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Despite showing early promise, several recent clinical trials of noninvasive brain stimulation (NIBS) failed to augment rehabilitative outcomes of the paretic upper limb. This article addresses why pairing NIBS with unilateral approaches is weakly generalizable to patients in all ranges of impairments. The article also addresses whether alternate therapies are better suited for the more impaired patients, where they may be more feasible and offer neurophysiologic advantages not offered with unilateral therapies. The article concludes by providing insight on how to create NIBS paradigms that are tailored to distinctly augment the effects of therapies across patients with varying degrees of impairment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Reproducibility of transcranial magnetic stimulation (TMS) metrics is essential in accurately tracking recovery and disease. However, majority of evidence pertains to reproducibility of metrics for distal upper limb muscles. We investigate for the first time, reliability of corticospinal physiology for a large proximal muscle - the biceps brachii and relate how varying statistical analyses can influence interpretations., Methods: 14 young right-handed healthy participants completed two sessions assessing resting motor threshold (RMT), motor evoked potentials (MEPs), motor map and intra-cortical inhibition (ICI) from the left biceps brachii. Analyses included paired t-tests, Pearson's, intra-class (ICC) and concordance correlation coefficients (CCC) and Bland-Altman plots., Results: Unlike paired t-tests, ICC, CCC and Pearson's were >0.6 indicating good reliability for RMTs, MEP intensities and locations of map; however values were <0.3 for MEP responses and ICI., Conclusions: Corticospinal physiology, defining excitability and output in terms of intensity of the TMS device, and spatial loci are the most reliable metrics for the biceps. MEPs and variables based on MEPs are less reliable since biceps receives fewer cortico-motor-neuronal projections. Statistical tests of agreement and associations are more powerful reliability indices than inferential tests., Significance: Reliable metrics of proximal muscles when translated to a larger number of participants would serve to sensitively track and prognosticate function in neurological disorders such as stroke where proximal recovery precedes distal., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes., Approach: Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg(-1). The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation., Main Results: Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals., Significance: Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

Despite the promising potential of intracortical microelectrodes, current designs suffer from short functional lifetimes, due in large part to the neuroinflammatory response to the implanted devices. An increasing body of literature is beginning to link neuroinflammatory-mediated oxidative damage to both the loss of neuronal structures around the implanted microelectrodes, and the degradation/corrosion of electrode materials. The goal of this viewpoint paper was to summarize the current progress toward understanding the role of oxidative damage to neurons and microelectrodes. Further, we seek to highlight the initial antioxidative approaches to mitigate oxidative damage, as well as suggest how current advances in macromolecular science for various applications may play a distinct role in enabling intracortical microelectrodes as reliable choices for long-term neuroprosthetic applications.

Systematic review is an invaluable tool for the practicing clinician. A well-designed systematic review represents the latest and most complete information available on a particular topic or intervention. This article highlights the key elements of systematic review, what it is and is not, and provides an overview of several reputable organizations supporting the methodological development and conduct of systematic review. Important aspects for evaluating the quality of a systematic review are also included., (Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Crohn's disease (CD) is an idiopathic, chronic, transmural inflammatory disorder of the gastrointestinal tract. Because mucosal involvement is near-universal, endoscopic healing has emerged as an important aspect in improving outcome. However, resolution of histologic disease activity has potential to convey additional benefit beyond that attained with endoscopic healing alone. Validated scoring systems of histologic disease activity are required to further assess this possibility. The aim of this study was to systematically review the existing histologic disease activity indices (HDAI) for CD and to assess their operating properties and potential use as outcome measures in clinical trials., Methods: MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week (DDW) abstracts were searched from 1981 to April 2013 for applicable studies to identify relevant studies for review and analysis., Results: In total, 3732 citations were screened to obtain 89 articles for inclusion. Sixty-six HDAIs were characterized as either stepwise or numerical instruments. These HDAIs were used for either assessment of response to medical therapy or for comparison with biomarkers or imaging tests. None of the HDAIs identified was developed according to currently accepted methods for developing evaluative instruments, and none have been formally validated., Conclusions: Measurement of histologic disease activity has potential value in CD; however, no validated measures are available. Additional research is needed to develop a methodologically rigorous instrument for use in clinical investigation and potentially for clinical practice.

Background: Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials., Methods: A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized., Results: The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties., Conclusions: Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Background: Assessment of endoscopic disease activity, as measured by various endoscopic evaluative instruments, is an essential part of quantifying disease activity in clinical trials in patients with ulcerative colitis (UC). Evaluative instruments have specific definitions and operating properties that influence the interpretation of clinical trial results. Our objective was to systematically review all endoscopic evaluative instruments that measure endoscopic disease activity in UC and to describe their definitions and operating characteristics (reliability, responsiveness, and predictive validity)., Methods: We performed a systematic review of evaluative instruments assessing endoscopic disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week abstracts of clinical trials were searched from inception to January 2013., Results: In total, 5885 studies were identified and screened for inclusion criteria. Four hundred twenty-two studies involving 31 evaluative instruments were identified. Two types of indices were found, numerical scoring systems and stepwise grading scales., Conclusions: Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for UC. Currently, the sigmoidoscopic component of the Mayo Score and the ulcerative colitis endoscopic index of severity show the most promise as reliable evaluative instruments of endoscopic disease activity. However, further validation is required.

Rat models have emerged as a common tool to study neuroinflammation to intracortical microelectrodes. While a number of studies have attempted to understand the factors resulting in neuroinflammation using rat models, a complete understanding of key mechanistic pathways remains elusive. Transgenic mouse models, however, could facilitate a deeper understanding of mechanistic pathways due to an ease of genetic alteration. Therefore, the goal of the present study is to compare neuroinflammation following microelectrode implantation between the rat and the mouse model. Our study suggests that subtle differences in the classic neuroinflammatory markers exist between the animal models at both two and sixteen weeks post implantation. Most notably, neuronal densities surrounding microelectrodes were significantly lower in the rat model at two weeks, while similar densities were observed between the animal models at sixteen weeks. Physiological differences between the species and slight alterations in surgical methods are likely key contributors to the observed differences. Moving forward, we propose that differences in the time course of neuroinflammation between the animal models should be considered when trying to understand and prevent intracortical microelectrode failure., (Published by Elsevier Ltd.)

Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio-availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces.

Background: Ulcerative colitis (UC) is an idiopathic inflammatory disorder. Currently, the main goals of treatment are to induce and maintain clinical and/or endoscopic remission. However, evidence indicates that persistent disease activity on colonic biopsies in the setting of clinical or endoscopic remission is an independent predictor of poor outcomes. A number of previous studies have proposed histologic indices for use in specific trials of UC. The aim of this study was to systematically review the existing histological indices for UC and assess their potential use in both patient management and clinical trials., Methods: We performed a systematic review of histological indices evaluating disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Diseases Week (DDW) abstracts of randomized and/or controlled trials clinical trials were searched from inception to February 2013 for applicable studies. Data from these studies were reviewed and analyzed., Results: After systematically applying inclusion criteria, we identified 108 scientific articles including 88 clinical studies and 21 related clinical reviews. Eighteen indices of histological activity in UC were identified and reviewed., Conclusions: Although multiple histological scoring indices for assessment of UC disease activity currently exist, none of these instruments were developed using a formal validation process and their operating properties remain poorly understood. Future studies are needed to address this deficiency.

Amphiphile selection is a critical step for structural studies of membrane proteins (MPs). We have developed a family of steroid-based facial amphiphiles (FAs) that are structurally distinct from conventional detergents and previously developed FAs. The unique FAs stabilize MPs and form relatively small protein-detergent complexes (PDCs), a property considered favorable for MP crystallization. We attempted to crystallize several MPs belonging to different protein families, including the human gap junction channel protein connexin 26, the ATP binding cassette transporter MsbA, the seven-transmembrane G protein-coupled receptor-like bacteriorhodopsin, and cytochrome P450s (peripheral MPs). Using FAs alone or mixed with other detergents or lipids, we obtained 3D crystals of the above proteins suitable for X-ray crystallographic analysis. The fact that FAs enhance MP crystallizability compared with traditional detergents can be attributed to several properties, including increased protein stability, formation of small PDCs, decreased PDC surface flexibility, and potential to mediate crystal lattice contacts.

Voltage-gated K(+) channels underlie the electrical excitability of cells. Each subunit of the functional tetramer consists of the tandem fusion of two modules, an N-terminal voltage-sensor and a C-terminal pore. To investigate how sensor coupling to the pore generates voltage-dependent channel opening, we solved the crystal structure and characterized the function of a voltage-gated K(+) channel pore in a lipid membrane. The structure of a functional channel in a membrane environment at 3.1 Å resolution establishes an unprecedented connection between channel structure and function. The structure is unique in delineating an ion-occupied ready to conduct selectivity filter, a confined aqueous cavity, and a closed activation gate, embodying a dynamic entity trapped in an unstable closed state.

Bites from Macaca mulatta monkeys, native to Afghanistan, can cause serious infections. To determine risk for US military members in Afghanistan, we reviewed records for September-December 2011. Among 126 animal bites and exposures, 10 were monkey bites. Command emphasis is vital for preventing monkey bites; provider training and bite reporting promote postexposure treatment.

This pilot study investigated the prevalence and specific reasons for usage of complementary and alternative medicine (CAM) among patients of a dental school clinic. Four hundred and two patients completed a 30-page survey on CAM usage. A higher rate of CAM usage was found in this dental school clinic population than rates previously reported in a general population. More than three-quarters (76.1%) of the respondents reported using at least one CAM treatment in the past 12 months; 93.3% reported using at least one CAM treatment at some time in their lives. High rates of chiropractic use were found in this population. Tooth pain was the most frequently reported dental condition motivating CAM use. About 10% of dental school clinic patients use topical oral herbal and/or natural products to treat dental conditions, most frequently for preventive/oral health reasons or for tooth pain., (© 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.)

High-concentration solar-power optics require precise two-axis tracking. The planar micro-optic solar concentrator uses a lenslet array over a planar waveguide with small reflective facets at the focal point of each lenslet to couple incident light into the waveguide. The concentrator can use conventional tracking, tilting the entire assembly, but the system geometry also allows tracking by small lateral translation of the lenslet relative to the waveguide. Here, we experimentally demonstrate such microtracking with the existing concentrator optics and present optimized optical designs for systems with higher efficiency and angle range.

Background: Moderate to severe chronic hand dermatitis (CHD) is not well controlled by current medical strategies; however, recent studies have shown significant improvement in patients treated with up to 6 months of oral alitretinoin (9-cis-retinoic acid). The results of longer-term continuous treatment are lacking., Objective: To evaluate the long-term safety and efficacy of alitretinoin for the treatment of CHD., Methods: The Physician's Global Assessment (PGA) and Modified Total Lesion Symptom Score (MTLSS) were used to assess CHD improvement in three patients treated with alitretinoin (10-30 mg/d). Patients had routine bloodwork and were monitored for adverse events., Results: Significant improvement in MTLSS scores (≈ 76%) was seen at 2 months (p < .002) and maintained for the 3-year treatment period with occasional dosage adjustments. No significant adverse events developed that necessitated treatment withdrawal., Conclusion: Alitretinoin was well tolerated in the treatment of these three CHD patients who were carefully monitored over this prolonged treatment period.

Background: Hidradenitis suppurativa (HS) is a severe chronic inflammatory follicular disease characterized by nodules and abscesses affecting apocrine gland-bearing regions. HS is not well-controlled with conventional medical therapies such as topical therapy, oral antibiotics and retinoids, however, abrogation of tumour necrosis factor-α (TNF-α) function has proven effective in some patients., Objective: To assess the safety and efficacy of the interleukin-12/23 inhibitor, ustekinumab for treatment of HS in three patients with moderate-severe disease., Methods: The subjects received 3-45 mg subcutaneous injections of ustekinumab at 0, 1 and 4 months. Improvement was assessed by the dermatology life quality index (DLQI), visual analogue scale of pain (VAS) and physician's global assessment (PGA) at each monthly visit., Results: Prior to treatment, subjects had moderate-severe HS (Hurley stage II-III) with a DLQI score between 8 and 12. At 6 months, one patient showed complete disease remission, while a 25-49% improvement was seen in a second patient and no change in a third. A moderate but statistically significant relationship was observed between VAS and DLQI scores (r=0.75; P<0.01)., Conclusion: Ustekinumab may provide a safe and effective new treatment strategy for HS in some patients. Interleukin 12/23 inhibition is a potential therapeutic option for patients in which other therapies prove ineffective., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Étendue limits angular acceptance of high-concentration photovoltaic systems and imposes precise two-axis mechanical tracking. We show how a planar micro-optic solar concentrator incorporating a waveguide cladding with a nonlinear optical response to sunlight can reduce mechanical tracking requirements. Optical system designs quantify the required response: a large, slow, and localized increase in index of refraction. We describe one candidate materials system: a suspension of high-index particles in a low-index fluid combined with a localized space-charge field to increase particle density and average index. Preliminary experiments demonstrate an index change of aqueous polystyrene nanoparticles in response to a low voltage signal and imply larger responses with optimized nanofluidic materials.

Objective: Radial artery harvesting has been questioned because of purported long-term circulatory consequences. Previous midterm Doppler ultrasonographic results are inconsistent regarding ulnar arterial effects. Flow-mediated vasodilatation more sensitively measures response to shear stress as index of arterial reactivity and function., Methods: We contacted 231 patients who had undergone radial artery harvesting at least 10 years previously (mean follow-up, 12.9 ± 0.8 years). Subcohort of 25 volunteers (mean age, 69.2 ± 8.4 years) underwent ultrasonographic evaluation of ipsilateral (harvest) and contralateral (control) ulnar arteries. Flow-mediated vasodilatation compared changes in ulnar arterial diameters before and after occlusion., Results: In subcohort, peak systolic velocity of harvest ulnar artery was 0.82 ± 0.15 m/s, versus 0.63 ± 0.23 m/s on control side (P < .001), with no differences in intimomedial thickness (P = .763) or presence of atherosclerotic plaques (P = .364). Baseline diameter of harvest ulnar artery was 3.0 ± 0.5 mm, versus 2.7 ± 0.6 mm on control side (P = .007). Postocclusion diameter of harvest ulnar artery was 3.2 ± 0.5 mm, versus 2.9 ± 0.6 mm on control side (P = .001). No differences were seen in preocclusion and postocclusion absolute and percentage changes in ulnar arterial diameter (Table 1)., Conclusions: Despite increased shear stress, no deterioration in either ulnar arterial structure or functional reactivity was measured by flow-mediated vasodilatation more than 10 years after radial artery harvesting. With appropriate preoperative evaluation, radial arterial grafting for coronary artery bypass grafting is not associated with long-term donor limb vascular insufficiency., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The ability of bacteria to utilize ethanolamine (EA) as a carbon and nitrogen source may confer an advantage for survival, colonization, and pathogenicity in the human intestinal tract. Enterococcus faecalis, a Gram-positive human commensal organism, depends on a two-component signaling system (TCS-17) for sensing EA and regulating the expression of the ethanolamine utilization genes. Multiple promoters participate in eut gene expression in the presence of EA as the sole carbon source and cobalamin (CoB12), an essential cofactor in the enzymatic degradation process. By means of in vivo and in vitro approaches, this study characterized the transcriptional activity identified in the eutT-eutG intergenic region of the E. faecalis eut cluster. Two novel promoters in this region were shown to be active in vivo. The distal P2-1 promoter was associated with a B12 riboswitch that terminated transcription in the presence of CoB12. Transcription elongation from the proximal P2-2 promoter was regulated by antitermination mediated by the phosphorylated form of the response regulator of TCS-17 (RR17). 3'-Rapid amplification of cDNA ends (RACE) analyses of the terminated RNA products allowed precise identification of the hairpin loop structures involved in termination/antitermination. The results uncovered the role of the B12 riboswitch and RR17 in eut gene expression, adding to the complexity of this regulatory pathway and extending the knowledge of possible means of transcription regulation in Gram-positive organisms.

Evidence-based practice (EBP) incorporates use of the best scientific knowledge, expert opinion, clinician experience, and patient preferences to facilitate the best patient outcomes in healthcare. Recent studies have suggested that nurses lack the skills and expertise to facilitate EBP in a meaningful way. This replication study (n = 225) investigated the EBPs of gastroenterology nurses in the United States. Findings generally support the previous studies that suggest nurses do not yet possess the skills or resources to implement EBP. Recommendations for addressing this deficit in the specialty of gastroenterology nursing are discussed.