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Κυριακή 29 Ιανουαρίου 2017

An MR-compatible gyroscope-based arm movement tracking system

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Publication date: Available online 29 January 2017
Source:Journal of Neuroscience Methods
Author(s): S.Iman Shirinbayan, Jochem W. Rieger
BackgroundFunctional magnetic resonance imaging is well suited to link neural population activation with movement parameters of complex natural arm movements. However, currently existing MR-compatible arm tracking devices are not constructed to measure arm joint movement parameters of unrestricted movements. Therefore, to date most research focuses on simple arm movements or includes very little knowledge about the actual movement kinematics.New methodWe developed a low cost gyroscope-based arm movement tracking system (GAMTS) that features MR-compatibility. The system consists of dual-axis analogue gyroscopes that measure rotations of upper and lower arm joints. After MR artifact reduction, the rotation angles of the individual arm joints are calculated and used to animate a realistic arm model that is implemented in the OpenSim platform. The OpenSim platform can then provide the kinematics of any point on the arm model.ResultsIn order to demonstrate the capabilities of the system, we first assessed the quality of reconstructed wrist movements in a low-noise environment where typical MR-related problems are absent and finally, we validated the reconstruction in the MR environment.Comparison with existing methodsThe system provides the kinematics of the whole arm when natural unrestricted arm movements are performed inside the MR-scanner.ConclusionThe GAMTS is reliably capable of reconstructing the kinematics of trajectories and the reconstruction error is small in comparison with the movement induced variation of speed, displacement, and rotation. Moreover, the system can be used to probe brain areas for their correlation with movement kinematics.



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The Plastic Surgery Compass: Navigating the Reconstructive Ladder in the Personalized Health Care Era

imageSummary: The reconstructive ladder and the reconstructive elevator have withstood the test of time as didactic tools for resident education. Over time, many alternative models have been suggested to incorporate the technological advances in plastic surgery, but none of them have focused on the patient. Changes in practice and the trend toward personalized health care demand a 360-degree evaluation and solution of surgical problems incorporating patient-specific characteristics. We, therefore, suggest the concept of the plastic surgery compass to navigate the ladder.

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Metallurgical-based prediction of stress-temperature induced rapid heating and cooling phase transformations for high speed machining Ti-6Al-4V alloy

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Qingqing Wang, Zhanqiang Liu, Dong Yang, Aziz Ul Hassan Mohsan
Local phase transformations of materials during mechanical machining influence the variation of surface integrity directly. The aim of this work is to investigate the relationship between cutting parameters and phase transformations during high speed machining (HSM) of Ti-6Al-4V. Rapid heating and cooling phase transformation models are firstly proposed based on phase transformation dynamics. Then, the proposed models are implemented into the Ti-6Al-4V cutting simulation model as a user subroutine of Abaqus/Explicit. The simulated results indicate that, in the chip formation process, β phase volume fraction increases from 8% to 90% in the serrated chips and the machined surface at the cutting speed range of 50–600m/min. In the rapid cooling process, the ratio of the transformed α" phase is about 4%. Finally, comparisons of the simulated results and high speed cutting experiments indicate that the developed models can precisely predict the phase transformations during HSM Ti-6Al-4V. The results help to get deeper insights into understanding the phase transformation mechanisms during HSM o Ti-6Al-4V. The research can also provide an instruction for optimizing the cutting parameters to control the surface integrity in machining of Ti-6Al-4V.

Graphical abstract

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The effects of hydroporation on melasma with anti-aging cocktail

Summary

Background

Jet-M is a device for epidermal peeling and is used to deliver substances by spraying air and microdroplets. Previously, a case was treated with a mixed solution of copper-GHK, oligo-hyaluronic acid, Rhodiola extract, tranexamic acid, and β-glucan. The results showed significant improvement of aged skin.

Aims

This study was conducted to evaluate the effects of hydroporation on melasma with the formulation in a small group of volunteers.

Methods

Clinical effects were evaluated by both subjective and objective methods including melanin index (MI) and erythema index (EI) measurement.

Results

Clinically, pigmentation and erythema were relieved and also both MI and EI decreased. Histopathologic observation revealed that type IV collagen and procollagen were increased in the upper dermis. Furthermore, the number of p63-positive cells is increased along the basement membrane. These results all suggest that hydroporation with GHR formulation induced anti-aging effects by reconstruction of extracellular matrix.

Conclusion

These findings suggest that the treatment may have depigmenting effects and erythema decreasing effects by enhancing the microenvironment of the skin.



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Acne RA-1,2, a novel UV-selective face cream for patients with acne: Efficacy and tolerability results of a randomized, placebo-controlled clinical study

Summary

Background

General skincare measures such as the use of moisturisers and products containing adequate photoprotection are important components of acne patients' management to complement the pharmacological regimen. Acne RA-1,2 is a novel dermato-cosmetic product which contains selective photofilters and active ingredients against the multifactorial pathophysiology of acne.

Objectives

To evaluate the tolerability of Acne RA-1,2 and its effect on the clinical signs of acne.

Methods

This double-blind, placebo-controlled study randomized 40 adult patients with 10-25 comedones per half face to once-daily application of Acne RA-1,2 or placebo for 8 weeks. Evaluations after 4 and 8 weeks included the number of comedones, transepidermal water loss (TEWL), sebum production, and tolerability.

Results

In the Acne RA-1,2 group, there was a significant 35% decrease in the mean number of comedones from 26 at baseline to 17 at Week 8 (P<.001), a 7% significant reduction in TEWL (9.32 to 8.66 g/h/m2; P<.001), and a 24% significant reduction in sebum production (154.8 to 117.6 μg/cm2; P<.001). The reductions in TEWL and sebum production were significantly greater than those in the placebo group at Weeks 4 and 8 (P<0.05). There were no adverse events.

Conclusions

Acne RA-1,2 was well tolerated and effective at reducing comedones and sebum production and improving epidermal barrier function. These results suggest that Acne RA-1,2 is useful against acne-prone facial skin, particularly as it targets sebum production, which topical pharmacological acne therapies do not address.



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Glassy dynamics in polymers

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Publication date: Available online 29 January 2017
Source:Materials Today
Author(s): David Bradley




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The recent structure-based coarse graining of polymer melts using PRISM theory does not give thermodynamic consistency

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Qiang Wang, Delian Yang
The full thermodynamic consistency claimed by Guenza and co-workers in their recent papers (J. McCarty et al., Macromolecules 45 (2012) 8482; A. J. Clark et al., Phys. Rev. Lett. 109 (2012) 168301; and A. J. Clark et al., J. Chem. Phys. 139 (2013) 124906), where they performed structure-based coarse graining of homopolymer melts using the polymer reference interaction site model theory, directly contradicts the well-established and widely cited finding by several research groups. In this Communication, we clearly showed that (1) the full thermodynamic consistency claimed by Guenza and co-workers is simply due to the (incorrect) approximations used in their analytical derivation, (2) none of their criticisms on our work (D. Yang, Q. Wang, J. Chem. Phys. 142 (2015) 054905) given in their Comment (A. J. Clark et al., J. Chem. Phys. 143 (2015) 067101) is valid, and (3) the simulation-free coarse-graining strategy presented in our work is crucially different from the coarse-graining approach in their recent papers.

Graphical abstract

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Hybrid peptides in the landscape of drug discovery

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Publication date: Available online 29 January 2017
Source:Peptides
Author(s): Daniel Fourmy




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Evaluation of cognitive performance in professional divers by means of event-related potentials and neuropsychology

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Mehmet Ergen, Atilla Uslu, Ozlem Caglar, Sukriye Akca-Kalem, Maide Cimsit, Hakan Gurvit
ObjectiveWe investigated whether professional air diving with no decompression illness causes any long-term changes in cognitive functions.MethodsThe all-male participants consisted of 18 healthy control (HC) volunteers and 32 divers. Divers were divided into two subgroups as moderate exposure group, Divers-I (DI) and extensive exposure group, Divers-II (DII). Participants were administered a comprehensive neuropsychological battery and event-related potentials (ERPs) were recorded while they performed auditory oddball task and visual continuous performance test (CPT).ResultsP3 waves in oddball and CPT were significantly attenuated and peak latencies were prolonged in both diver groups compared with HC. Amplitude decrements in CPT P3 were graded with respect to level of diving exposure. Neuropsychologically, DII group displayed significantly poorer performance than HC and DI groups in measures of visuo-constructional and visual long-term memory tests. DI group performed better than HC group in some measures of planning ability.ConclusionsMost of the changes in neurophysiological measures and poorer neuropsychological performance were found in DII group, and this might be interpreted as a red flag for the reflection of the slowly progressing deleterious effects of silent bubbles in brain function.SignificanceThis study reports impairments in certain neuropsychological measures and apparent neurophysiological markers pointing to slow cognitive decline referring to long-term effects of diving.



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Corticokinematic coherence as a new marker for somatosensory afference in newborns

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Eero Smeds, Sampsa Vanhatalo, Harri Piitulainen, Mathieu Bourguignon, Veikko Jousmäki, Riitta Hari
ObjectiveSomatosensory evoked potentials have high prognostic value in neonatal intensive care, but their recording from infants is challenging. Here, we studied the possibility to elicit cortical responses in newborns by simple passive hand movements.MethodsWe examined 13 newborns (postnatal age 1–46 days) during clinically indicated 19-channel electroencephalography (EEG) recordings in the neonatal intensive care unit; EEG indications included birth asphyxia and suspected epileptic seizures. The experimenter moved the infant's wrist or fingers at 1 or 2 Hz for 5–10 min, separately on both sides. We measured movement kinematics with an accelerometer attached to the infant's hand, and computed coherence between the EEG and acceleration signals (corticokinematic coherence, CKC).ResultsStatistically significant CKC (amplitude 0.020–0.511) with characteristic scalp topography was observed in all infants at twice the movement frequency. CKC was contralaterally dominant on the central scalp (median laterality index 0.53 for right-hand and –0.63 for left-hand movements).ConclusionsPassive movements elicit cortical responses that can be readily observed in clinical EEG recordings from newborns in the intensive care environment.SignificanceCKC is a novel, noninvasive marker for the somatosensory system. Its robustness and practical ease make it attractive for bedside assessment of neurologically compromised newborns.



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Sharpening a classic scalpel to face the growth of Alzheimer’s dementia

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Tarek K. Rajji




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Status Epilepticus after Cardiac Arrest: Some Strides

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): G. Bryan Young




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Peripheral nerve ultrasonography in patients with transthyretin amyloidosis

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Simon Podnar, Stayko Sarafov, Ivailo Tournev, Gregor Omejec, Janez Zidar
ObjectiveTo systematically study peripheral nerve morphology in patients with transthyretin (TTR) amyloidosis and TTR gene mutation carriers using high-resolution ultrasonography (US).MethodsIn this prospective cross-sectional study we took a structured history, performed neurological examination, and measured peripheral nerve cross-sectional areas (CSAs) bilaterally at 28 standard locations using US. Demographic and US findings were compared to controls.ResultsPeripheral nerve CSAs were significantly larger in 33 patients with familial amyloid polyneuropathy (FAP) compared to 50 controls, most dramatically at the common entrapment sites (median nerve at the wrist, ulnar nerve at the elbow), and in the proximal nerve segments (median nerve in the upper arm, sciatic nerve in the thigh). Findings in 21 asymptomatic TTR gene mutation carriers were less marked compared to controls, with CSAs being larger only in the median nerve in the upper arm. Nerve CSAs correlated with abnormalities on nerve conduction studies.ConclusionUsing US, we confirmed previous pathohistological and imaging reports in FAP of the most pronounced peripheral nerve thickening in the proximal limb segments.SignificanceSimilar to US findings in diabetic and vasculitic neuropathies these predominantly proximal locations of nerve thickening may be attributed to ischaemic nerve damage caused by poor perfusion in the watershed zones along proximal limb segments.



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Effects of tDCS on motor learning and memory formation: a consensus and critical position paper

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Ethan R Buch, Emiliano Santarnecchi, Andrea Antal, Jan Born, Pablo A Celnik, Joseph lassen, Christian Gerloff, Mark Hallett, Friedhelm C Hummel, Michael A Nitsche, Alvaro Pascual-Leone, Walter J Paulus, Janine Reis, Edwin M Robertson, John C Rothwell, Marco Sandrini, Heidi M Schambra, Eric M Wassermann, Ulf Ziemann, Leonardo G Cohen
Motor skills are required for activities of daily living. Transcranial direct current stimulation (tDCS) applied in association with motor skill learning has been investigated as a tool for enhancing training effects in health and disease. Here, we review the published literature investigating whether tDCS can facilitate the acquisition, retention or adaptation of motor skills. Work in multiple laboratories is underway to develop a mechanistic understanding of tDCS effects on different forms of learning and to optimize stimulation protocols. Efforts are required to improve reproducibility and standardization. Overall, reproducibility remains to be fully tested, effect sizes with present techniques vary over a wide range, and the basis of observed inter-individual variability in tDCS effects is incompletely understood. It is recommended that future studies explicitly state in the Methods the exploratory (hypothesis-generating) or hypothesis-driven (confirmatory) nature of the experimental designs. General research practices could be improved with prospective pre-registration of hypothesis-based investigations, more emphasis on the detailed description of methods (including all pertinent details to enable future modeling of induced current and experimental replication), and use of post-publication open data repositories. A checklist is proposed for reporting tDCS investigations in a way that can improve efforts to assess reproducibility.



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Cyclic seizures in critically ill patients: clinical correlates, DC recordings and outcomes

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Lecio F Pinto, Emily J Gilmore, Ognen A Petroff, Adithya Sivaraju, Nishi Rampal, Lawrence J Hirsch, Nicolas Gaspard
ObjectiveTo describe EEG and clinical correlates, DC recordings and prognostic significance of cyclic seizures (CS).MethodsWe reviewed our prospective continuous EEG database to identify patients with CS, controls with non-cyclic status epilepticus (SE) and controls without seizure matched for age and etiology. EEG was reviewed with DC settings.Results39/260 (15%) patients with electrographic seizures presented with CS. These patients were older (62 vs 54 yrs.; p=0.04) and more often had acute or progressive brain injury (77% vs 52%; p=0.03) than patients with non-cyclic SE and had a lower level of consciousness, were more severely ill, than matched controls. CS almost always had focal onset, often from posterior regions. Patients with CS trended towards worse prognosis. When available (12 patients), DC recordings showed an infraslow cyclic oscillation of EEG baseline synchronized to the seizures in all cases.ConclusionsCS occur mostly in older patients with acute or progressive brain injury, are more likely to be associated with poor outcome than patients with other forms of nonconvulsive SE, and are accompanied by synchronous oscillations of the EEG baseline on DC recordings.SignificanceCS are a common form of non-convulsive status epilepticus in critically ill patients and provide further insights into the relationship between infraslow activity and seizures; further study on this relationship may shed light on the mechanisms of seizure initiation and termination.



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Event-related brain potential indices of cognitive function and brain resource reallocation during working memory in patients with Multiple Sclerosis

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Thomas J. Covey, Janet L. Shucard, David W. Shucard
ObjectiveTo examine event-related brain potentials (ERPs) in Multiple Sclerosis (MS) during a visual n-back working memory (WM) task, and test the hypothesis that compensatory brain function may be associated with variance in task performance in MS patients.MethodsMidline ERPs for 25 MS patients and 18 HCs were obtained for a visual n-back task that placed increasing demands on WM. N-back behavioral measures and neuropsychological performance measures of WM were also obtained.ResultsMS patients had slower reaction times (RTs) than HCs during the n-back task. Accuracy on the n-back and on neuropsychological tests did not differ between groups. P3 ERP amplitude decreased for both groups as WM demand increased. MS patients had lower overall P1 and P3 amplitudes compared to HCs. In MS, anteriorization of P3 amplitude was associated with better n-back performance. P1 and P3 amplitudes were also related to neuropsychological test performance in MS.ConclusionsMS patients had reduced ERP amplitude compared to HCs during the n-back, and changes in ERP anterior-posterior midline amplitude distribution in MS were associated with cognitive performance.SignificanceERPs, and in particular the P3 component obtained during a visual n-back task, are sensitive to subtle WM dysfunction in MS and may reflect compensatory reallocation of brain resources.



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Diagnostic yield of ambulatory EEGs in the elderly

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Benjamin Tolchin, Jong Woo Lee, Milena Pavlova, Barbara A. Dworetzky, Rani A. Sarkis R
ObjectiveThe diagnostic yield of ambulatory EEG in the elderly is not known. We sought to determine diagnostic yield and identify factors predicting diagnostic findings in this elderly population.MethodsWe reviewed 156 consecutive 24-72 hour ambulatory EEGs performed on patients aged 60 or older.ResultsOf the 156 studies, 58 studies (37%) revealed potentially diagnostic findings: either epileptiform discharges, an epileptic seizure, or a typical nonepileptic event. Focal slowing on routine EEG predicted epileptiform abnormalities on ambulatory EEG with an odds ratio of 4.0 (95% CI 1.7 – 9.7, p=0.002). Age, the presence of a focal lesion on MRI, and duration of ambulatory EEG failed to predict epileptiform abnormalities on ambulatory EEG.Duration of ambulatory EEG predicted capture of a typical nonepileptic event with an odds ratio of 2.7 (95% CI 1.3 - 5.7, p=0.009) for every additional day of study duration.ConclusionsFocal slowing on routine EEGs may warrant an ambulatory EEG in the setting of diagnostic uncertainty.Longer ambulatory EEGs have a higher yield in capturing patients' typical non-epileptic events, and should be considered in patients where nonepileptic events are a likely diagnostic possibility.Signficance: These findings offer guidance in the use of ambulatory EEGs in the elderly.



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Epileptiform Abnormalities Predict Delayed Cerebral Ischemia in Subarachnoid Hemorrhage

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): J.A. Kim, E.S. Rosenthal, S. Biswal, S. Zafar, A.V. Shenoy, K.L. O'Connor, S.C. Bechek, J. Valdery Moura, M.M. Shafi, A.B. Patel, S.S. Cash, M.B. Westover
ObjectiveTo identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI).MethodsRetrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI).ResultsOur data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI.ConclusionsThus, IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH.SignificanceThese findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development.



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Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

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Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Gregor Thut, Til Ole Bergmann, Flavio Fröhlich, Surjo R. Soekadar, John-Stuart Brittain, Antoni Valero-Cabré, Alexander Sack, Carlo Miniussi, Andrea Antal, Hartwig Roman Siebner, Ulf Ziemann, Christoph S. Herrmann
Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges.



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Reversible brain atrophy in glutaric aciduria type 1

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Publication date: Available online 29 January 2017
Source:Brain and Development
Author(s): Yurika Numata-Uematsu, Osamu Sakamoto, Yosuke Kakisaka, Yukimune Okubo, Yoshitsugu Oikawa, Natsuko Arai-Ichinoi, Shigeo Kure, Mitsugu Uematsu
Glutaric aciduria type 1 (GA1) is a rare metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase. The typical clinical onset features an acute encephalopathic crisis developed in early childhood, causing irreversible striatal injury. Recently, tandem mass spectrometry of spots of dried blood has allowed pre-symptomatic detection of GA1 in newborns. Early treatment can prevent irreversible neurological injury. We report the case of a girl with GA1 who exhibited a characteristic reversible change upon brain magnetic resonance imaging (MRI). She was diagnosed with GA1 as a newborn. She commenced dietary carnitine and her intake of lysine and tryptophan were reduced at the age of 4weeks. After treatment commenced, her mean glutarylcarnitine level was lower than that in the previous reports. The plasma lysine and tryptophan levels were maintained below the normal ranges. At 4months, brain MRI revealed a widened operculum with dilatation of the subarachnoid spaces surrounding the atrophic bilateral frontotemporal lobes; this is typical of GA1 patients. However, at 17months, MRI revealed that the atrophic lesion had disappeared and she subsequently underwent normal maturation. She has never suffered a metabolic decompensation episode. At 26months, her development and brain MRI were normal. The present reversible brain atrophy in a patient with GA1 indicates that early dietary modifications with a lower level of glutarylcarnitine and administration of carnitine can lead to normal development.



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The role of dietary polyphenols in the management of erectile dysfunction–Mechanisms of action

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Chinedum Eleazu, Nwite Obianuju, Kate Eleazu, Winner Kalu
The incidence of erectile dysfunction (ED) is on the increase and it is estimated that it will affect about 322 million men globally by the year 2025 if adequate measures are not taken to curb it. Natural polyphenols in plant based diets have gained public interest in recent times due to their roles in the prevention of various disease that implicate free radicals/reactive oxygen species and recently on ED. However, the role of polyphenols in the management of ED has not been explored due perhaps to limited data available. Hence this study which reviewed the role of dietary polyphenols in the management of ED and their mechanisms of action. Literature search was carried out in several electronic data bases such as Pubmed, Google Scholar, Medline, Agora and Hinari from1972 to 2016 to identify the current status of knowledge on the role of polyphenols in the management of erectile dysfunction. Progress made so far in this direction suggests inhibition of arginase, acetylcholinesterase, angiotensin converting enzyme, rho-kinase II; activation of endothelial and neuronal NO synthase; decreased synthesis of luteinizing hormone and testosterone reduction; activation of silent information regulator 2-related enzymes (sirtuin1) as well as free radical/reactive oxygen species inhibition as the mechanisms through which the polyphenols identified in this review exert beneficial roles in the management of ED.



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Timing of Initiation of Adjuvant Chemotherapy for Gastric Cancer: A Case-Matched Comparison Study of Laparoscopic vs. Open Surgery

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Publication date: Available online 29 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Akio Kaito, Takahiro Kinoshita, Kouhei Shitara, Hidehito Shibasaki, Toshirou Nishida
BackgroundLaparoscopic gastrectomy (LG) is reported to be associated with faster recovery than open gastrectomy (OG); however, the influence of the surgical approach on initiation timing of adjuvant chemotherapy (AC) remains unclear.MethodsThis was a single-institutional retrospective observational study. Patients with pathological stage II/III gastric cancer undergoing LG with D2 lymphadenectomy (LG group: n=74) were matched 1:1 with patients selected from 214 similar patients undergoing OG (OG group: n=74), identically matching gender, age, pathological stage, and type of gastrectomy, and comparing AC initiation timing between the two groups. Factors associated with delayed initiation of AC were investigated in a multivariable analysis.ResultsAC was performed in 86.5% (LG) and 83.8% (OG) of patients (p=0.64). The median time interval before AC was significantly shorter in the LG vs. OG group (5.7 vs. 6.6 weeks, respectively, p<0.001), and significantly more patients received AC within 6 weeks (60.8% vs. 27.0%, p<0.001). Independent factors associated with delayed initiation of AC (>6 weeks) were: morbidity (≥grade 3a; odds ratio (OR): 16.1, 95% confidence interval (CI): 1.86–143), open surgery (OR: 5.17, 95% CI: 2.50–13.1), and postoperative weight loss ≥ 8% (OR: 2.47, 95% CI: 1.07–5.71).ConclusionsLG may be associated with shorter intervals before AC. Postoperative morbidity should be reduced as much as possible.



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Embryonic Origin of Primary Colon Cancer Predicts Survival in Patients Undergoing Ablation for Colorectal Liver Metastases

Publication date: Available online 29 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Suguru Yamashita, Bruno C. Odisio, Steven Y. Huang, Scott E. Kopetz, Kamran Ahrar, Yun Shin Chun, Claudius Conrad, Thomas A. Aloia, Sanjay Gupta, Samer Harmoush, Marshall E. Hicks, Jean-Nicolas Vauthey
BackgroundIn patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin of the tumor is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear.MethodsWe identified 74 patients with CLM who underwent image-guided percutaneous liver ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n=18) and hindgut origin tumors (n=56) were analyzed. Prognostic value of embryonic origin was evaluated by multivariable analysis.ResultsRecurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with CLM from midgut origin tumors (3-year RFS rate: 5.6% vs. 24%, P=0.004; 3-year OS rate: 25% vs. 70%, P<0.001). In Cox proportional hazards regression analysis, factors associated with worse OS were midgut embryonic origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P<0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P=0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P=0.013). At a median follow-up of 25 months, 56 patients (76%) had developed a recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin tumors (P=0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin tumors (P=0.022).ConclusionCompared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin tumors were more frequently candidates for local therapy at recurrence.



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Long-term regional chemotherapy for patients with epithelial malignant peritoneal mesothelioma results in improved survival

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Publication date: Available online 29 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Paul H. Sugarbaker, David Chang
PurposeMalignant peritoneal mesothelioma (MPM) is a rare disease with about 300 new cases per year in the USA. Its natural history is described as local progression within the peritoneal space in the absence of liver metastases or systemic disease.MethodsCytoreductive surgery (CRS) is a series of peritonectomy procedures and visceral resections with a goal of complete removal of all visible disease from the abdomen and pelvis. Over 20 years, three protocols investigating increasing efficacy of additional chemotherapy treatments added to CRS have been initiated. Initially, hyperthermic perioperative chemotherapy (HIPEC) with doxorubicin and cisplatin was used in the operating room. Then, early postoperative intraperitoneal chemotherapy (EPIC) with paclitaxel was added for the first 5 days after CRS. The third protocol employed HIPEC, then EPIC, and then long-term intraperitoneal (IP) paclitaxel or IP pemetrexed plus intravenous (IV) cisplatin as a adjuvant normothermic intraperitoneal chemotherapy (NIPEC).ResultThe median survival of 42 patients treated with CRS and HIPEC was 44%, for 58 patients treated with EPIC and HIPEC was 52% and 29 patients who received HIPEC, EPIC, and NIPEC was 75% (p=0.0374). Prognostic variables of age, gender, treatment administered, peritoneal cancer index (PCI) and completeness of cytoreduction were significant by univariate analysis and treatments administered and completeness of cytoreduction significant by multivariate analysis.ConclusionsLong-term regional chemotherapy was associated with improved survival in patients with MPM. In this rare disease, additional phase 2 investigations are suggested.

Teaser

Synopsis: Malignant peritoneal mesothelioma was treated over a 20 year time period with a consistent surgical procedure followed by an escalation of regional chemotherapy treatments. When regional chemotherapy long term was added to the treatment plan survival improved significantly (p=0.0108).


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Circulating tumor cells and circulating tumor DNA: what surgical oncologists need to know?

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Publication date: Available online 29 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Luc Cabel, Charlotte Proudhon, Pascale Mariani, Dimitri Tzanis, Guillaume Beinse, Ivan Bieche, Jean-Yves Pierga, François-Clément Bidard
As a result of recent progress in detection techniques, circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) can now be accurately detected in the blood of most cancer patients. While these new biomarkers can provide a better understanding of key biological mechanisms underlying cancer growth and dissemination, they also open up a wide range of possible clinical applications in medical oncology, radiation oncology and surgical oncology.In this review, we summarize the results obtained with ctDNA and CTC together with their potential future clinical applications in the field of surgical oncology, with particular focus on the perioperative setting of various types of cancer. These applications include, but are not limited to, cancer screening, early diagnosis, prognostic assessment, evaluation and management of preoperative systemic or local therapies, post-surgical detection of minimal residual disease and early detection of cancer relapse.



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Subclinical atherosclerosis in Systemic Lupus Erythematosus: Comparable risk with Diabetes Mellitus and Rheumatoid arthritis

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Publication date: Available online 29 January 2017
Source:Autoimmunity Reviews
Author(s): Maria G. Tektonidou, Evrydiki Kravvariti, George Konstantonis, Nicholas Tentolouris, Petros P. Sfikakis, Athanasios Protogerou
ObjectiveAlthough a high risk of clinical and subclinical atherosclerosis has been reported in systemic lupus erythematosus (SLE), it is not directly compared with that observed in other rheumatic and non-rheumatic high-cardiovascular (CVD) risk diseases, such as Rheumatoid Arthritis (RA) and Diabetes Mellitus (DM). Our objective was to evaluate the relative risk (RR) of subclinical atherosclerosis in SLE, RA and DM patients compared to healthy controls, and examine potential associations with traditional and disease-related CVD risk factors in SLE.MethodsWe examined for atherosclerotic plaques 460 individuals (92% female) without CVD history, using carotid and femoral artery ultrasound: 115 SLE patients and matched 1:1 for age and gender RA, DM, and control subjects. Multivariate models were used to determine relative risk estimates for the number of atherosclerotic plaques in patient groups versus controls, and associations of plaques with traditional CVD and disease-related factors in SLE.ResultsA nearly two-fold higher number of atherosclerotic plaques in the carotid and femoral arteries was detected in each of SLE, RA and DM groups compared to controls, after adjusting for the effect of traditional CVD risk factors (RR=1.80, 95% CI 1.05–3.08, p=0.033, RR=1.90 (1.11–3.26), p=0.019, RR=1.93 (1.14–3.28), p=0.015, respectively). In SLE patients, the number of atherosclerotic plaques was associated with age (p<0.001), smoking (p=0.016), hypertension (p=0.029), and cumulative corticosteroid dose (p=0.007).ConclusionThe relative risk of subclinical atherosclerosis in SLE was comparable to that found in RA and DM, indicating that SLE patients merit a similar diligence in CVD risk assessment and management measures.



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Efficacy of belimumab on renal outcomes in patients with systemic lupus erythematosus: A systematic review

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Publication date: Available online 29 January 2017
Source:Autoimmunity Reviews
Author(s): S Sciascia, M Radin, J Yazdany, RA Levy, D Roccatello, M Dall'Era, Maria J Cuadrado
Both BLISS-52 and BLISS-76 international phase III trials in Systemic Lupus Erythematosus (SLE) met their primary outcomes; however, they were not designed to assess the efficacy of belimumab for the treatment of lupus nephritis (LN). LN is a frequent cause of SLE-associated morbidity and mortality, and emerging evidence suggests a potential therapeutic role for agents that target B lymphocyte stimulator (BLyS).We conducted a systematic review to identify data on the effect of belimumab on LN.A total of 2004 patients with SLE were identified from 11 studies. Three hundred and twenty-six patients had LN at baseline and 234 (71.8%) of those received belimumab. Thirteen patients out of 234 (5.5%) received belimumab for active LN. Due to the heterogeneous definitions of treatment response, clinical presentation and renal involvement, it was not possible to compare results using a single outcome parameter. However, the majority of these studies defined clinical response in terms of rates of renal flare, renal remission, and/or renal organ disease improvement. One hundred twenty-nine (55.1%) of the 234 patients with LN at baseline showed an improvement in renal parameters after treatment with belimumab. In patients with baseline proteinuria >0.2g/24h, (n=687), those receiving belimumab had a median reduction in proteinuria during follow-up as high as 38%. When focusing on patients with proteinuria ≥1g/24h (n=228), 70.7% of those treated with belimumab (n=157) achieved a renal response.In the pooled population of patients receiving belimumab, we found an overall annual renal flare rate of 1.7% [24/1448, mean observation time 1,1years (0,5–3)].Despite the limitations of the studies included in this analysis, available data are promising and provide preliminary support for targeting BlyS to induce or maintain a renal response. Further trials should examine whether belimumab (alone or following rituximab) represents an additional therapeutic option in the treatment of LN.



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Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study

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Publication date: Available online 29 January 2017
Source:Autoimmunity Reviews
Author(s): Elena Bartoloni, Miguel A. Gonzalez-Gay, Carlo Scirè, Santos Castaneda, Roberto Gerli, Francisco Javier Lopez-Longo, Julia Martinez-Barrio, Marcello Govoni, Federica Furini, Trinitario Pina, Florenzo Iannone, Margherita Giannini, Laura Nuño, Luca Quartuccio, Norberto Ortego-Centeno, Alessia Alunno, Christopher Specker, Carlomaurizio Montecucco, Konstantinos Triantafyllias, Silvia Balduzzi, Walter Alberto Sifuentes-Giraldo, Giuseppe Paolazzi, Elena Bravi, Andreas Schwarting, Raffaele Pellerito, Alessandra Russo, Carlo Selmi, Lesley-Ann Saketkoo, Enrico Fusaro, Simone Parisi, Nicolò Pipitone, Franco Franceschini, Ilaria Cavazzana, Rossella Neri, Simone Barsotti, Veronica Codullo, Lorenzo Cavagna
ObjectiveArthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients.MethodsAnti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients.Results165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p=0.002).ConclusionAnti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.



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Repair of Oxidative DNA Damage in Saccharomyces cerevisiae

Publication date: Available online 28 January 2017
Source:DNA Repair
Author(s): Jisha Chalissery, Deena Jalal, Zeina Al Natour, Ahmed H. Hassan
Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomolecules including DNA and consequently activates various DNA repair pathways. The nature of DNA damage and the cell cycle stage at which DNA damage occurs determine the appropriate repair pathway to rectify the damage. Oxidized DNA bases are primarily repaired by base excision repair and nucleotide incision repair. Nucleotide excision repair acts on lesions that distort DNA helix, mismatch repair on mispaired bases, and homologous recombination and non-homologous end joining on double stranded breaks. Post-replication repair that overcomes replication blocks caused by DNA damage also plays a crucial role in protecting the cell from the deleterious effects of oxidative DNA damage. Mitochondrial DNA is also prone to oxidative damage and is efficiently repaired by the cellular DNA repair machinery. In this review, we discuss the DNA repair pathways in relation to the nature of oxidative DNA damage in Saccharomyces cerevisiae.



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Leucine-rich α-2 glycoprotein is an innovative biomarker for psoriasis

Publication date: Available online 29 January 2017
Source:Journal of Dermatological Science
Author(s): Hideki Nakajima, Satoshi Serada, Minoru Fujimoto, Tetsuji Naka, Shigetoshi Sano




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MicroRNA-135a is up-regulated and aggravates myocardial depression in sepsis via regulating p38 MAPK/NF-κB pathway

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Ge Zheng, Minli Pan, Weimin Jin, Guoxin Jin, Yumao Huang
MicroRNA-135a (miR-135a) is implicated in the pathological processes of several cancers. However, the roles and regulatory mechanism of miR-135a in sepsis-induced myocardial depression (MD) remain largely unknown. In this study, the serum of patients with sepsis and healthy controls was obtained. The miR-135a expression was then measured. Then lentiviruses (miR-135a mimic, inhibitor and scramble control) were transfected into BALB/c mice. After 4days of transfection, polymicrobial sepsis model was established by cecal ligation and puncture (CLP) surgery. The serum tumor-necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 were detected. Cardiac function was assessed. In addition, the protein expressions of p38 MAPK/NF-κB pathway-related proteins were determined. Besides, SB203580 and JSH-23, the inhibitors of p38 MAPK and NF-κB respectively, were used to treat the isolated ventricular myocytes in vitro. MiR-135a was significantly up-regulated in the serum of patients with sepsis. In comparison with CLP group, the concentrations of TNF-α, IL-1β and IL-6 and the expressions of p-p38 and p-p65 in CLP+miR-135a mimic group were significantly increased, while markedly decreased in CLP+miR-135a inhibitor group. Moreover, EF, FS, LVdP/dt (max), LVdP/dt (min) and LVDP of CLP+miR-135a mimic group were all significantly decreased, while markedly increased in CLP+miR-135a inhibitor group. Besides, the increased expressions of p-p38 and p-p65, decreased expression of p-IKBα and the decreased percentage of contraction amplitude in miR-135a mimic group were markedly reversed by SB203580 or JSH-23 treatments. Up-regulation of miR-135a could aggravate sepsis-induced inflammation and myocardial dysfunction via activation of p38 MAPK/NF-κB pathway.



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Heavy metals fractionation and desorption in pine bark amended mine soils

Publication date: 1 May 2017
Source:Journal of Environmental Management, Volume 192
Author(s): David Fernández-Calviño, Laura Cutillas-Barreiro, Remigio Paradelo-Núñez, Juan Carlos Nóvoa-Muñoz, María J. Fernández-Sanjurjo, Esperanza Álvarez-Rodríguez, Avelino Núñez-Delgado, Manuel Arias-Estévez
The European Community Bureau of Reference method (BCR) was used for evaluating the effects of pine bark amendment (0, 24 and 48 g kg−1) and ageing (1 and 30 days) on Cd, Cu, Ni, Pb and Zn fractionation, on samples from an acid mine soil. In addition, the stirred flow chamber technique was applied for analyzing heavy metals desorption from the unamended and pine bark amended mine soil. When the unamended soil were not subjected to ageing, the added heavy metals were mainly accumulated as soluble fraction (>90% for Cd, Ni and Zn; 71% for Cu; and 45% for Pb). Pine bark amendment and ageing had little effect on Cd, Ni and Zn fractionation, whereas important changes were detected for Cu and Pb in response to both pine bark amendment and ageing (decrease in the soluble fractions, and increase in less mobile fractions). Desorption experiments showed that both pine bark amendment and ageing decreased heavy metals release from the mine soil. The results of this study indicate that pine bark amendment could be used to increase heavy metals retention (especially in the case of Cu and Pb) in acid mine soils, thus reducing the risks of metal transfer to uncontaminated environmental zones.



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An Unlikely Cause of Hypokalemia

Publication date: Available online 28 January 2017
Source:The Journal of Emergency Medicine
Author(s): Jason Hine, Ari Schwell, Norah Kairys
BackgroundHypokalemia is a common clinical disorder caused by a variety of different mechanisms. Although the most common causes are diuretic use and gastrointestinal losses, elevated cortisol levels can also cause hypokalemia through its effects on the renin–angiotensin–aldosterone system. Cushing's syndrome refers to this general state of hypercortisolemia, which often manifests with symptoms of generalized weakness, high blood pressure, diabetes mellitus, menstrual disorders, and psychiatric changes. This syndrome is most commonly caused by exogenous steroid use, but other etiologies have also been reported in the literature. Ectopic adrenocorticotropic hormone production by small-cell lung cancer is one rare cause of Cushing's syndrome, and may be associated with significant hypokalemia.Case ReportWe describe the case of a 62-year-old man who presented to the emergency department with weakness and hypokalemia. The patient was initially misdiagnosed with furosemide toxicity. Despite having a 30-pack-year smoking history, this patient's lack of respiratory complaints allowed him to present for medical attention twice before being diagnosed with lung cancer. It was later determined that this patient's hypokalemia was due to Cushing's syndrome caused by ectopic adrenocorticotropic hormone production from small-cell lung cancer.Why Should an Emergency Physician Be Aware of This?This case reminds emergency physicians to consider a broad differential when treating patients with hypokalemia. More importantly, it prompts emergency physicians to recognize comorbid conditions and secondary, less common etiologies in patients with repeated visits for the same complaint.



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SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies

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Publication date: Available online 28 January 2017
Source:Vaccine
Author(s): Elizabeth Begier, David Joshua Seiden, Michael Patton, Edward Zito, Joseph Severs, David Cooper, Joseph Eiden, William C. Gruber, Kathrin U. Jansen, Annaliesa S. Anderson, Alejandra Gurtman
BackgroundStaphylococcus aureus is a leading cause of healthcare-associated infections. No preventive vaccine is currently licensed. SA4Ag is an investigational 4-antigen S. aureus vaccine, composed of capsular polysaccharide conjugates of serotypes 5 and 8 (CP5 and CP8), recombinant surface protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (rMntC). This Phase 1 study aimed to confirm the safety and immunogenicity of SA4Ag produced by the final manufacturing process before efficacy study initiation in a surgical population.MethodsHealthy adults (18–<65years) received one intramuscular SA4Ag injection. Serum functional antibodies were measured at baseline and Day 29 post-vaccination. An opsonophagocytic activity (OPA) assay measured the ability of vaccine-induced antibodies to CP5 and CP8 to kill S. aureus clinical isolates. For MntC and ClfA, antigen-specific immunogenicity was assessed via competitive Luminex® immunoassay (cLIA) and via fibrinogen-binding inhibition (FBI) assay for ClfA only. Reactogenicity and adverse event data were collected.ResultsOne hundred participants were vaccinated. SA4Ag was well tolerated, with a satisfactory safety profile. On Day 29, OPA geometric mean titers (GMTs) were 45,738 (CP5, 95% CI: 38,078–54,940) and 42,652 (CP8, 95% CI: 32,792–55,477), consistent with 69.2- and 28.9-fold rises in bacteria-killing antibodies, respectively; cLIA GMTs were 2064.4 (MntC, 95% CI: 1518.2–2807.0) and 3081.4 (ClfA, 95% CI: 2422.2–3920.0), consistent with 19.6- and 12.3-fold rises, respectively. Similar to cLIA results, ClfA FBI titers rose 11.0-fold (GMT: 672.2, 95% CI: 499.8–904.2). The vast majority of participants achieved the pre-defined biologically relevant thresholds: CP5: 100%; CP8: 97.9%, ClfA: 87.8%; and MntC 96.9%.ConclusionsSA4Ag was safe, well tolerated, and rapidly induced high levels of bacteria-killing antibodies in healthy adults. A Phase 2B efficacy trial in adults (18–85years) undergoing elective spinal fusion is ongoing to assess SA4Ag's ability to prevent postoperative invasive surgical site and bloodstream infections caused by S. aureus.Clinicaltrials.gov Identifier: NCT02364596.



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Survey of vaccination knowledge and acceptance among adults admitted to an urban emergency department

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Publication date: Available online 28 January 2017
Source:Vaccine
Author(s): Kathryn Sutcliffe, Paul E. Kilgore, Kaitlyn DeHoff, Richard Evans, Keith S. Kaye, Ryan E. Malosh, Robert Sherwin, Emily T. Martin
BackgroundAdult vaccination rates in the United States have fallen below national target levels and may be exacerbated by lack of access to a primary care physician. We assessed patient knowledge of and attitudes towards vaccines in an urban emergency department population and analyzed the feasibility of using this setting as a vaccine delivery site from a patient perspective.MethodsIn-person interviewers administered surveys to 250 adult patients presenting to the Detroit Receiving Hospital emergency department in Detroit, Michigan. Respondents were asked about vaccination status, preferences, and willingness to accept vaccination reminders via text messaging. Odds ratios and 95% Wald confidence intervals assessing differences between vaccinated and non-vaccinated individuals were generated with univariate logistic regression.ResultsVaccinated adults were more likely to have a primary care provider than non-vaccinated adults (OR 1.94, 95% CI: 1.09–3.45). Non-vaccinated adults were significantly more likely to have unvaccinated adult relatives (OR8.64, 95% CI: 4.10–18.22). Nearly all respondents used a cell phone, and 75.8% of unvaccinated adults were willing to receive text messages reminders about vaccines.ConclusionsAlthough less likely to have a primary care access point than vaccinated participants, non-vaccinated respondents reported interest in receiving vaccinations. Emergency departments could serve as vaccination hubs for patients and unvaccinated accompanying family members. Text message reminders offer a potential source of additional vaccine prompts and education.



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In Pursuit of Cancer Metastasis Therapy by Bacteria and Its Biofilms: History or Future

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Publication date: Available online 28 January 2017
Source:Medical Hypotheses
Author(s): Mohd Adnan, Saif Khan, Eyad Al-Shammari, Mitesh Patel, Mohd Saeed, Sibte Hadi
The 20th century observation of increasing comprehensive load of cancer, advanced cancer prevention strategies, creative hypotheses and control procedures by research communities are being traversed and stimulated in multiple facets. Inference of genetically modified non-pathogenic and natural bacterial species as potential anti-tumor agents is one such original perspective. Live, genetically modified non-pathogenic or attenuated bacterial species are able to form biofilms by multiplying selectively or non-selectively on cancer cells, which will lead to metastasis disruption. However, the appearance of gene-directed prodrug therapy and recombinant DNA technology has invigorated the notice in range of applications employing bacteria and bacterial therapy and a have been carried out. The most possible and promising upcoming strategies are bacteria mediated cancer treatment. Significant efficacy in pre-clinical studies have been demonstrated and some are presently under clinical investigation. The theorem is that cancer metastasis can either be blunt by opponent bacterial biofilm infection or serve as model vectors for delivering therapeutic proteins to tumors or generation of the new phenotypes during the SOS reaction incite by anticancer drugs.



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Predictors of renal survival in antineutrophil cytoplasmic antibody–associated vasculitis

Publication date: February 2017
Source:Human Pathology, Volume 60
Author(s): Valentina Binda, Gabriella Moroni




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Masthead

Publication date: February 2017
Source:Human Pathology, Volume 60





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Table of Contents

Publication date: February 2017
Source:Human Pathology, Volume 60





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Editorial Board

Publication date: February 2017
Source:Human Pathology, Volume 60





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In This Issue

Publication date: February 2017
Source:Human Pathology, Volume 60





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Predictors of renal survival in antineutrophil cytoplasmic antibody–associated vasculitis—reply

Publication date: February 2017
Source:Human Pathology, Volume 60
Author(s): Francisco Javier Diaz Crespo, Javier Villacorta, Gema Fernandez Juarez




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Editorial Board

Publication date: February 2017
Source:Pathology - Research and Practice, Volume 213, Issue 2





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Up-regulation of Pim-3 in Chronic Obstructive Pulmonary Disease (COPD) patients and its potential therapeutic role in COPD rat modeling

Publication date: Available online 29 January 2017
Source:Pathology - Research and Practice
Author(s): Cheng Yang, Li Li, Junhua Guo, Weiqiang Zhang, Wenbiao Zhu, Xinhui Rao, Wenjie Huang
BackgroundPim-3 belongs to the PIM kinase family and plays an important role in promoting inflammation, which is essential in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD).MethodsImmunohistochemistry (IHC), western blot, and RT-PCR analyses were performed to assess the expression of Pim-3 in both COPD and healthy lung tissue samples. SMA (Smooth Muscle Actin) and Cyclin D1 expression were detected by IHC. We also constructed animal models for the control, COPD, and Pim-3 inhibition groups, in order to analyze the effects of Pim-3 inhibition on COPD, and the role of Pim-3 in the p38 pathway.ResultsCompared with normal lung tissue, Pim-3 mRNA and protein were up-regulated in COPD tissue. Expression of Cyclin D1 and SMA were also up-regulated in the COPD group. In the animal model experiment, we found that suppression of Pim-3 decreased Pim-3, Cyclin D1, and SMA expression, as well as ameliorated lung damage in COPD patients. The inhibition of Pim-3 also resulted in the suppression of the p38 pathway.ConclusionOur study suggests that up-regulation of Pim-3 successfully accelerated COPD development, and aggravated lung damage. The molecular mechanism of Pim-3 in COPD might be related to the p38 pathway, and is correlated with Cyclin D1 and SMA expression.



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Evaluation of the Presence of Epstein-Barr virus (EBV) In Iranian Patients with Thyroid Papillary Carcinoma

Publication date: Available online 28 January 2017
Source:Pathology - Research and Practice
Author(s): Maryam Homayouni, Seyed Ali Mohammad Arabzadeh, Fatemeh Nili, Farideh Razi, Mahsa Mohammad Amoli
Background and purpose:Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma.Material and methodsIn this study the presence of Epstein-Barr Nuclear Antigen 1(EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N=41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene.ResultsIn 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages.ConclusionThe significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important.



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PLCE1 Promotes Esophageal Cancer Cell Progression by Maintaining the Transcriptional Activity of Snail

Publication date: March 2017
Source:Neoplasia, Volume 19, Issue 3
Author(s): Shicong Zhai, Cui Liu, Lichen Zhang, Jian Zhu, Jiqiang Guo, Jinghang Zhang, Zhijun Chen, Wenping Zhou, Tingmin Chang, Siguang Xu, Yijun Qi, Ting Zhuang, Na Yu, Weilong Wang, Hui Wang, Sifan Yu, Xiumin Li
Esophageal cancer is among the most deadly malignant diseases. However, the genetic factors contributing to its occurrence are poorly understood. Multiple studies with large clinic-based cohorts revealed that variations of the phospholipase C epsilon (PLCE1) gene were associated with esophageal cancer susceptibility. However, the causative role of PLCE1 in esophageal cancer is not clear. We inactivated the functional alleles of PLCE1 by CRISPR/Cas9 genome editing technology. The resultant PLCE1 inactivated cells were analyzed both in vitro and in vivo. Our results showed that loss of PLCE1 dramatically decreased the invasion and proliferation capacity of esophageal carcinoma cells in vitro. Moreover, such PLCE1 inactivated tumor grafts exhibited significantly decreased tumor size in mice. We found that PLCE1 was required to maintain protein level of snail a key transcription factor responsible for invasion. Our further transcriptomic data revealed that deficient cells were significantly decreased in expression of genes enriched as targets of Snail. Strikingly, recovery of Snail protein at least partially rescued the invasion and proliferation capacity in PLCE1 inactivated cells. In ESCC clinical specimens, PLCE1 was correlated with tumor stage (P<.0001). Interestingly, PLCE1 expression was positively correlated Snail by immunohistochemistry in such specimens (P<.0001). Therefore, our functional experiments showed the essential roles of PLCE1 in esophageal carcinoma cells and provided evidences that targeting PLCE1 and its downstream molecules could be effective therapies for esophageal cancer.



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The Heparanase Inhibitor PG545 Attenuates Colon Cancer Initiation and Growth, Associating with Increased p21 Expression

Publication date: March 2017
Source:Neoplasia, Volume 19, Issue 3
Author(s): Preeti Singh, Alexandra Blatt, Sari Feld, Yaniv Zohar, Esraa Saadi, Liza Barki-Harrington, Edward Hammond, Neta Ilan, Israel Vlodavsky, Yehuda Chowers, Elizabeth Half
Heparanase activity is highly implicated in cellular invasion and tumor metastasis, a consequence of cleavage of heparan sulfate and remodeling of the extracellular matrix underlying epithelial and endothelial cells. Heparanase expression is rare in normal epithelia, but is often induced in tumors, associated with increased tumor metastasis and poor prognosis. In addition, heparanase induction promotes tumor growth, but the molecular mechanism that underlines tumor expansion by heparanase is still incompletely understood. Here, we provide evidence that heparanase down regulates the expression of p21 (WAF1/CIP1), a cyclin-dependent kinase inhibitor that attenuates the cell cycle. Notably, a reciprocal effect was noted for PG545, a potent heparanase inhibitor. This compound efficiently reduced cell proliferation, colony formation, and tumor xenograft growth, associating with a marked increase in p21 expression. Utilizing the APC Min+/− mouse model, we show that heparanase expression and activity are increased in small bowel polyps, whereas polyp initiation and growth were significantly inhibited by PG545, again accompanied by a prominent induction of p21 levels. Down-regulation of p21 expression adds a novel feature for the emerging pro-tumorigenic properties of heparanase, while the potent p21 induction and anti-tumor effect of PG545 lends optimism that it would prove an efficacious therapeutic in colon carcinoma patients.



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A Three-Dimensional Neural Spheroid Model for Capillary-Like Network Formation

Publication date: Available online 29 January 2017
Source:Journal of Neuroscience Methods
Author(s): Molly E. Boutin, Liana L. Kramer, Liane L. Livi, Tyler Brown, Christopher Moore, Diane Hoffman-Kim
BackgroundIn vitro three-dimensional neural spheroid models have an in vivo-like cell density, and have the potential to reduce animal usage and increase experimental throughput. The aim of this study was to establish a spheroid model to study the formation of capillary-like networks in a three-dimensional environment that incorporates both neuronal and glial cell types, and does not require exogenous vasculogenic growth factors.New MethodWe created self-assembled, scaffold-free cellular spheroids using primary-derived postnatal rodent cortex as a cell source. The interactions between relevant neural cell types, basement membrane proteins, and endothelial cells were characterized by immunohistochemistry. Transmission electron microscopy was used to determine if endothelial network structures had lumens.ResultsEndothelial cells within cortical spheroids assembled into capillary-like networks with lumens. Networks were surrounded by basement membrane proteins, including laminin, fibronectin and collagen IV, as well as key neurovascular cell types.Comparison with Existing Method(s)Existing in vitro models of the cortical neurovascular environment study monolayers of endothelial cells, either on transwell inserts or coating cellular spheroids. These models are not well suited to study vasculogenesis, a process hallmarked by endothelial cell cord formation and subsequent lumenization.ConclusionsThe neural spheroid is a new model to study the formation of endothelial cell capillary-like structures in vitro within a high cell density three-dimensional environment that contains both neuronal and glial populations. This model can be applied to investigate vascular assembly in healthy or disease states, such as stroke, traumatic brain injury, or neurodegenerative disorders.

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The function and transcriptome analysis of a bZIP transcription factor CgAP1 in Colletotrichum gloeosporioides

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Publication date: Available online 29 January 2017
Source:Microbiological Research
Author(s): Xiaoyu Li, Yateng Wu, Zhiqiang Liu, Chenghui Zhang
Colletotrichum gloeosporioides is an important pathogen of anthracnose, which is able to infect numerous crops in tropical and subtropical regions, causing great economic losses. To investigate the fungal response to host-generated reactive oxygen species (ROS), we cloned and characterized the CgAP1 gene of C. gloeosporioides. CgAP1 encoded a bZIP transcription factor which had a bZIP DNA-binding domain and two cysteine-rich domains structurally and functionally related to Saccharomyces cerevisiae YAP1. Deletion of CgAP1 in C. gloeosporioides resulted in increasing sensitivity to H2O2, changes in cell wall integrity and loss of pathogenicity. To understand the regulatory network of CgAP1, RNA sequencing was used to identify differentially expressed genes in the CgAP1 mutant. It was shown that several genes involved in ROS detoxification and cell wall integrity were affected by CgAP1. Moreover, CgAP1 was also involved in many biological processes especially ribosome, cellular transport and amino acid metabolism. In conclusion, CgAP1 is an important transcription factor involved in oxidative stress, cell wall integrity and pathogenicity in C. gloeosporioides.



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Acclimation strategy of Rhodopseudomonas palustris to high light irradiance

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Publication date: Available online 28 January 2017
Source:Microbiological Research
Author(s): Dayana Muzziotti, Alessandra Adessi, Cecilia Faraloni, Giuseppe Torzillo, Roberto De Philippis
The ability of Rhodopseudomonas palustris cells to rapidly acclimate to high light irradiance is an essential issue when cells are grown under sunlight. The aim of this study was to investigate the photo-acclimation process in Rhodopseudomonas palustris 42OL under different culturing conditions: (i) anaerobic (AnG), (ii) aerobic (AG), and (iii) under H2- producing (HP) conditions both at low (LL) and high light (HL) irradiances. The results obtained clearly showed that the photosynthetic unit was significantly affected by the light irradiance at which Rp. palustris 42OL was grown. The synthesis of carotenoids was affected by both illumination and culturing conditions. At LL, lycopene was the main carotenoid synthetized under all conditions tested, while at HL under HP conditions, it resulted the predominant carotenoid. Oppositely, under AnG and AG at HL, rhodovibrin was the major carotenoid detected. The increase in light intensity produced a deeper variation in light- harvesting complexes (LHC) ratio. These findings are important for understanding the ecological distribution of PNSB in natural environments, mostly characterized by high light intensities, and for its growth outdoors.



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Studies on the formation of formaldehyde during 2-ethylhexyl 4-(dimethylamino)benzoate demethylation in the presence of reactive oxygen and chlorine species

Abstract

In order to protect the skin from UV radiation, personal care products (PCPS) often contain chemical UV-filters. These compounds can enter the environment causing serious consequences on the water ecosystems. The aim of this study was to examine, the effect of different factors, such as UV light, the presence of NaOCl and H2O2 on the formaldehyde formation during popular UV filter, 2-ethylhexyl 4-(dimethylamino)benzoate (ODPABA) demethylation. The concentration of formaldehyde was determined by VIS spectrophotometry after derivatization. The reaction mixtures were qualitatively analyzed using GC/MS chromatography. The highest concentration of formaldehyde was observed in the case of ODPABA/H2O2/UV reaction mixture. In order to describe two types of demethylation mechanisms, namely, radical and ionic, the experimental results were enriched with Fukui function analysis and thermodynamic calculations. In the case of non-irradiated system containing ODPABA and NaOCl, demethylation reaction probably proceeds via ionic mechanism. As it was established, amino nitrogen atom in the ODPABA molecule is the most susceptible site for the HOCl electrophilic attack, which is the first step of ionic demethylation mechanism. In the case of irradiated mixtures, the reaction is probably radical in nature. The results of thermodynamic calculations showed that abstraction of the hydrogen from N(CH3)2 group is more probable than from 2-ethylhexyl moiety, which indicates higher susceptibility of N(CH3)2 to the oxidation.



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