Impaired flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives: The effect of genetic loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia. © 2008 The Authors.published_or_final_versio

Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C.elegans.

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Biodegradable, flexible silicon nanomembrane-based NO x gas sensor system with record-high performance for transient environmental monitors and medical implants

Abstract: A novel transient electronics technology that is capable of completely dissolving or decomposing in certain conditions after a period of operation offers unprecedented opportunities for medical implants, environmental sensors, and other applications. Here, we describe a biodegradable, flexible silicon-based electronic system that detects NO species with a record-breaking sensitivity of 136 Rs (5 ppm, NO2) and 100-fold selectivity for NO species over other substances with a fast response (~30 s) and recovery (~60 s). The exceptional features primarily depend on not only materials, dimensions, and design layouts but also temperatures and electrical operations. Large-scale sensor arrays in a mechanically pliable configuration exhibit negligible deterioration in performance under various modes of applied loads, consistent with mechanics modeling. In vitro evaluations demonstrate the capability and stability of integrated NOx devices in severe wet environments for biomedical applications

The problem of sharp notch in microstructured solids governed by dipolar gradient elasticity

In this paper, we deal with the asymptotic problem of a body of infinite extent with a notch (re-entrant corner) under remotely applied plane-strain or anti-plane shear loadings. The problem is formulated within the framework of the Toupin-Mindlin theory of dipolar gradient elasticity. This generalized continuum theory is appropriate to model the response of materials with microstructure. A linear version of the theory results by considering a linear isotropic expression for the strain-energy density that depends on strain-gradient terms, in addition to the standard strain terms appearing in classical elasticity. Through this formulation, a microstructural material constant is introduced, in addition to the standard Lamé constants . The faces of the notch are considered to be traction-free and a boundary-layer approach is followed. The boundary value problem is attacked with the asymptotic Knein-Williams technique. Our analysis leads to an eigenvalue problem, which, along with the restriction of a bounded strain energy, provides the asymptotic fields. The cases of a crack and a half-space are analyzed in detail as limit cases of the general notch (infinite wedge) problem. The results show significant departure from the predictions of the standard fracture mechanics

Development and content validity of a patient reported outcomes measure to assess symptoms of major depressive disorder

<p>Abstract</p> <p>Background</p> <p>Although many symptoms of Major Depressive Disorder (MDD) are assessed through patient-report, there are currently no patient-reported outcome (PRO) instruments that incorporate documented evidence of patient input in PRO instrument development. A review of existing PROs used in MDD suggested the need to conduct qualitative research with patients with MDD to better understand their experience of MDD and develop an evaluative instrument with content validity. The aim of this study was to develop a disease-specific questionnaire to assess symptoms important and relevant to adult MDD patients.</p> <p>Methods</p> <p>The questionnaire development involved qualitative interviews for concept elicitation, instrument development, and cognitive interviews to support content validity. For concept elicitation, ten MDD severity-specific focus group interviews with thirty-eight patients having clinician-confirmed diagnoses of MDD were conducted in January 2009. A semi-structured discussion guide was used to elicit patients' spontaneous descriptions of MDD symptoms. Verbatim transcripts of focus groups were coded and analyzed to develop a conceptual framework to describe MDD. A PRO instrument was developed by operationalizing concepts elicited in the conceptual framework. Cognitive interviews were carried out in patients (n = 20) to refine and test the content validity of the instrument in terms of item relevance and comprehension, instructions, recall period, and response categories.</p> <p>Results</p> <p>Concept elicitation focus groups identified thirty-five unique concepts falling into several domains: i) emotional, ii) cognitive, iii) motivation, iv) work, v) sleep, vi) appetite, vii) social, viii) activities of daily living, ix) tired/fatigue, x) body pain, and xi) suicidality. Concept saturation, the point at which no new relevant information emerges in later interviews, was achieved for each of the concepts. Based on the qualitative findings, the PRO instrument developed had 15 daily and 20 weekly items. The cognitive interviews confirmed that the instructions, item content, and response scales were understood by the patients.</p> <p>Conclusions</p> <p>Rigorous qualitative research resulted in the development of a PRO measure for MDD with supported content validity. The MDD PRO can assist in understanding and assessing MDD symptoms from patients' perspectives as well as evaluating treatment benefit of new targeted therapies.</p

Shared neural representations of tactile roughness intensities by somatosensation and touch observation using an associative learning method

Previous human fMRI studies have reported activation of somatosensory areas not only during actual touch, but also during touch observation. However, it has remained unclear how the brain encodes visually evoked tactile intensities. Using an associative learning method, we investigated neural representations of roughness intensities evoked by (a) tactile explorations and (b) visual observation of tactile explorations. Moreover, we explored (c) modality-independent neural representations of roughness intensities using a cross-modal classification method. Case (a) showed significant decoding performance in the anterior cingulate cortex (ACC) and the supramarginal gyrus (SMG), while in the case (b), the bilateral posterior parietal cortices, the inferior occipital gyrus, and the primary motor cortex were identified. Case (c) observed shared neural activity patterns in the bilateral insula, the SMG, and the ACC. Interestingly, the insular cortices were identified only from the cross-modal classification, suggesting their potential role in modality-independent tactile processing. We further examined correlations of confusion patterns between behavioral and neural similarity matrices for each region. Significant correlations were found solely in the SMG, reflecting a close relationship between neural activities of SMG and roughness intensity perception. The present findings may deepen our understanding of the brain mechanisms underlying intensity perception of tactile roughness

Infinitesimal sulfur fusion yields quasi-metallic bulk silicon for stable and fast energy storage

A fast-charging battery that supplies maximum energy is a key element for vehicle electrification. High-capacity silicon anodes offer a viable alternative to carbonaceous materials, but they are vulnerable to fracture due to large volumetric changes during charge???discharge cycles. The low ionic and electronic transport across the silicon particles limits the charging rate of batteries. Here, as a three-in-one solution for the above issues, we show that small amounts of sulfur doping (&lt;1 at%) render quasi-metallic silicon microparticles by substitutional doping and increase lithium ion conductivity through the flexible and robust self-supporting channels as demonstrated by microscopy observation and theoretical calculations. Such unusual doping characters are enabled by the simultaneous bottom-up assembly of dopants and silicon at the seed level in molten salts medium. This sulfur-doped silicon anode shows highly stable battery cycling at a fast-charging rate with a high energy density beyond those of a commercial standard anode

Diagnosis of bladder cancer by immunocytochemical detection of minichromosome maintenance protein-2 in cells retrieved from urine.

BACKGROUND: We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine. METHODS: Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy. RESULTS: In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05). CONCLUSIONS: Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups