Phase diagram of a model of the protein amelogenin

There has been considerable recent interest in the self-assembly and phase behavior of models of colloidal and protein particles with anisotropic interactions. One example of particular interest is amelogenin, an important protein involved in the formation of dental enamel. Amelogenin is primarily hydrophobic with a 25-residue charged C-terminus tail. This protein undergoes a hierarchical assembly process that is crucial to mineral deposition, and experimental work has demonstrated that the deletion of the C-terminus tail prevents this self-assembly. A simplified model of amelogenin has been proposed in which the protein is treated as a hydrophobic sphere, interacting via the Asakura-Oosawa (AO) potential, with a tethered point charge on its surface. In this paper, we examine the effect of the Coulomb interaction between the point charges in altering the phase diagram of the AO model. For the parameter case specific to amelogenin, we find that the previous in vitro experimental and model conditions correspond to the system being near the low-density edge of the metastable region of the phase diagram. Our study illustrates more generally the importance of understanding the phase diagram for proteins, in that the kinetic pathway for self-assembly and the resulting aggregate morphology depends on the location of the initial state in the phase diagram.

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The initial magnetic susceptibility of polydisperse ferrofluids: A comparison between experiment and theory over a wide range of concentration

Temperature dependencies of the static initial magnetic susceptibility for ferrofluids at various concentrations are studied using experiment and statistical-mechanical theories. Magnetic susceptibility measurements are carried out for twelve samples of magnetite-based fluids stabilized with oleic acid over a wide range of temperatures (210 K ≲T ≲ 390 K); all samples have the same granulometric composition but different volume ferroparticle concentrations (0.2 ≲ φ ≲ 0.5). Experimental results are analyzed using three theories: the second-order modified mean-field theory (MMF2) [A. O. Ivanov and O. B. Kuznetsova, Phys. Rev. E 64, 41405 (2001)]; its correction for polydisperse ferrofluids arising from Mayer-type cluster expansion and taking into account the first terms of the polydisperse second virial coefficient [A. O. Ivanov and E. A. Elfimova, J. Magn. Magn. Mater 374, 327 (2015)]; and a new theory based on MMF2 combined with the first terms of the polydisperse second and third virial contributions to susceptibility. It turns out that the applicability of each theory depends on the experimental sample density. If twelve ferrofluid samples are split into three groups of strong, moderate, and low concentrated fluids, the temperature dependences of the initial magnetic susceptibility in each group are very precisely described by one of the three theories mentioned above. The determination of a universal formula predicting a ferrofluid susceptibility over a broad range of concentrations and temperatures remains as a challenge.

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The second virial coefficient and critical point behavior of the Mie Potential

Aspects of the second virial coefficient, b 2, of the Mie m : n potential are investigated. The Boyle temperature, T 0, is shown to decay monotonically with increasing m and n, while the maximum temperature, Tmax, exhibits a minimum at a value of m which increases as n increases. For the 2n : n special case T 0 tends to zero and Tmax approaches the value of 7.81 in the n → ∞ limit which is in quantitative agreement with the expressions derived in Rickayzen and Heyes [J. Chem. Phys. 126, 114504 (2007)] in which it was shown that the 2n : n potential in the n → ∞ limit approaches Baxter's sticky-sphere model. The same approach is used to estimate the n − dependent critical temperature of the 2n : n potential in the large n limit. The ratio of T 0 to the critical temperature tends to unity in the infinite n limit for the 2n : n potential. The rate of convergence of expansions of b 2 about the high temperature limit is investigated, and they are shown to converge rapidly even at quite low temperatures (e.g., 0.05). In contrast, a low temperature expansion of the Lennard-Jones 12 : 6 potential is shown to be an asymptotic series. Two formulas that resolve b 2 into its repulsive and attractive terms are derived. The convergence at high temperature of the Lennard-Jones b 2 to the m = 12 inverse power value is slow (e.g., requiring T ≃ 10⁴ just to attain two significant figure accuracy). The behavior of b 2 of the ∞ : n and the Sutherland potential special case, n = 6, is explored. By fitting to the exact b 2 values, a semiempirical formula is derived for the temperature dependence of b 2 of the Lennard-Jones potential which has the correct high and low temperature limits.

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Collective dynamic dipole moment and orientation fluctuations, cooperative hydrogen bond relaxations, and their connections to dielectric relaxation in ionic acetamide deep eutectics: Microscopic insight from simulations

The paper reports a detailed simulation study on collective reorientational relaxation, cooperative hydrogen bond (H-bond) fluctuations, and their connections to dielectric relaxation (DR) in deep eutectic solvents made of acetamide and three uni-univalent electrolytes, lithium nitrate (LiNO3), lithium bromide (LiBr), and lithium perchlorate (LiClO4). Because cooperative H-bond fluctuations and ion migration complicate the straightforward interpretation of measured DR timescales in terms of molecular dipolar rotations for these conducting media which support extensive intra- and inter-species H-bonding, one needs to separate out the individual components from the overall relaxation for examining the microscopic origin of various timescales. The present study does so and finds that reorientation of ion-complexed acetamide molecules generates relaxation timescales that are in sub-nanosecond to nanosecond range. This explains in molecular terms the nanosecond timescales reported by recent giga-Hertz DR measurements. Interestingly, the simulated survival timescale for the acetamide-Li⁺ complex has been found to be a few tens of nanosecond, suggesting such a cation-complexed species may be responsible for a similar timescale reported by mega-Hertz DR measurements of acetamide/potassium thiocyanate deep eutectics near room temperature. The issue of collective versus single particle relaxation is discussed, and jump waiting time distributions are determined. Dependence on anion-identity in each of the cases has been examined. In short, the present study demonstrates that assumption of nano-sized domain formation is not required for explaining the DR detected nanosecond and longer timescales in these media.

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Translation-rotation states of H2 in C60: New insights from a perturbation-theory treatment

We report an investigation of the translation-rotation (TR) level structure of H2 entrapped in C60, in the rigid-monomer approximation, by means of a low-order perturbation theory (PT). We focus in particular on the degree to which PT can accurately account for that level structure, by comparison with the variational quantum five-dimensional calculations. To apply PT to the system, the interaction potential of H2@C60 is decomposed into a sum over bipolar spherical tensors. A zeroth-order Hamiltonian, , is then constructed as the sum of the TR kinetic-energy operator and the one term in the tensor decomposition of the potential that depends solely on the radial displacement of the H2 center of mass (c.m.) from the cage center. The remaining terms in the potential are treated as perturbations. The eigenstates of , constructed to also account for the coupling of the angular momentum of the H2 c.m. about the cage center with the rotational angular momentum of the H2 about the c.m., are taken as the PT zeroth-order states. This zeroth-order level structure is shown to be an excellent approximation to the true one except for two types of TR-level splittings present in the latter. We then show that first-order PT accounts very well for these splittings, with respect to both their patterns and magnitudes. This allows one to connect specific features of the level structure with specific features of the potential-energy surface, and provides important new physical insight into the characteristics of the TR level structure.

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Computational simulations of hydrogen circular migration in protonated acetylene induced by circularly polarized light

The hydrogens in protonated acetylene are very mobile and can easily migrate around the C2 core by moving between classical and non-classical structures of the cation. The lowest energy structure is the T-shaped, non-classical cation with a hydrogen bridging the two carbons. Conversion to the classical H2CCH⁺ ion requires only 4 kcal/mol. The effect of circularly polarized light on the migration of hydrogens in oriented C2H3 ⁺ has been simulated by Born-Oppenheimer molecular dynamics. Classical trajectory calculations were carried out with the M062X/6-311+G(3df,2pd) level of theory using linearly and circularly polarized 32 cycle 7 μm cosine squared pulses with peak intensity of 5.6 × 10¹³ W/cm² and 3.15 × 10¹³ W/cm², respectively. These linearly and circularly polarized pulses transfer similar amounts of energy and total angular momentum to C2H3 ⁺. The average angular momentum vectors of the three hydrogens show opposite directions of rotation for right and left circularly polarized light, but no directional preference for linearly polarized light. This difference results in an appreciable amount of angular displacement of the three hydrogens relative to the C2 core for circularly polarized light, but only an insignificant amount for linearly polarized light. Over the course of the simulation with circularly polarized light, this corresponds to a propeller-like motion of the three hydrogens around the C2 core of protonated acetylene.

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How polarizabilities and C6 coefficients actually vary with atomic volume

In this work, we investigate how atomic C 6 coefficients and static dipole polarizabilities α scale with effective volume. We show, using confined atoms covering rows 1-5 of the periodic table, that and (for volume ), where , α^R, and V^R are the reference values and effective volume of the free atom. The scaling exponents pZ and vary substantially as a function of element number Z = N, in contrast to the standard "rule of thumb" that pZ = 2 and . Remarkably, we find that the polarizability and C 6 exponents p′ and p are related by p′ ≈ p − 0.615 rather than the expected p′ ≈ p/2. Results are largely independent of the form of the confining potential (harmonic, cubic, and quartic potentials are considered) and kernel approximation, justifying this analysis.

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Reverse energy partitioning—An efficient algorithm for computing the density of states, partition functions, and free energy of solids

A robust and model free Monte Carlo simulation method is proposed to address the challenge in computing the classical density of states and partition function of solids. Starting from the minimum configurational energy, the algorithm partitions the entire energy range in the increasing energy direction ("upward") into subdivisions whose integrated density of states is known. When combined with the density of states computed from the "downward" energy partitioning approach [H. Do, J. D. Hirst, and R. J. Wheatley, J. Chem. Phys. 135, 174105 (2011)], the equilibrium thermodynamic properties can be evaluated at any temperature and in any phase. The method is illustrated in the context of the Lennard-Jones system and can readily be extended to other molecular systems and clusters for which the structures are known.

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Eigenvector method for umbrella sampling enables error analysis

Umbrella sampling efficiently yields equilibrium averages that depend on exploring rare states of a model by biasing simulations to windows of coordinate values and then combining the resulting data with physical weighting. Here, we introduce a mathematical framework that casts the step of combining the data as an eigenproblem. The advantage to this approach is that it facilitates error analysis. We discuss how the error scales with the number of windows. Then, we derive a central limit theorem for averages that are obtained from umbrella sampling. The central limit theorem suggests an estimator of the error contributions from individual windows, and we develop a simple and computationally inexpensive procedure for implementing it. We demonstrate this estimator for simulations of the alanine dipeptide and show that it emphasizes low free energy pathways between stable states in comparison to existing approaches for assessing error contributions. Our work suggests the possibility of using the estimator and, more generally, the eigenvector method for umbrella sampling to guide adaptation of the simulation parameters to accelerate convergence.

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The influence of the “cage” effect on the mechanism of reversible bimolecular multistage chemical reactions proceeding from different sites in solutions

Manifestations of the "cage" effect at the encounters of reactants have been theoretically treated on the example of multistage reactions (including bimolecular exchange reactions as elementary stages) proceeding from different active sites in liquid solutions. It is shown that for reactions occurring near the contact of reactants, consistent consideration of quasi-stationary kinetics of such multistage reactions (possible in the framework of the encounter theory only) can be made on the basis of chemical concepts of the "cage complex," just as in the case of one-site model described in the literature. Exactly as in the one-site model, the presence of the "cage" effect gives rise to new channels of reactant transformation that cannot result from elementary event of chemical conversion for the given reaction mechanism. Besides, the multisite model demonstrates new (as compared to one-site model) features of multistage reaction course.

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Fas/FasL gene polymorphism in patients with Hashimoto’s thyroiditis in Turkish population

Abstract

Objective

Hashimoto's disease is a polygenic disorder with complex etiopathogenesis. Apoptosis is proposed as one of its mechanisms. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. This study aims to evaluate the influence of Fas and FasL gene polymorphism in Hashimoto's thyroiditis in Turkish population.

Materials and methods

A total of 112 patients with Hashimoto's thyroiditis and 112 cases of healthy control people were included in this study. The evaluation of genotype for Fas -670 A/G and FasL 843 C/T gene polymorphism was performed by using PCR-RFLP method.

Results

The FAS genotype and gene allele frequency distribution did differ between the control group (AA 36.6 %, AG 50.0 %, GG 13.4 %, A 61.6 %, G 38.4 %) and the Hashimoto's thyroiditis patients (AA 21.4 %, AG 50.9 %, GG 27.7 %, A 46.9 %, G 53.1 %) (p < 0.01). The evaluation of FasL genotype and gene allele frequency did not show statistically significant difference between the patient group (CC 27.7 %, CT 45.5 %, TT 26.8 %, C 50.4 %, T 49.6 %) and control group (CC 33.9 %, CT 44.6 %, TT 21,4 %, C 56.3 %, T 43.8 %) (p > 0.05).

Conclusions

Gene polymorphism of Fas and G allele frequency may play a role in the regulation of apoptosis in thyroid autoimmune disorders. There is a need for further studies to clarify the genetic role of apoptosis in HT.

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Adapting another person’s affective state modulates brain potentials to unpleasant pictures

Publication date: Available online 29 August 2016
Source:Biological Psychology
Author(s): Sandra Paul, Tanja Endrass, Norbert Kathmann, Daniela Simon
Emotional processing is influenced by top-down processes such as reappraisal of emotion-inducing events. Besides one's own stimulus appraisal, information from the social environment can be used to modify the stimulus' meaning. This study investigated whether perspective taking changes participants' brain potentials to unpleasant pictures. Event-related potentials (ERPs) were measured while twenty-nine participants evaluated arousal of neutral or negative pictures. Subsequently, they received bogus feedback about another persons' picture evaluation. Then, the same picture was presented again and participants were instructed to view the picture from the other person's perspective. Higher bogus- versus self-ratings of picture arousal increased P300 and late positive potential (LPP) amplitudes to unpleasant stimuli, whereas lower bogus- versus self-ratings did not influence ERPs. Thus, perspective taking only modulated ERPs when bogus ratings signaled potential underestimation of arousal. Resulting increases in responsiveness might constitute an adaptive mechanism preparing the organism against harm.



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Directory: AAO Officers and Organizations

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Information for readers

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Psychosocial impact of dental esthetics regulates motivation to seek orthodontic treatment

The aim of this study was to evaluate the psychosocial impact of dental esthetics for adults seeking orthodontic treatment.

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Editorial Board

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Efficiency of Class II subdivision malocclusion treatment with 3 and 4 premolar extractions

In this study, we compared the efficiency of Class II subdivision malocclusion treatment with symmetric and asymmetric extractions.

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Table of Contents

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In-vitro impact of insertion angle on primary stability of miniscrews

The use of miniscrews as anchorage has become increasingly popular, but there is no consensus on the best insertion angle. The purpose of this study was to determine the impact of insertion angle on implant primary stability.

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First recipient of the Lifetime Achievement Award for Orthodontic Research

As you may recall, the American Association of Orthodontists (AAO) established a new award in 2015 entitled the Lifetime Achievement Award for Orthodontic Research. Early in 2016, nominations were solicited to identify persons with the following characteristics. Nominees should be those who have made significant contributions to the science related to the specialty of orthodontics. Their research would be considered original, outstanding, or innovative. Additional consideration was to be given to those who have established a legacy of research and discovery that is inspiring to the academic community.

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Neuropsychiatric Disturbances in Alzheimer’s Disease: What Have We Learned from Neuropathological Studies?

Neuropsychiatric symptoms (NPS) are an integral part of the dementia syndrome and were therefore recently included in the core diagnostic criteria of dementia. The near universal prevalence of NPS in Alzheimer's disease (AD), combined with their disabling effects on patients and caregivers, is contrasted by the fact that few effective and safe treatments exist, which is in part to be attributed to our incomplete understanding of the neurobiology of NPS. In this review, we describe the pathological alterations typical for AD, including spreading and evolution of burden, effect on the molecular and cellular integrity, functional consequences and atrophy of NPS-relevant brain regions and circuits in correlation with specific NPS assessments. It is thereby clearly established that NPS are fundamental expressions of the underlying neurodegenerative brain disease and not simply reflect the patients' secondary response to their illness. Neuropathological studies, moreover, include a majority of end-stage patient samples, which may not correctly represent the pathophysiological environment responsible for particular NPS that may already be present in an early stage, or even prior to AD diagnosis. The burdensome nature and high prevalence of NPS, in combination with the absence of effective and safe pharmacotherapies, provide a strong incentive to continue neuropathological and neurochemical, as well as imaging and other relevant approaches to further improve our apprehension of the neurobiology of NPS.

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Butyrylcholinesterase as a Diagnostic and Therapeutic Target for Alzheimer’s Disease

The serine hydrolase butyrylcholinesterase (BChE), like the related enzyme acetylcholinesterase (AChE), co-regulates metabolism of the neurotransmitter acetylcholine. In the human brain BChE is mainly expressed in white matter and glia and in distinct populations of neurons in regions that are important in cognition and behavior, functions compromised in Alzheimer's disease (AD). AD is a neurodegenerative disorder causing dementia with no cure nor means for definitive diagnosis during life. In AD, BChE is found in association with pathology, such as β-amyloid (Aβ) plaques, particularly in the cerebral cortex where BChE is not normally found in quantity. Up to 30% of cognitively normal older adults have abundant Aβ deposition in the brain. We have designed an imaging agent that can detect, through autoradiography, BChE-associated Aβ plaques in the cerebral cortex of AD brains, but does not visualize Aβ plaques in brains of cognitively normal individuals. Furthermore, in an AD mouse model with BChE gene knocked out, there are up to 70% fewer fibrillar Aβ brain plaques, suggesting diminished BChE activity could prove beneficial as a curative approach to AD. To that end, we have examined numerous N-10-carbonyl phenothiazines that are specific inhibitors of human BChE, revealing important details of the enzyme's active site gorge. These phenothiazines can be designed without potential side effects caused by neurotransmitter receptor interactions. In conclusion, BChE is potentially an important target for diagnosis and treatment of AD.

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IL-17F regulates psoriasis-associated genes through IκBζ

Abstract

Psoriasis is a common chronic inflammatory and immune-mediated skin disease. Antagonists of TNFα and, recently, IL-17 have proven to be highly effective in the treatment of psoriasis; however, the molecular mechanisms involved in the pathogenesis of psoriasis are poorly understood. Recently, we presented evidence that IκBζ is a key regulator in the development of psoriasis through its role in mediating IL-17A-driven effects. Like IL-17A, IL-17F is produced by a variety of immune cells, and the expression of IL-17F is increased in psoriatic skin. The purpose of this study was to characterize the role of IL-17F in the regulation of IκBζ expression and to investigate whether IL-17F regulates psoriasis-associated genes in human keratinocytes through IκBζ. Here, we demonstrate that IL-17F stimulation induces IκBζ expression at both the mRNA and the protein levels in normal human keratinocytes. Moreover, silencing IκBζ by siRNA revealed that IκBζ is a key regulator of specific IL-17F-inducible psoriasis-associated genes and proteins, including DEFB4/hBD2, S100A7, CCL20, IL-8 and CHI3L1. In addition, IL-17F-induced IκBζ expression is mediated by a mechanism involving the p38 MAPK and NF-κB signalling pathways, as shown by the clear reduction in IL-17F-mediated expression of IκBζ during chemical inhibition of these two signalling pathways. In summary, we present IκBζ as a novel key regulator of IL-17F-driven effects in psoriasis. Thus, antagonists to IκBζ could potentially provide a more targeted approach for treating psoriasis as well as for treating the other inflammatory and immune-mediated diseases for which IL-17-targeting drugs have recently been approved.

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Targeting of NADPH oxidase in vitro and in vivo suppresses fibroblast activation and experimental skin fibrosis

Abstract

Although there is increasing evidence that oxidative stress is involved in collagen synthesis and myofibroblast activation the NADPH oxidase (Nox) system is incompletely investigated in the context of human dermal fibroblasts (HDFs) and skin fibrosis. Using the pan-Nox inhibitor diphenyleneiodonium (DPI) as an initial tool we show that gene expression of collagen type I, α-smooth muscle actin (α-SMA) and fibronectin 1 is suppressed in HDFs. Detailed expression analysis of all Nox isoforms and adaptors revealed expression of RNA and protein expression of Nox4, p22^phox, and Poldip2 but neither Nox1 nor Nox2. Nox4 could be immnolocalized to the endoplasmic reticulum. Importantly, TGF-β₁ had a dose- and time-dependent upregulating effect on NADH activity and Nox4 gene expression in HDFs. Genetic silencing of Nox4 as demonstrated by siRNA in HDFs as well as in murine fibroblasts established from Nox4 knock-out mice confirmed that TGF-β₁-mediated collagen type I gene, α-SMA and fibronectin 1 gene expression was Nox4-dependent. This TGF-β₁ effect was mediated by Smad3 as shown by in silico promoter analysis, pharmacological inhibition, and gene silencing of Smad3. The relevance of these findings is highlighted in the bleomycin-induced scleroderma mouse model. DPI treatment attenuated skin fibrosis and myofibroblast activation. Moreover, Nox4 knock-down by siRNA reduced skin collagen synthesis, α-SMA and fibronectin 1 expression in vivo. Finally, analyses of HDFs from patients with systemic sclerosis confirmed the expression of Nox4 and its adaptors whereas Nox1 and Nox2 were not detectable. Our findings indicate that Nox4 targeting is a promising future treatment for fibrotic skin diseases.

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The efficacy of electrical stimulation in lower extremity cutaneous wound healing: a systematic review

Abstract

Current gold standard lower extremity cutaneous wound management is not always effective. Cutaneous wounds generate a "current of injury" which is directly involved in wound healing processes. Application of exogenous electrical stimulation has been hypothesised to imitate the natural electric current that occurs in cutaneous wounds. The aim of this extensive review is to provide a detailed update on the variety of electrical stimulation modalities used in the management of lower extremity wounds. Several different waveforms and delivery methods of electrical stimulation have been used. Pulsed current appears superior to other electrical modalities available. The majority of studies support the beneficial effects of pulsed current over conservative management of lower extremity cutaneous wounds. Although it appears to have no benefit over causal surgical intervention, it is a treatment option which could be utilised in those patients unsuitable for surgery. Other waveforms and modalities appear promising; however, they still lack large trial data to recommend a firm conclusion with regards to their use. Current studies also vary in quantity, quality and protocol across the different modalities. The ideal electrical stimulation device needs to be non-invasive, portable, cost effective and provide minimal interference with patients' daily life. Further studies are necessary to establish the ideal electrical stimulation modality, parameters, method of delivery and duration of treatment. The development and implementation of newer devices in the management of acute and chronic wounds provides an exciting direction in the field of electrotherapy.

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The pathogenesis of pemphigus: controversy versus complexity

Life is highly complex and, as quantum physics would predict, follows the rule of "everything is possible with varying probabilities". Accordingly, science may be sometimes as confusing as political debates, where the same matter is addressed in different and misleading ways even in the absence of a real controversy. The Viewpoint by Ahmed et al. provides a paradigmatic example of a debate about two theories for pemphigus pathogenesis, i.e. "Monopathogenic vs. multipathogenic explanations of pemphigus pathophysiology", both being possible but occurring with variable probabilities (1).

This article is protected by copyright. All rights reserved.

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Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR-exposed human skin: a randomised controlled study

Abstract

Langerhans cells (LC) are sentinels of skin's immune system, their loss from epidermis contributing to UVR-suppression of cell mediated immunity (CMI). Omega-3 polyunsaturated fatty acids show potential to abrogate UVR-suppression of CMI in mice and humans, potentially through modulation of LC migration. Our objectives were to examine if eicosapentaenoic acid (EPA) ingestion influences UV-mediated effects on epidermal LC numbers and levels of immunomodulatory mediators including prostaglandin (PG)D₂, which is expressed by LC.

In a double-blind randomised controlled study, healthy individuals took 5g EPA-rich (n=40) or control (n=33) lipid for 12-weeks; UVR exposed and unexposed skin samples were taken pre- and post-supplementation. Epidermal LC numbers were assessed by immunofluorescence for CD1a, and skin blister fluid PG and cytokines quantified by LC-MS/MS and Luminex assay, respectively. Pre-supplementation, UVR reduced mean (SEM) LC number/mm² from 913 (28) to 322 (40) (p<0.001), and mean PGD₂ level by 37% from 8.1 (11.6) to 5.1 (5.6) pg/μl; p<0.001), while IL-8 level increased (p<0.001). Despite confirmation of EPA bioavailability in red blood cells and skin in the active group, no between-group effect of EPA was found on UVR-modulation of LC numbers, PGD₂ or cytokine levels post-supplementation.

Thus no evidence was found for EPA abrogation of photoimmunosuppression through an impact on epidermal LC numbers. Intriguingly, UVR-exposure substantially reduced cutaneous PGD₂ levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD₂ levels could reflect LC loss from the epidermis and/or altered dendritic cell activity, and may be relevant for phototherapy of skin disease.

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Is there a relation between autonomic nervous system activity and skin aging? Evaluation of heart rate variability and skin aging in 209 elderly subjects

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PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes

PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes

Modern Pathology 29, 1104 (September 2016). doi:10.1038/modpathol.2016.95

Authors: Matthew W Rosenbaum, Jacob R Bledsoe, Vicente Morales-Oyarvide, Tiffany G Huynh & Mari Mino-Kenudson

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The flowering of pathology as a medical discipline in Boston, 1892-c.1950: W.T. Councilman, FB Mallory, JH Wright, SB Wolbach and their descendants

The flowering of pathology as a medical discipline in Boston, 1892-c.1950: W.T. Councilman, FB Mallory, JH Wright, SB Wolbach and their descendants

Modern Pathology 29, 944 (September 2016). doi:10.1038/modpathol.2016.91

Authors: David N Louis, Michael J O'Brien & Robert H Young

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The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes

The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes

Modern Pathology 29, 1058 (September 2016). doi:10.1038/modpathol.2016.98

Authors: Olca Basturk, Marcus Tan, Umesh Bhanot, Peter Allen, Volkan Adsay, Sasinya N Scott, Ronak Shah, Michael F Berger, Gokce Askan, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Carlie Sigel, Christine Iacobuzio-Donahue & David S Klimstra

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KCC3 axonopathy: neuropathological features in the central and peripheral nervous system

KCC3 axonopathy: neuropathological features in the central and peripheral nervous system

Modern Pathology 29, 962 (September 2016). doi:10.1038/modpathol.2016.90

Authors: Roland N Auer, Janet L Laganière, Yves O Robitaille, John Richardson, Patrick A Dion, Guy A Rouleau & Masoud Shekarabi

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Poor outcome of hepatocellular carcinoma with stemness marker under hypoxia: resistance to transarterial chemoembolization

Poor outcome of hepatocellular carcinoma with stemness marker under hypoxia: resistance to transarterial chemoembolization

Modern Pathology 29, 1038 (September 2016). doi:10.1038/modpathol.2016.111

Authors: Hyungjin Rhee, Ji Hae Nahm, Haeryoung Kim, Gi Hong Choi, Jeong Eun Yoo, Hye Sun Lee, Myoung Ju Koh & Young Nyun Park

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Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

Modern Pathology 29, 977 (September 2016). doi:10.1038/modpathol.2016.93

Authors: Heewon A Kwak, Xiuli Liu, Daniela S Allende, Rish K Pai, John Hart & Shu-Yuan Xiao

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Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria

Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria

Modern Pathology 29, 1083 (September 2016). doi:10.1038/modpathol.2016.94

Authors: Joanne K L Rutgers, Andres A Roma, Kay J Park, Richard J Zaino, Abbey Johnson, Isabel Alvarado, Dean Daya, Golnar Rasty, Teri A Longacre, Brigitte M Ronnett & Elvio G Silva

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Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

Modern Pathology 29, 985 (September 2016). doi:10.1038/modpathol.2016.115

Authors: Snjezana Dogan, Lu Wang, Ryan N Ptashkin, Robert R Dawson, Jatin P Shah, Eric J Sherman, R Michael Tuttle, James A Fagin, David S Klimstra, Nora Katabi & Ronald A Ghossein

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Inside the USCAP Journals

Inside the USCAP Journals

Modern Pathology 29, 942 (September 2016). doi:10.1038/modpathol.2016.142

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Significance of myelodysplastic syndrome-associated somatic variants in the evaluation of patients with pancytopenia and idiopathic cytopenias of undetermined significance

Significance of myelodysplastic syndrome-associated somatic variants in the evaluation of patients with pancytopenia and idiopathic cytopenias of undetermined significance

Modern Pathology 29, 996 (September 2016). doi:10.1038/modpathol.2016.100

Authors: Sebastian Fernandez-Pol, Lisa Ma, Robert S Ohgami & Daniel A Arber

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Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas

Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas

Modern Pathology 29, 1050 (September 2016). doi:10.1038/modpathol.2016.114

Authors: Xuejun Tian, Ashley Pelton, Ali Shahsafaei & David M Dorfman

http://ift.tt/2bCc70v

Region of interest identification and diagnostic agreement in breast pathology

Region of interest identification and diagnostic agreement in breast pathology

Modern Pathology 29, 1004 (September 2016). doi:10.1038/modpathol.2016.85

Authors: Dilip B Nagarkar, Ezgi Mercan, Donald L Weaver, Tad T Brunyé, Patricia A Carney, Mara H Rendi, Andrew H Beck, Paul D Frederick, Linda G Shapiro & Joann G Elmore

http://ift.tt/2byAcrO

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup

Modern Pathology 29, 1070 (September 2016). doi:10.1038/modpathol.2016.99

Authors: Jen-Chieh Lee, Tzu-Pin Lu, Chun A Changou, Cher-Wei Liang, Hsien-Neng Huang, Alexandra Lauria, Hsuan-Ying Huang, Chin-Yao Lin, Ying-Cheng Chiang, Ben Davidson, Ming-Chieh Lin & Kuan-Ting Kuo

http://ift.tt/2bCc4Sn

Genomic profiling of malignant phyllodes tumors reveals aberrations in FGFR1 and PI-3 kinase/RAS signaling pathways and provides insights into intratumoral heterogeneity

Genomic profiling of malignant phyllodes tumors reveals aberrations in FGFR1 and PI-3 kinase/RAS signaling pathways and provides insights into intratumoral heterogeneity

Modern Pathology 29, 1012 (September 2016). doi:10.1038/modpathol.2016.97

Authors: Su-Yang Liu, Nancy M Joseph, Ajay Ravindranathan, Bradley A Stohr, Nancy Y Greenland, Poonam Vohra, Elizabeth Hosfield, Iwei Yeh, Eric Talevich, Courtney Onodera, Jessica A Van Ziffle, James P Grenert, Boris C Bastian, Yunn-Yi Chen & Gregor Krings

http://ift.tt/2byB8fJ

Interferon-Related Depression: A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem

Background: Depression is among the commonest of psychiatric disorders, and inflammatory mechanisms have been suggested to play a role in its pathophysiology. Interferons are a superfamily of proinflammatory cytokines that play a role in host defence mechanisms. Interferons are used in the treatment of a variety of autoimmune (e.g. multiple sclerosis), viral (e.g. chronic hepatitis B and C), and malignant (e.g. malignant melanoma, hairy cell leukemia) disorders; depression, however, is a notable and clinically troublesome adverse effect. </p><p> Objective: This article seeks to present a simple explanation and update for the reader about what interferons are, how interferons are classified, the clinical conditions in which interferons are used, the occurrence of depression as a clinical adverse effect of interferon therapy, possible mechanisms that explain interferon-related depression, the treatment of interferon-related depression, and the prevention of interferon-related depression. </p><p> Methods: A qualitative literature review is presented. </p><p> Results and Conclusions: Irrespective of the indication for IFN therapy, IFNs are associated with a 30- 70% risk of treatment-emergent depression. This risk could be due to the IFN, or to an interaction between the IFN and the indication for which it was prescribed. Various neurohormonal, neurochemical, neurohistological, and other mechanisms have been put forth to explain IFN-related depression. Prophylactic treatment with antidepressants reduces the risk of IFN-related depression; antidepressants also effectively treat the condition. Recent alternatives to IFNs have shown to decrease the risk of treatment-emergent depression. </p><p>

http://ift.tt/2c5555n

Stress, the Autonomic Nervous System, and the Immune-kynurenine Pathway in the Etiology of Depression

The autonomic nervous system is one of the major neural pathways activated by stress. In situations that are often associated with chronic stress, such as major depressive disorder, the sympathetic nervous system can be continuously activated without the normal counteraction of the parasympathetic nervous system. As a result, the immune system can be activated with increased levels of proinflammatory cytokines. These inflammatory conditions have been repeatedly observed in depression. In the search for the mechanism by which the immune system might contribute to depression, the enhanced activity of indoleamine 2,3- dioxygenase by pro-inflammatory cytokines has been suggested to play an important role. Indoleamine 2,3-dioxygenase is the first enzyme in the kynurenine pathway that converts tryptophan to kynurenine. Elevated activity of this enzyme can cause imbalances in downstream kynurenine metabolites. This imbalance can induce neurotoxic changes in the brain and create a vulnerable glial-neuronal network, which may render the brain susceptible to depression. This review focuses on the interaction between stress, the autonomic nervous system and the immune system which can cause imbalances in the kynurenine pathway, which may ultimately lead to major depressive disorder.

http://ift.tt/2bxk0tz

Animal Models of Maternal Immune Activation in Depression Research

Background: Depression and schizophrenia are debilitating mental illnesses with significant socio-economic impact. The high degree of comorbidity between the two disorders, and shared symptoms and risk factors, suggest partly common pathogenic mechanisms. Supported by human and animal studies, maternal immune activation (MIA) has been intimately associated with the development of schizophrenia. However, the link between MIA and depression has remained less clear, in part due to the lack of appropriate animal models. </p><p> Objective: Here we aim to summarize findings obtained from studies using MIA animal models and discuss their relevance for preclinical depression research. </p><p> Methods: Results on molecular, cellular and behavioral phenotypes in MIA animal models were collected by literature search (PubMed) and evaluated for their significance for depression. </p><p> Results: Several reports on offspring depression-related behavioral alterations indicate an involvement of MIA in the development of depression later in life. Depression-related behavioral phenotypes were frequently paralleled by neurogenic and neurotrophic deficits and modulated by several genetic and environmental factors. </p><p> Conclusion: Literature evidence analyzed in this review supports a relevance of MIA as animal model for a specific early life adversity, which may prime an individual for the development of distinct psychopathologies later life. MIA animal models may present a unique tool for the identification of additional exogenous and endogenous factors, which are required for the manifestation of a specific neuropsychiatric disorder, such as depression, later in life. Hereby, novel insights into the molecular mechanisms involved in the pathophysiology of depression may be obtained, supporting the identification of alternative therapeutic strategies. </p><p>

http://ift.tt/2bSND5F

A Potential Contribution of Chemokine Network Dysfunction to the Depressive Disorders

In spite of many years of research, the pathomechanism of depression has not yet been elucidated. Among many hypotheses, the immune theory has generated a substantial interest. Up till now, it has been thought that depression is accompanied by the activation of inflammatory response and increase in pro-inflammatory cytokine levels. However, recently this view has become controversial, mainly due to the family of small proteins called chemokines. They play a key role in the modulation of peripheral function of the immune system by controlling immune reactions, mediating immune cell communication, and regulating chemotaxis and cell adhesion. Last studies underline significance of chemokines in the central nervous system, not only in the neuromodulation but also in the regulation of neurodevelopmental processes, neuroendocrine functions and in mediating the action of classical neurotransmitters. Moreover, it was demonstrated that these proteins are responsible for maintaining interactions between neuronal and glial cells both in the developing and adult brain also in the course of diseases. </p><p> This review outlines the role of chemokine in the central nervous system under physiological and pathological conditions and their involvement in processes underlying depressive disorder. It summarizes the most important data from experimental and clinical studies. </p><p>

http://ift.tt/2bSObII

Radioimmunotherapy with 131 I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma

Abstract

Purpose

The aim of this study was to assess the clinical activity and toxicity of ¹³¹I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone).

Methods

Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled.

Results

A total of 16 patients were enrolled and treated with a single dose of ¹³¹I-rituximab as consolidation therapy after the completion of six or eight cycles of R-CHOP between December 2005 and June 2011. This trial was terminated before the scheduled enrollment owing to low recruitment. Among the 16 patients who were treated with consolidative ¹³¹I-rituximab, 6 achieved complete response (CR) after three cycles of R-CHOP, and another 9 patients further achieved CR after the completion of six or eight cycles of R-CHOP. During the median follow-up period of 73 months, only four patients (25 %) experienced relapse. Two-year relapse-free survival was 88 %, and 5-year relapse-free survival was 81 %. Grade 3 or 4 treatment-related toxicity occurred in four patients and included neutropenia and thrombocytopenia.

Conclusions

¹³¹I-rituximab showed promising efficacy as consolidation treatment for patients with DLBCL. A future randomized phase III study to confirm our results is warranted.

http://ift.tt/2copBCD

QSAR and Molecular Modeling Studies on a Series of Indole-based Pyridone Analogues as HCV NS5B Polymerase Inhibitors

Quantitative structure-activity relationship (QSAR) and molecular modeling studies have been performed on a series of indole-based pyridone analogues as hepatitis C virus (HCV) NS5B polymerase inhibitors. A multiple linear regression (MLR) analysis has shown that the presence of hydrogen- bond donors in the molecule plays a negative role, but the substituents present on the indole ring sterically favor the activity of indole-based pyridine analogues. Using the MLR analysis model, some new analogues of indole-based pyridone with better potency have been predicted. Docking study has been performed on all the predicted compounds to study their binding modes with the receptor.

http://ift.tt/2bORiCs

International Journal of Cosmetic Science

Original Articles

Dynamics of glycerin and water transport across human skin from binary mixtures Stephanie A. Ventura and Gerald B. Kasting Accepted manuscript online: 26 AUG 2016 10:35PM EST | DOI: 10.1111/ics.12362

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

International Forum of Allergy & Rhinology

Original Articles

Prediction of the originating site of sinonasal inverted papilloma by preoperative magnetic resonance imaging and computed tomography Gaoli Fang, Hongfei Lou, Wenling Yu, Xiangdong Wang, Bentao Yang, Junfang Xian, Xiaohong Song, Erzhong Fan, Ying Li, Chengshuo Wang and Luo Zhang Version of Record online: 25 AUG 2016 | DOI: 10.1002/alr.21836 The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q): a validated 6-item questionnaire as a diagnostic aid for empty nose syndrome patients Nathalia Velasquez, Andrew Thamboo, Al-Rahim R. Habib, Zhenxiao Huang and Jayakar V. Nayak Version of Record online: 24 AUG 2016 | DOI: 10.1002/alr.21842 Association of olfactory dysfunction in chronic rhinosinusitis with economic productivity and medication usage Rodney J. Schlosser, Kristina A. Storck, Luke Rudmik, Timothy L. Smith, Jess C. Mace, Jose Mattos and Zachary M. Soler Version of Record online: 23 AUG 2016 | DOI: 10.1002/alr.21841 The pain–depression dyad and the association with sleep dysfunction in chronic rhinosinusitis Daniel R. Cox, Shaelene Ashby, Jess C. Mace, John M. DelGaudio, Timothy L. Smith, Richard R. Orlandi and Jeremiah A. Alt Version of Record online: 23 AUG 2016 | DOI: 10.1002/alr.21843 Factors impacting cerebrospinal fluid leak rates in endoscopic sellar surgery Tom T. Karnezis, Andrew B. Baker, Zachary M. Soler, Sarah K. Wise, Shruthi K. Rereddy, Zara M. Patel, Nelson M. Oyesiku, John M. DelGaudio, Constantinos G. Hadjipanayis, Bradford A. Woodworth, Kristen O. Riley, John Lee, Michael D. Cusimano, Satish Govindaraj, Alkis Psaltis, Peter John Wormald, Steve Santoreneos, Raj Sindwani, Samuel Trosman, Janalee K. Stokken, Troy D. Woodard, Pablo F. Recinos, W. Alexander Vandergrift III and Rodney J. Schlosser Version of Record online: 23 AUG 2016 | DOI: 10.1002/alr.21783 Immunoglobulin replacement therapy reduces chronic rhinosinusitis in patients with antibody deficiency Jarrett E. Walsh, Jose G. Gurrola II, Scott M. Graham, Sarah L. Mott and Zuhair K Ballas Version of Record online: 23 AUG 2016 | DOI: 10.1002/alr.21839

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com