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Shorter-Duration Therapy Using Vincristine, Dactinomycin, and Lower-Dose Cyclophosphamide With or Without Radiotherapy for Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
PURPOSE: Intergroup Rhabdomyosarcoma Study Group (IRSG) studies III and IV showed improved failure-free survival (FFS) rates with vincristine, dactinomycin, and cyclophosphamide (VAC; total cumulative cyclophosphamide dose, 26.4 g/m2) compared with vincristine and dactinomycin (VA) for patients with subset-one low-risk...
Utility of Routine Post-Therapy Surveillance Imaging in Diffuse Large B-Cell Lymphoma.
PURPOSE: We examined the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the United States and confirmed our results in an independent cohort of patients from France. METHODS: Patients with newly diagnosed DLBCL and treat...
Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12.
PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive ...
Association of Electrocardiographic Left Ventricular Hypertrophy With Incident Cardiovascular Disease in Japanese Older Hypertensive Patients.
BACKGROUND: Our aim was to assess whether electrocardiographic left ventricular hypertrophy (ECG-LVH) is associated with a higher risk of cardiovascular disease (CVD) events, independent of 24-hour blood pressure (BP) and circulating levels of norepinephrine and hemostatic factors. METHODS: In 514 older hypertensive pa...
Impaired Fasting Glucose and Impaired Glucose Tolerance Do Not Predict Hypertension: A Community Cohort Study.
BACKGROUND: Insulin resistance has an important role in the pathogenesis of hypertension. We hypothesized that impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) which represents insulin resistance would predict the development of hypertension. METHODS: A total of 4,039 subjects without hypertension or ...
Acupuncture therapy for fever induced by viral upper respiratory tract infection (URTI) in military medical service: a case series.
We report the cases of eight military patients with fever (>/=38 degrees C) induced by viral upper respiratory tract infection (URTI) who requested treatment with acupuncture in the military medical service room. All patients were treated immediately after diagnosis with classical acupuncture (GV14, GB20, TE8 points) a...
Management of metastatic phaeochromocytoma and paraganglioma: use of Iodine-131-meta-iodobenzylguanidine (131I-MIBG) therapy in a tertiary referral centre.
BACKGROUND: Phaeochromocytoma (phaeo) and paraganglioma (PGL) are rare conditions which are malignant in up to 30%. Optimal treatment is controversial but, in patients with metastatic 123I-MIBG avid tumours, we offer 131I-MIBG therapy. We summarise response rates, survival and safety in a cohort of such patients treate...
SRY Interference of Normal Regulation of the RET Gene Suggests a Potential Role of the Y-Chromosome Gene in Sexual Dimorphism in Hirschsprung Disease.
The Hirschsprung disease (HSCR) is a complex congenital disorder, arising from abnormalities in enteric nervous system (ENS) development. There is a gender disparity among the patients, with the male to female ratio as high as 5:1. Loss-of-function mutations of HSCR genes and haploinsufficiency of their gene products a...
Investigating Substrate-induced Motion between the Scaffold and Transport Domains in the Glutamate Transporter EAAT1.
Excitatory amino acid transporter 1 (EAAT1) plays an important role in keeping the synaptic glutamate concentration below neurotoxic levels by translocating this neurotransmitter into the cell. Both reentrant hairpin loops, HP 1 and 2, have been shown to take part in binding the substrate and the more deeply buried sod...
Incidence of Cancer and Mortality in Patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Trial.
The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new inci...
The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity.
BACKGROUND: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. METHODS: Fourteen tracers segmented 10 Alzheimer's Dis...
Radiation exposure to anaesthetists during endovascular procedures.
Medical radiation exposure increases the likelihood of cataract formation. A personal dosimeter was attached to the left temple of 77 anaesthetists during 45 endovascular aortic aneurysm repairs and 32 interventional neuroradiology procedures. Compared with interventional neuroradiology, the median (IQR [range]) total ...
Quantitative Susceptibility Mapping: Current Status and Future Directions.
Quantitative susceptibility mapping (QSM) is a new technique for quantifying magnetic susceptibility. It has already found various applications in quantifying in vivo iron content, calcifications and changes in venous oxygen saturation. The accuracy of susceptibility mapping is dependent on several factors. In this rev...
Simulation study of the effect of golden-angle KWIC with generalized kinetic model analysis on diagnostic accuracy for lesion discrimination.
PURPOSE: To quantitatively evaluate temporal blurring of dynamic contrast-enhanced MRI data generated using a k-space weighted image contrast (KWIC) image reconstruction technique with golden-angle view-ordering. METHODS: K-space data were simulated using golden-angle view-ordering and reconstructed using a KWIC algori...
Yogurt for treating acute gastroenteritis in children: Systematic review and meta-analysis.
BACKGROUND: In May 2014, the updated guidelines for the management of acute gastroenteritis (AGE) were published. The use of yogurt in the nutritional management of AGE was not addressed, although it is frequently used in many countries for this purpose. We aimed to systematically evaluate the efficacy of yogurt consum...
The Role of Gender and Distance Mentoring in the Surgical Education Research Fellowship.
OBJECTIVE: The nature of the mentor-mentee relationship is important in the pursuit of successful research projects. The purpose of this study is to evaluate the mentor-mentee relationships in the Surgical Education Research Fellowship (SERF) based on gender and geographical distances regarding program completion. We h...
Vocal fold paralysis: Improved adductor recovery by vincristine blockade of posterior cricoarytenoid.
OBJECTIVES/HYPOTHESIS: A new treatment for acute unilateral vocal-fold paralysis (UVFP) was proposed in which a drug is injected into the posterior cricoarytenoid muscle (PCA) shortly after nerve injury, before the degree of natural recovery is known, to prevent antagonistic synkinetic reinnervation. This concept was t...
The Mini-Mental State Examination as a diagnostic and screening test for delirium: systematic review and meta-analysis.
OBJECTIVE: To analyse the evidence concerning the accuracy of the Mini-Mental State Examination (MMSE) as a diagnostic and screening test for the presence of delirium in adults. METHOD: Two authors searched MEDLINE, PsychINFO and EMBASE from inception till March 2014. Articles were included that investigated the diagno...
Aortic Valve Replacement Reduces Valvuloarterial Impedance but Does Not Affect Systemic Arterial Compliance in Elderly Men with Degenerative Calcific Trileaflet Aortic Valve Stenosis.
OBJECTIVE: Standard methods of quantifying aortic valve stenosis (AS), which focus entirely on the valve itself, do not adequately characterize the magnitude, predict the onset, progression, and severity of symptoms, or identify the incidence of subsequent adverse events. Valvuloarterial impedance (Zva) is an index of ...
Analysis of Vascular Closure Devices After Transbrachial Artery Access.
INTRODUCTION: We seek to determine whether vascular closure devices (VCDs) are safe and effective for brachial artery access. METHODS: A retrospective review of brachial artery access using either manual compression (MC) or a VCD for hemostasis from November 2005 to February 2011 was performed. RESULTS: Brachial artery...
Penicillinase-producing plasmid types of Neisseria gonorrhoeae clinical isolates from Australia.
Penicillinase-producing Neisseria gonorrhoeae (PPNG) carrying the blaTEM-135 gene is of particular concern as it is considered a stepping stone towards resistance to extended spectrum cephalosporins. Here, we sought to characterise plasmid types and the occurrence of the blaTEM-135 gene for N. gonorrhoeae clinical isol...
Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against gamma-herpesviruses.
The susceptibility of gamma-herpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) and animal rhadinoviruses, to various nucleoside analogs was investigated in this report. Besides examining the antiviral activity and mode of action of antivirals currently marketed for the tre...
Potency and Resistance Analysis of Hepatitis C Virus NS5B Polymerase Inhibitor BMS-791325 on All Major Genotypes.
BMS-791325 is a Hepatitis C virus (HCV) inhibitor binding to the thumb domain of the NS5B RNA-dependent RNA polymerase. BMS-791325 is well characterized in genotype (GT) 1 and exhibits good inhibitory activity (EC50 < 10 nM) against hybrid replicons containing patient NS5B sequences from GT3a, 4a, and 5a while potency ...
Effect of fluorescent dyes on in-vitro differentiated, late-stage Plasmodium falciparum gametocytes.
Plasmodium falciparum gametocytes are not associated with clinical symptoms but they are responsible for transmitting the pathogen to mosquitoes. Therefore gametocytocidal interventions are important for malaria control and resistance containment but currently available drugs and vaccines are not well suited for that p...
Genome Sequencing of an Extended Series of NDM-Klebsiella pneumoniae Neonatal Infections in a Nepali Hospital Characterizes the Extent of Community Versus Hospital-associated Transmission in an Endemic Setting.
BACKGROUND: NDM-producing Klebsiella pneumoniae represent a major clinical and infection control challenge, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid or bacterial strain level, within hospital and/or the community, h...
Complex polymorphisms in the Plasmodium falciparum Multidrug Resistance Protein 2 gene and its contribution to antimalarial response.
Plasmodium falciparum has the capacity to escape essentially all antimalarial drugs action. ATP-binding cassette (ABC) transporter proteins are known to be causative of multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding fo...
Sensitization of Intracellular Salmonella to Aminoglycosides in vitro and in vivo by a Host-Targeted Antimicrobial Agent.
Aminoglycosides exhibit relatively poor activity against intracellular Salmonella due to their low permeability across eukaryotic cell membranes. Previously, we identified the unique ability of AR-12, a celecoxib-derived small-molecule agent, to eradicate intracellular Salmonella Typhimurium in macrophages by facilitat...
The Pharmacokinetics and Pharmacodynamics of (+) and (-) Primaquine Enantiomers in Rhesus macaques (Macaca mulatta).
Primaquine (PQ) remains the sole available drug to prevent relapse of P. vivax malaria after more than 60 years. While administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential anti-relapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prep...
A Beneficial Effect of Oral Tigecycline Treatment on Clostridium difficile Infection in Gnotobiotic Piglets.
The efficacy of oral tigecycline treatment (2mg/kg for 7 days) on Clostridium difficile infection (CDI) was evaluated in the gnotobiotic pig model, and its effect on human gut microflora transplanted into the gnotobiotic pig was determined. Tigecycline oral treatment improved survival, clinical signs and lesion severit...
New colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rational.
BACKGROUND: Colistin is an old antibiotic that has recently gained a considerable renew of interest as the last line defense therapy against Multi Drug Resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin...
Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes.
Previous studies in type 1 diabetes (T1D) in the nonobese diabetic mouse demonstrated that a crucial insulin epitope (B:9-23) is presented to diabetogenic CD4 T cells by IAg7 in a weakly bound register. The importance of antigenic peptides with low-affinity HLA binding in human autoimmune disease remains less clear. Th...
Massive isotopic effect in vacuum UV photodissociation of N2 and implications for meteorite data.
Nitrogen isotopic distributions in the solar system extend across an enormous range, from -400 per thousand, in the solar wind and Jovian atmosphere, to about 5,000 per thousand in organic matter in carbonaceous chondrites. Distributions such as these require complex processing of nitrogen reservoirs and extraordinary ...
Memory trace and timing mechanism localized to cerebellar Purkinje cells.
The standard view of the mechanisms underlying learning is that they involve strengthening or weakening synaptic connections. Learned response timing is thought to combine such plasticity with temporally patterned inputs to the neuron. We show here that a cerebellar Purkinje cell in a ferret can learn to respond to a s...
Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases.
Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mecha...
Liver-directed gene therapy corrects cardiovascular lesions in feline mucopolysaccharidosis type I.
Patients with mucopolysaccharidosis type I (MPS I), a genetic deficiency of the lysosomal enzyme alpha-l-iduronidase (IDUA), exhibit accumulation of glycosaminoglycans in tissues, with resulting diverse clinical manifestations including neurological, ocular, skeletal, and cardiac disease. MPS I is currently treated wit...
Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB.
Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disease characterized by profound intellectual disability, dementia, and a lifespan of about two decades. The cause is mutation in the gene encoding alpha-N-acetylglucosaminidase (NAGLU), deficiency of NAGLU, and accumulation ...
Disruption of the immune-checkpoint VISTA gene imparts a proinflammatory phenotype with predisposition to the development of autoimmunity.
V domain-containing Ig suppressor of T-cell activation (VISTA) is a negative checkpoint regulator that suppresses T cell-mediated immune responses. Previous studies using a VISTA-neutralizing monoclonal antibody show that VISTA blockade enhances T-cell activation. The current study describes a comprehensive characteriz...
Tissue injury and hypoxia promote malignant progression of prostate cancer by inducing CXCL13 expression in tumor myofibroblasts.
Prostate cancer (PC) is a slowly progressing malignancy that often responds to androgen ablation or chemotherapy by becoming more aggressive, acquiring a neuroendocrine phenotype, and undergoing metastatic spread. We found that B lymphocytes recruited into regressing androgen-deprived tumors by C-X-C motif chemokine 13...
ICAM-1 as a molecular target for triple negative breast cancer.
Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a pote...
Quantitative and stoichiometric analysis of the microRNA content of exosomes.
Exosomes have been proposed as vehicles for microRNA (miRNA) -based intercellular communication and a source of miRNA biomarkers in bodily fluids. Although exosome preparations contain miRNAs, a quantitative analysis of their abundance and stoichiometry is lacking. In the course of studying cancer-associated extracellu...
Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration.
Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor...
H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection.
An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier par...
ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers.
Aggressive neuroendocrine lung cancers, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), represent an understudied tumor subset that accounts for approximately 40,000 new lung cancer cases per year in the United States. No targeted therapy exists for these tumors. We determined that achae...
Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.
Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates with T helper (Th)1 di...
Bevel direction of epidural needles reliably predicts direction of catheter placement and contrast spread in human cadavers: results of a pilot study.
STUDY OBJECTIVE: To confirm the relationship between bevel orientation, catheter direction, and radiopaque contrast spread in the lumbar region. DESIGN: Pilot cadaver study. SETTING: Anatomy laboratory of a university hospital. MEASUREMENTS: Cadavers were randomized to two groups of 4 cadavers each. In Group 1, needle ...
Design of smart home sensor visualizations for older adults.
BACKGROUND: Smart home sensor systems provide a valuable opportunity to continuously and unobtrusively monitor older adult wellness. However, the density of sensor data can be challenging to visualize, especially for an older adult consumer with distinct user needs. OBJECTIVE: We describe the design of sensor visualiza...
Qualitative research on point-of-care testing strategies and programs for HIV.
Point-of-care (POC) testing in communities, home settings and primary healthcare centers plays an important role in cutting delays in HIV diagnosis and in the uptake of voluntary testing and counseling. Qualitative research methods have important potential to overcome the current challenges in expanding HIV POC testing...
Is residential treatment effective for opioid use disorders? A longitudinal comparison of treatment outcomes among opioid dependent, opioid misusing, and non-opioid using emerging adults with substance use disorder.
BACKGROUND: Opioid misuse and dependence rates among emerging adults have increased substantially. While office-based opioid treatments (e.g., buprenorphine/naloxone) have shown overall efficacy, discontinuation rates among emerging adults are high. Abstinence-based residential treatment may serve as a viable alternati...
A Glycogene Mutation Map (GlyMAP) for Discovery of Diseases of Glycosylation.
Glycosylation of proteins and lipids involves over 200 known glycosyltransferases, and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as Congenital Disorders of Glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that effects glycosylation g...
Gastroesophageal and extraesophageal reflux symptoms: Similarities and differences.
OBJECTIVES/HYPOTHESIS: The association between extraesophageal reflux (EER) and symptoms of gastroesophageal reflux disease (GERD) is inadequately understood. We used the Comprehensive Reflux Symptom Scale (CReSS) to evaluate EER and reflux-symptom prevalence in gastroenterology and otolaryngology outpatients and sympt...