Disruption of glycosylphosphatidylinositol biosynthesis is genetically and chemically validated as a drug target against the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. The N-acetylglucosamine-phosphatidylinositol de-N-acetylase (deNAc) is a zinc metalloenzyme responsible for the second step of glycosylphosphatidylinositol biosynthesis. We recently reported the synthesis of eight deoxy-2-C-branched ...

Recently demonstrated neuronal loss in the inner nuclear layer of the retina in multiple sclerosis (MS) and glaucoma raises the question of a primary (possibly immune-mediated) or secondary (transsynaptic) mechanism of retinal damage in these diseases. In the present study we used optical coherence tomography to investigate retrograde retinal transsynaptic ...

Objectives: This study examines how the prevalence and correlates of binge drinking among older adults vary by race/ethnicity. Methods: Drawn from the 2007 California Health Interview Survey, adults aged 60 and older (n = 18,772) were selected. Binge drinking was measured dichotomously based on whether individuals reported consuming five or more drinks ...

Better understanding of electron transfer (ET) taking place at the nano-bio interface can guide design of more effective functional materials used in fuel cells, biosensors, and medical devices. Single-walled carbon nanotube (SWCNT) coupled with biological enzymes serves as a model system for studying the ET mechanism, as demonstrated in the ...

The pediatric medical home is an approach to the delivery of family-centered health care. Policy-makers and payers are interested in potential changes to health care utilization and expenditures under this model. To test associations between having a medical home and health service use and expenditures among US children and youth. ...

To explore the pattern of repeat pregnancies among diagnosed HIV-infected women in the United Kingdom and Ireland, estimate the rate of these sequential pregnancies, and investigate the demographic and clinical characteristics of women experiencing them. Diagnosed HIV-infected pregnant women are reported through an active confidential reporting scheme to the National ...

Solid lipid nanoparticles (SLNs), as a drug carrier, are a very attractive strategy for sustained and controlled drug release. In this study, we investigated the feasibility of SLNs to prolong the action of lidocaine for potential application in epidural anesthesia and analgesia. Lidocaine-loaded SLNs were prepared with different lipids, including ...

Objectives: The aim of this paper is to provide further detail about the results of a randomised controlled study published in this journal (Raglio et al., 2010, 14, 900-904), in which we assessed the efficacy of music therapy (MT) on the behavioural disturbances in people with moderate-severe dementia. Methods: Sixty ...

To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by ...

Trans-3'-Hydroxycotinine (3HC) and its glucuronide are major nicotine metabolites excreted in the urine of smokers and other tobacco users. Although several members of the UDP-glucuronosyltransferase (UGT) family of enzymes were previously shown to be active in catalyzing the formation of 3HC and its glucuronide, a comprehensive screening of all known ...

To analyze choroidal changes associated with reticular pseudodrusen by indocyanine green angiography (ICGA) and enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT). Twenty-two consecutive patients (22 eyes) with reticular pseudodrusen, and without medium/large drusen, underwent ICGA and EDI OCT. Twenty-one age- and sex-matched subjects (21 eyes) with early age-related ...

To evaluate the association of symptomatic soft contact lens (SCL)-related corneal infiltrative events (CIEs) with SCL material, lens care products (LCPs), and other risk factors. Cases with symptomatic CIEs were identified in a retrospective, multicenter case-control study at five academic eye care centers. Each case was matched to three controls ...

To describe corneal and crystalline lens dimensions before, during, and after myopia onset compared with age-matched emmetropic values. Subjects were 732 children aged 6 to 14 years who became myopic and 596 emmetropic children participating between 1989 and 2007 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study. ...

This review summarizes the available data on the role of hypomethylating agents in the setting of hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). Although hypomethylating agents have been established as standard of therapy for MDS in the nontransplant setting, the role of these agents in patients who are candidates ...

Despite the evidence in support of the anti-inflammatory and triglyceride-lowering effects of fenofibrate, little is known about genetic determinants of the observed heterogeneity in treatment response. This study provides the first genome-wide examination of fenofibrate effects on systemic inflammation. Biomarkers of inflammation were measured in participants of the Genetics of ...

To give an overview of promising novel agents under development for the prevention and reduction of gastrointestinal radiation injury. Currently, several novel agents are being tested as drugs to prevent or reduce gastrointestinal radiation injury. These drugs may not only prevent injury, but also mitigate toxicity, that is, reduce injury ...

Sonographic evaluation of adnexal masses is subject to a variety of potential pitfalls that can lead to diagnostic overcalls and undercalls. Familiarity with the pitfalls associated with sonographic findings related to normal ovarian physiology, hemorrhagic ovarian cysts, endometriomas, cystic teratomas, extraovarian cystic masses, and exophytic uterine masses helps the imager ...

Blood doping practices in sports have been around for at least half a century and will likely remain for several years to come. The main reason for the various forms of blood doping to be common is that they are easy to perform, and the effects on exercise performance are ...

Myeloproliferative neoplasms (MPNs) are diseases that carry the JAK2 (V617F) mutation in about 70% of the patients. The purpose of this review is to describe the recent advances in the therapy of MPNs with JAK2 inhibitors. Many drugs are now under investigations targeting different pathways critical for MPN development, such ...

This review summarizes the development and implementation of a large clinical trial, HIV Prevention Trials Network (HPTN) 052, whose initial results were recently presented and published. A randomized, clinical trial demonstrated that antiretroviral therapy reduces the sexual transmission of HIV in HIV-serodiscordant couples by more than 96%. The logistical challenges ...

An elevation in the neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with a poorer prognosis in patients with various tumors. The aim of this retrospective study was to clarify the correlation of the pretherapeutic NLR with the prognostic value of the pathologic response to neoadjuvant chemotherapy (NAC) in ...

The objective of the study was to examine time trends and differences in medical expenditures between noncitizens, foreign-born, and US-born citizens. We used multi-year Medical Expenditures Panel Survey (2000-2008) data on noninstitutionalized adults in the United States (N=190,965). Source specific and total medical expenditures were analyzed using regression models, bootstrap ...

The aim was to determine the repeatability of ultralong scan depth spectral-domain optical coherence tomography (SD-OCT) measurements of the ocular anterior segment during accommodation. The center wavelength of the SD-OCT light source was 840 nm with a bandwidth of 50 nm. The ocular axial resolution of the system was approximately ...

Producing descriptive epidemiology data is essential to understand the burden of rheumatic diseases (prevalence) and their dynamic in the population (incidence). IMPORTANT CONSIDERATIONS: No matter how simple such indicators may look, the correct collection of data and the appropriate interpretation of the results face several challenges: distinguishing indicators, facing the ...

Rett syndrome (RTT) is a neurodevelopmental disability characterized by mutations in the X-linked methyl-CpG-binding protein 2 located at the Xq28 region. The severity is modified in part by X chromosomal inactivation resulting in wide clinical variability. We hypothesized that the ability to perform the activities of daily living (ADL) is ...

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case-control study included the 2,753 cases diagnosed in mainland France over 2002-2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the ...

  Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled out-patient trial tested topiramate for treating methamphetamine addiction.   Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 25 mg/day [DOSAGE ERROR CORRECTED] to the target maintenance of ...

Although end-stage kidney disease in African Americans (AAs) is four times greater than in whites, AAs are less than one half as likely to undergo kidney transplantation (KT). This racial disparity has been found even after controlling for clinical factors such as comorbid conditions, dialysis vintage and type, and availability ...

Morphological analysis is an essential step in verifying the success of a tissue engineering strategy where the presence of a desired cellular phenotype must be determined. While morphometry has transitioned from observational grading to computational quantification, established quantitative methods eliminate information by relying on two-dimensional (2D) analysis to describe three-dimensional ...

Using a combination of deep sequencing and bioinformatics approach, we for the first time identify miRNAs and their relative abundance in mature, metaphase II arrested eggs in Xenopus laevis. We characterize 115 miRNAs that have been described either in Xenopus tropicalis (85), X. laevis (9), or other vertebrate species (21) ...

Derivation of pluripotent stem cells (iPSCs) induced from somatic cell types and the subsequent genetic modifications of disease-specific or patient-specific iPSCs are crucial steps in their applications for disease modeling as well as future cell and gene therapies. Conventional procedures of these processes require co-culture with primary mouse embryonic fibroblasts ...

The oxidative process of disulfide-bond formation is essential for the folding of most secretory and membrane proteins in the endoplasmic reticulum (ER). It is driven by electron relay pathways that transfer two electrons derived from the fusion of two adjacent cysteinyl side chains onto various types of chemical oxidants. The ...

In this study, manganese oxide (MnO) nanorods and its association with polyamidoamine dendrimer (PAMAM) and macromolecular RNA were analyzed. Because manganese is found naturally in cells and tissues and binds proteins and nucleic acids, nanomaterials derived from manganese, such as first generation MnO, may have potential as a biocompatible delivery ...

Screening efforts led to the identification of PI-8182 (1), an inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome. Compound 1 contains a hydronaphthoquinone pharmacophore with a thioglycolic acid side chain at position 2 and thiophene sulfonamide at position 4. An efficient synthetic route to the hydronaphthoquinone sulfonamide scaffold was ...

Formal cycloaddition reactions between imines and cyclic anhydrides serve as starting point for the synthesis of diverse libraries of small molecules. The synthesis of succinic anhydrides substituted with electron-withdrawing groups is facilitated by new mild conditions for alkylation of aryl-substituted acetyl esters with ethyl bromoacetate. These anhydrides are then used ...

Manipulation of cell patterns in three dimensions in a manner that mimics natural tissue organization and function is critical for cell biological studies and likely essential for successfully regenerating tissues--especially cells with high physiological demands, such as those of the heart, liver, lungs, and articular cartilage.(1, 2) In the present ...

All-trans-retinal and its condensation-products can cause retinal degeneration in a light-dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt's disease and age-related macular degeneration. Although these toxic retinoid by-products originate from rod and cone photoreceptor cells, the contribution of each cell type to light-induced retinal ...

Nerve regeneration in an injured spinal cord is often restricted, contributing to the devastating outcome of neurologic impairment below the site of injury. Although implantation of tissue-engineered scaffolds has evolved as a potential treatment method, the outcomes remain sub-optimal. One possible reason may be the lack of topographical signals from ...

Previous studies with the novel once daily glucagon-like peptide-1 (GLP-1) analogue liraglutide and the GLP-1 receptor agonist exenatide have revealed profound insulinotrophic and antidiabetic effects, but also potent effects on gastric emptying (GE) and long-term and lasting reductions in body weight. In this study, we examined the acute and chronic ...

The Biopharmaceutics Drug Disposition Classification System (BDDCS) was successfully employed for predicting drug-drug interactions (DDIs) with respect to drug metabolizing enzymes (DMEs), drug transporters and their interplay. The major assumption of BDDCS is that the extent of metabolism (EoM) predicts high versus low intestinal permeability rate, and vice versa, at ...

Serine hydroxymethyltransferase (SHMT) catalyzes the transfer of a β-carbon from serine to tetrahydrofolate to form glycine and 5,10-methylene-tetrahydrofolate. This reaction plays an important role in neurotransmitter synthesis and metabolism. We set out to resequence SHMT1 and SHMT2, followed by functional genomic studies. We identified 87 and 60 polymorphisms in SHMT1 ...

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the ...

The repellent semaphorin 3A (Sema3A) causes growth cone turning or collapse by triggering cytoskeletal rearrangements and detachment of adhesion sites. Growth cone detachment is dependent on eicosanoid activation of protein kinase C epsilon (PKCε), but the characterization of the phospholipase A(2) (PLA(2) ) that releases arachidonic acid (AA) for eicosanoid ...

To determine whether proton radiation affects coagulation. Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood ...

Cerebellin precursor protein (Cbln1) is essential for synapse integrity in cerebellum through assembly into complexes that bridge pre-synaptic β-neurexins (Nrxn) to post-synaptic GluRδ2. However, GluRδ2 is largely cerebellum-specific, yet Cbln1 and its little studied family members, Cbln2 and Cbln4, are expressed throughout brain. Therefore, we investigated whether additional proteins mediate ...

Mass spectrometry is used to investigate global changes in protein abundance in cell lysates. Increasingly powerful methods of data collection have emerged over the past decade, but this has left researchers with the task of sifting through mountains of data for biologically significant results. Often, the end result is a ...

Ligand bias is a recently introduced concept in the receptor signaling field that underlies innovative strategies for targeted drug design. Ligands, as a consequence of conformational selectivity, produce signaling bias in which some downstream biochemical pathways are favored over others, and this contributes to variability in physiological responsiveness. Though the ...

In a recent study of polyketide biosynthetic gene clusters cloned directly from soil, we isolated two antibiotics, fasamycins A and B, which showed activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. To identify the target of the fasamycins, mutants with elevated fasamycin A minimum inhibitory concentrations were selected from ...

This case demonstrates extraosseous 99m-technetium methylene diphosphonate (Tc-99m MDP) accumulation from a gastrointestinal stromal tumor. A 75-year-old woman underwent a temporal bone CT for conductive hearing loss that showed sclerosis in the right occipital condyle. Follow-up Tc-99m MDP bone scan for osseous metastases instead showed a mass-like extraosseous accumulation of ...

Unilateral hypermetabolic lesion of parotid gland demonstrated on PET/CT imaging may originate from a large spectrum of benign or malignant processes, such as adenoma, Warthin's tumor, oncocytic neoplasm, lymphoma, and primary or secondary malignancy of the gland. Bilateral and multifocal parotid gland disease is less common but possible because of ...