A new type of distance metric and its use for clustering

Abstract

In order to address high dimensional problems, a new 'direction-aware' metric is introduced in this paper. This new distance is a combination of two components: (1) the traditional Euclidean distance and (2) an angular/directional divergence, derived from the cosine similarity. The newly introduced metric combines the advantages of the Euclidean metric and cosine similarity, and is defined over the Euclidean space domain. Thus, it is able to take the advantage from both spaces, while preserving the Euclidean space domain. The direction-aware distance has wide range of applicability and can be used as an alternative distance measure for various traditional clustering approaches to enhance their ability of handling high dimensional problems. A new evolving clustering algorithm using the proposed distance is also proposed in this paper. Numerical examples with benchmark datasets reveal that the direction-aware distance can effectively improve the clustering quality of the k-means algorithm for high dimensional problems and demonstrate the proposed evolving clustering algorithm to be an effective tool for high dimensional data streams processing.

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Effects of salinity on oil dispersant toxicity in the eastern mud snail, Ilyanassa obsoleta

Abstract

Chemical dispersants can be a beneficial method for breaking up oil slicks; however, their use in mitigation could pose potential toxic effects on the marine ecosystem. Dispersants may be transported to lower salinity habitats, where toxicity data for aquatic species have not been established. This study examined the effect of salinity on oil dispersant toxicity in the eastern mud snail, Ilyanassa obsoleta, using two dispersants authorized for oil spill response, Corexit® 9500A and Finasol® OSR 52. Median lethal toxicity values (LC50) and sublethal effects were examined at 10, 20, and 30 ppt salinity in adult and larval mud snails. Two biomarkers (lipid peroxidation and acetylcholinesterase) were used to measure sublethal effects. The 96-h static renewal LC50 values indicated significant differences in toxicity between dispersants and salinities. Larval snails were significantly more sensitive than adult snails to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Larval snails were more sensitive to dispersants at lower salinity, but adult snails were more sensitive at higher salinities. Dispersants increased lipid peroxidation and decreased acetylcholinesterase activity. These results demonstrate that dispersant toxicity varies among compounds and organism life stages, and that physicochemical properties of the environment, such as salinity, can affect the potential toxicity to estuarine species.

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Central Retinal Vein Occlusion in 2 Patients Using Antipsychotic Drugs

Purpose: To report our findings in 2 patients who developed a central retinal vein occlusion (CRVO) and were chronic users of antipsychotic medications. Case Presentation: Case 1 was a 62-year-old woman who had a sudden reduction of vision in her right eye to 20/2,000. Her fundus showed signs of an impending CRVO with marked macular edema. She had been taking antipsychotic drugs (quetiapine fumarate and risperidone) for about 2 years. She refused anti-VEGF therapy for her macular edema but selected systemic kallidinogenase. Two days later, the macular edema was significantly reduced but the number of cotton wool spots (CWS) was increased. Ten days later, the macular edema was resolved and her BCVA improved to 20/60. The CWS gradually disappeared, and her BCVA improved to 20/20. Case 2 was a 43-year-old man who presented with vision reduction in his right eye of 1 week's duration. His BCVA was 20/50 and his fundus showed signs of a CRVO-related macular edema with CWS in the peripapillary area. He had been taking sulpiride (Dogmatyl^TM) for depression for 1 year, and his blood test showed an increase in red blood cells and hematocrit. Anti-VEGF therapy was performed, and the macular edema was resolved with vision improving to 20/20. There has been no recurrence to date in both cases. Conclusions: These results indicate that a CRVO can be a complication of chronic use of antipsychotic medications. However, early treatment can lead to good outcomes. Clinicians should question patients who develop a sudden CRVO whether they are using antipsychotic medications.
Case Rep Ophthalmol 2017;8:410–415

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Fundus Findings in Wernicke Encephalopathy

Wernicke encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine (vitamin B₁) deficiency, classically characterized by the triad of ophthalmoplegia, confusion, and ataxia. While commonly associated with chronic alcoholism, WE may also occur in the setting of poor nutrition or absorption. We present a 37-year-old woman who underwent laparoscopic sleeve gastrectomy and presented with visual disturbance with bilateral horizontal nystagmus, confusion, and postural imbalance. Fundus examination revealed bilateral optic disc edema with a retinal hemorrhage in the left eye. Metabolic workup demonstrated thiamine deficiency. Her symptoms resolved after thiamine treatment. This case raises the awareness of the possibility of posterior segment findings in WE, which are underreported in WE.
Case Rep Ophthalmol 2017;8:406–409

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Neuroanesthesiology: the ineludible path toward super-specialty.

No abstract available

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Neuroanesthesiology: the ineludible path toward super-specialty.

No abstract available

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Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria

Abstract

According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, assessment of exon 4 mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1 or IDH2) is an essential step in the characterization of gliomas. The p.R132H mutation is the most frequent alteration in IDH genes, however other non-canonical IDH mutations can be identified. The aim of this study is to investigate in depth the prevalence of non-R132H IDH ("non-canonical") mutations in brain tumors classified according to the 2016 WHO scheme and their clonal distribution in neoplastic cells. A total of 288 consecutive cases of brain gliomas (grade II–IV) were analyzed for exon 4 IDH1 and IDH2 mutations. IDH1 and IDH2 analysis was performed using next generation sequencing. Non-canonical IDH mutations were identified in 13/52 (25.0%) grade II gliomas (astrocytomas: 8/31, 25.8%; oligodendrogliomas: 5/21, 23.8%) and in 5/40 (12.5%) grade III gliomas (astrocytomas: 3/25, 12.0%; oligodendrogliomas: 2/15, 13.3%). They were not identified in 196 grade IV gliomas (192 glioblastomas, 4 gliosarcomas). In the large majority (>80%) of tumors IDH mutations, both IDH1-R132H and the non-canonical ones, were present in the large majority (>80%) of neoplastic cells. Our data highlight the importance of investigating not only the IDH1-R132H mutation but also the non-canonical ones. These mutations are clonally distributed, with proportions of mutated neoplastic cells overlapping with those of p.R132H, a finding consistent with their driver role in gliomagenesis.

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Internal carotid, external carotid and vertebral artery blood flow responses to a 3-day of head-out dry immersion

Abstract

We have recently demonstrated that heterogeneous cerebral blood flow (CBF) response in each cerebral artery may contribute to the maintenance of circulatory homeostasis in the brain. However, to what extent weightlessness associated with fluid shift from peripheral to central circulations influences distribution of CBF in each cerebral artery remains unknown. We hypothesised that dry immersion-induced fluid shift (weightlessness condition) would cause heterogeneous CBF response in each cerebral artery. During and after a 3-day dry immersion, internal carotid (ICA), external carotid (ECA) and vertebral arteries (VA) blood flows were measured by Doppler ultrasonography using an 8-MHz linear transducer. Although the 3-day dry immersion and the 2-day recovery period did not change blood flow in each cerebral artery, both ICA and VA conductance decreased during dry immersion on day 2 and day 3 (ICA, 2.95 and 3.23 ml min⁻¹ mmHg⁻¹; VA, 1.10 and 1.05 ml min⁻¹ mmHg⁻¹) from the baseline (ICA, 3.47 ml min⁻¹ mmHg⁻¹, P = 0.027; VA, 1.23 ml min⁻¹ mmHg⁻¹, P = 0.004). In addition, Pearson correlation analysis demonstrated that the 3-day dry immersion-induced a decrease in cardiac output (P = 0.004) was associated with changes in ICA (P = 0.046) and VA blood flow (P = 0.021), but not ECA blood flow (P = 0.466). These findings suggest that short exposures to weightlessness via a cephalad redistribution of fluid volume and blood flow in the human body influenced cerebral vasculature in each cerebral artery but did not cause heterogeneous CBF response in each cerebral artery.

This article is protected by copyright. All rights reserved

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A Small Cellulose-Binding-Domain Protein (CBD1) in Phytophthora is Highly Variable in the Non-binding Amino Terminus

Abstract

The small cellulose-binding-domain protein CBD1 is tightly bound to the cellulosic cell wall of the plant pathogenic stramenopile Phytophthora infestans. Transgene expression of the protein in potato plants also demonstrated binding to plant cell walls. A study was undertaken using 47 isolates of P. infestans from a worldwide collection, along with 17 other Phytophthora species and a related pathogen Plasmopara halstedii, to determine if the critical cell wall protein is subject to amino acid variability. Within the amino acid sequence of the secreted portion of CBD 1, encoded by the P. infestans isolates, 30 were identical with each other, and with P. mirabilis. Four isolates had one amino acid difference, each in a different location, while one isolate had two amino acid substitutions. The remaining 13 isolates had five amino acid changes that were each in identical locations (D17/G, D31/G, I32/S, T43/A, and G50/A), suggesting a single origin. Comparison of P. infestans CBD1 with other Phytophthora species identified extensive amino acid variation among the 60 amino acids at the amino terminus of the protein, and a high level of conservation from G61, where the critical cellulose-binding domain sequences begin, to the end of the protein (L110). While the region needed to bind to cellulose is conserved, the region that is available to interact with other cell wall components is subject to considerable variation, a feature that is evident even in the related genus Plasmopara. Specific changes can be used in determining intra- and inter-species relatedness. Application of this information allowed for the design of species-specific primers for PCR detection of P. infestans and P. sojae, by combining primers from the highly conserved and variable regions of the CBD1 gene.

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Changes in the Intestinal Microbiota of Gibel Carp ( Carassius gibelio ) Associated with Cyprinid herpesvirus 2 (CyHV-2) Infection

Abstract

Gut microbiota are integral to the host, and have received increased attention in recent years. However, information regarding the intestinal microbiota of many aquaculture animals is insufficient; elucidating the dynamics of the intestinal microbiota can be beneficial for nutrition, immunity, and disease control. In this study, we used 16S rRNA sequencing to observe changes in the intestinal microbiota of gibel carp (Carassius auratus gibelio) associated with cyprinid herpesvirus 2 (CyHV-2) infection. Our results indicate that the diversity of the intestinal microbiota was strongly reduced, and the composition was dramatically altered following CyHV-2 infection. The most dominant species in healthy fish were Cetobacterium, Rhodobacter, and Crenothrix; meanwhile, Cetobacterium, Plesiomonas, Bacteroides, and Flavobacterium were the most abundant species in sick fish. Plesiomonas was highly abundant in infected samples, and could be used as a microbial biomarker for CyHV-2 infection. Chemical properties of the aquaculture water were significantly correlated with the microbial community structure; however, it is difficult to determine whether these changes are a cause or consequence of infection. However, it may be possible to use probiotics or prebiotics to restore the richness of the host intestinal microbiota in infected animals to maintain host health.

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Masthead

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8





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Editorial Board Page

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8





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Table of Contents

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8





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AAOMS Author Disclosure forms

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8





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Making Research One of Our Key Priorities

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8
Author(s): James R. Hupp




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Influence of Lateral-Medial Sinus Width on No-Grafting Inlay Osteotome Sinus Augmentation Outcomes

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8
Author(s): Xiaohui Cheng, Xiucheng Hu, Shuangquan Wan, Xiachen Li, Yiming Li, Feilong Deng
PurposeIntrasinus new bone formation (BF) has been observed after no-grafting osteotome sinus augmentation, and it is hypothesized to be influenced by the dimensions of the maxillary sinus. The aim of this clinical trial is to evaluate the influence of lateral-medial sinus width (SW) on no-grafting osteotome sinus augmentation outcomes using cone-beam computed tomography.Patients and MethodsAll patients recruited for this prospective study were treated with no-grafting osteotome sinus augmentation with simultaneous implant placement. Cone-beam computed tomography was obtained before, immediately after, and 6 months after the surgical procedure to use for measurements. Descriptive statistics were calculated and univariate, bivariate, and multivariate analysis were conducted to evaluate the influence of average SW and other relevant factors on procedure outcomes, including new BF, residual bone resorption (BR), and change of peri-implant bone height (CPBH).ResultsA total of 48 implants placed in 32 elevated sinuses of 29 patients were included. The average SW was 11.3 ± 1.8 mm. Intrasinus BF measured 1.7 ± 0.9 mm at 6 months after surgery. The amount of BR was 0.3 ± 0.9 mm, and CPBH was calculated as 1.3 ± 1.3 mm. Multivariate analysis showed a negative correlation between SW and BF (r = –0.469, P = .001), as well as between SW and CPBH (r = –0.562, P = .001). A positive correlation was discovered between SW and BR (r = 0.311, P = .027) in general.ConclusionsThe lateral-medial SW was observed to have a negative correlation with new BF and CPBH after no-grafting osteotome sinus augmentation.



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Surgical Uprighting Is a Successful Procedure for Management of Impacted Mandibular Second Molars

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8
Author(s): Bonnie L. Padwa, Rushil R. Dang, Cory M. Resnick
PurposeImpacted mandibular second molars can cause caries and root resorption on adjacent molars and can lengthen orthodontic treatment. Surgical uprighting is one management option. The purposes of this study were to 1) evaluate radiographic outcomes for surgical uprighting of impacted mandibular second molars and 2) propose an etiology for impaction.Materials and MethodsThis was a retrospective cohort study of patients who had surgical uprighting of mandibular second molars and had preoperative and at least 12-month postoperative panoramic images and an age- and gender-matched control group of patients undergoing routine orthodontic treatment. Predictor variables included age, gender, impaction type, preoperative angle of impaction, preoperative periodontal bone level distal to an adjacent first molar, posterior eruption space, pathology, and concomitant extraction of the adjacent third molar. Outcome variables were change in impaction type, postoperative periodontal bone levels around the first and second molars, postoperative tooth angle and posterior eruption space, periapical radiolucency, pulpal obliteration, root resorption, and need for extraction. Descriptive statistics were calculated.ResultsThe sample and control groups each had 16 patients. The mean ages at the first radiographs were 13 ± 1.1 and 13.19 ± 0.61 years for the treatment and control groups, respectively, and the mean follow-up radiographs were obtained 2.4 ± 1.4 and 2.3 ± 0.82 years later. No preoperative images showed pathologic lesions obstructing eruption. Postoperatively, all uprighted molars were Pell and Gregory type IA. The mean change in the angles of the uprighted teeth was 23.5 ± 16.1° (P < .001). The mean distal bone levels of the adjacent first molar were 3.41 ± 1.52 mm preoperatively and 1.45 ± 0.54 mm postoperatively (improvement, 42.5%; P < .001). The preoperative posterior eruption space was 53.6% longer in the control than in the treatment group (P < .001), and the increase in this distance postoperatively was greater for the treatment group than for the control group (P < .001). Pulpal obliteration (n = 6; 31.5%), periapical radiolucency (n = 2; 10.5%), and root resorption (n = 1; 5.3%) were seen on postoperative radiographs. There were 2 failures (10.5%).ConclusionsSurgical uprighting of mandibular second molars is a useful procedure with a low failure rate. Insufficient space for eruption is the likely primary etiology for impaction.



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Oculocardiac Reflex in an Orbital Fracture Without Entrapment

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8
Author(s): Timothy C. Woernley, Thomas L. Wright, Duc N. Lam, Jonathon S. Jundt
Large orbital fractures in older patients are infrequently associated with an exaggerated oculocardiac reflex. This report describes the case of a patient in his 40s with a large right orbital floor and medial wall fracture without radiographic evidence of extraocular muscle compression or entrapment who developed severe nausea and bradycardia with movement of his affected eye. The patient exhibited bradycardia to 17 beats per minute during the initial examination and was taken urgently to the operating room for reconstruction of the right orbital floor and medial wall. Additional episodes of bradycardia intraoperatively were responsive to glycopyrrolate. After the procedure, the patient's pain was decreased, a normal range of motion was restored, and the bradycardia and nausea resolved. An explanation for induction of the oculocardiac reflex is considered in the absence of clinical or radiologic entrapment because large orbital fractures are not often considered to induce this reflex.



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A Review of In-Office Dynamic Image Navigation for Extraction of Complex Mandibular Third Molars

Publication date: August 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 8
Author(s): Robert W. Emery, Oxana Korj, Ravi Agarwal
PurposeWe performed a retrospective review of in-office removal of complex mandibular third molars with a dynamic image navigation system (DINS).Materials and MethodsA retrospective review was conducted of cases completed from 2010 to 2014 by a single oral and maxillofacial surgeon. The average age of the patients was 47 years (range, 27 to 72 years). Extraction complexity was classified with Juodzbalys and Daugela's classification system. The included study cases had complexity scores of 9 or greater. Each patient received custom intraoral splints to secure the tracking array and underwent cone beam computed tomography image acquisition. All surgical procedures were performed with a precalibrated tracking straight handpiece under dynamic navigation.ResultsAll 25 cases were treated successfully with the use of the DINS. Twelve of these cases were associated with pathologic lesions. Three patients were noted to have inferior alveolar nerve paresthesia. One patient sustained a pathologic fracture at week 2. Postoperative infections were noted in 7 cases, 2 of which had a pre-existing infection. One patient reported temporary limitation of mouth opening. A coronectomy was performed in 1 case.ConclusionsWe present results using a new technology, the DINS, for removal of complex mandibular third molars. Potential advantages are 1) improved visualization and localization of anatomic structures such as the inferior alveolar nerve, lingual cortical plate, and adjacent roots; 2) improved control during osteotomy; 3) decreased surgical access requirements and reduction in overall bone removal; 4) ability to perform complex procedures successfully in an in-office setting; 5) decreased surgical time resulting from improved visualization; and 6) potential use as a teaching tool. Possible limitations of the use of an in-office DINS include increased cost, increased time attributed to presurgical planning, initial learning curve, and optical array interference by the surgeon or assistants during surgery.



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The role of GLI2-ABCG2 signaling axis for 5Fu resistance in gastric cancer

Publication date: Available online 25 July 2017
Source:Journal of Genetics and Genomics
Author(s): Beiqin Yu, Dongsheng Gu, Xiaoli Zhang, Bingya Liu, Jingwu Xie
Gastric cancer is a leading cause of cancer-related mortality worldwide, and options to treat gastric cancer are limited. Fluorouracil (5Fu)-based chemotherapy is frequently used as a neoadjuvant or an adjuvant agent for gastric cancer therapy. Most patients with advanced gastric cancer eventually succumb to the disease despite the fact that some patients respond initially to chemotherapy. Thus, identifying molecular mechanisms responsible for chemotherapy resistance will help design novel strategies to treat gastric cancer. In this study, we discovered that residual cancer cells following 5Fu treatment have elevated expression of hedgehog target genes GLI1 and GLI2, suggestive of hedgehog (Hh) signaling activation. Hh signaling, a pathway essential for embryonic development, is an important regulator for putative cancer stem cells/residual cancer cells. We found that high GLI1/GLI2 expression is associated with some features of putative cancer stem cells, such as increased side population. We demonstrated that GLI2 knockdown sensitized gastric cancer cells to 5Fu treatment, decreased ABCG2 expression, and reduced side population. Elevated GLI2 expression is also associated with an increase in tumor sphere size, another marker for putative cancer stem cells. We believe that GLI2 regulates putative cancer stem cells through direct regulation of ABCG2. ABCG2 can rescue the Gli2 shRNA effects in 5Fu response, tumor sphere formation and side population changes, suggesting that ABCG2 is an important mediator for GLI2-associated 5Fu resistance. The relevance of our studies to gastric cancer patient care is reflected by our discovery that high GLI1/GLI2/ABCG2 expression is associated with a high incidence of cancer relapse in two cohorts of gastric cancer patients who underwent chemotherapy (containing 5Fu). Taken together, we have identified a molecular mechanism by which gastric cancer cells gain 5Fu resistance.



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Comparative Assessment of Response to Cadmium in Heavy Metal-Tolerant Shrubs Cultured In Vitro

Abstract

Two species of Pb-adapted shrubs, Alyssum montanum and Daphne jasminea, were evaluated in vitro for their tolerance to elevated concentrations of cadmium. Shoot cultures were treated with 0.5, 2.5, and 5.0 μM CdCl₂ for 16 weeks and analyzed for their organogenic response, biomass accretion, pigment content, and macronutrient status. Cadmium accumulation and its root-to-shoot translocation were also determined. In both species, rooted microplantlets, suitable for acclimatization, were obtained in the presence of Cd applied as selection agent. In A. montanum, low and moderate dose of Cd stimulated multiplication, rooting, and biomass production. Growth tolerance index (GTI) in Cd-treated shoots ranged from 120 to 215%, while in the roots 51–202%. In turn, in Cd-treated D. jasminea proliferation and rooting were inhibited, and GTI for shoots decreased with increasing doses of Cd. However, roots exposed to Cd had higher biomass accretion. Both species accumulated Cd in developed organs, and its content increased with increasing CdCl₂ dose. Interestingly, D. jasminea accumulated higher amounts of Cd in the roots than A. montanum and immobilized this metal in the root system. On the contrary, A. montanum translocated some part of accumulated Cd to the shoots, but with low efficiency. In the presence of Cd, A. montanum maintained macronutrient homeostasis and synthesized higher amounts of phytosynthetic pigments in the shoots. D. jasminea accumulated root biomass, immobilized Cd, and restricted its translocation at the expense of nutrient balance. Considering remediation potential, A. montanum could be exploited in phytoextraction, while D. jasminea in phytostabilization of polluted substrate.

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Erratum to: Portuguese agriculture and the evolution of greenhouse gas emissions—can vegetables control livestock emissions?

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Highlights of the Issue 8, 2017

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Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in a young female athlete at 36 weeks gestation: a case report

Publication date: Available online 25 July 2017
Source:Pathology - Research and Practice
Author(s): Hae Yoon Grace Choung, Monika Vyas, Daniel Jacoby, Brian West
A 26year old east African professional athlete presented to the obstetric clinic for a routine visit at 36 weeks gestation. She had a history of Right Ventricular Outflow Tract − Ventricular Tachycardia (RVOT-VT) with an episode of cardiac arrest in the past, and had been treated with ablation 4 years earlier. Her current visit was uneventful, her pregnancy progressing normally. Following the visit she went to a local restaurant where she suffered a cardiac arrest that was unresponsive to therapy. Chest compressions were continued from the time of her collapse until an emergency caesarian section was performed, delivering a healthy female infant. At autopsy a focal area of subtle pallor and myocardial thinning was present at the apex of the right ventricle. Histology showed myocyte degeneration and loss with focal full thickness replacement of myocardium by adipose tissue, consistent with the fatty form of arrhythmogenic right ventricular cardiomyopathy (ARVC). Molecular studies revealed a variant of unknown significance in the MYBPC3 gene, but no variant known to be associated with ARVC. In view of the subtlety of the lesion on gross examination this diagnosis could have been easily missed, emphasizing the importance of performing histologic examination of subtle gross cardiac lesions.



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Pancreatic Heterotropia in wall of Extra-hepatic Choledochal Cysts: A Retrospective Analysis of Thirteen of such cases from North India

Publication date: Available online 25 July 2017
Source:Pathology - Research and Practice
Author(s): Pragya Sharma, Tripti Nakra, Gaurav Khanna, Rajni Yadav, Rajesh Panwar, Madhusudhan KS, Khushbu khetan, Nihar R Dash, Sujoy Pal, Peush Sahni, Siddhartha Datta Gupta, Prasenjit Das
IntroductionHeterotopic pancreas (HP) has rarely been identified in the wall of choledochal cyst (CC).MethodsRetrospectively we screened 200 excised specimens of CC received at our Institute over a period of last eight years and looked for presence of HP rests in them. All the specimens were processed in their entirety.ResultHP was identified in the wall of 13 (6.5%) CCs, out of which 11 were Heinrich Type 2, and two were Heinrich Type 1. In half of the cases peribiliary mucous glands were observed intermingled with the HP rests. Features of chronic fibrosing pancreatitis were identified in these rests, with ulceration of overlying cyst lining.ConclusionsHP rests in the wall of CC though rare; their coexistence with peribiliary glands may possibly indicate their common embryonic origin. As a common site of inflammation, HP rest may be one of the common causes of CC.



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Effects of NOx on the molecular composition of secondary organic aerosol formed by the ozonolysis and photooxidation of α-pinene

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Jun-Hyun Park, Zaeem Bin Babar, Sun Jong Baek, Hyun Sik Kim, Ho-Jin Lim
The molecular composition of secondary organic aerosol (SOA), obtained from the ozonolysis and photooxidation of α-pinene, was investigated using ultrahigh-resolution Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) in negative ion mode electrospray ionization (ESI). SOA formation was performed in an indoor smog chamber. The molecular formulae of individual species were identified on the basis of the measured ionic mass using guidelines, such as number of atoms, elemental ratios, and the nitrogen rule. In each of the SOAs obtained, 815–3501 monomeric and oligomeric (mainly dimeric) species were identified below m/z 800. From ozonolysis, mainly 95% of the typical oxygenated species (CHO) were detected, whereas from photooxidation under high NOx conditions, 32% of nitrogen-containing species (CHON) were detected. Several common intense species (e.g., C9H14O6, C10H14O6, C10H16O5, C17H26O7, C19H28O9, C10H15NO8, and C10H15NO9) could be listed as candidate tracers for the conventional tracers for α-pinene SOA. The increased percentage of CHON as a primary effect of NOx on the SOA composition evidently affected other physicochemical parameters, such as elemental ratios (i.e., O/C, H/C, and N/C), the double-bond equivalent (DBE), the carbon oxidation state (OSC), and the organic-mass-to-carbon ratio (OM/OC). The O/C and OM/OC for CHON were greater than those observed for CHO, indicating that nitrogen preferentially exists in the oxidized form (e.g., -ONO2). The complexity of oligomerization was observed in DBE and OM/OC according to the number of carbon atoms.

Graphical abstract

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Differences between emissions measured in urban driving and certification testing of heavy-duty diesel engines

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Poornima Dixit, J. Wayne Miller, David R. Cocker, Adewale Oshinuga, Yu Jiang, Thomas D. Durbin, Kent C. Johnson
Emissions from eight heavy-duty diesel trucks (HDDTs) equipped with three different exhaust aftertreatment systems (ATS) for controlling nitrogen oxide (NOx) emissions were quantified on a chassis dynamometer using driving schedules representative of stop-and-go and free-flow driving in metropolitan areas. The three control technologies were: 1) cooled exhaust gas recirculation (CEGR) plus a diesel particulate filter (DPF); 2) CEGR and DPF plus advanced engine controls; and 3) CEGR and DPF plus selective catalytic reduction with ammonia (SCR). Results for all control technologies and driving conditions showed PM emission factors were less than the standard, while selected non-regulated emissions (ammonia, carbonyls, and C4–C12 hydrocarbons) and a greenhouse gas (nitrous oxide) were at measurement detection limits. However, NOx emission factors depended on the control technology, engine calibration, and driving mode. For example, emissions from engines with cooled-exhaust gas recirculation (CEGR) were 239% higher for stop-and-go driving as compared with free-flow. For CEGR plus selective catalytic reduction (SCR), the ratio was 450%. A deeper analysis was carried out with the assumption that emissions measured for a drive cycle on either the chassis or in-use driving would be similar. Applying the same NTE rules to the chassis data showed emissions during stop-and-go driving often exceeded the certification standard and >90% of the driving did not fall within the Not-To-Exceed (NTE) control area suggesting the NTE requirements do not provide sufficient emissions control under in-use conditions. On-road measurement of emissions using the same mobile lab while the vehicle followed a free-flow driving schedule verified the chassis results. These results have implications for scientists who build inventories using certification values instead of real world emission values and for metropolitan populations, who are exposed to elevated emissions. The differences in values between real world emissions and certification cycles should be narrowed. For example, one might use a different mix of cold and hot start testing to greater emphasize low temperature/load operation, a separate cycle to specifically characterize low-load operation, or broaden the in-use compliance testing requirements and associated conformity factors to incorporate a wider envelope of vehicle operation, especially at low load conditions. .



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New insights on humic-like substances associated with wintertime urban aerosols from central and southern Europe: Size-resolved chemical characterization and optical properties

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Aristeidis Voliotis, Roman Prokeš, Gerhard Lammel, Constantini Samara
Although Humic-LIke Substances (HULIS) are important contributors to the mass of organic aerosol in airborne particulate matter (PM), little is known about their chemical composition, while, their size-resolved optical properties have not been studied yet. Here, HULIS fractions were isolated from size-resolved aerosol samples (≤0.49, 0.49–0.95, 0.95–3 and 3–10 μm) collected in urban and suburban environments of four European cities during wintertime. The bulk (i.e., sum of all size fractions) concentration of HULIS ranged between 1.29 and 2.80 μg m⁻³ across sites with highest values in the ≤0.49 μm particle size fraction. The contribution of the carbon mass of HULIS (HULIS-C) to the water-soluble organic carbon content (WSOC) of PM was 32–43%, which is typical for urban sites affected by biomass burning. The Mass Absorption Efficiency (MAE), which characterizes the efficiency of absorbing solar energy per carbon mass of HULIS decreased with particle size, suggesting that the finest size fractions contain more light-absorbing chromophores, which could affect the light-absorbing ability of organic aerosols. The good correlation of HULIS with effective biomass tracers such as K⁺, as well as with secondary inorganic aerosol components, proposed that HULIS had both primary (i.e., biomass burning) and secondary sources. The Fourier Transfer Infrared coupled to Attenuation Total Reflectance (FTIR-ATR) spectra demonstrated prevalence of aromatic over carboxylic functional groups in most HULIS fractions, indicating contribution from coal combustion emissions in addition to fresh biomass burning aerosol. The new findings add to better understanding the sources and chemical structure of HULIS in urban and suburban environments.

Graphical abstract

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Hepatic Portocholecystostomy: 97 Cases From a Single Institution.

Objectives: About 20% of cases of biliary atresia (BA) do not involve the gallbladder, the cystic duct and the common bile duct. In these cases, a hepatoportocholecystostomy (HPC) may be performed instead of the classical hepatoportoenterostomy (HPE). Methods: We reviewed our cohort to investigate the efficacy of HPC as well as the associated surgical complications and clinical problems. Results: From 1984 to 2009, 97 patients underwent HPC in our institution. In the first 6 months of the postoperative period no patient presented with bacterial cholangitis. Nine patients had bile leakage and one patient had a gallbladder obstruction. For these ten patients, HPC was modified in HPE. Jaundice clearance was maintained after HPE, but four of the patients presented one or more cholangitis episodes. After six months, there were no cases of cholangitis recorded, two patients presented bile leakage and four patients experienced gallbladder obstruction. After 5 years of follow up, 46% of the patients were jaundice free with their native liver and 29.4% were transplanted. Conclusion: In patients with BA with patent extrahepatic bile ducts, hepatoportocholecystomy is a good surgical technique that can prevent cholangitis. These results are counterbalanced by specific surgical complications that need to be known and looked for in the postoperative period. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Attention Deficit Hyperactivity Disorder and Functional Defecation Disorders in Children.

Objectives: To assess the prevalence of attention deficit hyperactivity disorder (ADHD) in children presenting with functional defecation disorders (FDDs) and to assess the prevalence of FDDs in children with ADHD. Methods: A cross-sectional cohort study was carried out between September 2014 and May 2016. Group 1: Parents of children with FDDs according to the Rome III criteria completed the Child Behavior Checklist (CBCL) and the VvGK (Dutch questionnaire based on the American Disruptive Behavior Disorder rating scale). Patients with ADHD subarea scores >=70 on the CBCL and/or >=16 on the VvGK were referred for further psychiatric evaluation. Group 2: Parents of children treated for ADHD at a specialized ADHD-outpatient clinic completed a standardized questionnaire regarding their child's defecation pattern. Results: In group 1 (282 children with FDDs), 10.3% (7.1-13.5% BCaCI) were diagnosed with ADHD. Group 2 consisted of 198 children with ADHD, 22.7% (17.6-28.8 BCaCI) fulfilled the Rome III criteria for an FDD. Children with both an FDD and ADHD reported urinary incontinence significantly more often compared to children with an FDD or ADHD alone: 57.1% in FDD+ADHD vs. 22.8% in FDD alone (p

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Pediatric Gastroenterologists' Approach to Venous Thromboembolism Prophylaxis in Pediatric Inflammatory Bowel Disease.

The risk of venous thromboembolism (VTE) is significantly increased in inflammatory bowel disease (IBD) patients. For the adult population, prophylaxis guidelines exist to help guide physicians in their management of high-risk IBD patients. While it is known that children with IBD also experience increased rates of VTE, there is no clear consensus on how best to prevent these unwanted complications. We sought to better understand practicing pediatric gastroenterologists' awareness of this issue and practices surrounding prevention of VTE in their pediatric patients. We found that pediatric gastroenterologists are well aware of the increased risk for VTE in children with IBD, that anticoagulant prophylaxis is infrequently used for pediatric patients, and that the most commonly cited reason for not providing prophylaxis is the lack of available guidelines in the literature. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Quo vadis: tracing the fate of neural crest cells

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Luis Zurkirchen, Lukas Sommer
The neural crest is a transient structure in vertebrate embryos that produces migratory cells with an astonishing developmental potential. While neural crest fate maps have originally been established through interspecies transplantation assays, dye labeling, and retroviral infection, more recent methods rely on approaches involving transgenesis and genome editing. These technologies allowed the identification of minor neural crest-derived cell populations in tissues of non-neural crest origin. Furthermore, in vivo multipotency at the single cell level and stage-dependent fate acquisitions were demonstrated using genetic technologies. Finally, recent reports indicate that neural crest-derived cells become activated in response to injury to secrete factors supporting tissue repair. Thus, neural crest-derived cells apparently contribute to tissue formation and regeneration by cell autonomous and non-autonomous mechanisms.



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Sleep and slow-wave activity in depressed adolescent boys: a preliminary study

Adolescence is a vulnerable period of life which is characterized by increasing incidence of depression. Sleep disturbance is one of the diagnostic symptoms of depressive disorder. Adolescence is also characterized by dramatic maturational changes in sleep and its regulation. The goal of this study was to assess sleep macroarchitecture and slow-wave activity (SWA) in depressed adolescent boys.

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The future of medical robotics is formulated at Óbuda University

ISO/IECROBOTICS STANDARDIZATION MEETING IN BUDAPEST

The Antal Bejczy Center for Intelligent Robotics (IROB) at Óbuda University is hosting the ISO/IEC Robotics meetings in Budapest. The participants of the 10-day-long meeting are experts of robotics, and are working towards new international standards in the field of service robotics.

The ISO (International Organization for Standardization) and IEC (International Electrotechnical Committee) are the world's most influential standardization bodies. They initiated the TC 299 Robotics committee, which has 8 working groups (3 of those joint). These working groups are now elaborating new robotic standards during their meetings at Obuda University. The groups are responsible for the majority of international robotics standards, and devoted to promote the scientific and technological advancement of robotics through standardization. Service robotics is the new big, emerging domain, which needs standardization as well. Particular target areas include collaborative, nursing, rehabilitation and surgery robotics. In the latter two fields, the experts are now finalizing the standards documents.

Robots are already applied to numerous fields, continuously expanding, and new markets and applications are steadily growing, such as household robots and personal assistants. Within these domains, the robots need to get along in a complex, human-centered environment, therefore it has to possess a higher degree of autonomy. Basic safety standards are badly needed to adopt to the advanced autonomous systems. With the increasing usage of robots, the need for standardized solutions has intensified. The process of standardization is a complicated one, where international experts from the Academia, Industry and Government are working together towards clear targets. These meetings also provide an excellent opportunity to peek into the upcoming standardization environment of the domain, and to network with the senior experts. Hungary has been an active member in these working groups via the Hungarian Standards Institution (MSZT).

The ISO/IEC Standardization Meeting is hosted by the UniversityResearch, Innovation and Service Center (EKIK); wherein the Antal Bejczy Center for Intelligent Robotics is a leading research division of EKIK. There are almost 100 international experts from 17 countries attending the Budapest event. Accredited delegates of their national standardization bodies, accompanied by observers to the committees. Following a great tradition, the last day of the program (28.07.2017) is aMedical Robotics Workshop in the main building of Óbuda University, where invited experts deliver keynote talks regarding the current achievements and upcoming research and development results in the domain. The workshop is open to the public.

Beyond bearing the technical support of Óbuda University, the event benefits from the generous support of the Austrian Center for Medical Innovation Technology (ACMIT) and the Óbuda University Students' Union (HÖK).

More information at UniObuda.

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Doxazosin nanoencapsulation improves its in vitro antiproliferative and anticlonogenic effects on breast cancer cells

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): J. Krai, A. Beckenkamp, M.M. Gaelzer, A.R. Pohlmann, S.S. Guterres, E.C. Filippi-Chiela, C. Salbego, A. Buffon, R.C.R. Beck
Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue^® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.

Graphical abstract

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Combined calcitriol and menadione reduces experimental murine triple negative breast tumor

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Luciana Bohl, Solange Guizzardi, Valeria Rodríguez, Lucila Hinrichsen, Viviana Rozados, David Cremonezzi, Nori Tolosa de Talamoni, Gabriela Picotto
BackgroundCalcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN+D resulted more effective than D or MEN alone.Objective: To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host.MethodsTumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN+D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination.ResultsNone of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN+D, P<0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth.ConclusionsAs previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects.



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Protective effects of wedelolactone on dextran sodium sulfate induced murine colitis partly through inhibiting the NLRP3 inflammasome activation via AMPK signaling

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Wencheng Wei, Meiling Ding, Kai Zhou, Haifeng Xie, Mian Zhang, Chaofeng Zhang
It has been reported that the ethanol extract of Wedelia chinensis attenuates murine colitis. Wedelolactone (WEL), a coumestane-type compound with many pharmacological activities, was isolated from W. chinensis. The present study aims to investigate the beneficial effects and underlying mechanisms of WEL on ulcerative colitis. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of WEL (50mg/kg) significantly attenuated pathological colonic damage and inhibited inflammatory infiltration, myeloperoxidase and alkaline phosphatase activities through MAPKs and NF-κB signaling pathways, while activating AMPK in colons treated with DSS. Further study revealed that WEL treatment dramatically inhibited NLRP3 inflammasome activation and caspase-1 phosphorylation to decrease IL-1β release in colons treated with DSS. In addition, WEL effectively regulates the disorder of skeleton proteins in colonic epithelial cells NCM460 exposed to TNF-α and protects the intestinal barrier function by activating AMPK in vivo. In summary, the AMPK-NLRP3-IL-1β signaling axis plays an important role in colitis following WEL treatments. These findings provide new insights into the pharmacological actions of WEL as a potential therapeutic agent for colitis.

Graphical abstract

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Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Josiane Weber Tessmann, Julieti Buss, Karine Rech Begnini, Lucas Moraes Berneira, Favero Reisdorfer Paula, Claudio Martin Pereira de Pereira, Tiago Collares, Fabiana Kömmling Seixas
Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a–2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer.



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MiR-136 controls neurocytes apoptosis by regulating Tissue Inhibitor of Metalloproteinases-3 in spinal cord ischemic injury

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Rilong Jin, Sanzhong Xu, Xiangjin Lin, Miaoda Shen
BackgroundSpinal cord ischemia is a serious injury that threatens human health and life. Furthermore, it was widely accepted that miR-136 was mediated in the spinal injury, while whether it regulated neurocytes apoptosis in I/R-induced spinal cord injury remains unclear.MethodsSpinal cord ischemia injury (SCII) rats were induced by clamping the nontraumatic vascular clip on the abdominal aorta. Real-time PCR was conducted to determine the mRNA expression, and western blot was carried out to measure protein expression. TUNEL assay was used to measure cell apoptosis.ResultsMiR-136 was up-regulated, while Tissue Inhibitor of Metalloproteinases-3 (TIMP3) was down-regulated in both SCII rats and hypoxic neurocytes. MiR-136 overexpression protected neurocytes against injury that induced by hypoxia. TIMP3 was the target gene of miR-136. Hypoxia supplementation decreased the expression of miR-136, promoted TIMP3 expression, and urged cell apoptosis, cells transfected with miR-136 mimic reversed the effect that induced by hypoxia, while cells co-transfected with pcDNA-TIMP3 abolished the results that induced by overexpressed miR-136.ConclusionMiR-136 regulated neurocytes apoptosis of SCII by mediating TIMP3.



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Long noncoding RNA PCAT1 regulates extrahepatic cholangiocarcinoma progression via the Wnt/β-catenin-signaling pathway

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Fumin Zhang, Ming Wan, Yi Xu, Zhenglong Li, Kaiming Leng, Pengcheng Kang, Yunfu Cui, Xingming Jiang
Extrahepatic cholangiocarcinoma (ECC) is a deadly disease that often responds poorly to conventional chemotherapy or radiotherapy. Long noncoding RNAs (lncRNAs) play important roles in human cancers, including ECC, and recent studies indicated that the lncRNA prostate cancer-associated transcript 1 (non-protein coding) (PCAT1) is involved in multiple cancers. However, the role of PCAT1 in ECC is unclear. Previously, we showed that PCAT1 is up-regulated in both ECC tissue samples and cell lines. Here, we showed that downregulation of PCAT1 following transfection with silencing RNA reduced ECC cell growth and increased cell apoptosis. Additionally, PCAT1 suppression inhibited ECC cell migration and invasion as determined by transwell assay. Furthermore, we determined that PCAT1 is a competing endogenous for microRNA (miR)-122, with bioinformatics analysis and luciferase-reporter assay results demonstrating that PCAT1 regulated WNT1 expression via miR-122. Moreover, PCAT1 downregulation increased levels of glycogen synthase kinase 3β and significantly decreased β-catenin levels in whole cell lysates and nuclear fractions, indicating that PCAT1 silencing inhibited the Wnt/β-catenin-signaling pathway. We also observed that exogenous expression of WNT1 reversed PCAT1-silencing-induced inhibition of ECC cell growth inhibition. These results indicated that PCAT1 silencing inhibited ECC progression by reducing Wnt/β-catenin signaling through miR-122 repression and WNT1 expression. Our findings revealed an important role of PCAT1 in ECC and suggested that PCAT1 might be a potential ECC-related therapeutic target.



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Diallyl trisulfide induces apoptosis and mitotic arrest in AGS human gastric carcinoma cells through reactive oxygen species-mediated activation of AMP-activated protein kinase

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Yung Hyun Choi
Diallyl trisulfide (DATS), one of the principal constituents of garlic oil, is a kind of organosulfur compound with high anti-cancer activity. Although inhibition of cancer cell proliferation by DATS is known to be associated with the induction of apoptosis and cell cycle arrest related to reactive oxygen species (ROS) production, it is still necessary to study the detailed mechanisms. In this study, we investigated the role of ROS on the activation of AMP-activated protein kinase (AMPK) in DATS-induced apoptosis and cell cycle arrest in AGS human gastric carcinoma cells. The results of the present study indicate that DATS inhibited proliferation of AGS cells by promoting apoptosis, and accumulating cellular portion of G2/M phase via the induction of cyclin B1 and cyclin-dependent kinase p21(WAF1/CIP1). The phosphorylation of histone H3 was also markedly increased following treatment with DATS, revealing that DATS stimulated a mitotic arrest, not the G2 phase. Furthermore, we found that DATS concurrently induced phosphorylation of AMPK; however, chemical inhibition of AMPK by compound C, an AMPK inhibitor, significantly blocked apoptosis induced by DATS, suggesting that DATS induces cytotoxicity of AGS cells through the AMPK-dependent pathway. Moreover, DATS provoked intracellular ROS generation and the loss of mitochondrial membrane potential, and in particular, when ROS production was blocked by antioxidant N-acety-l-cysteine, both AMPK activation and growth inhibition by DATS were completely abolished. Collectively, these findings suggest that DATS inhibited growth of AGS cells, which was mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis, and cell cycle arrest, through a ROS-dependent activation of AMPK pathway.



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Adherence to evidence-based pressure injury prevention guidelines in routine clinical practice: a longitudinal study

Abstract

The aim of this longitudinal study was to describe adherence to evidence-based pressure injury (PI) prevention guidelines in routine clinical practice in Australian hospitals. Data were analysed from four control sites of a larger-cluster randomised trial of a PI intervention. The sample of 799 included 220 (27·5%) Not at risk, 344 (43·1%) At risk and 110 (13·8%) At high risk patients. A total of 84 (10·5%) patients developed a PI during the study: 20 (9·0% of 220) in the Not at risk group, 45 (13·1% of 344) in the At risk group, 15 (13·6% of 110) in the At high risk group and 4 (3·2% of 125) patients who did not have a risk assessment completed. Of all patients, 165 (20·7%) received only one PI prevention strategy, and 494 (61·8%) received ≥2 strategies at some point during the study period. There was no statistical difference in the proportion of time the three risk groups received ≥1 and ≥2 strategies; on average, this was less than half the time they were in the study. Thus, patients were not receiving PI prevention strategies consistently throughout their hospital stay, although it is possible patients' risk changed over the study period.

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The detrimental impact of extracellular bacterial proteases on wound healing

Abstract

In addition to clinical signs of infection (e.g. inflammation, purulence and pain), a microbial count of ≥10⁵ colony-forming units/g has historically been used to define wound infection. However, it is increasingly recognised that, rather than a high bioburden level alone being detrimental to wound healing, it is the virulence of the invading microorganism and the host's immune status that can affect clinical outcomes. Bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, have developed a range of virulence factors to help them overcome host defences and proliferate within the underlying soft tissue. More specifically, bacterial proteases are one such virulence factor that has been implicated in promoting the invasion and destruction of the host tissue. Because of the complexities of microorganisms, the proteases can negatively impact the wound environment, leading to delayed wound healing. The aim of the present paper is to describe various extracellular bacterial proteases; review the impact they have on the wound environment, the host immune response and biofilms; and discuss potential wound management strategies against them. The evidence discussed suggests that proteases may play a profound role in wound infections, contribute to the development of an inflammatory response and impede wound healing.

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Compression therapy – cross-sectional observational survey about knowledge and practical treatment of specialised and non-specialised nurses and therapists

Abstract

Knowledge about methods and materials and their correct usage is the basis for compression therapy. This study compares knowledge and practical skills of participants with further training with those who had no training. This comparison provides information on whether further qualifications have an impact on knowledge and practical skills.

In seminars for compression therapy, data on specific and non-specific expertise were acquired. A practical test determined the participants' skills for creating a compression bandage in a pressure value range of 50–60 mmHg.

In total, 1338 participants with specific expertise and 138 participants with non-specific expertise took part. Knowledge evaluation showed that 7·9% of the specific expertise group had knowledge regarding padding, 10% regarding multi-component systems and 13·6% regarding ulcer stocking systems. In the practical test, 12·3% of all participants achieved the target range.

The majority of users in both groups is not familiar with the different compression materials or their appropriate usage. In the non-specific expertise group, knowledge concerning up-to-date materials and methods is one-third lower. The practical test showed major deficits on both sides. Appropriate exercises, for example, with pressure-measuring devices, should be mandatory for all professional groups who perform compression bandaging.

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Nanoscale deformation mechanisms and yield properties of hydrated bone extracellular matrix

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Jakob Schwiedrzik, Aidan Taylor, Daniele Casari, Uwe Wolfram, Philippe Zysset, Johann Michler
Bone features a hierarchical architecture combining antagonistic properties like toughness and strength. In order to better understand the mechanisms leading to this advantageous combination, its postyield and failure behavior was analyzed on the length scale of a single lamella. Micropillars were compressed to large strains under hydrated conditions to measure their anisotropic yield and post-yield behavior. An increase in strength compared to the macroscale by a factor of 1.55 and a strong influence of hydration with a decrease by 60% in yield stress compared to vacuum conditions were observed. Post-compression transmission electron microscopic analysis revealed anisotropic deformation mechanisms. In axial pillars, where fibrils were oriented along the loading axis, kink bands were observed and shear cracks emerged at the interface of ordered and disordered regions. Micromechanical analysis of fibril kinking allowed an estimate of the extrafibrillar matrix shear strength to be made: 120±40MPa . When two opposing shear planes met a wedge was formed, splitting the micropillar axially in a mode 1 crack. Making use of an analytical solution, the mode 1 fracture toughness of bone extracellular matrix for splitting along the fibril direction was estimated to be 0.07MPam. This is 1-2 orders of magnitude smaller than on the macroscale, which may be explained by the absence of extrinsic toughening mechanisms. In transverse pillars, where fibrils were oriented perpendicular to the loading axis, cracks formed in regions where adverse fibril orientation reduced the local fracture resistance. This study underlines the importance of bone's hierarchical microstructure for its macroscopic strength and fracture resistance and the need to study structure-property relationships as well as failure mechanisms under hydrated conditions on all length scales.Statement of SignificanceBone's hierarchical architecture combines toughness and strength. To understand the governing deformation mechanisms, its postyield behavior was analyzed at the microscale. Micropillars were compressed in physiological solution; an increased strength compared to macroscale and an influence of hydration was found. Transmission electron microscopy revealed cracks forming in regions with adverse fibril orientation in transverse pillars with fibrils oriented perpendicular to the loading axis. In axial pillars kink bands were observed and shear cracks emerged at the interface of ordered and disordered regions. It was estimated that bone's fracture toughness for splitting between fibrils is significantly smaller than on the macroscale. This study underlines the importance of bone's hierarchical microstructure and the need to study structure-property relationships on all length scales.

Graphical abstract

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Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with ultrahigh porosity and surface area imply potential drug delivery and cell engineering applications

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Ahmed El-Fiqi, Jennifer O. Buitrago, Sung Hee Yang, Hae-Won Kim
Here we communicate the generation of biomimetically grown apatite spheres from aggregated bioglass nanoparticles and the potential properties applicable for drug delivery and cell/tissue engineering. Ion releasing nanoparticulates of bioglass (85%SiO2-15%CaO) in a mineralizing medium show an intriguing dynamic phenomenon – aggregation, mineralization to apatite, integration and growth into micron-sized (1.5-3 μm) spheres. During the progressive ionic dissolution/precipitation reactions, nano-to-micro-morphology, glass-to-crystal composition, and the physico-chemical properties (porosity, surface area, and charge) change dynamically. With increasing reaction period, the apatite becomes more crystallized with increased crystallinity and crystal size, and gets a composition closer to the stoichiometry. The developed microspheres exhibit hierarchical surface nanostructure, negative charge (ς-potential of -20 mV), and ultrahigh mesoporosity (mesopore size of 6.1 nm, and the resultant surface area of 63.7 m²/g and pore volume of 0.153 cm³/g) at 14 days of mineralization, which are even higher than those of its precursor bioglass nanoparticles. Thanks to these properties, the biomimetic mineral microspheres take up biological molecules effectively, i.e., loading capacity of positive-charged protein is over 10%. Of note, the release is highly sustainable at a constant rate, i.e., profiling almost 'zero-order' kinetics for 4 weeks, suggesting the potential usefulness as protein delivery systems. The biomimetic mineral microspheres hold some remnant Si in the core region, and release calcium, phosphate, and silicate ions over the test period, implying the long-term ionic-related therapeutic functions. The mesenchymal stem cells favour the biomimetic spheres with an excellent viability. Due to the merit of sizes (a few micrometers), the spheres can be intercalated into cells, mediating cellular interactions in 3D cell-spheroid engineering, and also can stimulate osteogenic differentiation of cells when incorporated into cell-laden gels. The intriguing properties observed in this study, including biomimetic composition, high mesoporosity, release of therapeutic ions, effective loading and long-term release of proteins, and diverse yet favorable 3D cellular interactions, suggest great potential of the newly developed biomimetic microspheres in biomedical applications, such as drug delivery and cell/tissue engineering.Statement of SignificanceThis work reports the generation of apatite spheres with a few micrometers in size biomimetically grown from bioactive glass nanoparticles, through a series of intriguing yet unprecedented phenomenon involving aggregation of nanoparticles, mineralization and sphere growth. The mineral microspheres possess some unique physico-chemical properties including mesoporosity, ultrahigh surface area, and therapeutic ionic release. Furthermore, the spheres show excellent loading and delivery capacity of protein molecules, and mediate favorable cellular interactions in 2D and 3D culture conditions, demonstrating a future multifunctional microcarrier platform for the therapeutics delivery and cell/tissue engineering.

Graphical abstract

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Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Suzanne E. Thomson, Chloe Charalambous, Carol-Anne Smith, Penelope M Tsimbouri, Theophile Déjardin, Paul J. Kingham, Andrew M. Hart, Mathis O. Riehle
Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model. Linear topographical cues enhanced neurite outgrowth and our results demonstrated that the mTOR pathway is important in regulating these responses.mTOR gene expression peaked between 48-72 hours, coincident with the onset of rapid neurite outgrowth and glial migration, and correlated with neurite length at 48 hours. mTOR protein was located to glia and in a punctate distribution along neurites. mTOR levels peaked at 72 hours and were significantly increased by patterned topography (p < 0.05). Furthermore, the topographical cues could override pharmacological inhibition. Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin highlighted mTORC2 as an important mediator, and more specific therapeutic target. Quantitative immunohistochemistry confirmed the presence of the mTORC2 component rictor at the regenerating front where it co-localised with F-actin and vinculin. Collectively, these results provide a deeper understanding of the mechanism of action of topography on neural regeneration, and support the incorporation of topographical patterning in combination with pharmacological mTORC2 potentiation within biomaterial constructs used to repair peripheral nerves.Statement of SignificancePeripheral nerve injury is common and functionally devastating. Despite microsurgical repair, healing is slow and incomplete, with lasting functional deficit. There is a clear need to translate bioengineering approaches and increase our knowledge of the molecular processes controlling nerve regeneration to improve the rate and success of healing. Topographical cues are powerful determinants of neurite outgrowth and represent a highly translatable engineering strategy. Here we demonstrate, for the first time, that microtopography potentiates neurite outgrowth via the mTOR pathway, with the mTORC2 subtype being of particular importance. These results give further evidence for the incorporation of microtopographical cues into peripheral nerve regeneration conduits and indicate that mTORC2 may be a suitable therapeutic target to potentiate nerve regeneration.

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Stretching Single Fibrin Fibers Hampers Their Lysis

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Wei Li, Tomas Lucioni, Rongzhong Li, Keith Bonin, Samuel S. Cho, Martin Guthold
Blood clots, whose main structural component is a mesh of microscopic fibrin fibers, experience mechanical strain from blood flow, clot retraction and interactions with platelets and other cells. We developed a transparent, striated and highly stretchable substrate made from fugitive glue (a styrenic block copolymer) to investigate how mechanical strain affects lysis of single, suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself by fiber elongation, thickening (disassembly), fraying and collapse. Stretching single fibrin fibers significantly hampered their lysis. This effect was seen in uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also hampered single fiber lysis.Our data suggest that strain is a novel mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at the single fiber level. At the molecular level of single fibrin molecules, strain may distort, or hinder access to, plasmin cleavage sites and thereby hamper lysis.Statement of SignificanceFibrin fibers are the major structural component of a blood clot. We developed a highly stretchable substrate made from fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect of stretching on single fibrin fibers lysis. The key findings from our experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked fibers; and 4) stretching fibers has similar effect on reducing lysis as crosslinking fibers. On the molecular level, strain may distort plasmin cleavage sites, or restrict access to those sites. Our results suggest that strain may be a novel mechanobiological factor that regulates fibrinolysis.

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Horizontal changes of the proximal mandibular segment after mandibular setback surgery using 3D CT data

Publication date: Available online 25 July 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Bo-Ram Yeo, Jeong-Joon Han, Seunggon Jung, Hong-Ju Park, Hee-Kyun Oh, Min-Suk Kook
Objectives.To evaluate horizontal changes of the proximal mandibular segment after mandibular setback surgery using three-dimensional computed tomography (3D CT).Study Design.This study included 66 patients who underwent bilateral sagittal split ramus osteotomy (BSSRO) for correction of mandibular prognathism Using 3D CT data obtained preoperatively (T1), immediately postoperatively (T2), and 6 months postoperatively (T3), horizontal changes of the proximal mandibular segment including intercondylar width (ICW), intergonial width (IGW), and frontal-ramal inclination (FRI) were evaluated.Results.The value of right-FRI was 11.43 ± 1.36° at T1, 11.91 ± 1.96° at T2, and 10.7 ± 1.5° at T3. The values of left-FRI were 6.10 ± 1.03° at T1, 8.17 ± 1.66° at T2, and 7.66 ± 1.65° at T3. The values of IGW were 99.67 ± 1.67 mm at T1, 98.24 ± 1.72 mm at T2, and 97.08 ± 1.71 mm at T3. IGW was significantly decreased at T3 compared with T1 (p < 0.001). The values of ICW were 123.51 ± 1.66 mm at T1, 123.9 ± 1.66 mm at T2, and 122.88 ± 1.58 mm at T3.Conclusion.Lower facial width at mandibular angle region decreased immediately after mandibular setback surgery and showed further decreases during the postoperative period.



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Big GABA: Edited MR spectroscopy at 24 research sites

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Mark Mikkelsen, Peter B. Barker, Pallab K. Bhattacharyya, Maiken K. Brix, Pieter F. Buur, Kim M. Cecil, Kimberly L. Chan, David Y.-T. Chen, Alexander R. Craven, Koen Cuypers, Michael Dacko, Niall W. Duncan, Ulrike Dydak, David A. Edmondson, Gabriele Ende, Lars Ersland, Fei Gao, Ian Greenhouse, Ashley D. Harris, Naying He, Stefanie Heba, Nigel Hoggard, Tun-Wei Hsu, Jacobus F.A. Jansen, Alayar Kangarlu, Thomas Lange, R. Marc Lebel, Yan Li, Chien-Yuan E. Lin, Jy-Kang Liou, Jiing-Feng Lirng, Feng Liu, Ruoyun Ma, Celine Maes, Marta Moreno-Ortega, Scott O. Murray, Sean Noah, Ralph Noeske, Michael D. Noseworthy, Georg Oeltzschner, James J. Prisciandaro, Nicolaas A.J. Puts, Timothy P.L. Roberts, Markus Sack, Napapon Sailasuta, Muhammad G. Saleh, Michael-Paul Schallmo, Nicholas Simard, Stephan P. Swinnen, Martin Tegenthoff, Peter Truong, Guangbin Wang, Iain D. Wilkinson, Hans-Jörg Wittsack, Hongmin Xu, Fuhua Yan, Chencheng Zhang, Vadim Zipunnikov, Helge J. Zöllner, Richard A.E. Edden
Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.



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3D-MB-MUSE: A robust 3D multi-slab, multi-band and multi-shot reconstruction approach for ultrahigh resolution diffusion MRI

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Iain P. Bruce, Hing-Chiu Chang, Christopher Petty, Nan-Kuei Chen, Allen W. Song
Recent advances in achieving ultrahigh spatial resolution (e.g. sub-millimeter) diffusion MRI (dMRI) data have proven highly beneficial in characterizing tissue microstructures in organs such as the brain. However, the routine acquisition of in-vivo dMRI data at such high spatial resolutions has been largely prohibited by factors that include prolonged acquisition times, motion induced artifacts, and low SNR. To overcome these limitations, we present here a framework for acquiring and reconstructing 3D multi-slab, multi-band and interleaved multi-shot EPI data, termed 3D-MB-MUSE. Through multi-band excitations, the simultaneous acquisition of multiple 3D slabs enables whole brain dMRI volumes to be acquired in-vivo on a 3 T clinical MRI scanner at high spatial resolution within a reasonably short amount of time. Representing a true 3D model, 3D-MB-MUSE reconstructs an entire 3D multi-band, multi-shot dMRI slab at once while simultaneously accounting for coil sensitivity variations across the slab as well as motion induced artifacts commonly associated with both 3D and multi-shot diffusion imaging. Such a reconstruction fully preserves the SNR advantages of both 3D and multi-shot acquisitions in high resolution dMRI images by removing both motion and aliasing artifacts across multiple dimensions. By enabling ultrahigh resolution dMRI for routine use, the 3D-MB-MUSE framework presented here may prove highly valuable in both clinical and research applications.



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Investigations into within- and between-subject resting-state amplitude variations

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Janine Bijsterbosch, Samuel Harrison, Eugene Duff, Fidel Alfaro-Almagro, Mark Woolrich, Stephen Smith
The amplitudes of spontaneous fluctuations in brain activity may be a significant source of within-subject and between-subject variability, and this variability is likely to be carried through into functional connectivity (FC) estimates (whether directly or indirectly). Therefore, improving our understanding of amplitude fluctuations over the course of a resting state scan and variation in amplitude across individuals is of great relevance to the interpretation of FC findings. We investigate resting state amplitudes in two large-scale studies (HCP and UK Biobank), with the aim of determining between-subject and within-subject variability. Between-subject clustering distinguished between two groups of brain networks whose amplitude variation across subjects were highly correlated with each other, revealing a clear distinction between primary sensory and motor regions ('primary sensory/motor cluster') and cognitive networks. Within subjects, all networks in the primary sensory/motor cluster showed a consistent increase in amplitudes from the start to the end of the scan. In addition to the strong increases in primary sensory/motor amplitude, a large number of changes in FC were found when comparing the two scans acquired on the same day (HCP data). Additive signal change analysis confirmed that all of the observed FC changes could be fully explained by changes in amplitude. Between-subject correlations in UK Biobank data showed a negative correlation between primary sensory/motor amplitude and average sleep duration, suggesting a role of arousal. Our findings additionally reveal complex relationships between amplitude and head motion. These results suggest that network amplitude is a source of significant variability both across subjects, and within subjects on a within-session timescale. Future rfMRI studies may benefit from obtaining arousal-related (self report) measures, and may wish to consider the influence of amplitude changes on measures of (dynamic) functional connectivity.



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Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Candace R. Lewis, Katrin H. Preller, Rainer Kraehenmann, Lars Michels, Philipp Staempfli, Franz X. Vollenweider
Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations.



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Accelerating permutation testing in voxel-wise analysis through subspace tracking: A new plugin for SnPM

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Felipe Gutierrez-Barragan, Vamsi K. Ithapu, Chris Hinrichs, Camille Maumet, Sterling C. Johnson, Thomas E. Nichols, Vikas Singh
Permutation testing is a non-parametric method for obtaining the max null distribution used to compute corrected p-values that provide strong control of false positives. In neuroimaging, however, the computational burden of running such an algorithm can be significant. We find that by viewing the permutation testing procedure as the construction of a very large permutation testing matrix, T, one can exploit structural properties derived from the data and the test statistics to reduce the runtime under certain conditions. In particular, we see that T is low-rank plus a low-variance residual. This makes T a good candidate for low-rank matrix completion, where only a very small number of entries of T (∼0.35% of all entries in our experiments) have to be computed to obtain a good estimate. Based on this observation, we present RapidPT, an algorithm that efficiently recovers the max null distribution commonly obtained through regular permutation testing in voxel-wise analysis. We present an extensive validation on a synthetic dataset and four varying sized datasets against two baselines: Statistical NonParametric Mapping (SnPM13) and a standard permutation testing implementation (referred as NaivePT). We find that RapidPT achieves its best runtime performance on medium sized datasets (50≤n≤200), with speedups of 1.5× - 38× (vs. SnPM13) and 20x-1000× (vs. NaivePT). For larger datasets (n≥200) RapidPT outperforms NaivePT (6× - 200×) on all datasets, and provides large speedups over SnPM13 when more than 10000 permutations (2× - 15×) are needed. The implementation is a standalone toolbox and also integrated within SnPM13, able to leverage multi-core architectures when available.



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The influence of food consistency on chewing rate and muscular work

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): A. van der Bilt, J.H. Abbink
Food properties influence the parameters of the masticatory process, such as jaw movement, muscle activity and chewing rate. Firm foods will require more muscle activity than softer foods. However, the influence of food hardness on chewing rate is ambiguous as both slower and higher chewing rates have been reported for harder foods. Rheological characteristics of the food, such as plasticity and elasticity, may help to explain differences in chewing rate. The aim of our study was to determine the influence of food properties on chewing rate and muscular work in five phases of a chewing sequence. Eighty-four participants chewed on five foods, which strongly differed in consistency. Chewing gum was used as a reference food. The phase in the chewing sequence had a large significant effect on cycle duration for the five foods. A significant decrease in cycle duration at the beginning of chewing was followed by an increase in later phases, leading to U-shaped curves. Food type had a small effect on the average cycle duration. However, large significant differences in cycle duration were observed between the foods at the beginning of a chewing sequence. In that phase, the firm foods were chewed much slower than the soft foods. Muscular work was significantly influenced by both chewing phase and food type.



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Ethanol production from chitosan by the nematophagous fungus Pochonia chlamydosporia and the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

Publication date: Available online 25 July 2017
Source:Microbiological Research
Author(s): Almudena Aranda-Martinez, Miguel Ángel Naranjo Ortiz, Isabel Sofía Abihssira García, Ernesto A. Zavala-Gonzalez, Luis Vicente Lopez-Llorca
Ethanol production is mainly obtained from plant biomass. Chitin is the second most abundant biopolymer after cellulose and virtually unexplored as raw material for bioethanol production. In this paper, we investigate chitosan, the deacetylated form of chitin which is the main component of shellfish waste, as substrate for bioethanol production by fungi. Fungal parasites of invertebrates such as the nematophagous Pochonia chlamydosporia (Pc) or the entomopathogens Beauveria bassiana (Bb) and Metarhizium anisopliae (Ma) are biocontrol agents of plant parasitic nematodes (eg. Meloidogyne spp.) or insect pests such as the red palm weevil (Rhynchophorus ferrugineus). These fungi degrade chitin-rich barriers for host penetration. We have therefore tested the chitin/chitosanolytic capabilities of Pc, Bb and Ma for generating reducing sugars using chitosan as only nutrient. Among the microorganisms used in this study, Pc is the best chitosan degrader, even under anaerobic conditions. These fungi have alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) encoding genes in their genomes. We have therefore analyzed their ethanol production under anaerobic conditions using chitosan as raw material. P. chlamydosporia is the largest ethanol producer from chitosan. Our studies are a starting point to develop chitin-chitosan based biofuels.



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Histopathological and clinical evaluation of chronic spontaneous urticaria patients with neutrophilic and non-neutrophilic cutaneous infiltrate

Publication date: Available online 25 July 2017
Source:Allergology International
Author(s): Cíntia Freitas Martins, Karina Lopes Morais, Pamela Figueroa, Natasha Favoretto Dias, Neusa Sakai Valente, Celina Wakisaba Maruta, Paulo Ricardo Criado
BackgroundChronic urticaria has an expressive prevalence in general population, especially in adults, and is defined by the presence of intermittent hives for six weeks or longer. Our study aims to characterize the histological patterns of chronic spontaneous urticaria, based on the inflammatory cell infiltrate, and correlate them to laboratory exams.MethodsIt was performed a retrospective analysis of laboratory, histopathology and direct immunofluorescence data of 93 patients with chronic urticaria. For histopathological analysis, cell count was performed in four fields at high magnification (×400) for each specimen. The resulting cell count medians were submitted to statistical analysis and, then, were correlated to laboratorial findings.ResultsWe found a female predominance (76.34%) of chronic urticaria cases, and an average age of 42.5 years (SD ± 15). Two histological groups were distinctive: 1) chronic urticaria with predominance of neutrophils or eosinophils – N (%) = 39 (42.4%) – and 2) chronic urticaria with predominance of lymphocytes – N (%) = 53 (57.6%). There was not significant correlation between histological groups and laboratorial tests. Moreover, direct immunofluorescence was positive in 21 (33,87%) from 62 patients.ConclusionsThere is not enough scientific evidence to support neutrophilic urticaria as a solid, separate entity.



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