[(124)I]m-iodobenzylguanidine ((124)I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [(131)I]m-iodobenzylguanidine ((131)I-mIBG) targeted radionuclide therapy of neuroblastoma. (124)I (T (1/2) = 4.2 days) has a comparable half-life to that of (131)I (T (1/2) = 8.02 days) and can be imaged by positron emission tomography (PET) ...

Metformin, a biguanide glucose lowering agent, is commonly used to manage type 2 diabetes. The molecular mechanisms of metformin have not been fully identified, but turnover of biomarkers such as glucose and signalling pathways or translocation of glucose transporters are closely related to the glucose-lowering effects of metformin. The PK/PD ...

Hepatic drug clearance is thought to be reduced with age. However for highly protein bound drugs, which are cleared by capacity-limited metabolism, studies on total clearance have been conflicting. The hypothesis that protein binding decreases with age has been used to explain this. Warfarin is a highly protein bound drug, ...

The analgesic activity of tilidine is mediated by its active metabolite, nortilidine, which easily penetrates the blood-brain barrier and binds to the µ-opioid receptor as a potent agonist. Tilidine undergoes an extensive first-pass metabolism, which has been suggested to be mediated by CYP3A4 and CYP2C19; furthermore, strong inhibition of CYP3A4 ...

The global rise in non-communicable disease (NCD) suggests that US-based refugees are increasingly affected by chronic conditions. However, health services have focused on the detection of infectious disease, with relatively limited data on chronic NCDs. Using data from a retrospective medical record review of a refugee health program in the ...

MicroRNAs (miRNAs) are small noncoding RNAs that silence target gene expression posttranscriptionally, and their impact on gene expression has been reported in various diseases. It has been reported that the expression of the hypoxia-inducible factor-1α (HIF-1α) is reduced and that of p53 is increased in lungs from patients with COPD. ...

Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk. Our laboratory has previously revealed gene clusters specifically linked to HMO metabolism in selected bifidobacteria isolated from fecal samples of infants. Our objective was to test the hypothesis that growth of selected bifidobacteria on HMO stimulates the ...

Cyclophosphamide, the precursor to the active 4-hydroxycyclophosphamide, is used in active glomerulonephritis despite limited pharmacokinetics data. The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were evaluated. The influence of laboratory and pharmacogenomic covariates on pharmacokinetics was evaluated as a secondary aim. Glomerulonephritis patients (n = 23) participated in a pharmacokinetic evaluation. Blood ...

Ivacaftor (VX-770) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that was approved in the United States for the treatment of cystic fibrosis (CF) in patients ≥ 6 years of age who have a G551D mutation; however, the most prevalent disease-causing CFTR mutation, F508del, causes a different functional defect. ...

Effects of β(2)-adrenergic receptor gene (ADRB2) polymorphism on therapeutic responses to long-acting β(2)-adrenergic agonists have not been evaluated in long-term COPD trials. We aimed to investigate the effects of the ADRB2 Gly16Arg polymorphism on response to formoterol alone or in combination with the inhaled corticosteroid budesonide in patients with COPD. ...

Spinal hardware has been adapted for fixation in the setting of anterior pelvic injury. This anterior subcutaneous pelvic fixator consists of pedicle screws placed in the supraacetabular region connected by a contoured connecting rod placed subcutaneously and above the abdominal muscle fascia. We examined the placement of the components for ...

Silicosis is a progressive, fibrotic, occupational lung disease resulting from inhalation of respirable crystalline silica. This disease is preventable through appropriate workplace practices. We systematically assessed an outbreak of silicosis among patients referred to our center for lung transplant. This retrospective cohort analysis included all patients with a diagnosis of ...

Inequality within partner relationships is associated with HIV acquisition and gender violence, but little is known about more pervasive effects on women's health. We performed a cross-sectional analysis of associations between sexual relationship power and nutritional status among women in Uganda. Participants completed questionnaires and anthropometric measurements. We assessed sexual ...

This study analyzed data from a large prospective epidemiologic cohort study among men who have sex with men (MSM), the Multicenter AIDS Cohort Study, to assess syndemic relationships among black MSM in the cohort (N = 301). We hypothesized that multiple interconnections among psychosocial health conditions would be found among these men, ...

Cl(-) /HCO3- anion exchanger 2 (AE2) participates in intracellular pH homeostasis and secretin-stimulated biliary bicarbonate secretion. AE2/SLC4A2 gene expression is reduced in liver and blood mononuclear cells from patients with primary biliary cirrhosis (PBC). Our previous findings of hepatic and immunological features mimicking PBC in Ae2-deficient mice strongly suggest that ...

Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated ...

The present study assessed direction discrimination with moving random-dot cinematograms at retinal eccentricities of 0, 8, 22, and 40 deg. In addition, Landolt-C acuity was assessed at these eccentricities to determine whether changes in motion discrimination performance covaried with acuity in the retinal periphery. The results of the experiment indicated ...

Longitudinal stent deformation (LSD) is a recently described complication of PCI, but mechanisms contributing to its occurrence and associated clinical outcomes remain unclear. The FDA Manufacturer and User Facility Device Experience (MAUDE) database was searched to identify cases of LSD to gain insight into procedural and anatomical factors that predispose ...

Current advances in structural biology provide valuable insights into structure-function relationship of membrane transporters by solving crystal structures of bacterial homologs of human transporters. Therefore, scientists consider bacterial transporters as useful structural models for designing of drugs targeted in human diseases. The functional homology between Vibrio parahaemolyticus Na(+)/galactose transporter (vSGLT) ...

To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. We evaluated the association of maternal TDF use during pregnancy with small for ...

We assessed the protective effect of medical male circumcision (MMC) against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD) incidence. Two thousand, seven hundred and eighty-seven men aged 18-24 years living in Kisumu, Kenya were randomly assigned to circumcision (n=1391) or delayed circumcision (n=1393) and assessed ...

HIV-infected individuals are at high risk of developing cardiovascular disease. Whether earlier initiation of HIV therapy at higher CD4 cell counts has any effect on cardiovascular risk as assessed by endothelial function is unknown. Cross-sectional study of 74 antiretroviral-treated men with undetectable plasma HIV RNA levels. Participants underwent noninvasive assessment ...

The US National HIV/AIDS Strategy identifies retention in care as an important quality performance measure. There is no gold standard to measure retention in care. This study is the first to compare different measures of retention, using a large geographically diverse sample. A prospective cohort of 17,425 HIV-infected adults enrolled ...

It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis. Data ...

To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context. The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration ...

To evaluate baseline T-cell activation and neurodevelopmental outcomes over time in a cohort of perinatally HIV-infected (PHIV-infected) children with severe disease. Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366) was a partially randomized, open-label, multicenter 96-week antiretroviral treatment-algorithm study. Neurodevelopmental status, measured by age-dependent evaluations (Bayley scales of infant ...

Antihormonal and chemotherapy are standard treatments for nonorgan-confined prostate cancer. The effectivity of these therapies is limited and the development of alternative approaches is necessary. In the present study, we report on the use of the multikinase inhibitor sorafenib in a panel of prostate cancer cell lines and their derivatives ...

This biographical sketch on William Little corresponds to the historic text, The Classic: Hospital for the Cure of Deformities: Course of Lectures on the Deformities of the Human Frame (1843), available at DOI 10.1007/s11999-012-2302-y .

This review introduces the fundamental concepts of network medicine and explores the feasibility and potential impact of network-based methods on predicting and ameliorating individual manifestations of human cardiovascular disease. Complex cardiovascular diseases rarely result from an abnormality in a single molecular effector, but, rather, nearly always are the net result ...

Entecavir is an effective treatment for chronic hepatitis B. However, data from clinical practice are limited, especially in hepatitis B e antigen (HBeAg)-positive patients. We retrospectively analysed data from 190 nucleos(t)ide-naive chronic hepatitis B patients treated with entecavir (0.5 mg/day) in 25 Spanish centres. Virological response (hepatitis B virus DNA ...

Thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) has recently been introduced as an alternative to 5-bromo-2-deoxyuridine (BrdU) for cell labeling and tracking. Incorporation of EdU into replicating DNA can be detected by azide-conjugated fluors (eg, Alexa-azide) through a Cu(i)-catalyzed click reaction between EdU's alkyne moiety and azide. While this cell labeling method has ...

Dyslipidemia from highly active antiretroviral therapy (HAART) use has been reported to be less severe among persons with HIV and hepatitis C (HCV) compared to those with HIV monoinfection. However, the effect on lipoprotein ratios is less clear. The total cholesterol/high-density lipoprotein ratio (TC/HDL-C ratio) is a robust measure of ...

Tumor-initiating stem cells (also referred to as cancer stem cells, CSCs) are a subpopulation of cancer cells that play unique roles in tumor propagation, therapeutic resistance and tumor recurrence. It is increasingly important to understand how molecular signaling regulates the self-renewal and differentiation of CSCs. Basic helix-loop-helix (bHLH) transcription factors ...

Information is accumulating which implicates airway inflammation resulting from respiratory viral infections, acting against a background of atopy, in both the cause and pathogenesis of atopic asthma. This review brings together the most recent publications relevant to this rapidly evolving area, particularly those focusing on underlying pathogenic mechanisms. Salient findings ...

Current investments in preventive lifestyle interventions are relatively low, despite the significant impact of unhealthy behaviour on population health. This raises the question of whether the criteria used in reimbursement decisions about healthcare interventions put preventive interventions at a disadvantage. In this paper, we highlight the decision-making framework used in ...

We present a patient with DiGeorge syndrome and an isolated right subclavian artery arising from the right pulmonary artery via a right-sided ductus arteriosus. The patient showed a subclavian and pulmonary steal with perfusion of the right arm and right lung via retrograde circulation in the right vertebral artery. The ...

We introduce a mixture model whereby each mixture component is itself a mixture of a multivariate Gaussian distribution and a multivariate uniform distribution. Although this model could be used for model-based clustering (model-based unsupervised learning) or model-based classification (model-based semi-supervised learning), we focus on the more general model-based classification framework. ...

Aim:  To investigate the advantages of using pressure support ventilation (PSV) vs spontaneous ventilation via ProSeal™ laryngeal mask airway in children undergoing ambulatory surgery. Background:  In our ambulatory surgical unit, the use of unassisted spontaneous breathing via laryngeal mask airway is a common anesthetic technique during general anesthesia. However, this ...

Attention is an integral part of the human visual system and has been widely studied in the visual attention literature. The human eyes fixate at important locations in the scene, and every fixation point lies inside a particular region of arbitrary shape and size, which can either be an entire ...

Oral Diseases (2012) 18, 315-316 The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric ...

During exercise, substrate utilization plays a major role in performance and disease prevention. The contribution of fat and carbohydrates to energy expenditure during exercise is modulated by several factors, including intensity and duration of exercise, age, training and diet, but also gender. Because sex hormone levels change throughout a woman's ...

Delayed cerebral ischemia resulting from extracellular hemoglobin is an important determinant of outcome in subarachnoid hemorrhage. Hemoglobin is scavenged by the CD163-haptoglobin system in the circulation, but little is known about this scavenging pathway in the human CNS. The components of this system were analyzed in normal cerebrospinal fluid and ...

In this investigation, semiempirical NMR chemical shift prediction methods are used to evaluate the dynamically averaged values of backbone chemical shifts obtained from unbiased molecular dynamics (MD) simulations of proteins. MD-averaged chemical shift predictions generally improve agreement with experimental values when compared to predictions made from static X-ray structures. Improved ...

Targeting the tumor suppressor p53 to the mitochondria triggers a rapid apoptotic response as efficiently as transcription-dependent p53. (1, 2) p53 forms a complex with the antiapoptotic Bcl-XL, which leads to Bak and Bax oligomerization resulting in apoptosis via mitochondrial outer membrane permeabilization. (3, 4) Although p53 performs its main ...

The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity ...

Changes in the density of NMDA (GluN) receptors in the neuronal membrane are critical for plasticity, whereas malfunction of precisely regulated GluN receptor activity may be involved in neurotoxicity. In cultured rat neocortical interneurons, we have studied the regulation of the surface density of GluN1, GluN2A and GluN2B subunits. Application ...

Advancements toward an improved vaccine against Bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (PA) adsorbed to aluminum hydroxide. However, due to the labile nature of PA, antigen stability is a primary concern for vaccine development. Thus, there is a need for ...

Gene association studies in humans have linked the α5 subunit gene CHRNA5 to an increased risk for nicotine dependence. In the CNS, nicotinic acetylcholine receptors (nAChRs) that contain the α5 subunit are expressed at relatively high levels in the habenulo-interpeduncular system. Recent experimental evidence furthermore suggests that α5-containing receptors in ...

Not only has immunopharmacotherapy grown into a field that addresses the abuse of numerous illicit substances, but also the treatment methodologies within immunopharmacotherapy have expanded from traditional active vaccination to passive immunization with anti-drug monoclonal antibodies, optimized mAb formats, and catalytic drug-degrading antibodies. Many laboratories have focused on transitioning distinct ...

A membrane alignment technique has been used to measure the distance between two TOAC nitroxide spin labels on the membrane-spanning M2δ, peptide of the nicotinic acetylcholine receptor (AChR), via CW-EPR spectroscopy. The TOAC-labeled M2δ peptides were mechanically aligned using DMPC lipids on a planar quartz support, and CW-EPR spectra were ...