Use of whole-blood transcriptomic profiling to highlight several pathophysiologic pathways associated with response to rituximab in patients with rheumatoid arthritis: data from a randomized, controlled, open-label trial.

Objective: To identify a molecular signature that could be predictive of the clinical response to rituximab (RTX) and elucidate the transcriptomic changes after RTX therapy in patients with rheumatoid arthritis (RA), with the use of whole-blood transcriptomic profiling.

Methods: A microarray assay of the whole human genome was performed using RNA from peripheral blood samples obtained before the first cycle of RTX from 68 patients with RA in the SMART study. The transcriptomic profile was also assessed 24 weeks after the first administration of RTX (among 24 nonresponders and 44 responders, according to the European League Against Rheumatism response criteria at week 24).

Drug dealers, retaliation, and deterrence.

Background: Illicit drug sellers have limited access to formal mediation and therefore are rational targets to predators. As such, dealers are especially reliant on retaliation to deter victimization. Prior scholarship on dealers, retaliation, and deterrence has focused largely on general deterrence, or the effect of punishing one person on others.

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death.

Put on a happy face! Inhibitory control and socioemotional knowledge predict emotion regulation in 5- to 7-year-olds.

Children's developing capacity to regulate emotions may depend on individual characteristics and other abilities, including age, sex, inhibitory control, theory of mind, and emotion and display rule knowledge. In the current study, we examined the relations between these variables and children's (N=107) regulation of emotion in a disappointing gift paradigm as well as their relations with the amount of effort to control emotion children exhibited after receiving the disappointing gift. Regression analyses were also conducted to identify unique predictors.

Continence and micturition: an anatomical basis.

Urinary incontinence remains an important clinical problem worldwide, having a significant socio-economic, psychological, and medical burden. Maintaining urinary continence and coordinating micturition are complex processes relying on interaction between somatic and visceral elements, moderated by learned behavior. Urinary viscera and pelvic floor must interact with higher centers to ensure a functionally competent system.

Investigation of expression and activity levels of primary rat hepatocyte detoxication genes under various flow rates and cell densities in microfluidic biochips.

We investigated the behavior of primary rat hepatocytes in biochips using a microfluidic platform (the integrated dynamic cell culture microchip). We studied the effects of cell inoculation densities (0.2-0.

Drug dealers' rational choices on which customers to rip-off.

Background: Drug dealers are infamous for overcharging customers and handing over less than owed. One reason rip-offs frequently occur is blackmarket participants have limited access to formal means of dispute resolution and, as such, are attractive prey. Yet drug dealers do not cheat every customer.

Evaluation of a liver microfluidic biochip to predict in vivo clearances of seven drugs in rats.

We investigated metabolic clearances of phenacetin, midazolam, propranolol, paracetamol, tolbutamide, caffeine, and dextromethorphan by primary rat hepatocytes cultivated in microfluidic biochips. The levels of mRNA of the HNF4α, PXR, AHR, CYP3A1, and CYP1A2 genes were enhanced in the biochip cultures when compared with postextraction levels. We measured a high and rapid adsorption on the biochip walls and inside the circuit for dextromethorphan and midazolam, a moderate adsorption for phenacetin and propranolol, and a low adsorption for caffeine, tolbutamide, and paracetamol.

Targeting the splicing of mRNA in autoimmune diseases: BAFF inhibition in Sjögren's syndrome as a proof of concept.

BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome (pSS). ΔBAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7 RNA was reengineered to deliver antisense sequences targeting BAFF splice regions.

Preeclamptic plasma induces transcription modifications involving the AP-1 transcriptional regulator JDP2 in endothelial cells.

Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line.

Pair distribution function computed tomography.

An emerging theme of modern composites and devices is the coupling of nanostructural properties of materials with their targeted arrangement at the microscale. Of the imaging techniques developed that provide insight into such designer materials and devices, those based on diffraction are particularly useful. However, to date, these have been heavily restrictive, providing information only on materials that exhibit high crystallographic ordering.

Third trimester fetal demise occurring at time of delivery: correlation of autopsy findings and placental pathology with emphasis on antenatal central nervous system injury.

Objective: Third trimester fetal deaths occurring in the hospital at the time of delivery are unusual. We report an autopsy series of such cases with emphasis on neuropathological injury and other lesions predating delivery.

Methods: We identified autopsies performed on third trimester fetuses documented to be alive shortly before delivery, but that expired during, or very close to, time of delivery, and we correlate autopsy and placental findings.

Metastatic colorectal adenocarcinoma in cervicovaginal cytology specimens confirmed by immunocytochemical stains on liquid base specimens: Two study cases with review of the literature.

Only a few cases of adenocarcinoma (ACA) metastatic to the female lower genital tract diagnosed on cervicovaginal Pap smear have been reported during the past several decades. Both conventional and liquid based cytology (LBC) have limited sensitivity and specificity in diagnosing metastatic disease and immunocytochemical (ICC) staining may be needed for confirming the diagnosis. We present two cases of metastatic colorectal ACA diagnosed on cervicovaginal ThinPrep (TP) Pap smears, with one confirmed by ICC staining method.

Non-invasive imaging of the crystalline structure within a human tooth.

The internal crystalline structure of a human molar tooth has been non-destructively imaged in cross-section using X-ray diffraction computed tomography. Diffraction signals from high-energy X-rays which have large attenuation lengths for hard biomaterials have been collected in a transmission geometry. Coupling this with a computed tomography data acquisition and mathematically reconstructing their spatial origins, diffraction patterns from every voxel within the tooth can be obtained.

Cognitive flexibility among individuals with Down syndrome: assessing the influence of verbal and nonverbal abilities.

The influences of verbal mental age (VMA) and performance mental age (PMA) on cognitive flexibility were examined among a group of participants with Down syndrome (DS), in order to disentangle the relative contributions of each. The impaired cognitive flexibility typically observed among individuals with DS in combination with uneven VMA and PMA development suggests an opportunity to further understand the developmental relationship between VMA, PMA, and cognitive flexibility. We examined the performance of 22 participants with DS on the Flexible Item Selection Task (FIST), used for measuring cognitive flexibility among preschoolers.

Optical properties of biological tissues: a review.

A review of reported tissue optical properties summarizes the wavelength-dependent behavior of scattering and absorption. Formulae are presented for generating the optical properties of a generic tissue with variable amounts of absorbing chromophores (blood, water, melanin, fat, yellow pigments) and a variable balance between small-scale scatterers and large-scale scatterers in the ultrastructures of cells and tissues.

Reflexive retaliation for violent victimization: the effect of social distance on weapon lethality.

During the course of being victimized, why do people sometimes fight back with their fists; in other cases, with a knife or blunt object; and at other times, with a firearm? One theory is that the weapons involved in self-defense, also known as reflexive retaliation, become less lethal as offenders and victims become more intimate and alike culturally. Using National Crime Victimization Survey data, we test hypotheses derived from this theory and primarily find support. This article concludes by discussing implications for future work.

Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry.

We present an optical vibrometer based on delay-encoded, dual-beamlet phase-sensitive Fourier domain interferometric system to provide depth-resolved subnanometer scale vibration information from scattering biological specimens. System characterization, calibration, and preliminary vibrometry with biological specimens were performed. The proposed system has the potential to provide both amplitude and direction of vibration of tissue microstructures on a single two-dimensional plane.

"Trophoblast islands of the chorionic connective tissue" (TICCT): a novel placental histologic feature.

Introduction: We found isolated or clustered trophoblasts in the chorionic connective tissue of the extraplacental membranes, and defined this novel histologic feature as the "trophoblast islands of the chorionic connective tissue" (TICCT). This study was conducted to determine the clinical significance of TICCT.

Methods: Immunohistochemistry for cytokeratin-7 was performed on the chorioamniotic membranes (N = 2155) obtained from singleton pregnancies of 1199 uncomplicated term and 956 preterm deliveries.

Selective attention to emotional pictures as a function of gambling motives in problem and nonproblem gamblers.

Problem gambling may reflect a maladaptive means of fulfilling specific affect-regulation motives, such as enhancing positive affect or coping with negative affect. Research with clinical populations indicates that disorders with prominent affective symptoms are characterized by attentional biases for symptom-congruent information. Thus, we assessed whether problem gamblers with enhancement motives for gambling would demonstrate attentional biases for positive emotional information, relative to other types of emotional information, and problem gamblers with coping motives for gambling would demonstrate attentional biases for negative emotional information, compared with other types of emotional information.

Metabolic characterization of primary rat hepatocytes cultivated in parallel microfluidic biochips.

The functionality of primary rat hepatocytes was assessed in an Integrated Dynamic Cell Cultures in Microsystem (IDCCM) device. We characterized the hepatocytes over 96 h of culture and evaluated the impact of dynamic cell culture on their viability, inducibility, and metabolic activity. Reverse Transcription quantitative Polymerase Chain Reaction (RTqPCR) was performed on selected genes: liver transcription factors (HNF4α and CEBP), nuclear receptors sensitive to xenobiotics (AhR, PXR, CAR, and FXR), cytochromes P450 (CYPs) (1A2, 3A2, 3A23/3A1, 7A1, 2B1, 2C6, 2C, 2D1, 2D2, and 2E1), phase II metabolism enzymes (GSTA2, SULT1A1, and UGT1A6), ABC transporters (ABCB1b and ABCC2), and oxidative stress related enzymes (HMOX1 and NQO1).

Plant proteins under oxidative attack.

Reactive oxygen and nitrogen species can modify various biomolecules, including proteins. The resulting protein modifications are highly diverse, can be reversible as well as irreversible, and might affect protein structure and function. Besides random modifications, targeted modifications at specific amino acids in surface-accessible protein regions occur.

Goniometric measurements of thick tissue using Monte Carlo simulations to obtain the single scattering anisotropy coefficient.

The scattering anisotropy, g, of tissue can be a powerful metric of tissue structure, and is most directly measured via goniometry and fitting to the Henyey-Greenstein phase function. We present a method based on an independent attenuation measurement of the scattering coefficient along with Monte Carlo simulations to account for multiple scattering, allowing the accurate determination of measurement of g for tissues of thickness within the quasi-ballistic regime. Simulations incorporating the experimental geometry and bulk optical properties show that significant errors occur in extraction of g values, even for tissues of thickness less than one scattering length without modeling corrections.

A laboratory system for element specific hyperspectral X-ray imaging.

X-ray tomography is a ubiquitous tool used, for example, in medical diagnosis, explosives detection or to check structural integrity of complex engineered components. Conventional tomographic images are formed by measuring many transmitted X-rays and later mathematically reconstructing the object, however the structural and chemical information carried by scattered X-rays of different wavelengths is not utilised in any way. We show how a very simple; laboratory-based; high energy X-ray system can capture these scattered X-rays to deliver 3D images with structural or chemical information in each voxel.