoaneurysm in haemophilia is very low. The diagnosis should be suspected if the patient has a history of arterial trauma. Pseudoaneurysms can appear anywhere where trauma occurs. This can include arterial access for catheterization, blunt trauma or penetrating trauma. The diagnosis should be confirmed using Duplex ultrasonography, computed tomography (CT) angiogram or conventional angiogram. Many options exist for the treatment of pseudoaneurysms. Although surgery was the gold standard treatment in the past (surgical ligation with or without distal bypass), several less invasive treatment options are popular today. They include covered stent, ultrasound probe compression and ultrasound-guided thrombin injection. So far, only 14 pseudoaneurysms have been reported in patients with haemophilia: nine were located in the musculoskeletal system (four in the hand, four in the knee, one in the ankle), whereas five were non-musculoskeletal. Early diagnosis and treatment of this complication is vital. Endovascular treatment offers a minimally invasive treatment option. If arterial embolization fails to solve the pseudoaneurysm, open vascular surgery with surgical ligation with or without distal bypass should be performed. Whatever the procedure, a correct surgical haemostasis must be achieved by the infusion of factor concentrate (recombinant or plasma-derived) at the right dose and tranexamic acid. The advent of activated prothrombin complex concentrates and recombinant factor VIII (rFVIIa) has made invasive procedures possible in haemophilia patients with high-titre inhibitors.
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Global challenges in pediatric oncology.
Curr. Opin. Pediatr.
PUBLISHED: 01-09-2013
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Reduction of child mortality is one of the Millennium Development Goals; as low-income and middle-income countries (LMICs) advance toward the achievement of this goal, initiatives aimed at reducing the burden of noncommunicable diseases, including childhood cancer, need to be developed.
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Plasmid-mediated quinolone resistance (PMQR) and mutations in the topoisomerase genes of Salmonella enterica strains from Brazil.
Braz. J. Microbiol.
PUBLISHED: 01-01-2013
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The objective of this study was to identify mutations in the Quinolone Resistance Determining sources Regions (QRDR) of the gyrA, gyrB, parC, and parE genes and to determine if any of the qnr variants or the aac(6)-Ib-cr variant were present in strains of Salmonella spp. isolated in Brazil. A total of 126 Salmonella spp. strains from epidemic (n = 114) and poultry (n = 12) origin were evaluated. One hundred and twelve strains (88.8%) were resistant to nalidixic acid (NAL) and 29 (23.01%) showed a reduced susceptibility to ciprofloxacin (Cip). The mutations identified were substitutions limited to the QRDR of the gyrA gene in the codons for Serine 83, Aspartate 87 and Alanine 131. The sensitivity to NAL seems to be a good phenotypic indication of distinguishing mutated and non-mutated strains in the QRDR, however the double mutation in gyrA did not cause resistance to ciprofloxacin. The qnrA1 and qnrB19 genes were detected, respectively, in one epidemic strain of S. Enteritidis and one strain of S. Corvallis of poultry origin. Despite previous detection of qnr genes in Brazil, this is the first report of qnr gene detection in Salmonella, and also the first detection of qnrB19 gene in this country. The results alert for the continuous monitoring of quinolone resistance determinants in order to minimize the emergence and selection of Salmonella spp. strains showing reduced susceptibility or resistance to quinolones.
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Colorimetric and longitudinal analysis of leukocoria in recreational photographs of children with retinoblastoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Retinoblastoma is the most common primary intraocular tumor in children. The first sign that is often reported by parents is the appearance of recurrent leukocoria (i.e., "white eye") in recreational photographs. A quantitative definition or scale of leukocoria - as it appears during recreational photography - has not been established, and the amount of clinical information contained in a leukocoric image (collected by a parent) remains unknown. Moreover, the hypothesis that photographic leukocoria can be a sign of early stage retinoblastoma has not been tested for even a single patient. This study used commercially available software (Adobe Photoshop®) and standard color space conversion algorithms (operable in Microsoft Excel®) to quantify leukocoria in actual "baby pictures" of 9 children with retinoblastoma (that were collected by parents during recreational activities i.e., in nonclinical settings). One particular patient with bilateral retinoblastoma ("Patient Zero") was photographed >7, 000 times by his parents (who are authors of this study) over three years: from birth, through diagnosis, treatment, and remission. This large set of photographs allowed us to determine the longitudinal and lateral frequency of leukocoria throughout the patients life. This study establishes: (i) that leukocoria can emerge at a low frequency in early-stage retinoblastoma and increase in frequency during disease progression, but decrease upon disease regression, (ii) that Hue, Saturation and Value (i.e., HSV color space) are suitable metrics for quantifying the intensity of retinoblastoma-linked leukocoria; (iii) that different sets of intraocular retinoblastoma tumors can produce distinct leukocoric reflections; and (iv) the Saturation-Value plane of HSV color space represents a convenient scale for quantifying and classifying pupillary reflections as they appear during recreational photography.
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Biologically active thiosemicarbazone Fe chelators and their reactions with ferrioxamine B and ferric EDTA; a kinetic study.
Dalton Trans
PUBLISHED: 12-19-2011
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The Fe(III) abstraction from Fe(III)/DFO and Fe(III)/EDTA complex systems by thiosemicarbazone ligands derived from 2-acetylpyridine has been studied from a kinetico-mechanistic perspective at relevant pH conditions and at varying temperatures and buffer solutions. The reactions have been found to be extremely dependent on the dominant E/Z isomeric form of the TSC ligands present in the reaction medium. Consequently the isomerisation processes occurring on the free ligands have also been monitored under equivalent conditions. The isomerisation process is found to be acid dependent, despite the absence of protonation under the conditions used, and presumably proceeds via an azo-type tautomer of the ligand. In all cases the existence of outer-sphere interaction processes has been established, both promoting the reactions and producing dead-end complexes. The better oriented forms of the ligands (EZ thiolate) have been found to react faster with the [Fe(HDFO)](+) complex, although for mono-N(4) substituted thiosemicarbazones the process is retarded by the formation of a dead-end outer-sphere complex. A comparison with the abstraction of Fe(III) from [Fe(EDTA)(H(2)O)](-) has also been conducted with significant differences in the kinetic features that implicate keystone outer-sphere interactions which dominate reactivity, even with isomeric forms that are not the best suited for direct complexation.
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[Resistance phenotypes and genotypes of Streptococcus pyogenes clinical isolates in Chile over a 10-year period].
Rev Med Chil
PUBLISHED: 11-17-2011
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Macrolide and lincosamide resistance in Streptococcus pyogenes is due to the acquisition of mef, ermB and ermA genes, which confer different resistance phenotypes, namely M, MLSBconstitutive and MLSBinducible respectively. The last report of resistance in Chile was done in the period 1990-1998, in which resistance to macrolides was 5.4%, with M phenotype as the predominant one.
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Generic vancomycin enriches resistant subpopulations of Staphylococcus aureus after exposure in a neutropenic mouse thigh infection model.
Antimicrob. Agents Chemother.
PUBLISHED: 11-07-2011
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Previous studies have shown that "bioequivalent" generic products of vancomycin are less effective in vivo against Staphylococcus aureus than the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assess in vivo the impact of exposure to innovator and generic products of vancomycin on S. aureus susceptibility. A clinical methicillin-resistant S. aureus (MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ?7.0 log(10) CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than S. aureus ATCC 29213 but without vancomycin-intermediate S. aureus (VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide.
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Recent advances in the understanding of Langerhans cell histiocytosis.
Br. J. Haematol.
PUBLISHED: 10-24-2011
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Langerhans cell histiocytosis (LCH) is a proliferative disease of cells that share phenotypic characteristics with the primary antigen presenting cells of the epidermis. Its clinical manifestations are highly variable, extending from very benign forms to a disseminated, aggressive disease that causes significant mortality. Although many of the fundamental pathogenetic features of LCH have been enigmatic, recent advances have led to a much clearer understanding of the disease. In particular, careful molecular analyses of mouse models and human LCH samples suggest that LCHs cell of origin may not be the epidermal LC itself but a myeloid-derived precursor. Advanced genomic technologies have revealed the presence of activating, somatic BRAF mutations in the majority of patient specimens. Together, these observations have produced a new picture of LCH as a myeloid neoplasm. These advances are likely to have profound implications for the use of targeted therapeutics in LCH.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.