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Πέμπτη 5 Ιανουαρίου 2017

Applications of Burow's Grafts in the Reconstruction of Mohs Micrographic Surgery Defects.

BACKGROUND: Surgical defects in anatomically challenging locations, such as near free margins or crossing cosmetic subunits, may present reconstructive challenges to the dermatologic surgeon. For selected defects, Burow's grafts may produce functional and aesthetic results in a single operative session. OBJECTIVE: To describe the applications of the Burow's graft technique for the repair of defects after Mohs micrographic surgery. METHODS: An institutional review board-approved retrospective database review of surgical defects repaired with Burow's grafting after Mohs micrographic surgery at the Medical University of South Carolina was performed. The general technique of Burow's grafting is described, emphasizing proper graft sizing and direction of tension vectors. Varying anatomic locations and defect types are presented, with site-specific considerations and operative photographs. RESULTS: Burow's grafting provides ideal color and textural match, preserves subunit boundaries, results in a compact single-site wound, and may avoid complications of alternate repair choices. The tension vectors produced in closing the graft's harvest site may be designed to prevent distortion of free margins. Burow's grafting may be combined with hinge flaps to repair deep or avascular defects. CONCLUSION: Burow's grafts are reproducible, aesthetic, and useful reconstructive choices for a variety of surgical wounds. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Squamous Cell Carcinoma In Situ Upstaged to Invasive Squamous Cell Carcinoma: A 5-Year, Single Institution Retrospective Review.

BACKGROUND: Shave biopsy may not be able to accurately distinguish squamous cell carcinoma in situ (SCCIS) from invasive squamous cell carcinoma (SCC). Information on the incidence of biopsy-proven SCCIS upstaged to SCC after a more complete histologic examination is limited. OBJECTIVE: To determine the incidence and clinical risk factors associated with upstaging the biopsy diagnosis of SCCIS into invasive SCC based on findings during Mohs micrographic surgery (MMS). METHODS: All MMS cases of SCCIS performed between March 2007 and February 2012 were identified, MMS operative notes were examined, and invasive dermal components were confirmed by the MMS slide review. Upstaged SCCIS was defined as biopsy-diagnosed SCCIS subsequently found to be an invasive SCC during MMS. RESULTS: From 566 cases with the preoperative diagnosis of SCCIS, 92 (16.3%) cases were SCCIS upstaged to SCC. Location of ears, nose, lips, and eyelids, preoperative diameter >10 mm, and biopsy report mentioning a transected base were significant predictors of upstaged SCCIS. CONCLUSION: Considering the possibility that over 16% of SCCIS may be truly invasive SCC, biopsy-proven SCCIS should be treated adequately with margin-assessed treatment modalities such as surgical excision or Mohs surgery when indicated. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Commentary on Association Between Scalp Laxity, Elasticity, and Glidability and Donor Strip Scar Width in Hair Transplantation and a New Elasticity Measuring Method.

No abstract available

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Broader Practice Indications for Mohs Surgical Defect Healing by Secondary Intention: A Survey Study.

BACKGROUND: Recent reports have indicated secondary intention (SI) healing utilization for Mohs surgical defects beyond conventionally accepted indications. OBJECTIVE: To characterize potentially more expansive guidelines for when SI healing is indicated or appropriate in dermatologic surgery. METHODS: A survey study was e-mailed to the American College of Mohs Surgery in 2015. A group of 293 respondents addressed factors influencing decisions to heal surgical defects secondarily. RESULTS: The most experienced surgeons were significantly more likely to heal deep and larger wounds secondarily. Many surgeons elect SI healing in patients with current or previous wound dehiscence, flap necrosis, or infection; in patients who have undergone skin cancer excisions before, or who are elderly, and; if the lesion was sent for permanent section, or when treating high-risk, large, recurrent, or aggressive tumors. CONCLUSION: Broader indications for SI healing of Mohs surgical defects may be appropriate than previously understood. In addition to concave, temporal, periocular, perinasal, and periauricular sites, SI healing may be appropriate for convex sites such as the scalp and anterior lower extremity, deep wounds, and large wounds, as well as wounds with dehiscence, flap necrosis, or infection. Certain patient-specific and lesional factors are also appropriate indications for SI healing. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Targeting Epidermal Growth Factor Receptor in Triple Negative Breast Cancer: New Discoveries and Practical Insights for Drug Development

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Publication date: Available online 5 January 2017
Source:Cancer Treatment Reviews
Author(s): Ricardo Costa, Ami N. Shah, Cesar A. Santa-Maria, Marcelo R. Cruz, Devalingam Mahalingam, Benedito A. Carneiro, Young Kwang Chae, Massimo Cristofanilli, William J. Gradishar, Francis J. Giles
Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor + and HER2 + breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epithelial Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC.



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Efferent Vision Therapy.

Background: Traditional orthoptic therapy used by ophthalmologists, orthoptists, and optometrists is directed at improving visual acuity, ocular alignment, or both. For example, convergence exercises are used to treat convergence insufficiency (CI). However, other forms of "vision therapy" are directed at improving "visual processing and efficiency." The therapeutic regimen often entails repetitive ocular motor tasks performed during multiple office visits with a behavioral optometrist. These ocular motor tasks are used to treat diverse conditions such as learning disabilities, poor reading ability, dyslexia, and attention-deficit hyperactivity disorder (ADHD). Evidence regarding the efficacy of therapy directed at ocular motility for the treatment of multiple conditions is reviewed. Evidence Acquisition: Review of literature. Results: Randomized, controlled, double-masked studies show that convergence exercises reduce symptoms and improve signs of CI in otherwise healthy patients. However, the most efficacious convergence tasks, and the optimal duration and frequency of these tasks, remain unknown. Patients with learning disabilities, poor reading ability, dyslexia, or ADHD do not consistently have unique ocular motor deficits. Patients who acquire ocular motor deficits do not develop these conditions. There are no randomized, controlled studies that show treatment consisting of repetitive ocular motor tasks improves learning disabilities, reading, dyslexia, or ADHD. Conclusions: Convergence exercises effectively treat CI in healthy patients. The optimal treatment regimen is unknown. There is insufficient evidence to recommend "vision therapy" for the treatment of learning disabilities, impaired reading, dyslexia, or ADHD. (C) 2017 by North American Neuro-Ophthalmology Society

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Neuro-Ophthalmology in Portugal.

No abstract available

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A Giant Tumefactive Virshow-Robin Space: A Rare Cause of a Homonymous Quadrantanopia.

A 53-year-old woman was found to have a left inferior homonymous quadrantanopia. Brain MRI disclosed a giant Virchow-Robin space compressing the right optic tract. After fenestration of this cystic lesion, most of the visual field loss resolved. Giant Virchow-Robin spaces may cause homonymous field defects which, with appropriate management, may improve. (C) 2017 by North American Neuro-Ophthalmology Society

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Acral and digital angioleiomyomata: Fourteen year experience at the Cleveland Clinic and review of the literature

ABSTRACT

Background

Angioleiomyoma is a benign neoplasm thought to derive from the tunica media of small venous vessels. Angioleiomyomata most frequently occur in the lower extremities with less common occurrences on the trunk, head, and upper extremities. Few cases of acral and digital angioleiomyoma have been described in the literature.

Methods

We add a series of twenty-one patients with acral angioleiomyoma including six cases of digital angioleiomyoma to the body of clinical and histologic findings along with a review of the literature of digital angioleiomyomata.

Results

Digital angioleiomyoma are equally distributed between male and female patients and are more often painful than the angioleiomyoma of all body sites. Acral angioleiomyomata favor the feet over hands at a ratio of 2.5:1, while digital angioleiomyoma favor the fingers over toes at a ratio of 4.3:1.

Conclusions

We suggest that vascular leiomyoma be included in the differential diagnosis of smooth muscle tumors with particular regard to the digits of both the hands and feet. Digital angioleiomyomata differ from acral angioleiomyomata in their equal gender distribution, increased tendency to cause pain, and preponderance for the fingers over the toes.



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Is Psoriasis an autoimmune disease: interpretations from an immunofluorescence based study

Abstract

Introduction

Psoriasis is a multisystem, immune-mediated inflammatory disease. Some authors have proposed an autoimmune basis for psoriasis; however, till date, it has not been definitely established. The present study was conducted to explore the autoimmune nature of psoriasis.

Materials and methods

This was a prospective study in which 43 psoriasis patients were assessed for detailed clinical, histopathological and immunopathological features to explore the diagnostic utility of subtypes, intensity, and number of immunoreactants in lesional and non-lesional skin in these patients. In addition, the sera of these patients were analyzed for the presence of various autoantibodies.

Results

The patients' age ranged from 14 to 75 years with a M:F ratio of 1.52:1. Nine patients(20.93%) were positive for anti-nuclear and 2(4.65%) for anti-smooth muscle antibodies. Direct immunofluorescence (DIF) was positive in 31(72%) biopsies from the lesional and 27(63%) biopsies from non-lesional skin. In all these DIF positive cases, granular deposits of C5b-9 were detected at the dermo-epidermal junction. No significant difference was observed on comparing the type and pattern of immunoreactant positivity, amongst lesional and non-lesional skin biopsies(p > 0.05).

Conclusion

No significant association between psoriasis and immunoreactant deposition as well as autoantibody seroprevalence was observed, thereby refuting a definite autoimmune basis for psoriasis.



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“I've got you under my skin”: A challenge for both the allergist and the patient



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Letters to the Editor



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Influence of ultrasonic activation over final irrigants in the removal of photosensitizer from root canal walls after photodynamic therapy

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Publication date: Available online 5 January 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Matheus Albino Souza, Bianca Pazinatto, Karolina Frick Bischoff, Huriel Scartazzini Palhano, Doglas Cecchin, José Antônio Poli de Figueiredo
IntroductionThe aim of the present study was to evaluate the influence of ultrasonic activation (US) of the final irrigant in the removal of the photosensitizer from root canal walls after photodynamic therapy.MethodsThe root canals of 60 single-rooted bovine extracted teeth were filled with 0.01% methylene blue and submitted to photodynamic therapy for 90seconds. After that, the roots were divided into six groups (n=10) according to the final irrigation protocol: distilled water (DW), DW+US, 17% EDTA, QMix, EDTA+US, and QMix+US. Then, the samples were submitted to scanning electron microscopy where a scoring system was used to evaluate the images and effectiveness of proposed treatments in the cervical, middle and apical regions of the root canals. The data were statistically analyzed by the Kruskal-Wallis and Mann-Whitney U tests for intergroup comparisons as well as the Wilcoxon and Friedman tests for intragroup comparisons at 5% of significance.ResultsThe 17% EDTA+US and QMix+US treatments were most effective in the removal of the photosensitizer in all regions of the root canal; the difference was statistically significant when compared to all other groups (p<0.05). There were no significant differences in the intragroup analysis comparing the effectiveness in the different regions of the same group (p<0.05).ConclusionsUS can aid 17% EDTA and QMix in removing the photosensitizer after photodynamic therapy and contributes to cleaning root canal walls.



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Letters to the Editor



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Atopic dermatitis: Burden of illness, quality of life, and associated complications

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Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases

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Involvement of microRNAs in skin disorders: A literature review

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Diagnosis and management of allergic conjunctivitis in pediatric patients

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Albuterol multidose dry powder inhaler efficacy and safety versus placebo in children with asthma

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Clinical diagnosis and management of anaphylaxis in infancy

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Factors that determine parents' perception of their child's risk of life-threatening food-induced anaphylaxis

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Characteristics of children with food protein‐induced enterocolitis and allergic proctocolitis

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Childhood obesity in pediatric patients with difficult-to-control asthma in a tertiary pediatric subspecialty clinic

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Prevalence of dermatologic diseases among patients with selective immunoglobulin A deficiency

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Hypereosinophilic syndrome

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Letters to the Editor



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For the Patient



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Letters to the Editor



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Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases



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A framework for understanding sexual violence: Incentive-motivation and hierarchical control

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Publication date: Available online 5 January 2017
Source:Aggression and Violent Behavior
Author(s): Frederick Toates, Wineke Smid, Jan van den Berg
The article applies an incentive-motivation model to sexual violence. It suggests that insights can be gained by looking at the biopsychological processes that underlie 'conventional behavior'. It argues that sexual violence, as in rape, arises from a fusion between (i) sexual motivation and (ii) sensation-seeking and varying strengths of dominance/aggression motivations. The excitatory part of the motivational system is rooted in brain dopamine and sexual violence is expressed in behavior when excitation exceeds inhibition. The assumptions are framed within the principle of the hierarchical control of behavior. The incentive-motivation and hierarchical framework can yield insights into such phenomena as planning and impulsivity, future discounting, habituation and escalation, violence as addiction, the role of fetishes, sexual fantasy, stress, drugs and brain development.



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Prevalence of life-course-persistent, adolescence-limited, and late-onset offenders: A systematic review of prospective longitudinal studies

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Publication date: Available online 5 January 2017
Source:Aggression and Violent Behavior
Author(s): Darrick Jolliffe, David P. Farrington, Alex R. Piquero, John F. MacLeod, Steve van de Weijer
Little is known about the prevalence, frequency, onset, and criminal career duration of life-course-persistent offenders (LCP), compared to adolescence-limited (AL) and late-onset offenders (LO), despite the importance of these categories in criminology. This article is the first to use a systematic approach to identify the prospective longitudinal studies which could possess relevant information and to summarize the outputs of these studies. The principal investigators of these studies were also contacted to assist in identifying relevant data. Overall, 55 prospective longitudinal studies were identified; of these 14 had produced information on the prevalence of the various offending types. In seven additional studies, data was made available to explore criminal career parameters of the various offending types. The results showed that the estimates of the prevalence of LCP, AL, and LO offending varied considerably, and that few studies include criminal career duration in their definitions of LCP offenders. Surprisingly, the average ages of onset for LCP and Al offenders were similar. Much more research on LCP, AL, and LO offenders, which includes a consideration of criminal career duration, is desperately needed.



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A317491 relieved HIV gp120-associated neuropathic pain involved in P2X3 receptor in dorsal root ganglia

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Publication date: Available online 5 January 2017
Source:Brain Research Bulletin
Author(s): Zhihua Yi, Shenqiang Rao, Shuai Ouyang, Yi Bai, Jinpu Yang, Yucheng Ma, Xinyao Han, Bing Wu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Xiaju Hu, Qiongqiong Lei, Yun Gao, Shuangmei Liu, Hong Xu, Chunping Zhang, Shangdong Liang, Guilin Li
Glycoprotein 120 (gp120) is an HIV envelope glycoprotein. Gp120 can directly stimulate the primary sensory afferent neurons and cause hyperalgesia. The P2X3 receptor in dorsal root ganglia (DRG) is involved in the transmission of pain. In this study, we aimed to explore the role of the P2X3 receptor in gp120-induced neuropathic pain. Our data showed that mechanical and thermal hyperalgesia in rats treated with gp120 were increased compared to those in the control group. The expression levels of the P2X3 mRNA and protein in rats treated with gp120 were higher than those in the control group. The P2X3 antagonist A317491 decreased mechanical hyperalgesia and thermal hyperalgesia and the up-regulated expression levels of P2X3 mRNA and protein in rats treated with gp120. A317491 decreased ERK1/2 phosphorylation levels in the gp120-treated rat DRG. In addition, P2X3 agonist α,β-methylene ATP (α,β-meATP)-activated currents in DRG neurons cultured with gp120 were higher than those in control neurons. The inhibitory effect of A317491 on α,βme-ATP-induced currents in DRG neurons from the gp120-treated neurons was larger than that for control neurons. Molecular docking data showed that A317491 may be acted in the gp120 protein to inhibit the gp120 initiated the P2X3 activation, decrease the sensitizing DRG primary afferents and reduce the signal transmission of neuropathic pain in gp120-treated rats. Therefore, the inhibition of the P2X3 receptor in rat DRG neurons relieved gp120-induced mechanical hyperalgesia.



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Amelioration of apelin-13 in chronic normobaric hypoxia-induced anxiety-like behavior is associated with an inhibition of NF-κB in the hippocampus

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Publication date: Available online 5 January 2017
Source:Brain Research Bulletin
Author(s): Junming Fan, Lu Ding, Dongmei Xia, Danyang Chen, Pu Jiang, Wenhua Ge, Ru Zhao, Jinbin Guo, Xiaofang Fan, Feng Xue, Yongyu Wang, Sunzhong Mao, Lianggang Hu, Yongsheng Gong
Apelin, a small bioactive peptide, plays an important role in the pathogenesis of mood disorders through the endogenous ligand APJ. Although the anxiolytic effect of apelin is well established, the mechanisms are poorly understood. In this study, we hypothesized that apelin played an anxiolytic role in chronic normobaric hypoxia (CNH)-induced anxiety like behavior in mice, which might be associated with an inhibition of nuclear factor-κB (NF-κB) activation in the hippocampus. To this end, mice were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO2, ∼10%, 23h/d) with or without apelin-13 application (20 nmol.kg−1.d−1, i.p.), for 4 weeks. The anxiety-like behavior was tested by elevated plus maze and open field. Activities of NF-κB, microglial, and related signaling pathways in the hippocampus during this pathological process were examined. We found that CNH treatment decreased APJ but increased Iba-1 proteins expression, as well as nucleus translocation of p50 and p65 in the hippocampus, which were reversed by apelin-13 treatment. In addition, apelin-13 treatment ameliorated CNH-induced anxiety-like behavior in mice, suggesting anxiogenic effect of apelin-13 might be mediated by an inhibition of NF-κB activation in microglial of the hippocampus. Furthermore, apelin-13 treatment reversed p-CAMKII decrease in the hippocampus under CNH treatment. Apelin-13 treatment did not affect anxiety-like behavior and relative proteins expression in normoxia control mice. Finally, we found that rats with CNH treatment decreased APJ expression while enhanced NF-κB activation in the hippocampus, providing additional evidences that NF-κB activation in hippocampus in CNH-induced anxiety-like behavior in rats we reported previously might be associated with an inhibition of APJ activity. In conclusion, the present results illustrated that inhibition of APJ and promotion of NF-κB activation in the microglial of hippocampus might be involved in anxiogenic effect in CNH-exposed mice, and apelin-13 ameliorates CNH-induced anxiety-like behavior might be associated with an inhibition of NF-κB activation.



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Défaut d’information préalable : présomption de la souffrance morale et préjudice d’impréparation

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Publication date: Available online 4 January 2017
Source:Médecine & Droit
Author(s): Nicolas Brunet
Le Conseil d'État, suivant son arrêt en date du 16 juin 2016, poursuit la définition du régime du préjudice d'impréparation résultant du manquement des professionnels de santé à leur obligation d'informer les patients, ainsi qu'en dispose l'article L. 1111-2 du Code de la santé publique. À cette précision, s'ajoute une nouvelle convergence entre jurisprudences administrative et judiciaire. Néanmoins, le Conseil d'État semble marquer le pas vers la reconnaissance d'un droit à l'information qu'avait pu laisser espérer la Cour de cassation.The Conseil d'État, relatively to the ruling dated the 16th of June 2016, keeps defining the legal regime of the harm of unpreparedness which consists in a violation of the health professionals' duty to inform their patients, based on article L. 1111-2 of Code de la santé publique. Moreover, it can be highlighted a shared understanding between the judicial and administrative jurisprudences. Yet, the Conseil d'État is likely withholding the patients' right to information that the Cour de cassation may have headed toward.



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Atlas-Based Mosaicing of Left Atrial 3-D Transesophageal Echocardiography Images

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Publication date: Available online 5 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Harriët W. Mulder, Marijn van Stralen, Ben Ren, Alexander Haak, Max A. Viergever, Johan G. Bosch, Josien P.W. Pluim
Transesophageal echocardiography (TEE) is a promising imaging modality used to guide cardiac interventions, such as catheter ablation for the treatment of cardiac arrhythmias. These procedures rely on good visualization of the left atrium and pulmonary veins. To visualize these structures in a single volume, the acquisition, registration and fusion of multiple TEE views of the left atrium are required. We introduce atlas-based mosaicing as a method for the registration of images that are acquired according to a standardized protocol. Inspired by atlas-based segmentation approaches, compounded data of other patients serve as atlases for the registration of new data. The performance of atlas-based mosaicing is studied on 3-D TEE data of the left atrium and compared with that of regular pairwise registration. This study indicates that improved registration robustness and smaller registration errors are achieved with atlas-based mosaicing compared with regular pairwise registration. This is an important step toward the use of TEE for interventional guidance of ablation procedures.



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Cardiac Shear Wave Velocity Detection in the Porcine Heart

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Publication date: Available online 5 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Hendrik J. Vos, Bas M. van Dalen, Ilkka Heinonen, Johan G. Bosch, Oana Sorop, Dirk J. Duncker, Antonius F.W. van der Steen, Nico de Jong
Cardiac muscle stiffness can potentially be estimated non-invasively with shear wave elastography. Shear waves are present on the septal wall after mitral and aortic valve closure, thus providing an opportunity to assess stiffness in early systole and early diastole. We report on the shear wave recordings of 22 minipigs with high-frame-rate echocardiography. The waves were captured with 4000 frames/s using a programmable commercial ultrasound machine. The wave pattern was extracted from the data through a local tissue velocity estimator based on one-lag autocorrelation. The wave propagation velocity was determined with a normalized Radon transform, resulting in median wave propagation velocities of 2.2 m/s after mitral valve closure and 4.2 m/s after aortic valve closure. Overall the velocities ranged between 0.8 and 6.3 m/s in a 95% confidence interval. By dispersion analysis we found that the propagation velocity only mildly increased with shear wave frequency.



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Nodular Fasciitis: Sonographic–Pathologic Correlation

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Publication date: Available online 5 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Ho-Hsian Yen, Hong-Jen Chiou, Yi-Hong Chou, Chih-Hsueh Chen, Wan-Yuo Guo
We evaluated nodular fasciitis (NF) in 19 patients, focusing on the correlation between its sonographic and histopathologic features. Sonograms were retrospectively reviewed, and the location, shape, margin, echogenicity, echogenic rim, peripheral hyper-echoic nodules, posterior enhancement and vascularity of the lesions were recorded. In the histopathologic analysis, three patterns—infiltrating, pushing border and well circumscribed—were identified, and culture-like tissue centers were classified according to the distribution of focal keloid-like collagen bundles: uneven or even. For the sonographic–pathologic correlation, most NF cases were inhomogeneously hypo-echoic and had an echogenic rim, with an infiltrating or pushing border pattern. In addition, all NF cases with the infiltrating pattern were observed to have peripheral hyper-echoic nodules in sonograms. Thus, echogenic rims may be associated with the peripheral adipose tissues in infiltrating pattern, and the degree of infiltration may be associated with specific sonographic features of NF.



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The steroid metabolite 16(β)-OH-androstenedione generated by CYP21A2 serves as a substrate for CYP19A1

Publication date: Available online 5 January 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): J. Neunzig, M. Milhim, L. Schiffer, Y. Khatri, J. Zapp, A. Sánchez-Guijo, M.F. Hartmann, S.A. Wudy, R. Bernhardt
The 21-hydroxylase (CYP21A2) is a steroidogenic enzyme crucial for the synthesis of mineralo- and glucocorticoids. It is described to convert progesterone as well as 17-OH-progesterone, through a hydroxylation at position C21, into 11-deoxycorticosterone (DOC) and 11-deoxycortisol (RSS), respectively. In this study we unraveled CYP21A2 to have a broader steroid substrate spectrum than assumed. Utilizing a reconstituted in vitro system, consisting of purified human CYP21A2 and human cytochrome P450 reductase (CPR) we demonstrated that CYP21A2 is capable to metabolize DOC, RSS, androstenedione (A4) and testosterone (T). In addition, the conversion of A4 rendered a product whose structure was elucidated through NMR spectroscopy, showing a hydroxylation at position C16-beta. The androgenic properties of this steroid metabolite, 16(β)-OH-androstenedione (16bOHA4), were investigated and compared with A4. Both steroid metabolites were shown to be weak agonists for the human androgen receptor. Moreover, the interaction of 16bOHA4 with the aromatase (CYP19A1) was compared to that of A4, indicating that the C16 hydroxyl group does not influence the binding with CYP19A1. In contrast, the elucidation of the kinetic parameters showed an increased Km and decreased kcat value resulting in a 2-fold decreased catalytic efficiency compared to A4. These findings were in accordance with our docking studies, revealing a similar binding conformation and distance to the heme iron of both steroids. Furthermore, the product of 16bOHA4, presumably 16-hydroxy-estrone (16bOHE1), was investigated with regard to its estrogenic activity, which was negligible compared to estradiol and estrone. Finally, 16bOHA4 was found to be present in a patient with 11-hydroxylase deficiency and in a patient with an endocrine tumor. Taken together, this study provides novel information on the steroid hormone biosynthesis and presents a new method to detect further potential relevant novel steroid metabolites.

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4-HYDROXYNONENAL PROTEIN ADDUCTS: KEY MEDIATOR IN RETT SYNDROME OXINFLAMMATION

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Publication date: Available online 5 January 2017
Source:Free Radical Biology and Medicine
Author(s): Giuseppe Valacchi, Alessandra Pecorelli, Carlo Cervellati, Joussef Hayek
In the last 15 years a strong correlation between oxidative stress (OxS) and Rett syndrome (RTT), a rare neurodevelopmental disorder known to be caused in 95% of the cases, by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, has been well documented. Here, we revised, summarized and discussed the current knowledge on the role of lipid peroxidation byproducts, with special emphasis on 4-hydroxynonenal (4HNE), in RTT pathophysiology. The posttranslational modifications of proteins via 4HNE, known as 4HNE protein adducts (4NHE-PAs), causing detrimental effects on protein functions, appear to contribute to the clinical severity of the syndrome, since their levels increase significantly during the subsequent 4 clinical stages, reaching the maximum degree at stage 4, represented by a late motor deterioration. In addition, 4HNE-PA are only partially removed due to the compromised functionality of the proteasome activity, contributing therefore to the cellular damage in RTT. All this will lead to a characteristic subclinical inflammation, defined "OxInflammation", derived by a positive feedback loop between OxS byproducts and inflammatory mediators that in a long run further aggravates the clinical features of RTT patients. Therefore, in a pathology completely orphan of any therapy, aiming 4HNE as a  therapeutic target could represent a coadjuvant treatment with some beneficial impact in these patients.‬‬‬



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A pilot trial of In vivo NRT sampling to increase medication adherence in community corrections smokers

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Publication date: April 2017
Source:Addictive Behaviors, Volume 67
Author(s): Karen L. Cropsey, Peter S. Hendricks, Samantha Schiavon, Aaron Sellers, Morgan Froelich, Richard C. Shelton, Matthew J. Carpenter
BackgroundIndividuals in the criminal justice system demonstrate high rates of cigarette use (70–80%) and low adherence to smoking cessation medication. Educational approaches have not been shown to promote adherence or cessation, though medication sampling has boosted both use and cessation. The objective of the present study was to determine whether In vivo nicotine replacement therapy (NRT) sampling approach increases NRT adherence among criminal justice smokers during a subsequent quit attempt.MethodsWe conducted a pilot study with 43 community corrections smokers randomized to a 4-session (one 30-min session per week) precessation intervention of either In vivo NRT sampling (Session 1: patch; Session 2: gum; Session 3: combination NRT (cNRT); Session 4: review) vs. 4 time-matched sessions of standard smoking cessation with cNRT started after Session 1. Both groups received an additional 8weeks of cNRT following the four intervention sessions.ResultsDuring the in vivo administration of NRT, total withdrawal and craving severity significantly decreased from pre- to post-session compared to Control participants. In vivo participants evinced greater patch use at Session 4 and greater gum use through Week 8 relative to Controls.DiscussionIn vivo NRT sampling may increase NRT adherence relative to standard counseling sessions among criminal justice smokers. A larger trial of this novel intervention appears to be warranted.



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3D printing of large, complex metallic glass structures

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Yiyu Shen, Yingqi Li, Chen Chen, Hai-Lung Tsai
Metallic glasses (MGs) or amorphous alloys although have superior mechanical properties their products are limited to simple geometries such as foils/plates or rods with thin section-thickness due to the requirement of high cooling rates. In this study, 3D, large dimensions of amorphous structures with complex geometry are manufactured by our newly developed Laser Foil Printing (LFP) technology. Zr-based (LM105, provided by Liquidmetal Technologies, Inc.) amorphous foils of 100μm thickness are used as feedstock, and they are laser welded, layer-by-layer, to become 3D amorphous structures. Test results by X-Ray diffraction (XRD), differential scanning calorimetry (DSC), and micro-hardness confirm that the printed structures at selected process parameters achieve the same or better degree of amorphization as the raw foils. A mathematical model was developed to calculate the heating and cooling rates during structure manufacturing which helps the selection of process parameters. This study expands MG products to 3D arbitrary geometries with large dimensions due to the inherited advantages of the LFP technology which would open many potential applications.



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Low temperature superplastic-like deformation and fracture behavior of nano/ultrafine-grained metastable austenitic stainless steel

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): G.S. Sun, L.X. Du, J. Hu, H. Xie, R.D.K. Misra
We describe here the low temperature superplastic-like deformation in a nano/ultrafine-grained metasable austenitic stainless steel tensile tested at a strain rate of 2.5×10−4s−1 and temperature of 600°C (~0.43 of the absolute melting point). The nano/ultrafine-grained structure was obtained via a combination of cold rolling (~93% in reduction), followed by reversion annealing treatments at 650°C for 10min, 30min, and 700°C for 2min, 5min, respectively, an approach previously adopted by Misra's group (references 11–16). The reversion of martensite to austenite was dominated by diffusional mechanism. The nano/ultrafine-grained steel exhibited superplastic-like behavior with maximum elongation approaching ~153% and strain rate sensitivity of ~0.22. Furthermore, tensile deformation behavior at 20°C and 600°C, and the corresponding fracture characteristics are discussed. Observations of fracture surface indicated that the fracture was characterized by line-up of voids along the striations, when tensile tested at 20°C. Whereas, the fracture surface at 600°C mainly consisted of uniform distribution of dimples. To further study the fracture mechanism during superplastic-like deformation, deformed structures from the longitudinal region close to the tip of the fracture surface were studied. The fracture surface of superplastic-like deformed steel was characterized by interlinkage of cavities.

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Effect of Mn-doping on the structure and electric properties of 0.64Pb(In0.5Nb0.5)O3-0.36PbTiO3 ceramics

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Huimin Qiao, Chao He, Zujian Wang, Xiuzhi Li, Ying Liu, Xiaoming Yang, Hamel Tailor, Xifa Long
In order to study the effect of defect dipoles on relaxor-based ferroelectrics, 0.64Pb(In0.5Nb0.5)O3-0.36Pb(Ti1−xMnx)O3 (x=0−0.15) ferroelectric ceramics were synthesized using the two-step solid state reaction method. The phase structure, ferroelectric, piezoelectric and dielectric properties were investigated. Upon increasing the Mn content, the phase of the ceramics transforms from tetragonal to rhombohedral symmetry, the magnitude of remnant polarization and piezoelectric coefficient decreasing because of the hardening effect of the defect dipoles and the variation of composition. The coercive field, however, decreases from 22kV/cm to 12.5kV/cm with x≤0.04 initially owing to a phase transition, and then increasing since the defect dipoles provided a driving and stabilizing force for domain stability. The stabilizing force also resulted in constricted hysteresis loops for samples with composition of x≥0.04 after aging. The temperature dependence of dielectric properties showed that the Curie temperature decreased from 312°C (x=0) to 237°C (x=0.15), and the degree of relaxor behavior was enhanced with increase of Mn content. It indicates that the defect dipoles, confirmed by the existence of oxygen vacancies, play an important role in the electrical properties of Mn-doping PIN-PT ceramics.

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Protective effects of Tongxinluo on cerebral ischemia/reperfusion injury related to Connexin 43/Calpain II/Bax/Caspase-3 pathway in rat

Publication date: Available online 5 January 2017
Source:Journal of Ethnopharmacology
Author(s): Xiao Cheng, Zijun Hou, Jingbo Sun, Yan Huang, Lixin Wang, Ziyi Zhou, Li-Hua Zhou, Yefeng Cai
Ethnopharmacological relevanceTongxinluo (TXL) is a multifunctional traditional Chinese medicine and has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Numerous studies demonstrate that TXL is a novel neuroprotective drug, however, the mechanisms are largely unknown.Aim of the studywe aimed to demonstrate the protective effect of TXL on cerebral ischemia/reperfusion (I/R) injury and provide the evidence for the involvement of Connexin 43/Calpain II/ Bax/Caspase-3 pathway in TXL-mediated neuroprotection.MethodsFocal cerebral I/R injury were induced by transient middle cerebral artery occlusion (MCAO, for 90min) in adult male Sprague-Dawley rats. We estimated the effects of TXL on I/R injury including neurological deficit assessment and cerebral infarct volume measurement via TTC staining, and detected the protein expression of Connexin 43 (Cx43) by western blot. Furthermore, after the intracerebroventricular injection of carbenoxolone (CBX, the inhibitor of Cx43) at 30min before MCAO surgery, Calpain II, Bax and cleaved Caspased-3 immunoreactivity in ischemic penumbra region was detected by immunofluorescent staining, and cell apoptosis was detected by TUNEL staining.ResultsTXL treatment greatly improved neurological deficit and reduced the infarction volume compared to MCAO with buffer treatment (P<0.05), and TXL pre-post treatment showed better results than TXL pre-treatment. TXL pre-post treatment significantly up-regulated Cx43 protein expression at 3d, 7d and 14d post-injury compared to MCAO with buffer treatment (P<0.05). Meanwhile, the immunoreactivity of Calpain II, Bax and cleaved Caspase-3 in ischemic penumbra region was obviously decreased by TXL pre-post treatment compared to MCAO group (P<0.05). However, with the treatment of the Cx43 inhibitor, CBX, the down-regulated effect of TXL on Calpain II, Bax and cleaved Caspase-3 immunoreactivity was abolished (P<0.05). Moreover, the protective effect of TXL against neuron apoptosis in penumbra region was conteracted by CBX (P<0.05).ConclusionsTXL could effectively protect against I/R injury and reduced cell death via Cx43/Calpain II/Bax/Caspase-3 pathway, which contribute to I/R injury prevention and therapy.

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Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Liu-Cheng Li, Lian-Di Kan
Ethnopharmacological relevancePulmonary fibrosis (PF) is a chronic, debilitating and often lethal lung disorder. Despite the molecular mechanisms of PF are gradually clear with numerous researchers' efforts, few effective drugs have been developed to reverse human PF or even halt the chronic progression to respiratory failure. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years especially in China, often exerts wider action spectrum than previously attempted options in treating human diseases. Recent data have shown the anti-fibrotic benefits of the active ingredients from TCM in this field, which may represent an attractive source of the drug discovery against PF.Aim of the reviewThis review summarizes the pre-clinical and clinical evidence on the benefits of TCM and their active ingredients, and provides a comprehensive information and reliable basis for the exploration of new treatment strategies of botanical drugs in the therapy of PF.MethodsThe literature information was obtained from the scientific databases on ethnobotany and ethno medicines (up to Aug 2016), mainly from the Pubmed, Web of Science and CNKI databases, and was to identify the experimental studies on the anti-fibrotic role of the active agents from TCM and the involved mechanisms. The search keywords for such work included: "lung fibrosis" or "pulmonary fibrosis", and "traditional Chinese medicine", "extract" or "herb".ResultsA number of studies have shown that the active agents of single herbs and TCM formulas, particularly the flavonoids, glycosides and alkaloids, exhibit potential benefits against PF, the mechanisms of which appear to involve the regulation of inflammation, oxidant stress, and pro-fibrotic signaling pathways, etc. Besides, the processing methods for discovering TCM in treating PF were prospectively discussed.ConclusionThese research work have shown the therapeutic benefits of TCM in the treatment of PF. However, more continued researches should be undertaken to clarify the unconfirmed chemical composition and regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. The insights provided in present review will be needed for further exploration of botanical drugs in the development of PF therapy.

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Du-Huo-Ji-Sheng-Tang and its active component Ligusticum chuanxiong promote osteogenic differentiation and decrease the aging process of human mesenchymal stem cells

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Jir-You Wang, Wei-Ming Chen, Che-Sheng Wen, Shih-Chieh Hung, Pei-Wen Chen, Jen-Hwey Chiu
Ethnopharmacological relevancePostmenopausal osteoporosis is the most common bone disease worldwide. Information concerning the effects of herbal medicines on mesenchymal cell osteogenesis and senescence remains lacking.Aim of this studyThis study was designed to investigate the effects of Du-Huo-Ji-Sheng-Tang (DHJST), a Chinese herbal medicine and its active component Ligusticum chuanxiong on osteogenic differentiation and the aging process of human mesenchymal cells (hMSCs).Materials & methodshMSCs were used as in vitro model and osteogenesis was induced by administration of either osteogenesis inducing medium (OIM) or dexamethasone-depleted OIM (DDOIM) for 1-week or 2 weeks and the results were evaluated by measuring the formation of mineralization nodules. The effects of the compound recipe DHJST and its active component L. chuanxiong on hMSCs osteogenesis-related gene expression was determined by real-time PCR that targeted bone morphogenetic protein-2 (BMP2), RUNX2, ALP, COL-1, osteopontin (OPN), and osteocalcin (OCN). Antibodies against BMP-related signaling pathway proteins, such as BMP-2, ERK, SMAD 1/5/8, and RUNX2, were also detected at the protein level by Western blotting. Finally, the cumulative growth curve and senescence of the hMSCs were evaluated in order to assess the aging process.ResultsL. chuanxiong increased osteogenic activity in hMSCs and up-regulated BMP-2 and RUNX2 gene expression via the activation of SMAD 1/5/8 and ERK signaling. Furthermore DHJST also showed a trend towards promoting the same effects in the same system. In the absence of dexamethasone, DHJST did activate SMAD 1/5/8 and ERK signaling and hence increased RUNX2 protein expression in hMSCs. In addition, both DHJST and L. chuanxiong delayed the hMSCs aging process by decreasing cell senescence.ConclusionsWe concluded that DHJST and its active component L. chuanxiong are able to promote osteogenic activity and decrease hMSCs senescence as cells age.

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Anti-inflammatory and antioxidant effect of modified Bazhengsan in a rat model of chronic bacterial prostatitis

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Youyi Xiong, Xingtao Qiu, Weijing Shi, Hao Yu, Xiaolin Zhang
Ethnopharmacological relevanceBazhengsan is a commonly used traditional Chinese prescription for the treatment of the urogenital system diseases for thousands of years, which decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty.Aim of the studyIn this study, the potential of modified Bazhengsan (mBazhengsan) as a chronic bacterial prostate inflammation inhibitor was investigated in a rat model.Materials and methodsRat prostates were injected with Escherichia coli to induce inflammation by the sterile operation. The decoction of mBazhengsan was administered intragastrically once every day from the seventh day of modeling. After 8 weeks, prostates were lavaged with phosphate buffer saline (PBS) and lavages were collected to use for leukocyte and lecithin body count, and then prostate tissues were removed to detect prostate weight, prostate index and microbiological analyses. Prostate histopathological changes were detected by hematoxylin-eosin (HE) staining and masson staining. Bacterial growth in prostate was evaluated by the numbers of tissue culture colonies. The levels of interleukin (IL)-8, IL-1β and tumor necrosis factor (TNF)-a in serums and secretory immunoglobulin (SIg)-A in prostate fluids as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in prostate tissues were detected by analysis kits.ResultsCompared with model group, treatment with mBazhengsan could significantly inhibit the recruitment of leukocyte to prostate tissues and the deposition of collagen fibers in stromas, suppressed bacterial growth in prostate tissues, decreased the numbers of leukocyte and lecithin body in prostate fluids, lowered prostate index, down-regulated the levels of inflammatory mediators (IL-1β, IL-8 and TNF-a) in serums and up-regulated the levels of SIgA in prostate fluids, and reduced the production of free radical in prostate tissues.ConclusionmBazhengsan can significantly suppress rat prostate inflammation and oxidative stress reaction, showing great therapeutic potential to the chronic bacterial prostatitis.

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Effects of Panax notoginseng ginsenoside Rb1 on abnormal hippocampal microenvironment in rats

Publication date: Available online 5 January 2017
Source:Journal of Ethnopharmacology
Author(s): Shiyun Wang, Minghong Li, Ying Guo, Chen Li, Lanou Wu, Xin-Fu Zhou, Yaohui Luo, Dong An, Shude Li, Haiyun Luo, Lijin Pu
Cerebral ischemia damages central neurons, and abnormal microenvironment in ischemic condition is the key factor to the damages. The increase of local concentration of glutamic acid, the overload of Ca2+, and the mitochondrial stress caused by release of cytochrome C are important factors of abnormal microenvironment in cerebral ischemia. In this study ginsenoside Rb1, a compound from Panax Notoginseng, was used to intervene abnormal environment of neurons in the hippocampal CA1 region in two animal models (microperfusion model and photothrombosis model). Results: Compared with the vehical in the sham group, ginsenoside had following effects. a) ginsenoside Rb1 increased the regional cerebral blood flow (rCBF) and the stability of neuronal ultrastructure in in the hippocampal CA1 region and improved the adaptability of neurons in two models. b) ginsenoside Rb1 improved the expression level of glial glutamate transporter1 (GLT-1) and reversed the uptake of glutamate (Glu) after ischemia, and as a result thereby decreased the excitability of Glu and the expression level of GLT-1 was proportional to the dose of ginsenoside Rb1 and similar to that of Nimodipine. c) ginsenoside Rb1 inhibited the expression level of NMDAR and the overload of Ca2+, thereby reducing neuronal damages. Meanwhile, the expression level of NMDAR was inversely proportional to the dose of ginsenoside Rb1, which was similar to that of Nimodipine. d) ginsenoside Rb1 decreased the release of cytochrome C (Cyt-C) and reduced the damages caused by neuronal mitochondrial stress. Meanwhile, the release of Cyt-C was inversely proportional to the dose of ginsenoside Rb1, which was similar to that of Nimodipine.Ginsenoside Rb1 may be as an effective drug for neuroprotection and improve cerebral blood flow after acute ischemia and prevent the secondary brain damage induced by stroke..



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Drug-likeness prediction of chemical constituents isolated from Chinese materia medica Ciwujia

Publication date: Available online 5 January 2017
Source:Journal of Ethnopharmacology
Author(s): Shuai-nan Zhang, Xu-Zhao Li, Xu-yan Yang
Ethnopharmacological relevanceCiwujia (CWJ), one of the most commonly used Chinese materia medicas (CMMs), is derived from the roots, rhizomes, and stems of Acanthopanax senticosus harms (AS). CWJ has been used for the treatment of various central nervous system (CNS) and peripheral system diseases. Drug-likeness prediction can help to analyze the absorption, distribution, metabolism, and excretion (ADME) processes of the compounds in CWJ, as well as their potential therapeutic and toxic effects, which is of significance in the confirmation of the active material bases of CWJ.Materials and methodsThe ADME properties of the compounds were calculated through web based PreADMET program and ACD/I-Lab 2.0. The potential therapeutic and toxicity targets of these compounds were screened by the ChemQuery tool in DrugBank and T3DB.Results14/39 compounds had moderate or good oral bioavailability (OB). 29/39 compounds bound weakly to the plasma proteins. 18/39 compounds might pass across the blood-brain barrier (BBB). Most of these compounds showed low renal excretion ability. 25/39 compounds had 99 structurally similar drugs and 158 potential therapeutic targets. Additionally, 17/39 compounds had 53 structurally similar toxins and 126 potential toxicity targets.ConclusionOur study suggests that these compounds have a certain drug-likeness potentials, which are also likely to be the material bases of CWJ. These results may provide a reference for the safe use of CWJ and the expansion of its application scope.

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Creating dynamic virtual quarantines using “Pokémon Go” to limit infectious diseases spread

Publication date: Available online 5 January 2017
Source:Medical Hypotheses
Author(s): Martijn R. Tannemaat, N. Ahmad Aziz




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Lack of Eye Discipline During Headers in High School Girls Soccer: A Possible Mechanism for Increased Concussion Rates

Publication date: Available online 5 January 2017
Source:Medical Hypotheses
Author(s): Joseph F. Clark, Hagar T. Elgendy-Peerman, Jon G. Divine, Robert E. Mangine, Kimberly A Hasselfeld, Jane C. Khoury, Angelo J. Colosimo
The sport of soccer is the fastest growing and most popular sport worldwide. With this growth and popularity, attention needs to be given to this athletic population. Sports related concussions is a topic that has gained attention both in the media and by governmental organizations, with growing initiatives in diagnosis, prevention and treatment. The act of soccer heading is thought to contribute to increased concussion incidence. Current evidence reveals that within the high school soccer athletic population, female athletes incur a higher concussion rate than males. This is often attributed to many things including differing cervical spinal musculature, skull thickness, etc., but a definitive reason has not yet been found. Other behaviors, such as field awareness and eye discipline on the field of play, may also be contributing factors that result in females incurring a greater concussion rate than males. For the purposes of this paper we define eye discipline as the ability to keep the eyes engaged in sporting activity with high risk potential.We present our hypothesis that high school female soccer players are more likely to have their eyes closed when in position for heading the ball as compared to high school male soccer players and this lack of visual awareness may increase the risk of concussion. Should these differences be substantiated between males and females, it may initiate and promote discussion of the need for vision training in the high school athletic setting. As a tool for injury prevention, vision training may improve specific visual parameters improving athletes' abilities to process the field of play and prepare for or avoid injury causing situations. Through ocular motor and visual conditioning, an athlete may become more eye disciplined, and more likely to have their eyes open during heading of the ball, and more likely to avoid concussions.



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Prefabricated Flaps: Identification of Microcirculation Structure and Supercharging Technique Improving Survival Area

J reconstr Microsurg
DOI: 10.1055/s-0036-1597896



Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Complex Orofacial Reconstruction with the Intrinsic Chimeric Flap

J reconstr Microsurg
DOI: 10.1055/s-0036-1597656

Background Ablation of locally advanced or recurrent head and neck cancer often results in large composite orofacial defects with limited recipient vessels. These complex defects lend well to intrinsic chimeric flap reconstruction, which allows greater ability to inset various flap component tissue types than composite flaps and requires only one set of microvascular anastomoses. Methods A retrospective chart review was performed on all patients who underwent orofacial reconstruction with an intrinsic chimeric free flap from 2002 to 2015. Flaps with only one tissue type, such as two separate skin paddles with no additional component, were not considered chimeric flaps and therefore not included in this report. Patient demographic data, defect, and flap characteristics, as well as complications and outcomes were analyzed to create a guide for flap selection. Univariate and multivariate analysis was performed to determine risk factors for flap take-back and failure. Results Seventy-five patients underwent orofacial intrinsic chimeric free flap reconstruction. Results were organized based on defect characteristics to create a guide for flap selection. The number of chimeric flap components and operation duration were independently statistically associated with flap take-backs (p < 0.05). There were two (3%) total and five (7%) partial flap losses. Average follow-up time was 32.7 months. Conclusions Intrinsic chimeric flaps provide a versatile and elegant reconstructive option for a variety of complex orofacial defects. We provide a guide to facilitate decision making in flap selection for these challenging reconstructions and report factors associated with flap take-backs and losses.
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Plantar flexor muscle weakness and fatigue in spastic cerebral palsy patients

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Daria Neyroud, Stéphane Armand, Geraldo De Coulon, Sarah R Dias Da Silva, Nicola A. Maffiuletti, Bengt Kayser, Nicolas Place
BackgroundPatients with cerebral palsy develop an important muscle weakness which might affect the aetiology and extent of exercise-induced neuromuscular fatigue.AimThis study evaluated the aetiology and extent of plantar flexor neuromuscular fatigue in patients with cerebral palsy.MethodsTen patients with cerebral palsy and 10 age- and sex-matched healthy individuals (∼20 years old, 6 females) performed four 30-s maximal isometric plantar flexions interspaced by a resting period of 2–3s to elicit a resting twitch. Maximal voluntary contraction force, voluntary activation level and peak twitch were quantified before and immediately after the fatiguing task.ResultsBefore fatigue, patients with cerebral palsy were weaker than healthy individuals (341±134N vs. 858±151N, p<0.05) and presented lower voluntary activation (73±19% vs. 90±9%, p<0.05) and peak twitch (100±28N vs. 199±33N, p<0.05). Maximal voluntary contraction force was not significantly reduced in patients with cerebral palsy following the fatiguing task (−10±23%, p>0.05), whereas it decreased by 30±12% (p<0.05) in healthy individuals.ConclusionsPlantar flexor muscles of patients with cerebral palsy were weaker than their healthy peers but showed greater fatigue resistance.What this paper addsCerebral palsy is a widely defined pathology that is known to result in muscle weakness. The extent and origin of muscle weakness were the topic of several previous investigations; however some discrepant results were reported in the literature regarding how it might affect the development of exercise-induced neuromuscular fatigue. Importantly, most of the studies interested in the assessment of fatigue in patients with cerebral palsy did so with general questionnaires and reported increased levels of fatigue. Yet, exercise-induced neuromuscular fatigue was quantified in just a few studies and it was found that young patients with cerebral palsy might be more fatigue resistant that their peers. Thus, it appears that (i) conflicting results exist regarding objectively-evaluated fatigue in patients with cerebral palsy and (ii) the mechanisms underlying this muscle fatigue − in comparison to those of healthy peers − remain poorly understood. The present study adds important knowledge to the field as it shows that when young adults with cerebral palsy perform sustained maximal isometric plantar flexions, they appear less fatigable than healthy peers. This difference can be ascribed to a better preservation of the neural drive to the muscle. We suggest that the inability to drive their muscles maximally accounts for the lower extent of exercise-induced neuromuscular fatigue in patients with cerebral palsy.



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Systematic review of field-based physical fitness tests for children and adolescents with intellectual disabilities

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Marieke Wouters, Heleen M. Evenhuis, Thessa I.M. Hilgenkamp
BackgroundTesting physical fitness in children and adolescents with intellectual disabilities (ID) can be challenging. This review provides an overview on psychometric properties of field-based physical fitness tests studied in children and adolescents with ID.MethodsA literature search was performed in March 2014. Studies were included if they evaluated feasibility, reliability and/or validity of a field-based physical fitness test in children and adolescents with ID.ResultsTwenty-six papers met the inclusion criteria and described 18 tests on body composition (4), muscular strength (4), muscular endurance (6), and cardiorespiratory fitness (4). Best results on feasibility, reliability and/or validity were found for bioelectric impedance analysis, body mass index, grip strength, arm hang and distance run/walk tests. These results were mainly found in adolescents with mild to moderate ID.ConclusionSome tests were found feasible, reliable and/or valid in subgroups of children and adolescents with ID, but not in children and adolescents with all ages and levels of ID. Further assessment is needed before wider application in all children and adolescents with ID.



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Participation of adults with visual and severe or profound intellectual disabilities: Definition and operationalization

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Gineke Hanzen, Ruth M.A. van Nispen, Annette A.J. van der Putten, Aly Waninge
BackgroundThe available opinions regarding participation do not appear to be applicable to adults with visual and severe or profound intellectual disabilities (VSPID). Because a clear definition and operationalization are lacking, it is difficult for support professionals to give meaning to participation for adults with VSPID.AimsThe purpose of the present study was to develop a definition and operationalization of the concept of participation of adults with VSPID.MethodsParents or family members, professionals, and experts participated in an online concept mapping procedure. This procedure includes generating statements, clustering them, and rating their importance. The data were analyzed quantitatively using multidimensional scaling and qualitatively with triangulation.ResultsA total of 53 participants generated 319 statements of which 125 were clustered and rated. The final cluster map of the statements contained seven clusters: (1) Experience and discover; (2) Inclusion; (3) Involvement; (4) Leisure and recreation; (5) Communication and being understood; (6) Social relations; and (7) Self-management and autonomy. The average importance rating of the statements varied from 6.49 to 8.95. A definition of participation of this population was developed which included these seven clusters.ConclusionsThe combination of the developed definition, the clusters, and the statements in these clusters, derived from the perceptions of parents or family members, professionals, and experts, can be employed to operationalize the construct of participation of adults with VSPID. This operationalization supports professionals in their ability to give meaning to participation in these adults. Future research will focus on using the operationalization as a checklist of participation for adults with VSPID.



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Cognitive profiles of adults with high-functioning autism spectrum disorder and those with attention-deficit/hyperactivity disorder based on the WAIS-III

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Chieko Kanai, Ryuichiro Hashimoto, Takashi Itahashi, Masayuki Tani, Takashi Yamada, Haruhisa Ota, Akira Iwanami, Nobumasa Kato
The cognitive profile differences between adult patients with autism spectrum disorder (ASD) and those with attention-deficit/hyperactivity disorder (ADHD) are not well characterized. We examined the cognitive profiles of adults having either ASD (n=120) or ADHD (n=76) with no intellectual disabilities (IQ≥70) using the Wechsler Intelligence Scale III (WAIS-III). Verbal Intelligence (VIQ) − Performance Intelligence (PIQ) difference discrepancies were detected between the two groups. Information subtest scores of the Verbal Comprehension index and Arithmetic and Digit Span subtests of the Freedom from Distractibility index were significantly higher in ASD than in ADHD, while the Picture Completion subtest was significantly lower in ASD. To our knowledge, this is the first study to evaluate the difference in the cognitive profiles of adults with ASD and those with ADHD based on the WAIS III with a large number of participants.



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European Breast Cancer Conference manifesto on breast centres/units

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): Fatima Cardoso, Luigi Cataliotti, Alberto Costa, Susan Knox, Lorenza Marotti, Emiel Rutgers, Marc Beishon
Manifesto—CALL TO ACTION• The 2016 deadline for all patients in European Union countries to access specialist, multidisciplinary breast cancer units or centres, will be missed by most countries, despite numerous resolutions and declarations issued since the year 2000 that have called for universal specialist services. This means that many women, and some men, do not receive optimal breast cancer care in Europe.• We call on policymakers and politicians to ensure, as soon as possible, that all women and men with breast cancer in Europe are treated in a specialist breast unit.To do this, we ask that policymakers and politicians, together with healthcare professionals and patient advocates:- Promote, in public and professional settings, the evidence that breast units staffed with specialist multidisciplinary teams deliver superior care and quality of life to women and men with breast cancer.- Acknowledge the evidence that treatment in multidisciplinary units lead to overall cost savings as well as higher quality of care.- Audit the current national provision of breast cancer care using accredited auditors.- Implement mandatory reimbursement and care models that mean treatment can only be carried out in specialist breast units.- Introduce a breast unit quality certification scheme that is accredited by an accreditation body.- Join European-wide scientific societies and groups that promote the availability and quality of breast units, and together commit to providing access to such units for all patients.



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Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature

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Publication date: March 2017
Source:European Journal of Cancer, Volume 73
Author(s): S. Cuzzubbo, F. Javeri, M. Tissier, A. Roumi, C. Barlog, J. Doridam, C. Lebbe, C. Belin, R. Ursu, A.F. Carpentier
Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD1 constitute a promising class of cancer treatment but are associated with several immune-related disorders. We here review the literature reporting neurological adverse events (nAEs) associated with ICIs. A systematic search of literature, up to February 2016, mentioning nAEs in patients treated with ICIs was conducted. Eligible studies included case reports and prospective trials. One case seen in our ward was also added. Within the 59 clinical trials (totalling 9208 patients) analysed, the overall incidence of nAEs was 3.8% with anti-CTLA4 antibodies, 6.1% with anti-PD1 antibodies, and 12.0% with the combination of both. The clinical spectrum of neurological disorders was highly heterogeneous. Most of these nAEs were grade 1–2 and consisted of non-specific symptoms such as headache (55%). The incidence of high grade nAEs was below 1% for all types of treatment. Headaches, encephalopathies and meningitis were the most commonly reported (21%, 19% and 15%, respectively). Among the 27 case reports, the most common nAEs were encephalopathies, meningoradiculoneuritis, Guillain-Barré like syndromes and myasthenic syndromes. The median time of nAEs onset was 6 weeks. In most cases, drug interruption and steroids led to neurological recovery, even in conditions where steroids are not usually recommended such as Guillain-Barré syndrome.



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The World Health Organisation classification of myelodysplastic syndromes contains prognostically relevant information beyond the prognostic scores IPSS-R or WPSS

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Publication date: Available online 4 January 2017
Source:European Journal of Cancer
Author(s): Konradin Metze, Suiellen C. Reis-Alves, Irene Lorand-Metze




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Clinical effectiveness and cost-effectiveness of surgical options for the management of anterior and/or posterior vaginal wall prolapse: two randomised controlled trials within a comprehensive cohort study – results from the PROSPECT Study.

There was evidence of no benefit from using mesh or graft over standard repair for primary vaginal prolapse surgery at 2 years in terms of efficacy, quality of life and adverse effects.

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Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation

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Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Zi-Fei Zhou, Tuan-Wei Sun, Feng Chen, Dong-Qing Zuo, Hong-Sheng Wang, Ying-Qi Hua, Zheng-Dong Cai, Jun Tan
Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.



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Graphene quantum dots with nitrogen-doped content dependence for highly efficient dual-modality photodynamic antimicrobial therapy and bioimaging

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Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Wen-Shuo Kuo, Hua-Han Chen, Shih-Yao Chen, Chia-Yuan Chang, Pei-Chi Chen, Yung-I Hou, Yu-Ting Shao, Hui-Fang Kao, Chih-Li Lilian Hsu, Yi-Chun Chen, Shean-Jen Chen, Shang-Rung Wu, Jiu-Yao Wang
Reactive oxygen species is the main contributor to photodynamic therapy. The results of this study show that a nitrogen-doped graphene quantum dot, serving as a photosensitizer, was capable of generating a higher amount of reactive oxygen species than a nitrogen-free graphene quantum dot in photodynamic therapy when photoexcited for only 3 min of 670 nm laser exposure (0.1 W cm-2), indicating highly improved antimicrobial effects. In addition, we found that higher nitrogen-bonding compositions of graphene quantum dots more efficiently performed photodynamic therapy actions than did the lower compositions that underwent identical treatments. Furthermore, the intrinsically emitted luminescence from nitrogen-doped graphene quantum dots and high photostability simultaneously enabled it to act as a promising contrast probe for tracking and localizing bacteria in biomedical imaging. Thus, the dual modality of nitrogen-doped graphene quantum dots presents possibilities for future clinical applications, and in particular multidrug resistant bacteria.



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Adsorption-controlled preparation of anionic imprinted amino-functionalization chitosan for recognizing rhenium(VII)

Publication date: 28 April 2017
Source:Separation and Purification Technology, Volume 177
Author(s): Ying Xiong, Yang Song, Qiang Tong, Peng Zhang, Yuejiao Wang, Zhenning Lou, Feng Zhang, Weijun Shan
This study described the synthesis of the Mo(VI)-imprinted ethylenediamine (EDA) grafted chitosan (I-EDA-CS), which is a novel technique in combination with surface imprinting and polymer crosslinking. Results indicated that mass ratio of ammonium molybdate and chitosan as 1g:25g–3g:25g could be conducive to achieve higher adsorption capacity of Re(VII). The maximum adsorption capacity of Re(VII) was found to be 418.98mg·g−1 at 303K with an initial Re(VII) concentration of 500mg·L−1, while maximum adsorption of Re(VII) on the non-imprinted absorbent (N-EDA-CS) was just 83.92mg·g−1. The maximum selectivity coefficients of the I-EDA-CS for Re(VII)/Cu(II), Re(VII)/Zn(II), Re(VII)/Mn(II), Re(VII)/Fe(II) were 1.29, 1.9, 2.31, 1.81, respectively. It revealed that the Mo(VI)-imprinted adsorbent showed superior selectivity and affinity to Re(VII) in case of the existence of competition ions. The analysis results of FT-IR and XPS confirmed that the high adsorption selectivity of the I-EDA-CS attributed to the chelation and electrostatic attraction between the amine groups and Re(VII) anionic complexes in the "cavities". Imprinted I-EDA-CS was successfully employed for the selective adsorption of Re(VII) from industrial wastewater.

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Nature of fly ash amendments differently influences oxidative stress alleviation in four forest tree species and metal trace element phytostabilization in aged contaminated soil: A long-term field experiment

Publication date: April 2017
Source:Ecotoxicology and Environmental Safety, Volume 138
Author(s): Sonia Labidi, Stéphane Firmin, Anthony Verdin, Géraldine Bidar, Frédéric Laruelle, Francis Douay, Pirouz Shirali, Joël Fontaine, Anissa Lounès-Hadj Sahraoui
Aided phytostabilization using coal fly ashes (CFAs) is an interesting technique to clean-up polluted soils and valorizing industrial wastes. In this context, our work aims to study the effect of two CFAs: silico-aluminous (CFA1) and sulfo-calcic (CFA2) ones, 10 years after their addition, on the phytostabilization of a highly Cd (cadmium), Pb (lead) and Zn (zinc) contaminated agricultural soil, with four forest tree species: Robinia pseudoacacia, Alnus glutinosa, Acer pseudoplatanus and Salix alba. To assess the effect of CFAs on trees, leaf fatty acid composition, malondialdehyde (MDA), oxidized and reduced glutathione contents ratio (GSSG: GSH), 8-hydroxy-2′-deoxyguanosine (8-OHdG), Peroxidase (PO) and Superoxide dismutase (SOD) activities were examined. Our results showed that CFA amendments decreased the CaCl2-extractable fraction of Cd and Zn from the soil. However, no significant effect was observed on metal trace element (MTE) concentrations in leaves. Fatty acid percentages were only affected by the addition of sulfo-calcic CFA. The most affected species were A. glutinosa and R. pseudoacacia in which C16:0, C18:0 and C18:2 percentages increased significantly whereas the C18:3 decreased. The addition of sulfo-calcic CFA induced the antioxidant systems response in tree leaves. An increase of SOD and POD activities in leaves of trees planted on the CFA2-amended plot was recorded. Conversely, silico-aluminous CFA generated a reduction of lipid and DNA oxidation associated with the absence or low induction of anti-oxidative processes. Our study evidenced oxidative stress alleviation in tree leaves due to CFA amendments. MTE mobility in contaminated soil and their accumulation in leaves differed with the nature of CFA amendments and the selected tree species.



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Heme iron, non-heme iron, and mineral content of blood clams (Anadara spp.) compared to Manila clams (V. philippinarum), Pacific oysters (C. gigas), and beef liver (B. taurus)

Publication date: April 2017
Source:Journal of Food Composition and Analysis, Volume 57
Author(s): Chad N. Taniguchi, Joannie Dobbs, Michael A. Dunn
Dietary iron exists as heme and non-heme iron. Heme iron is more bioavailable making it more useful in meeting the RDA. Conversely, heme iron may be a risk factor for colorectal cancer. Therefore, it is important to know the heme iron content of foods. Clams have been purported to be excellent sources of both heme and non-heme iron. However, there are limited data on iron composition among bivalves. Our objective was to measure mineral composition in commonly consumed bivalves and highlight differences in heme iron content. Manila clams, Pacific oysters, frozen blood clams (A. granosa), canned blood clams, and canned akagai (A. broughtonii) were assayed. Beef liver was included as a reference food rich in heme iron. Heme iron content, expressed as mg/100g edible portion (EP), ranged from 0.5±0.1 in Manila clams and 0.85±0.03 in Pacific oysters, to 5.8±0.3 in frozen blood clams. Beef liver contained 3.6±0.2mg/100g EP. Non-heme iron ranged from 4.5±0.4 in Manila clams to 9.8±0.6mg/100g EP in canned blood clams. Most products contained nutritionally high levels (>10% DV) of Cu, Mn, Se, and Zn. Pacific oysters and canned blood clams contained potentially toxic levels of Cd if eaten regularly. We conclude that a broader analysis of bivalve products is needed to strengthen food composition databases for heme iron and potentially toxic minerals, and that blood clams would be a more reliable source of bioavailable iron than other bivalves.



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Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study

Abstract

Purpose

Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI.

Methods

Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/m2, respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs). Adverse events and the cabazitaxel pharmacokinetic profile were assessed.

Results

In C-2, three patients receiving cabazitaxel 25 mg/m2 experienced DLTs; maximum tolerated dose (MTD) was 20 mg/m2. In C-3, two patients receiving 20 mg/m2 experienced DLTs; MTD was 15 mg/m2. C-4 was discontinued early due to DLTs. The most frequent cabazitaxel-related, grade 3–4 toxicity was neutropenia (42%). Cabazitaxel clearance normalized to body surface area (CL/BSA) was lower in C-1 (geometric mean [GM] 13.4 L/h/m2) than expected (26.4 L/h/m2), but similar in C-2 (23.5 L/h/m2) and C-3 (27.9 L/h/m2). CL/BSA in C-4 was 18.1 L/h/m2. Compared with C-2, CL/BSA increased 19% in C-3 (GM ratio 1.19; 90% CI 0.74–1.91), but decreased 23% in C-4 (0.77; 0.39–1.53). Cabazitaxel free fraction was unaltered. No significant correlation was found between grade 3–4 toxicities and pharmacokinetic parameters.

Conclusions

Mild–moderate HI did not cause substantial decline in cabazitaxel clearance. Cabazitaxel dose reductions in patients with mild–moderate HI, and a contraindication in patients with severe HI, are justified based on safety data.



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Maspin inhibits macrophage phagocytosis and enhances inflammatory cytokine production via activation of NF-κB signaling

Publication date: February 2017
Source:Molecular Immunology, Volume 82
Author(s): Yimeng Wang, Luguo Sun, Zhenbo Song, Danfeng Wang, Yongli Bao, Yuxin Li
Maspin (mammary serine protease inhibitor) is a non-inhibitory member of the serine protease inhibitor superfamily and a tumor suppressor in several cancers due to its ability to inhibit cell invasion, angiogenesis, and promote apoptosis. However, its immunomodulatory function remains largely unexplored. Thus, we explored the potential link between Maspin and macrophage function, first evaluating the regulatory effects of conditioned medium (CM) of a Maspin-overexpressing CHO cell strain on mouse peritoneal macrophage phagocytosis and cytokine secretion. Next, we used a transwell co-culture system and recombinant Maspin (rMaspin) to confirm the effects of Maspin on macrophages, and attempted to clarify the underlying mechanisms. We found that irrespective of CM, rMaspin or co-culture of Maspin-overexpressing cells with macrophages impaired macrophages phagocytosing Saccharomyces cerevisiae. Furthermore, q-RT-PCR or ELISA confirmed increased IL-1β, TNF-α, IFN-γ, IL-6, IL-12, IL-10, and M1 marker iNOS production in macrophages after Maspin stimulation, but TGF-β and M2 marker Arg-1 production were suppressed. Western blot showed activated NF-κB signaling in Maspin-stimulated macrophages; upregulated cytokines were lowered, and impaired phagocytosis recovered after blocking NF-κB signaling with PDTC. Thus, Maspin mildly inhibited phagocytic activity, but markedly enhanced inflammatory cytokine production and likely skewed macrophages towards M1 polarization, partially due to activation of NF-κB signaling. These results reveal a novel biological function of Maspin in modulating macrophage activity and may open a new avenue for Maspin-based tumor therapy.

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Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice

Publication date: February 2017
Source:Molecular Immunology, Volume 82
Author(s): Ajay Amit, Vijayamahantesh, Manas R. Dikhit, Ashish Kumar Singh, Vikash Kumar, Shashi S. Suman, Ashu Singh, Akhilesh Kumar, Ajit Kumar Thakur, Vidyanand Ravi Das, Pradeep Das, Sanjiva Bimal
In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-γ, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future.

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Manufacture and optimization of low-cost tubular ceramic supports for membrane filtration: application to algal solution concentration

Abstract

Low-cost tubular macroporous supports for ceramic membranes were elaborated using the extrusion method, followed by curing, debinding, and sintering processes, from a powder mixture containing kaolin, starch, and sand. The obtained substrates were characterized using mercury intrusion porosimetry, water absorption test, water permeability, scanning electron microscopy, and three-point bending test to evaluate the effects of the additives on the relevant characteristics. According to experimental results, adding the starch ratio to the kaolin powder shows a notable impact on the membrane porosity and consequently on the water permeability of the tubular supports, whereas their mechanical strength decreased compared to those prepared from kaolin alone. It has been shown that the addition of an appropriate amount of starch to the ceramic paste leads to obtaining membrane supports with the desired porosity. Indeed, the water permeability increased significantly from 20 to 612 L h−1 m−2 bar−1 for samples without and with 20 wt% of starch, respectively, as well as the open porosity, the apparent porosity, and the pore size distribution. The bending strength decreased slightly and reached about 4 MPa for samples with the highest starch amounts. On the other hand, the incorporation of sand in a mixture of kaolin + 10 wt% starch increased the mechanical strength and the water permeability. The samples containing 3 wt% of sand exhibited a bending strength four times higher than the supports without sand; the water permeability measured was about 221 L h−1 m−2 bar−1. These elaborated tubular supports for membrane are found to be suitable for solution concentration; they were applied for algal solution and are also easily cleaned by water.



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Assessing geotechnical centrifuge modelling in addressing variably saturated flow in soil and fractured rock

Abstract

The vadose zone typically comprises soil underlain by fractured rock. Often, surface water and groundwater parameters are readily available, but variably saturated flow through soil and rock are oversimplified or estimated as input for hydrological models. In this paper, a series of geotechnical centrifuge experiments are conducted to contribute to the knowledge gaps in: (i) variably saturated flow and dispersion in soil and (ii) variably saturated flow in discrete vertical and horizontal fractures. Findings from the research show that the hydraulic gradient, and not the hydraulic conductivity, is scaled for seepage flow in the geotechnical centrifuge. Furthermore, geotechnical centrifuge modelling has been proven as a viable experimental tool for the modelling of hydrodynamic dispersion as well as the replication of similar flow mechanisms for unsaturated fracture flow, as previously observed in literature. Despite the imminent challenges of modelling variable saturation in the vadose zone, the geotechnical centrifuge offers a powerful experimental tool to physically model and observe variably saturated flow. This can be used to give valuable insight into mechanisms associated with solid–fluid interaction problems under these conditions. Findings from future research can be used to validate current numerical modelling techniques and address the subsequent influence on aquifer recharge and vulnerability, contaminant transport, waste disposal, dam construction, slope stability and seepage into subsurface excavations.



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Enhanced bacterial affinity of PVDF membrane: its application as improved sea water sampling tool for environmental monitoring

Abstract

Isolation of diversified bacteria from seawater is a major challenge in the field of environmental microbiology. In the present study, an attempt has been made to select specific membrane with improved property of attaching diversified bacteria. Initially, different concentrations (15, 18, and 20% W/W) of polysulfone (PSF) were used to check their affinity for the attachment of selected gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria. Among these, 20% W/W PSF showed maximum attachment. Therefore, membrane prepared with other materials such as polyvinylidene fluoride (PVDF) and polyether sulfone (PES) were used with the same concentration (20% W/W) to check their improved bacterial attachment property. Comparative study of bacterial attachment on three different membranes revealed that PVDF possessed the highest affinity towards both the groups of bacteria. This property was confirmed by different analytical methods viz. contact angle, atomic force microscopy, zeta potential, and flux study and further validated with seawater samples collected from seven sites of western coast and Lakshadweep island of India, using Biolog EcoPlate™. All the samples showed that bacterial richness and diversity was high in PVDF membrane in comparison to surrounding seawater samples. Interestingly, affinity for more diversified bacteria was reported to be higher in water sample with less turbidity and low bacteria load. This finding can facilitate the development of PVDF (20% W/W) membrane as a simple, cheap, and less labor intensive environmental sampling tool for the isolation of diversified bacteria from seawater sample wih different physiochemical properties.

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Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the Quality by Design method

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): A. Kovács, Sz. Berkó, E. Csányi, I. Csóka
The aim of our present work was to evaluate the applicability of the Quality by Design (QbD) methodology in the development and optimalization of nanostructured lipid carriers containing salicyclic acid (NLC SA). Within the Quality by Design methology, special emphasis is layed on the adaptation of the initial risk assessment step in order to properly identify the critical material attributes and critical process parameters in formulation development.NLC SA products were formulated by the ultrasonication method using Compritol 888 ATO as solid lipid, Miglyol 812 as liquid lipid and Cremophor RH 60® as surfactant. LeanQbD Software and StatSoft. Inc. Statistica for Windows 11 were employed to indentify the risks.Three highly critical quality attributes (CQAs) for NLC SA were identified, namely particle size, particle size distribution and aggregation. Five attributes of medium influence were identified, including dissolution rate, dissolution efficiency, pH, lipid solubility of the active pharmaceutical ingredient (API) and entrapment efficiency.Three critical material attributes (CMA) and critical process parameters (CPP) were identified: surfactant concentration, solid lipid/liquid lipid ratio and ultrasonication time. The CMAs and CPPs are considered as independent variables and the CQAs are defined as dependent variables. The 23 factorial design was used to evaluate the role of the independent and dependent variables. Based on our experiments, an optimal formulation can be obtained when the surfactant concentration is set to 5%, the solid lipid/liquid lipid ratio is 7:3 and ultrasonication time is 20min. The optimal NLC SA showed narrow size distribution (0.857±0.014) with a mean particle size of 114±2.64nm. The NLC SA product showed a significantly higher in vitro drug release compared to the micro-particle reference preparation containing salicylic acid (MP SA).

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When should contact precautions be discontinued for patients with methicillin-resistant Staphylococcus aureus?

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1
Author(s): Lauren E. Richey, Yumi Oh, Djeunou M. Tchamba, Michelle Engle, Linda S. Formby, Cassandra D. Salgado
When to discontinue contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA) remains unresolved and policies vary between hospitals. We prospectively performed admission active surveillance cultures on patients known to have been MRSA positive for at least 1 year to determine the proportion who remained positive. The proportion of patients with MRSA who remained positive was 19.9%; however, this significantly decreased over time, particularly after 5 years.



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Response to “Perspectives from the field in response to ‘It is time to revise our approach to registering antimicrobial agents [by the Environmental Protection Agency] for health care settings’”

Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1
Author(s): Evelyn Alvarez, Daniel Uslan, Timothy Malloy, Peter Sinsheimer, Hilary Godwin

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Hospital-wide chlorhexidine gluconate bed bathing protocol: A cross-sectional study in a single hospital

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Publication date: Available online 5 January 2017
Source:American Journal of Infection Control
Author(s): Sara M. Reese, Nicole Burnet, Jan Smith, Heather Escudero, Bryan C. Knepper, Heather L. Young
The objective of this study was to determine understanding of bed bathing practices over time after the implementation of a standardized bed bathing protocol. An online survey addressing bathing practices was administered preintervention and 6 and 18 months postintervention to all nurses and technicians caring for adult patients. Survey responses suggested that the intervention resulted in sustained understanding of the standardized bed bathing protocol.



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Table of Contents

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1





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Editorial Board

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1





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APIC Masthead

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1





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Information for Readers

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1





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Registration for the 44th Annual Conference is now open

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1





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Clostridium difficile contamination of health care workers' hands and its potential contribution to the spread of infection: Review of the literature

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1
Author(s): Ingrid Jullian-Desayes, Caroline Landelle, Marie-Reine Mallaret, Christian Brun-Buisson, Frédéric Barbut
BackgroundClostridium difficile infection (CDI) can be transmitted from patient to patient by the hands of health care workers (HCWs); however, the relative importance of this route in the spread of C difficile in the hospital is currently unknown. Our aim was to review studies examining HCWs' hand carriage and its potential role in CDI transmission.MethodsFirst, English-speaking references addressing HCWs' hand sampling obtained from the PubMed database were reviewed. Second, C difficile outbreaks definitely or probably implicating HCWs were retrieved from the Outbreak Database Web site (http://ift.tt/2hVJ76N). Finally, cases of C difficile occurring in HCWs after contact with an infected patient were retrieved from PubMed.ResultsA total of 11 studies dealing with HCWs' hand carriage were selected and reviewed. Between 0% and 59% of HCWs' hands were found contaminated with C difficile after caring for a patient with CDI. There were several differences between studies regarding site of hands sampling, timing after contact, and bacteriologic methods. Only 2 C difficile outbreaks implicating HCWs and 6 series of cases of transmission from patients to HCWs have been reported.ConclusionsThis review shows that HCWs' hands could play an important role in the transmission of C difficile. Hand hygiene and reduction of environmental contamination are essential to control C difficile transmission.



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Preparedness planning and care of patients under investigation for or with Ebola virus disease: A survey of physicians in North America

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Publication date: 1 January 2017
Source:American Journal of Infection Control, Volume 45, Issue 1
Author(s): Jessica D. Lewis, Kyle B. Enfield, Trish M. Perl, Costi D. Sifri
The West African Ebola virus disease (EVD) epidemic of 2014-2015 required North American hospitals to undertake comprehensive planning and training for the potential need to care for patients with EVD. Here we describe physician contributions to EVD preparedness planning and the care of persons under investigation for or patients with EVD.



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