Stable patterns of gene expression regulating carbohydrate metabolism determined by geographic ancestry.

Background: Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease).

Methodology/principal Findings: Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations.

Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study.

Polysomnographic studies of Parkinson's disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapine's efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study.

Long-term effect of home telehealth services on preventable hospitalization use.

In this study, we assessed the longitudinal effect of a Department of Veterans Affairs (VA) patient-centered Care Coordination Home Telehealth (CCHT) program on preventable hospitalization use by veterans with diabetes mellitus (DM) at four VA medical centers. We used a matched treatment-control design (n = 387 for both groups). All patients were followed for 4 years.

Complementary conductance changes by IKx and Ih contribute to membrane impedance stability during the rod light response.

In addition to the HCN1 channels that mediate the h current, the Kx current also performs signal filtering in rod photoreceptors. This current is known to be mediated by potassium channels and has similarities to the neuronal M current and EAG potassium channels. Although it is known that in filtering the light response of rods, I(h) and I(Kx) undergo complementary conductance changes, the qualities and significance of these changes are not clear.

Brain penetration effects of microelectrodes and deep brain stimulation leads in ventral intermediate nucleus stimulation for essential tremor.

Object: Microelectrode recording (MER) and macrostimulation (test stimulation) are used to refine the optimal deep brain stimulation (DBS) lead placement within the operative setting. It is well known that there can be a microlesion effect with microelectrode trajectories and DBS insertion. The aim of this study was to determine the impact of intraoperative MER and lead placement on tremor severity in a cohort of patients with essential tremor.

An evaluation of rating scales utilized for deep brain stimulation for dystonia.

The objective of this study was to examine globus pallidus internus deep brain stimulation (GPi-DBS) outcomes in primary and secondary dystonia, derived from blinded ratings using two scales and two raters. Twenty-five patients with variable presentations of dystonia were evaluated with videotaped standardized dystonia rating scales at preoperative baseline and at 6 and 12 months following GPi-DBS implantation. These 75 examination videos were retrospectively evaluated, independently and in random order, by two movement disorder neurologists who were blinded to the treatment status.

Genetic dissection of rod and cone pathways in the dark-adapted mouse retina.

A monumental task of the mammalian retina is to encode an enormous range (>10(9)-fold) of light intensities experienced by the animal in natural environments. Retinal neurons carry out this task by dividing labor into many parallel rod and cone synaptic pathways. Here we study the operational plan of various rod- and cone-mediated pathways by analyzing electroretinograms (ERGs), primarily b-wave responses, in dark-adapted wildtype, connexin36 knockout, depolarizing rod-bipolar cell (DBCR) knockout, and rod transducin alpha-subunit knockout mice [WT, Cx36(-/-), Bhlhb4(-/-), and Tralpha(-/-)].

Parvalbumin-immunoreactive amacrine cells of macaque retina.

A number of authors have observed amacrine cells containing high levels of immunoreactive parvalbumin in primate retinas. The experiments described here were designed to identify these cells morphologically, to determine their neurotransmitter, to record their light responses, and to describe the other cells that they contact. Macaque retinas were fixed in paraformaldehyde and labeled with antibodies to parvalbumin and one or two other markers, and this double- and triple-labeled material was analyzed by confocal microscopy.

Low-conductance HCN1 ion channels augment the frequency response of rod and cone photoreceptors.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are expressed in several tissues throughout the body, including the heart, the CNS, and the retina. HCN channels are found in many neurons in the retina, but their most established role is in generating the hyperpolarization-activated current, I(h), in photoreceptors. This current makes the light response of rod and cone photoreceptors more transient, an effect similar to that of a high-pass filter.

Psychosocial education improves low back pain beliefs: results from a cluster randomized clinical trial (NCT00373009) in a primary prevention setting.

The general population has a pessimistic view of low back pain (LBP), and evidence-based information has been used to positively influence LBP beliefs in previously reported mass media studies. However, there is a lack of randomized trials investigating whether LBP beliefs can be modified in primary prevention settings. This cluster randomized clinical trial investigated the effect of an evidence-based psychosocial educational program (PSEP) on LBP beliefs for soldiers completing military training.

Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus.

While deep brain stimulation (DBS) surgery is a well-accepted treatment for Parkinson disease (PD) that improves overall quality of life (QoL), its effects across different domains of QoL are unclear. The study reported here directly compared the effects of unilateral DBS in subthalamic nucleus (STN) or globus pallidus (GPi) on QoL in 42 non-demented patients with medication-refractory PD. Patients were enrolled in the COMPARE trial, a randomized clinical trial of cognitive and mood effects of STN versus GPi DBS conducted at the University of Florida Movement Disorders Center.

Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial.

Objective: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease.

Methods: Fifty-two subjects were randomized to unilateral STN or GPi DBS.

Simulation analysis of bandpass filtering properties of a rod photoreceptor network.

The bandpass filtering properties of a rod network were studied via computer simulations. Sinusoidal current stimuli were applied to a single rod model to characterize its temporal filtering properties. The simulated frequency response revealed that a single rod behaves as a bandpass filter whose characteristics are affected by the stimulus strength and frequency.

Mortality risk for diabetes patients in a care coordination, home-telehealth programme.

We assessed a home monitoring/care coordination programme for veterans with diabetes. Patients enrolled in the programme (n = 387) were followed for four years and compared with a retrospective control group (n = 387). Each patient in the intervention group used a messaging device in the home that was connected by a conventional telephone line.

Errorless practice as a possible adjuvant to donepezil in Alzheimer's disease.

Six individuals with probable Alzheimer's disease (AD) participated in a phase 1 study employing a repeated measures, parallel baseline design testing the hypothesis that error-free experience during word production practice combined with an acetyl cholinesterase inhibitor would improve confrontation naming ability. While acetyl cholinesterase inhibitors are safe and delay cognition decline associated with AD, improvement over baseline cognition is less evident; clinically significant cognitive deficits persist and progress. Both animal and clinical research strongly implicate acetylcholine in learning, a form of neuroplasticity.

Score statistics for mapping quantitative trait loci.

We propose a method to detect the existence of quantitative trait loci (QTL) in a backcross population using a score test. Since the score test only uses the MLEs of parameters under the null hypothesis, it is computationally simpler than the likelihood ratio test (LRT). Moreover, because the location parameter of the QTL is unidentifiable under the null hypothesis, the distribution of the maximum of the LRT statistics, typically the statistic of choice for testing H0: no QTL, does not have the standard chi-square distribution asymptotically under the null hypothesis.

Expression pattern of connexins in the corneal and limbal epithelium of a primate.

Purpose: To detect the expression pattern of connexins in epithelial cells of the central cornea and limbus of the macaque.

Methods: Total RNA was extracted from the central corneal and limbal epithelia of Macaca fascicularis and processed by reverse transcriptase-polymerase chain reaction with isoform primers to detect the expression of 16 connexin (Cx). Immunofluorescent staining of frozen sections of corneal tissue confirmed and localized connexin proteins expression.

Receptive fields of retinal bipolar cells are mediated by heterogeneous synaptic circuitry.

Center-surround antagonistic receptive field (CSARF) organization is the basic synaptic circuit that serves as elementary building blocks for spatial information processing in the visual system. Cells with such receptive fields converge into higher-order visual neurons to form more complex receptive fields. Retinal bipolar cells (BCs) are the first neurons along the visual pathway that exhibit CSARF organization.

Immunocytochemical analysis of photoreceptors in the tiger salamander retina.

In the tiger salamander retina, visual signals are transmitted to the inner retina via six morphologically distinct types of photoreceptors: large/small rods, large/small single cones, and double cones composed of principal and accessory members. The objective of this study was to determine the morphology of these photoreceptors and their synaptic interconnection with bipolar cells and horizontal cells in the outer plexiform layer (OPL). Here we showed that glutamate antibodies labeled all photoreceptors and recovering antibodies strongly labeled all cones and weakly labeled all rods.

From retinal circuitry to eye diseases--in memory of Henk Spekreijse.

This article summarizes our recent works on stratum-by-stratum structure-function rules for synaptic contacts between retinal bipolar cells and third-order retinal neurons in the inner plexiform layer. These rules were derived from large-scale voltage clamp recordings of various types of bipolar cells in the tiger salamander retina, and they appear applicable to bipolar cells in the mouse and other mammalian species. This review also gives a brief account of how we used pathway-specific knockout mouse models to dissect rod and cone signaling channels in the mammalian retina.

On identification of the number of best treatments using the Newman-Keuls test.

In this paper, we provide a stochastic ordering of the Studentized range statistics under a balanced one-way ANOVA model. Based on this result we show that, when restricted to the multiple comparisons with the best, the Newman-Keuls (NK) procedure strongly controls experimentwise error rate for a sequence of null hypotheses regarding the number of largest treatment means. In other words, the NK procedure provides an upper confidence bound for the number of best treatments.

Histamine enhances voltage-gated potassium currents of ON bipolar cells in macaque retina.

Purpose: The goal was to understand the functions of retinopetal axons containing histamine. In prior work, type 3 histamine receptors (HR3) have been localized to the tips of ON bipolar cell dendrites in macaque retinas. Voltage-gated potassium channels have also been localized to bipolar cell dendrites, and the hypothesis tested in the present study was that these are modulated by histamine.

Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males.

Background: Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive.

Results: We analyzed gene transcription data to identify expression spectra related to tobacco use in circulating leukocytes of 67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used as a surrogate marker for tobacco exposure.

Detection of HIV-1 p24 Gag in plasma by a nanoparticle-based bio-barcode-amplification method.

Background: Detection of HIV-1 in patients is limited by the sensitivity and selectivity of available tests. The nanotechnology-based bio-barcode-amplification method offers an innovative approach to detect specific HIV-1 antigens from diverse HIV-1 subtypes. We evaluated the efficacy of this protein-detection method in detecting HIV-1 in men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS).