Corrugated graphene exposes the limits of a widely used ab initio van der Waals DFT functional

Theoretical formulations capable of modeling chemical interactions over 3–4 orders of magnitude of bond strength, from covalent to van der Waals (vdW) forces, are one of the primary goals in materials physics, and chemistry. Development of vdW corrections for density-functional theory has thus been a major research field for two decades. While many of these corrections are semiempirical, more theoretically rigorous ab initio functionals have been developed. The ab initio functional vdW-DF2, when coupled with the reoptimized B86 exchange function (vdW-DF2-rB86), has typically performed as well, if not better than most semiempirical formulations. Here we present a system, Co intercalation of graphene on Ir(111), for which a semiempirical correction predicts local corrugation maxima in locations at which the vdW-DF2-rB86 functional predicts global minima. Sub-angstrom precision quantitative structural measurements show better agreement with the semiempirical correction. We posit that it is balancing the weak vdW interaction with the stronger, even covalent, interactions that proves a challenge for the vdW-DF2-rB86 functional

Improvement of lower extremity electrodiagnostic findings following a trial of spinal manipulation and motion-based therapy

BACKGROUND: Lumbar disc herniation is a problem frequently encountered in manual medicine. While manual therapy has shown reasonable success in symptomatic management of these cases, little information is known how manual therapy may affect the structure and function of the lumbar disc itself. In cases where lumbar disc herniation is accompanied by radicular symptoms, electrodiagnostic testing has been used to provide objective clinical information on nerve function. This report examines the treatment rendered for a patient with lower extremity neurological deficit, as diagnosed on electrodiagnostic testing. Patient was treated using spinal manipulation and exercises performed on a Pettibon Wobble Chair™, using electrodiagnostic testing as the primary outcome assessment. CASE PRESENTATION: An elderly male patient presented to a private spine clinic with right-sided foot drop. He had been prescribed an ankle-foot orthosis for this condition. All sensory, motor, and reflex findings in the right leg and foot were absent. This was validated on prior electromyography and nerve conduction velocity testing, performed by a board certified neurologist. Patient was treated using spinal manipulation twice-weekly and wobble chair exercises three times daily for 90 days total. Following this treatment, the patient was referred for follow-up electrodiagnostic studies. Significant improvements were made in these studies as well as self-rated daily function. CONCLUSION: Motion-based therapies, as part of a comprehensive rehabilitation program, may contribute to the restoration of daily function and the reversal of neurological insult as detected by electrodiagnostic testing. Electrodiagnostic testing may be a useful clinical tool to evaluate the progress of chiropractic patients with lumbar disc herniation and radicular pain syndromes

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988–1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50–70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N+) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N+ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N+ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01–0.39) in the 2–7 mm size category to 0.95 (0.64–1.40) in the 18–22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase

The Challenges of the External Vote

UID/CPO/04627/2019Over the last few decades, emigrants all over the world have gained expanded voting rights. Despite the normative debates about this issue, there are few empirical studies on why states decide to implement external voting and how electoral systems perform. This chapter seeks to fill this gap by looking at the Portuguese case. Our study suggests that a combination of political and socio-economic factors explains the implementa tion of external voting. On the other hand, the interests of political parties and the low level of civil society engagement are key factors in the failure of both electoral reforms and attempts to overcome the shortcomings of external voting.publishersversionpublishe

Adverse events from spinal manipulation in the pregnant and postpartum periods: a critical review of the literature

<p>Abstract</p> <p>Background</p> <p>The safety of spinal manipulation during pregnancy and the postpartum periods has been a matter of debate among manual therapists. Spinal manipulative therapy during these periods is a commonly performed intervention as musculoskeletal pain is common in these patients. To date there has not been an evaluation of the literature on this topic exclusively.</p> <p>Methods</p> <p>A literature search was conducted on PubMed, CINAHL and the Index to Chiropractic Literature along with reference searching for articles published in English and French in the peer-reviewed literature that documented adverse effects of spinal manipulation during either pregnancy or postpartum. Case reports, case series, and any other clinical study designs were deemed acceptable for inclusion, as were systematic reviews. The appropriate Scottish Intercollegiate Guidelines Network (SIGN) tools were used to rate included articles for quality when applicable.</p> <p>Results</p> <p>Five articles identifying adverse events in seven subjects following spinal manipulation were included in this review, along with two systematic reviews. The articles were published between 1978 and 2009. Two articles describing adverse effects from spinal manipulation on two postpartum patients were included, while the remaining three articles on five patients with adverse effects following spinal manipulation were on pregnant patients. Injury severity ranged from minor injury such as increasing pain after treatment that resolved within a few days to more severe injuries including fracture, stroke, and epidural hematoma. SIGN scores of the prospective observational cohort study and systematic reviews indicated acceptable quality.</p> <p>Conclusions</p> <p>There are only a few reported cases of adverse events following spinal manipulation during pregnancy and the postpartum period identified in the literature. While improved reporting of such events is required in the future, it may be that such injuries are relatively rare.</p

A Combined Synthetic-Fibrin Scaffold Supports Growth and Cardiomyogenic Commitment of Human Placental Derived Stem Cells

Aims: A potential therapy for myocardial infarction is to deliver isolated stem cells to the infarcted site. A key issue with this therapy is to have at one\u27s disposal a suitable cell delivery system which, besides being able to support cell proliferation and differentiation, may also provide handling and elastic properties which do not affect cardiac contractile function. In this study an elastic scaffold, obtained combining a poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating polymeric network (s-IPN) with fibrin, was used as a substrate for in vitro studies of human amniotic mesenchymal stromal cells (hAMSC) growth and differentiation. Methodology/Principal Findings: After hAMSC seeding on the fibrin side of the scaffold, cell metabolic activity and proliferation were evaluated by WST-1 and bromodeoxyuridine assays. Morphological changes and mRNAs expression for cardiac differentiation markers in the hAMSCs were examined using immunofluorescence and RT-PCR analysis. The beginning of cardiomyogenic commitment of hAMSCs grown on the scaffold was induced, for the first time in this cell population, by a nitric oxide (NO) treatment. Following NO treatment hAMSCs show morphological changes, an increase of the messenger cardiac differentiation markers [troponin I (TnI) and NK2 transcription factor related locus 5 (Nkx2.5)] and a modulation of the endothelial markers [vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR)]. Conclusions/Significance: The results of this study suggest that the s-IPN PEtU-PDMS/fibrin combined scaffold allows a better proliferation and metabolic activity of hAMSCs cultured up to 14 days, compared to the ones grown on plastic dishes. In addition, the combined scaffold sustains the beginning of hAMSCs differentiation process towards a cardiomyogenic lineage

Trazodone regulates neurotrophic/growth factors, mitogen-activated protein kinases and lactate release in human primary astrocytes

Background: In the central nervous system, glial cells provide metabolic and trophic support to neurons and respond to protracted stress and insults by up-regulating inflammatory processes. Reactive astrocytes and microglia are associated with the pathophysiology of neuronal injury, neurodegenerative diseases and major depression, in both animal models and human brains. Several studies have reported clear anti-inflammatory effects of anti-depressant treatment on astrocytes, especially in models of neurological disorders. Trazodone (TDZ) is a triazolopyridine derivative that is structurally unrelated to other major classes of antidepressants. Although the molecular mechanisms of TDZ in neurons have been investigated, it is unclear whether astrocytes are also a TDZ target. Methods: The effects of TDZ on human astrocytes were investigated in physiological conditions and following inflammatory insult with lipopolysaccharide (LPS) and tumour necrosis factor-aα (TNF-aα). Astrocytes were assessed for their responses to pro-inflammatory mediators and cytokines, and the receptors and signalling pathways involved in TDZ-mediated effects were evaluated. Results: TDZ had no effect on cell proliferation, but it decreased pro-inflammatory mediator release and modulated trophic and transcription factor mRNA expression. Following TDZ treatment, the AKT pathway was activated, whereas extracellular signal-regulated kinase and c-Jun NH2-terminal kinase were inhibited. Most importantly, a 72-h TDZ pre-treatment before inflammatory insult completely reversed the anti-proliferative effects induced by LPS-TNF-aα. The expression or the activity of inflammatory mediators, including interleukin-6, c-Jun NH2-terminal kinase and nuclear factor ΚB, were also reduced. Furthermore, TDZ affected astrocyte metabolic support to neurons by counteracting the inflammation-mediated lactate decrease. Finally, TDZ protected neuronal-like cells against neurotoxicity mediated by activated astrocytes. These effects mainly involved an activation of 5-HT1A and an antagonism at 5-HT2A/C serotonin receptors. Fluoxetine, used in parallel, showed similar final effects nevertheless it activates different receptors/intracellular pathways. Conclusions: Altogether, our results demonstrated that TDZ directly acts on astrocytes by regulating intracellular signalling pathways and increasing specific astrocyte-derived neurotrophic factor expression and lactate release. TDZ may contribute to neuronal support by normalizing trophic and metabolic support during neuroinflammation, which is associated with neurological diseases, including major depression

Drosophila IAP1-Mediated Ubiquitylation Controls Activation of the Initiator Caspase DRONC Independent of Protein Degradation

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition (“undead” cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in “undead” cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics

The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomic