Hold your horses: A comparison of human laryngomalacia with analogous equine airway pathology

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Rachael J. Lawrence, Matthew J. Butterell, James D. Constable, Matija Daniel
ObjectivesLaryngomalacia is the most common cause of stridor in infants. Dynamic airway collapse is also a well-recognised entity in horses and an important cause of surgical veterinary intervention. We compare the aetiology, clinical features and management of human laryngomalacia with equine dynamic airway collapse.MethodsA structured review of the PubMed, the Ovid Medline and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews).ResultsThere are numerous equine conditions that cause dynamic airway collapse defined specifically by the anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF) is the condition most clinically analogous to laryngomalacia in humans, and is likewise most prevalent in the immature equine airway. Both conditions are managed either conservatively, or if symptoms require it, with surgical intervention. The operative procedures performed for ADAF and laryngomalacia are technically comparable.ConclusionDynamic collapse of the equine larynx, especially ADAF, is clinically similar to human laryngomalacia, and both are treated in a similar fashion.



http://ift.tt/2CnPVYZ

Priorities for future research into asthma diagnostic tools: A PAN-EU Consensus exercise from the European asthma research innovation partnership (EARIP)

Abstract

The diagnosis of asthma is currently based on clinical history, physical examination and lung function; and to date there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state-of-the-art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients.

Using a two-stage e-Delphi process and a summarising workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face to face workshop.

The three most important diagnostic/predictive tools ranked were: "New biological markers of asthma (e.g. genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring", "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath".

This article is protected by copyright. All rights reserved.

http://ift.tt/2lvviQ4

Lipid-lowering and antiatherogenic effects of Vitex megapotamica (Spreng.) Moldenke in a mice experimental model

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Vanessa Aranega Pires, Euclides Lara Cardozo-Junior, Caroline Flach Ortmann, Jhonatan Christian Maraschin, Wagner Alex Jann Favreto, Carmen Maria Donaduzzi, Flávio Henrique Reginatto, Jamil Assreuy
Ethnopharmacological relevanceVitex megapotamica (Spreng.) Moldenke is a deciduous tree, native of South America. Its leaves are traditionally used to treat cardiovascular diseases. This activity is related to the presence of flavonoids, the major compounds of the crude extract.Aim of the studyThis study investigated the effects of the oral administration of crude extract and standardized fractions from V. megapotamica leaves on lipid profile and on the formation of atherosclerotic plaque in C57BL/6 LDLr-KO mice treated with high-fat diet (HFD).Materials and methodsMale C57BL/6 LDLr-KO mice were fed with HFD (cholesterol, 1.25%) for 30 days. They were treated with hydroethanolic extract (500 or 1000mg/kg/day) or fractions (125 or 250mg/kg/day). After 30 days of treatment, it was evaluated the serum lipid profile, atherogenic index, and atherosclerotic plaque.ResultsAll doses of the hydroethanolic extract reduced significantly the levels of total cholesterol, triglycerides, LDL-c and the atherogenic index. The n-butanolic fraction also reduced significantly the levels of total cholesterol, triglycerides, LDL-c and the atherogenic index, at all doses, with exception for the triglycerides, which only the lower dose was effective. The residual fraction reduced significantly the levels of total cholesterol, LDL-c and the atherogenic index, at all doses, with exception for the atherogenic index, which only the higher dose was effective. The atherosclerotic plaque formation was impaired only by the lower dose of the hydroethanolic extract.ConclusionsOverall, our data suggest that V. megapotamica has potential for the treatment of dyslipidemias.

Graphical abstract

http://ift.tt/2lvjLA9

Baccharis trimera protects against ethanol induced hepatotoxicity in vitro and in vivo

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Ana Carolina Silveira Rabelo, Karine de Pádua Lúcio, Carolina Morais Araújo, Glaucy Rodrigues de Araújo, Pedro Henrique de Amorim Miranda, Ana Claudia Alvarenga Carneiro, Érica Milena de Castro Ribeiro, Breno de Melo Silva, Wanderson Geraldo de Lima, Daniela Caldeira Costa
Ethnopharmacological relevanceBaccharis trimera has been traditionally used in Brazil to treat liver diseases.Aim of the studyTo evaluate the protective effect of Baccharis trimera in an ethanol induced hepatotoxicity model.Materials and methodsThe antioxidant capacity was evaluated in vitro by the ability to scavenged the DPPH radical, by the quantification of ROS, NO and the transcription factor Nrf2. Hepatotoxicity was induced in animals by administration of absolute ethanol for 2 days (acute) or with ethanol diluted for 28 days (chronic). The biochemical parameters of hepatic function (ALT and AST), renal function (urea and creatinine) and lipid profile (total cholesterol, triglycerides and HDL) were evaluated. In addition to antioxidant defense (SOD, catalase, glutathione), oxidative damage markers (TBARS and carbonylated protein), MMP-2 activity and liver histology.ResultsBaccharis trimera promoted a decrease in ROS and NO, and at low concentrations promoted increased transcription of Nrf2. In the acute experiment it promoted increase of HDL, in the activity of SOD and GPx, besides diminishing TBARS and microesteatosis. Already in the chronic experiment B. trimera improved the hepatic and renal profile, decreased triglycerides and MMP-2 activity, in addition to diminishing microesteatosis.ConclusionWe believe that B. trimera action is possibly more associated with direct neutralizing effects or inhibition of reactive species production pathways rather than the modulation of the antioxidant enzymes activity. Thus it is possible to infer that the biological effects triggered by adaptive responses are complex and multifactorial depending on the dose, the time and the compounds used.

Graphical abstract

http://ift.tt/2lvjKfz

High-expressed CKS2 is associated with hepatocellular carcinoma cell proliferation though down-regulating PTEN

Publication date: Available online 30 December 2017
Source:Pathology - Research and Practice
Author(s): Xiaonan Ji, Yayu Xue, Yu Wu, Fang Feng, Xiangdong Gao
BackgroundHepatocellular carcinoma (HCC) is a product of cumulative genetic, epigenetic, somatic, and endocrine aberrations. Identifying the differentially expressed genes (DEGs) in HCC is of critical importance for diagnosis and treatment. The purpose of the present study was to screen the key genes associated with hepatocellular carcinoma and to investigate the functions underlying hepatocellular carcinoma progression.Materials and MethodsThe gene expression profile of GSE64041, GSE40367 and GSE60502, including 100 specimens from HCC patients and 92 specimens from normal liver controls, was downloaded from the GEO database. DEGs were screened using the online analysis tool from the GCBI website and validated by Q-PCR and Kaplan-Meier survival analysis. After knockdown by siRNA in HepG2/C3A and Bel7402 HCC cells, the CCK-8 assay and colony formation assay were used to measure the clonogenic capacity of the tumor cells. Western blotting assay was used to measure the expression of PTEN.ResultsFive up-regulated genes were identified as overlapping genes associated with tumor cell activation. Upon validation by Q-PCR and Kaplan-Meier survival analysis, CKS2 was selected for further study. Although the results of CCK-8 did not show a significant difference, the colony formation assay results indicated that the silencing of CKS2 significantly inhibited cancer cell proliferation. Further study found that CKS2 knockdown induced PTEN up-regulation and may associate with P53 pathway activation.ConclusionThese findings indicated that CKS2 play a role in tumor activation and serve as a useful potential target for the treatment of HCC.



http://ift.tt/2DDSzH9

Novel metal modified diatomite, zeolite and carbon xerogel catalysts for mild conditions wet air oxidation of phenol: Characterization, efficiency and reaction pathway

Publication date: 31 May 2018
Source:Separation and Purification Technology, Volume 197
Author(s): Raluca Pleşa Chicinaş, Emese Gál, Horea Bedelean, Mircea Darabantu, Andrada Măicăneanu
Metal (Co, Ce, Ni, Fe, Zn, Mn and Cu) containing Diatomite (D), Zeolite (Z) and Carbon Xerogel (CX) catalysts were prepared, characterized (SEM-EDX, TEM, FTIR and XRD) and tested as new catalysts in Catalytic Wet Air Oxidation (CWAO) of phenol in aqueous solution. Maximum values of Chemical Oxygen Demand (COD) or Total Organic Carbon (TOC) efficiencies were obtained in the case of Fe-D, Cu-Z, and Co-CX catalysts. Reaction pathway and kinetics for CWAO of phenol revealed a pseudo first-order catalytic process and a kcat between 0.0473 × 10⁻³ and 1.4183 × 10⁻³ L/min g. (Di)carboxylic acids, acetic and oxalic were identified as oxidation organic products.



http://ift.tt/2Cl7iK5

Synthesis of core cross-linked star polymers carrying helical poly(phenyl isocyanide) arms via “core-first” strategy and their surface chiral recognition ability

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Qian Wang, Jian Huang, Zhi-Qiang Jiang, Li Zhou, Na Liu, Zong-Quan Wu
A norbornene functionalized alkyne-Pd(II) complex was designed and synthesized, which copolymerized with a bisnorbornene cross linker via ring-opening metathesis polymerization (ROMP) afforded a cross-linked Pd(II) macroinitiator. Living polymerization of phenyl isocyanides with the Pd(II) macroinitiator lead to the formation of well-defined core cross-linked star polymer carrying helical poly(phenyl isocyanide)s arms. Because of the living nature of Pd(II)-initiated phenyl isocyanide polymerization, a series of star polymers with controlled structure and tunable compositions was readily prepared. Optically active star polymers with excess of one handed helical arms were obtained by using enantiopure phenyl isocyanide monomers. Such star polymer exhibited excellent chiral recognition ability. The contact angle of the star polymer is strongly dependent on the chirality of the D/L-phenylglycinol droplets. The enantioselective surface recognition can be further applied to the chiral resolution of racemic D/L-phenylglycinol. The enantiomeric excess (ee) of the isolated enantiomer is up to 75%. The chiral star polymers can also be used to induce enantioselectively crystallization of racemic Boc-alanine. The ee value of the induced enantiomer can be up to 91%.

Graphical abstract

http://ift.tt/2DBs0SK

Effects of livestock exclusion on density, survival and biomass of the perennial sagebrush grass Hymenachne pernambucense (Poaceae) from a temperate fluvial wetland

Publication date: January 2018
Source:Acta Oecologica, Volume 86
Author(s): Andrea L. Magnano, Analía S. Nanni, Pamela Krug, Elizabeth Astrada, Ricardo Vicari, Rubén D. Quintana
In Argentina, the intensification of soybean production has displaced a substantial proportion of cattle ranching to fluvial wetlands such as those in the Delta of the Paraná River. Cattle grazing affects structure and dynamics of native forage plants but there is little information on this impact in populations from fluvial wetlands. This study addresses the effect of cattle ranching on density, survival, mean life-span and aerial biomass of Hymenachne pernambucense (Poaceae), an important forage species in the region. The study was carried out monthly for one year in permanents plots subject to continuous grazing and plots excluded from grazing in the Middle Delta of the Paraná River. In plots excluded from grazing, tillers showed significantly higher population density and survival, and a two-fold increase in mean life-span, while continuous grazing decreased survival of cohorts. The largest contribution to tiller density in ungrazed and grazed populations was made by spring and summer cohorts, respectively. Total and green biomass were significantly higher in the ungrazed population, with highest differences in late spring-early summer. Cattle grazing affected the relationship between tiller density and green biomass suggesting that cattle prefer sprouts because they are more palatable and nutritious than older tissue.



http://ift.tt/2lyVUzU

Hydrocephalus in pyridoxine-dependent epilepsy: New case and literature review

Publication date: Available online 30 December 2017
Source:Brain and Development
Author(s): Virginia Navarro-Abia, María Soriano-Ramos, Noemí Núñez-Enamorado, Ana Camacho-Salas, Ana Martinez-de Aragón, Elena Martín-Hernández, Rogelio Simón-de las Heras
IntroductionPyridoxine-dependent epilepsy (PDE) is a rare disorder of the lysine metabolism, characterized by a pharmacoresistant epileptic encephalopathy that usually begins in the neonatal period. However, its phenotypic spectrum is wide and not limited to seizures. We report a new case of PDE who developed hydrocephalus, along with an exhaustive review of the literature.Case reportOur patient presented with seizures at 13 h of life. Antiepileptic drugs, vitamins and cofactors were required to achieve seizure control. Laboratory tests were congruent with PDE. She remained seizure-free until age five months, when seizures reappeared in the context of increasing head size and irritability. A cranial ultrasound showed hydrocephalus, for which she underwent ventriculoperitoneal shunting.DiscussionSeven other patients with same features have been previously reported. Seizure onset occurred within the first 7 days in all patients. Most of the children developed hydrocephalus at 6–7 months of age. In 4 out of 7 a genetic mutation was identified, despite the accurate etiology of hydrocephalus was unknown in most of them. The case we report behaved similarly to the others previously described. We postulate that the pathogenesis of this complication could be related to the high expression of antiquitin in choroid plexus epithelium, where the cerebrospinal fluid is produced.Conclusionspatients with PDE should be closely monitored, since they may present severe complications. We highlight the development of hydrocephalus, an uncommon but potentially life-threatening problem reported in 8 patients up to present time.



http://ift.tt/2luV5bj

Differential effects on sodium current impairments by distinct SCN1A mutations in GABAergic neurons derived from Dravet syndrome patients

Publication date: Available online 30 December 2017
Source:Brain and Development
Author(s): Hyun Woo Kim, Zhejiu Quan, Young-Beom Kim, Eunji Cheong, Heung Dong Kim, Minjung Cho, Jiho Jang, Young Rang You, Joon Soo Lee, Ji Hun Kim, Yang In Kim, Dae-Sung Kim, Hoon-Chul Kang
BackgroundWe investigated how two distinct mutations in SCN1A differentially affect electrophysiological properties of the patient-derived GABAergic neurons and clinical severities in two Dravet syndrome (DS) patients.Materials and MethodsWe established induced pluripotent stem cells from two DS patients with different mutations in SCN1A and subsequently differentiated them into forebrain GABAergic neurons. Functionality of differentiated GABAergic neurons was examined by electrophysiological recordings.ResultsDS-1 patient had a missense mutation, c.4261G > T [GenBank: NM_006920.4] and DS-2 patient had a nonsense frameshift mutation, c.3576_3580 del TCAAA [GenBank: NM_006920.4]. Clinically, contrary to our expectations, DS-1 patient had more severe symptoms including frequency of seizure episodes and the extent of intellectual ability penetration than DS-2 patient. Electrophysiologic recordings showed significantly lower sodium current density and reduced action potential frequency at strong current injection (>60 pA) in GABAergic neurons derived from both. Intriguingly, unique genetic alterations of SCN1A differentially impacted electrophysiological impairment of the neurons, and the impairment's extent corresponded with the symptomatic severity of the donor from which the iPSCs were derived.ConclusionOur results suggest the possibility that patient-derived iPSCs may provide a reliable in vitro system that reflects clinical severities in individuals with DS.



http://ift.tt/2lptqsR

Prevalence of idiopathic epilepsy among school children in Gharbia Governorate, Egypt

Publication date: Available online 30 December 2017
Source:Brain and Development
Author(s): Azza Kamal Alshahawy, Amira Hamed Darwish, Safynaz Elsaid Shalaby, Wegdan Mawlana
BackgroundEpilepsy is one of the most common neurological disorders among children. Data about its prevalence in Egypt is limited. Our aim was to study the prevalence of idiopathic epilepsy among school children in Gharbia governorate, Egypt.Subjects and MethodsA Cross-sectional school-based survey study was conducted; a validated screening questionnaire was distributed among urban and rural primary and preparatory school children. Students with suspected epilepsy were subjected to clinical evaluation, Electroencephalogram (EEG), and neuroimaging.Results9545 students completed the questionnaire, of whom 69 children proved to have idiopathic epilepsy. The lifetime prevalence of idiopathic epilepsy among school students aged 6–14 years was 7.2/1000. Higher prevalence was reported in males (7.7/1000) and in children from urban areas (8.25/1000). Generalized seizures were observed in 56.5% of the children with epilepsy, whereas focal seizures were present in 43.5%. Thirty-four (49.27%) children were diagnosed with specific childhood epileptic syndrome: 25 children had benign childhood epilepsy with centrotemporal spikes and nine children had typical childhood absence epilepsy. Treatment gap is around 12.5% in the studied children. Family history of epilepsy and parental consanguinity were evident in 73.9% and 21.7% of the epileptic children, respectively. The odds ratio for idiopathic epilepsy in children with family history of epilepsy was 23.9.ConclusionThe prevalence of idiopathic epilepsy among school students aged 6–14 years in Gharbia Governorate was 7.2/1000. The reported prevalence is similar to the prevalence of epilepsy in other Arab countries, but lower than the prevalence in Upper Egypt and in most developing countries.



http://ift.tt/2luL4dY

Cortical inhibition assessed using paired-pulse TMS-EEG is increased in older adults

Publication date: Available online 30 December 2017
Source:Brain Stimulation
Author(s): George M. Opie, Simranjit K. Sidhu, Nigel C. Rogasch, Michael C. Ridding, John G. Semmler
BackgroundAlterations in inhibitory processes mediated by gamma-aminobutyric acid type B (GABAB) receptors may contribute to age-related functional impairments. However, investigation of these circuits using conventional paired-pulse transcranial magnetic stimulation (TMS) at long interstimulus intervals (∼100-200ms) have produced conflicting results in older adults, possibly due to the indirect nature of the TMS motor evoked potential (MEP).ObjectiveTo utilise electroencephalography and TMS coregistration (TMS-EEG) to more directly assess age-related changes in GABAB-mediated long-interval intracortical inhibition (LICI).MethodsIn 17 young (24.2 ± 1.1 years) and 17 older (71.4 ± 1.4 years) subjects, the TMS-evoked potential (TEP) was used to assess the global scalp response to single-pulse TMS and LICI applied at two interstimulus intervals of 100 ms (LICI100) and 150 ms (LICI150).ResultsFor single-pulse stimulation, P30 amplitude was unaffected by age. Despite this, N45 amplitude was increased in older adults and both N100 and P180 showed altered spatial distributions. Furthermore, the latency of P30 was shorter, while the latency of P180 was longer, in the elderly. In addition, inhibition of the N100 and P180 was increased in older adults following both LICI100 and LICI150.ConclusionsThese findings with TMS-EEG suggest that the ageing process is associated with a potentiation of GABAergic inhibition, particularly for the GABAB-receptor subtype.



http://ift.tt/2q0cHBl

Short Versions of Two Specific Phobia Measures: The Snake and the Spider Questionnaires

Publication date: Available online 30 December 2017
Source:Journal of Anxiety Disorders
Author(s): Andras N. Zsido, Nikolett Arato, Orsolya Inhof, Jozsef Janszky, Gergely Darnai
Zoophobias are the most prevalent form of specific phobia worldwide. Two of the most widely used measures, the Snake Questionnaire (SNAQ) and Spider Questionnaire (SPQ) are good indicators of specific fears, but researchers have recognised that shorter, yet nevertheless reliable measures are needed. Hence the aims of this research were to develop short forms of the SNAQ and SPQ using item response theory and to use receiver operating characteristic (ROC) curve analyses to determine cut-offs for use in future research. Twelve-item versions of both scales (SNAQ-12 and SPQ-12) demonstrated excellent discrimination along the latent continuum in a sample of 1354 people. The SNAQ-12 and SPQ-12 showed excellent reliability and were highly correlated with the corresponding full-length scale. The scales discriminated between participants who reported snake (3.25%) or spider (8.05%) phobia and those who did not. Further analyses revealed that non-phobic women report higher fear of both snakes and spiders than do men, but this difference was not present in phobics. These findings suggest that the SNAQ-12 and SPQ-12 have considerable strengths, including shorter assessment and scoring times, whilst retaining high reliability and potential utility as a clinical screening tool.



http://ift.tt/2pX86zy

Construct validation of the hybrid model of posttraumatic stress disorder: Distinctiveness of the new symptom clusters

Publication date: Available online 30 December 2017
Source:Journal of Anxiety Disorders
Author(s): Madison W. Silverstein, Nathalie Dieujuste, Lindsay B. Kramer, Daniel J. Lee, Frank W. Weathers
Despite the factor analytic support for the seven-factor hybrid model (Armour et al., 2015) of posttraumatic stress disorder (PTSD), little research has examined the degree to which newly established symptom clusters (i.e., negative affect, anhedonia, dysphoric arousal, anxious arousal, externalizing behavior) functionally and meaningfully differ in their associations with other clinical phenomena. The aim of the current study was to examine the degree to which newly established PTSD symptom clusters differentially relate to co-occurring psychopathology and related clinical phenomena through Wald testing using latent variable modeling. Participants were 535 trauma-exposed undergraduates who completed the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5; Weathers et al., 2013) and Personality Assessment Inventory (PAI; Morey, 1991). As expected and in line with results from previous studies, significant heterogeneity emerged for dysphoric arousal, anxious arousal, and externalizing behavior. However, there was less evidence for the distinctiveness of negative affect and anhedonia. Results indicate that only some of the newly established symptom clusters significantly differ in their associations with related clinical phenomena and that the hybrid model might not provide a meaningful framework for understanding which PTSD symptoms relate to associated features. Limitations include a non-clinical sample and reliance on retrospective self-report assessment measures.



http://ift.tt/2q3DqwR

Plumbagin suppresses the human large cell lung cancer cell lines by inhibiting IL-6/STAT3 signaling in vitro

Publication date: February 2018
Source:International Immunopharmacology, Volume 55
Author(s): Tao Yu, Yan-Yan Xu, Ying-Ying Zhang, Kai-Yu Li, Yi Shao, Gang Liu
BackgroundLarge cell lung cancer (LCLC) patients have a poor prognosis because their tumors are highly malignant and show resistance to chemotherapy and radiotherapy. Plumbagin has anticancer activity toward several tumor types, but its effects on LCLC are unknown. This study investigated the effects of plumbagin on human L9981 and NL9980 large cell lung cancer cells and the mechanisms underlying its action.MethodsThe effects of plumbagin on L9981 and NL9980 cells proliferative activity and invasion were analyzed using MTT and Boyden chamber assays, respectively. Exogenous IL-6 was used to detect the presence of the IL-6/STAT3 signaling pathway in LCLC cell lines. L9981 cells were harvested after plumbagin treatment at 9.0μmol/L (IC50), while NL9980 were harvested after treatment at 7.5μmol/L for 6, 24, and 48h, and the expression of IL-6, IL-6R, gp130, and STAT3 and the downstream genes Bcl-2, VEGF, and CycD1 was assessed by RT-PCR. ELISA was performed to determine secreted IL-6 levels, and intracellular phospho-STAT3 levels were measured by western blotting.ResultsAfter the introduction of exogenous IL-6, the mRNA expression of signaling genes and downstream genes was significantly increased in a concentration-dependent manner. Furthermore, plumbagin significantly inhibited the expression of the above mentioned genes in a dose-dependent and time-dependent manner. The mRNA expression levels of downstream genes were correlated with those of signaling genes.ConclusionPlumbagin was found to significantly inhibit the proliferation and invasion of L9981 and NL9980 cells, and may be an effective therapy for LCLC through targeting the IL-6/STAT3 signaling pathway.



http://ift.tt/2CuwjQv

Platelet-rich plasma inhibits Wnt/β-catenin signaling in rabbit cartilage cells activated by IL-1β

Publication date: February 2018
Source:International Immunopharmacology, Volume 55
Author(s): Jian Wu, Ji-Feng Huang, Xing-Xing Qin, Feng Hu, Zhao-Fei Chen, Yong Zheng, Yan-Xi Liu, Xian-Hua Cai
ObjectivePlatelet-rich plasma (PRP) has been reported to alleviate degenerative pathological damage to joint cartilage. This study aimed to investigate the effect of PRP on Wnt/β-catenin signaling in rabbit chondrocytes.MethodsUsing 3-month-old New Zealand white rabbits, PRP was prepared from venous blood, and chondrocytes were cultured from knee joint cartilage and identified by staining for type II collagen and proteoglycan. The effects of PRP on chondrocyte viability were measured. The chondrocytes were divided into 5 groups: control, IL-1β, PRP (100-fold dilution), Dkk-1 (100ng/mL) and Dkk-1+PRP. The IL-1β, PRP, Dkk-1 and Dkk-1+PRP groups were treated with interleukin (IL)-1β (50μL, 10μg/mL) for24h. Chondrocyte morphology was observed by electron microscopy. Levels of carboxy terminal peptide (CTX-II) and cartilage oligomeric matrix protein (COMP) in culture media were measured by ELISA. Wnt-1, β-catenin and GSK-3β mRNA and protein expression were determined by RT-PCR and western blot respectively.ResultsPRP enhanced chondrocyte proliferation. Chondrocytes in the IL-1β group showed ultrastructural abnormalities that were less pronounced in the PRP, Dkk-1 and Dkk-1+PRP groups. CTX-II and COMP concentrations were higher in the IL-1β group than in the control, PRP, Dkk-1 and Dkk-1+PRP groups (P<0.05). The IL-1β group had higher mRNA and protein Wnt1 and β-catenin levels and lower GSK-3β levels than the control, PRP, Dkk-1 and Dkk-1+PRP groups (P<0.05).ConclusionPRP may protect chondrocytes activated by IL-1β via inhibiting Wnt/β-catenin signaling.



http://ift.tt/2DCINVo

Overexpression of sprouty2 in human oral squamous cell carcinogenesis

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Pei-Hsien Liao, Yen-Yun Wang, Wen-Chen Wang, Chung-Ho Chen, Yu-Hsun Kao, Jing-Wei Hsu, Ching-Yi Chen, Ping-Ho Chen, Shyng-Shiou Yuan, Yuk-Kwan Chen
ObjectiveThis study investigated SPRY2 expression in human oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs).Methods75 OSCCs, 23 OPMDs with malignant transformation (MT), 17 OPMDs without MT, and eight normal oral mucosa (NOM) tissues were used for immunohistochemical staining; three OSCC tissues with normal tissue counterparts were used for western blotting. Three human oral cancer cell lines (OCCLs), an oral precancer cell line (DOK), and a NOM primary culture (NOMPC) were used for western blotting; OCCLs and NOMPC were employed for real-time quantitative reverse transcription-polymerase chain reaction. OCCLs were evaluated in terms of proliferation, migration, invasion and BRAF V600E point mutation assays.ResultsSignificantly increased SPRY2 protein expression was observed in OSCCs as compared with NOM, and SPRY2 expression also differed between OSCC patients with and without lymph-node metastasis. SPRY2 protein and mRNA expressions were significantly enhanced as compared with NOMPC. Increased phospho-ERK expression was observed in OCCLs as compared with NOMPC. Significant decreases in the proliferation rate, degrees of migration and invasion were noted in OCCLs with SPRY2 siRNA transfection as compared with those without SPRY2 siRNA transfection. No BRAF V600E point mutation was observed for OCCLs as compared with NOMPC. A significantly increased SPRY2 protein level was noted in OPMDs with MT as compared to those without MT, and was also found in OPMDs with MT in comparison with NOM, as well as in DOK in comparison with NOMPC.ConclusionsOur results indicated that SPRY2 overexpression is associated with human oral squamous-cell carcinogenesis.



http://ift.tt/2CfPxg5

Superhydrophilic co-polymer coatings on denture surfaces reduce Candida albicans adhesion—An in vitro study

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Masahiro Hirasawa, Chiaki Tsutsumi-Arai, Kensuke Takakusaki, Toyohisa Oya, Kenji Fueki, Noriyuki Wakabayashi
ObjectiveIn this study, we aimed to investigate denture-base-resin coatings prepared with a crosslinkable co-polymer containing sulfobetaine methacrylamide (SBMAm) and the relationship between their surface characteristics and the initial adhesion of Candida albicans (C. albicans).MethodsAcrylic resin discs were coated with co-polymers containing various concentrations of SBMAm and N,N'-(4,7,10-trioxa-1,13-tridecadiamine) diacrylamide (JDA) as crosslinking agent. Uncoated discs were used as controls. An acquired pellicle was formed on each disc using artificial saliva, and the discs were immersed in a suspension of C. albicans (JCM2085) cells. After incubation, tetrazolium salt (XTT-reduction) and colony forming unit (CFU) assays were performed and the morphogenesis of C. albicans was examined using scanning electron microscopy (SEM). The surface roughness, film thickness, and the water contact angle of each disc surface were measured.ResultsAll coating groups showed significantly lower amounts of adhered C. albicans in the XTT-reduction and CFU assays than the control, confirmed by the SEM images. Many wrinkle structures were observed on the surfaces coated with co-polymers containing more than 30% SBMAm. There were no significant differences in surface roughness among all groups. The co-polymer films on the coated discs were less than 5.0 μm in thickness, and these surfaces exhibited significantly lower mean water contact angles than the control.ConclusionCrosslinkable co-polymers containing SBMAm can enhance the hydrophilicity of the surface of denture-base resins and reduce the initial adhesion of C. albicans.



http://ift.tt/2zQe19v

Immunoexpression of proteins involved in cytoskeleton remodeling in benign odontogenic lesions

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Paula Nascimento Antonio, Natália Galvão Garcia, Agnes Assao, José Roberto Pereira Lauris, Fernando Augusto Soares, Denise Tostes Oliveira
ObjectiveThe present study was designed to analyze the immunolocalization of proteins involved in cytoskeleton remodeling, such as moesin and Rho-A, in benign odontogenic lesions that present with expansive growth and invasive clinical behavior.Materials and methodsExpressions of moesin and Rho-A in odontogenic epithelium were evaluated by immunohistochemical analysis in 45 odontogenic lesions using monoclonal antibodies.ResultsOur results demonstrated strong membranous and cytoplasmic expressions of moesin in the epithelial cells in 66.7% and 44.4% of the odontogenic lesions, respectively. Furthermore, Rho-A expression in odontogenic epithelium was strong in the membrane and cytoplasm of 51.1% and 62.2% of the odontogenic lesions, respectively. A statistically significant correlation was found between the membranous and cytoplasmic expressions of moesin (p = 0.000) and those of Rho-A (p = 0.048) in odontogenic epithelial cells, while no statistically significant correlation was found between moesin and Rho-A expressions (p > 0.05).ConclusionsThe present study confirmed the strong expressions of moesin and Rho-A by odontogenic epithelial cells, suggesting their involvement in the development of benign odontogenic lesions. However, this study has failed to detect the connection between the moesin and Rho-A interaction in expansive growth and local invasiveness of these lesions.



http://ift.tt/2CfiAjO

Outcomes of Endovascular Aneurysm Repair using the Ovation Stent Graft System in Adverse Anatomy

Publication date: Available online 29 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Nicholas S. Greaves, Aiden Moore, Dare Seriki, Jonathan Ghosh
ObjectiveThe aim was the evaluation of mid-term efficacy and safety outcome measures for the Ovation (Endologix, Santa Rosa, CA, USA) stent graft system in the management of infrarenal abdominal aortic aneurysms (iAAA) with adverse anatomy.MethodsA retrospective observational study of all patients undergoing elective iAAA repair was carried out from 2012 to 2017 using Ovation Prime or iX stent grafts with a minimum of 3 months follow-up at a single UK vascular centre. Post-operative surveillance involved computed tomography scans at 3 months and 1 year, with duplex ultrasound yearly thereafter. Outcome measures were established with retrospective analysis of pre- and post-operative imaging, and included peri-operative mortality, major adverse events, limb complications, aneurysm diameter change, and endoleak rates. All patients were within Ovation instructions for use (IFU), and assessment was made to determine whether aneurysms had anatomical features considered adverse for other commonly used stent graft platforms.ResultsOvation stent grafts were implanted in 52 patients (79% male, mean age 75.7 years) with a mean aneurysm diameter of 62.5 mm (range 55–107 mm). There was 100% technical deployment success. The 30 day mortality was 0% and there was no aneurysm related mortality during follow-up (median 24 months, range 3–48 months). There were no type I or III endoleaks, but 19% developed type II endoleaks with one patient requiring re-intervention. No iliac limb occlusions were identified but one case required relining for limb kinking. All 52 cases were within the IFU for Ovation but only 12% met the IFU criteria for the Cook and Medtronic devices.ConclusionsThe mid-term experience with Ovation demonstrates safe, durable treatment of iAAAs, including those with unfavourable anatomy, frequently off IFU for other commonly used devices.



http://ift.tt/2lvuZ7Z

Reconsidering the Rupture Risk Potential of Abdominal Aortic Aneurysms in High Risk Patients

Publication date: Available online 29 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Kosmas I. Paraskevas




http://ift.tt/2lo3LRw

Treatment of Femoral Vein Obstruction Concomitant with Iliofemoral Stenting in Patients with Severe Post-thrombotic Syndrome

Publication date: Available online 30 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Kaichuang Ye, Huihua Shi, Minyi Yin, Jinbao Qin, Xinrui Yang, Xiaobing Liu, Mier Jiang, Xinwu Lu
BackgroundThe aim was to assess the clinical and anatomical outcomes of iliofemoral stenting, with concomitant femoral stenting or balloon angioplasty alone, in patients with severe post-thrombotic syndrome (PTS) and compromised inflow.MethodsA database of patients with severe PTS who successfully underwent endovascular iliofemoral stenting was reviewed retrospectively. Patients with impaired inflow with chronic post-thrombotic obstructive lesions in the femoral vein (FV), but patent profunda vein, were selected and divided into two groups: the FV stenting (FV-S) group and the FV angioplasty (FV-A) group. Patients in the FV-S group were treated with concomitant iliofemoral and FV stenting, and patients in the FV-A group were treated with iliofemoral stenting and balloon angioplasty alone of the obstructed femoral vein. The clinical and stent outcomes were recorded and compared in the two groups.ResultsThere were 45 patients in the FV-S group and 69 patients in the FV-A group. The groups were well matched for age, gender, and diseased limbs. The pre-procedural symptoms, CEAP classifications, VCSS scores, Villalta scores, and prevalence of active ulcers were also similar between the two groups. Immediate failure (<30 days post-procedure) in the femoral segment occurred more frequently in the FV-A group (70% in FV-A group vs. 24% in FV-S group, p < .001); however, all treated femoral vein segments had occluded at 12 months. There was no significant difference between the FV-S and FV-A groups in cumulative primary and secondary patency rates of the iliofemoral stent at 3 years (55% vs. 52%, p = .71, and 77% vs. 85%, p = .32, respectively). Complete pain relief, swelling relief, VCSS score, Villalta score, and freedom from ulcers at a median of 22 months (1–48 months) following the procedure were similar in the two groups.ConclusionsStent placement to treat post-thrombotic iliofemoral obstruction with concomitant obstructed femoral vein but patent profunda vein shows cumulative patency rates and clinical outcomes similar to previous reports. Adjunctive femoral stenting or angioplasty of the obstructed femoral vein does not appear to improve clinical or stent outcomes in patients with severe PTS.



http://ift.tt/2lvqxWF

Synergy Theory in Radiobiology.

Related Articles

Synergy Theory in Radiobiology.

Radiat Res. 2017 Dec 29;:

Authors: Ham DW, Song B, Gao J, Yu J, Sachs RK

Abstract
Customized open-source software is used to characterize, exemplify, compare and critically evaluate mathematical/computational synergy analysis methods currently used in biology, and used or potentially applicable in radiobiology. As examples, we reanalyze some published results on murine Harderian gland tumors and on in vitro chromosome aberrations induced by exposure to single-ion radiations that simulate components of the galactic cosmic ray field. Baseline no-synergy/no-antagonism-mixture dose-effect relationships are calculated for corresponding mixed fields. No new experimental results are presented. Synergy analysis of effects due to a mixed radiation field whose components' individual dose-effect relationships are highly curvilinear should not consist of simply comparing to the sum of the components' effects. Such curvilinearity must often be allowed for in current radiobiology, especially when studying possible non-targeted ("bystander") effects. Consequently, many different synergy analysis theories are currently used in biology to replace simple effect additivity. We give evidence that for most synergy experiments and observations, incremental effect additivity is the most appropriate replacement. It has a large domain of applicability, being useful even when pronounced individual dose-effect relationship curvilinearity is a confounding factor. It allows calculation of 95% confidence intervals for baseline mixture dose-effect relationships taking into account parameter correlations; if non-targeted effects are important this gives much tighter intervals than neglecting the correlations. It always obeys two consistency conditions that simple effect additivity usually fails to obey: a "mixture of mixtures principle" and the standard "sham mixture principle". The mixture of mixtures principle is important in radiobiology because even nominally single-ion radiations are usually mixtures when they strike the biological target, due to intervening material. It is not yet clear whether mixing galactic cosmic ray components sometimes leads to statistically significant synergy for animal tumorigenesis. The substantial limitations of synergy theories are sometimes overlooked, and they warrant further study.

PMID: 29286257 [PubMed - as supplied by publisher]

http://ift.tt/2lpOdMU

The Sequence Preference of Gamma-Radiation-Induced Damage in End-Labeled DNA after Heat Treatment.

Related Articles

The Sequence Preference of Gamma-Radiation-Induced Damage in End-Labeled DNA after Heat Treatment.

Radiat Res. 2017 Dec 29;:

Authors: Gautam SD, Hardie ME, Murray V

Abstract
In this work, we examined the DNA sequence preference of gamma-radiation-induced DNA damage in purified DNA sequences after heat treatment. DNA was fluorescently end-labeled and gamma-radiation-induced DNA cleavage was examined using capillary electrophoresis with laser-induced fluorescence detection. Our findings provide evidence that gamma-radiation-induced DNA damage to end-labeled DNA is nonrandom and has a sequence preference. The degree of cleavage was quantified at each nucleotide, and we observed that preferential cleavage occurred at C nucleotides with lesser cleavage at G nucleotides, while being very low at T nucleotides. The differences in percentage cleavage at individual nucleotides ranged up to sixfold. The DNA sequences surrounding the most intense radiation-induced DNA cleavage sites were examined and a consensus sequence 5'-AGGC*C (where C* is the cleavage site) was found. The highest intensity gamma-radiation-induced DNA cleavage sites were found at the dinucleotides, 5'-GG*, 5'-GC*, 5'-C*C and 5'-G*G and at the trinucleotides, 5'-GG*C, 5'-TC*A, 5'-GG*G and 5'-GC*C. These findings have implications for our understanding of ionizing radiation-induced DNA damage.

PMID: 29286256 [PubMed - as supplied by publisher]

http://ift.tt/2lmP8Oj

Ethological approach to social isolation effects in behavioral studies of laboratory rodents

Publication date: 2 April 2018
Source:Behavioural Brain Research, Volume 341
Author(s): Hiroyuki Arakawa
The aim of the present review is to discuss how housing conditions affect behavioral performance in laboratory rodents from an ethological view. Commonly used laboratory rodents such as rats and mice, are originally captured animals that largely retain species-typical natural behaviors, while have fully adapted to a laboratory setting after long-term domestication. Laboratory settings including caging and artificial group housing are a considerable ethological factor influencing rodents' behaviors in commonly employed behavioral test paradigms, including emotional and defensive behaviors, learning and memory, and attention-related behaviors. Particularly, isolation rearing, single-housed in a cage, is referred to a deprivation of social relationships with cagemates, has a substantial impact on behavioral performance in laboratory rodents. In this review, we will fully examine the importance of caging related ethological factors, e.g., social relationships and its deprivation, which are essential for unraveling the nature of housing effect in laboratory rodents. These discussions regarding the housing conditions will provide valuable information for appropriately conducting behavioral studies and interpreting data of rodents' behaviors in neuroscience.



http://ift.tt/2BXizNd

A translational approach to the genetics of anxiety disorders

Publication date: 2 April 2018
Source:Behavioural Brain Research, Volume 341
Author(s): N.W. McGregor, J.J. Dimatelis, P.J. Van Zyl, S.M.J. Hemmings, C. Kinnear, V.A. Russell, D.J. Stein, C. Lochner
There have been important advances in our understanding of the genetic architecture of anxiety disorders. At the same time, relatively few genes have reached genome wide significance in anxiety disorders, and there is relatively little work on how exposure to an adverse environment impacts on gene expression in either animal models or human clinical populations. Here we assessed differential expression of genes of the dorsal striatum involved in synaptic transmission in an animal models of early adversity (maternal separation followed by restraint stress), and investigated whether variants in these genes were associated with risk for anxiety disorders, particularly in the presence of environmental stressors. Fifty-two male Sprague Dawley rats underwent maternal separation, and gene expression was studied using array technology. The human homologues of the differentially expressed genes were screened and analysed in a DSM-IV anxiety disorders cohort, and healthy controls (patients, n = 92; controls, n = 194), using blood. Two candidate genes (Mmp9 and Bdnf) were aberrantly expressed in the experimental rodent group relative to controls. Four single nucleotide polymorphisms (SNPs) in the human homologues of these genes were significantly associated with susceptibility for anxiety disorders (MMP9: rs3918242 and BDNF: rs6265, rs10835210 and rs11030107). Three of these (BDNF: rs6265, rs10835210, rs11030107) were found to interact significantly with childhood trauma severity resulting in increased likelihood of an anxiety disorder diagnosis. This study provides insights into the utility of rat models for identifying molecular candidates for anxiety disorders in humans.



http://ift.tt/2Cmjie7

A hypothetical pathogenesis model for androgenic alopecia: clarifying the dihydrotestosterone paradox and rate-limiting recovery factors

Publication date: Available online 30 December 2017
Source:Medical Hypotheses
Author(s): Robert S. English
Androgenic alopecia, also known as pattern hair loss, is a chronic progressive condition that affects 80% of men and 50% of women throughout a lifetime. But despite its prevalence and extensive study, a coherent pathology model describing androgenic alopecia's precursors, biological step-processes, and physiological responses does not yet exist. While consensus isthat androgenic alopecia is genetic and androgen-mediated by dihydrotestosterone, questions remain regarding dihydrotestosterone's exact role in androgenic alopecia onset. What causes dihydrotestosterone to increase in androgenic alopecia-prone tissues? By which mechanisms does dihydrotestosterone miniaturize androgenic alopecia-prone hair follicles? Why is dihydrotestosterone also associated with hair growth in secondary body and facial hair? Why does castration (which decreases androgen production by 95%) stop pattern hair loss, but not fully reverse it? Is there a relationship between dihydrotestosterone and tissue remodeling observed alongside androgenic alopecia onset?We review evidence supporting and challenging dihydrotestosterone's causal relationship with androgenic alopecia, then propose an evidence-based pathogenesis model that attempts to answer the above questions, account for additionally-suspected androgenic alopecia mediators, identify rate-limiting recovery factors, and elucidate better treatment targets. The hypothesis argues that: [1] chronic scalp tension transmitted from the galea aponeurotica induces an inflammatory response in androgenic alopecia-prone tissues; [2] dihydrotestosterone increases in androgenic alopecia-prone tissues as part of this inflammatory response; and [3] dihydrotestosterone does not directly miniaturize hair follicles. Rather, dihydrotestosterone is a co-mediator of tissue dermal sheath thickening, perifollicular fibrosis, and calcification – three chronic, progressive conditions concomitant with androgenic alopecia progression. These conditions remodel androgenic alopecia-prone tissues – restricting follicle growth space, oxygen, and nutrient supply – leading to the slow, persistent hair follicle miniaturization characterized in androgenic alopecia.If true, this hypothetical model explains the mechanisms by which dihydrotestosterone miniaturizes androgenic alopecia-prone hair follicles, describes a rationale for androgenic alopecia progression and patterning, makes sense of dihydrotestosterone's paradoxical role in hair loss and hair growth, and identifies targets to further improve androgenic alopecia recovery rates: fibrosis, calcification, and chronic scalp tension.



http://ift.tt/2BZhioJ

"Exp Ther Med"[jour]; +134 new citations

134 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Exp Ther Med"[jour]

These pubmed results were generated on 2017/12/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2EhC1FV

Profound Prolonged Bradycardia and Hypotension after Interscalene Brachial Plexus Block with Bupivacaine

Publication date: Available online 30 December 2017
Source:The Journal of Emergency Medicine
Author(s): Mathew Nelson, Alexandra Reens, Lara Reda, David Lee
BackgroundInterscalene brachial plexus blocks have been a routinely performed method of anesthesia for shoulder surgery that decreases the need for general anesthesia, length of stay, and recovery time. We describe a case of bupivacaine toxicity after an interscalene block.Case ReportThe patient was a 66-year-old man who presented to our Emergency Department by emergency medical services from an ambulatory surgery center where he had undergone rotator cuff surgery, with bradycardia and hypotension. His symptoms began upon completion of the surgery in which he received interscalene nerve block with bupivacaine and lidocaine. He was given three doses of 0.5 mg atropine and one dose of 1 mg epinephrine for a heart rate of 40 beats/min without any improvement prior to arrival. His bradycardia was refractory to atropine. He was started on a dopamine drip and transferred to the coronary care unit. The timing of his symptoms, minutes after his regional nerve block, and his complete recovery with only supportive care, make the diagnosis of bupivacaine toxicity likely.Why Should an Emergency Physician Be Aware of This?Despite the safety profile of local anesthetics, we must be aware of their potential side affects. Whereas most adverse reactions are secondary to misdirection of anesthetic or accidental vascular puncture, local anesthetic systemic toxicity (LAST) is the major cause of significant adverse events with regional anesthesia. As regional anesthesia becomes more common, emergency physicians must be more aware of the potential complications and be able to both diagnose and treat.



http://ift.tt/2lwbM65

Point-of-Care Ultrasound–Guided Percutaneous Cannulation of Extracorporeal Membrane Oxygenation: Make it Simple

Publication date: Available online 30 December 2017
Source:The Journal of Emergency Medicine
Author(s): Hong Joon Ahn, Jun Wan Lee, Ki Hyuk Joo, Yeon Ho You, Seung Ryu, Jin Woong Lee, Seung Whan Kim
BackgroundCannulation of the great vessels is required for extracorporeal membrane oxygenation (ECMO). Currently, there is no guideline for optimal imaging modalities during percutaneous cannulation of ECMO.ObjectiveThe purpose of this study was to describe percutaneous cannulation guided by point-of-care ultrasound (POCUS) for ECMO and compare it with fluoroscopy and landmark guidance.MethodsThree groups (POCUS-, fluoroscopy-, and landmark-guided) of percutaneous cannulation for ECMO were analyzed retrospectively in a tertiary academic hospital. In the POCUS-guided group, visual confirmation of guidewire and cannula by ultrasound in both the access and return cannula were essential for successful cannulation. Fluoroscopy- and landmark-guided groups were cannulated with the conventional technique.ResultsA total of 128 patients were treated by ECMO during the study period, of which 94 (73.4%) cases were venoarterial ECMO. This included 56 cases of extracorporeal cardiopulmonary resuscitation. Also, there were 30 (23.4%) cases of venovenous ECMO and 4 (3.1%) cases of venoarteriovenous ECMO. A total of 71 (55.5%) patients were cannulated under POCUS guidance, and 43 (33.6%) patients were cannulated under fluoroscopy guidance and 14 (10.9%) patients were cannulated by landmark guidance. No surgical cut downs were required. Misplacement of cannula occurred in 3 (2.3%) cases. All three occurred in the landmark-guided group.ConclusionsPOCUS-guided cannulation is comparable to fluoroscopy-guided cannulation in terms of avoiding cannula misplacement. In our experience, POCUS-guided cannulation is a useful strategy over fluoroscopy- and landmark-guided cannulation during peripheral ECMO.



http://ift.tt/2lo0IZw

Targeting the Warburg effect for Cancer Treatment: Ketogenic Diets for Management of Glioma

Publication date: Available online 30 December 2017
Source:Seminars in Cancer Biology
Author(s): Angela Poff, Andrew Kourtnik, Kathleen M. Egan, Solmaz Sahebjum, Dominic D'Agostino, Nagi B. Kumar




http://ift.tt/2CcWX3x

Deep brain stimulation for obsessive-compulsive disorder: Knowledge and concerns among psychiatrists, psychotherapists and patients.

Related Articles

Deep brain stimulation for obsessive-compulsive disorder: Knowledge and concerns among psychiatrists, psychotherapists and patients.

Surg Neurol Int. 2017;8:298

Authors: Naesström M, Blomstedt P, Hariz M, Bodlund O

Abstract
Background: Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. The number of implants worldwide is slowly increasing. Therefore, it is of importance to explore knowledge and concerns of this novel treatment among patients and their psychiatric healthcare contacts. This information is relevant for scientific professionals working with clinical studies for DBS for this indication. Especially, for future study designs and the creation of information targeting healthcare professionals and patients. The aim of this study was to explore the knowledge and concerns toward DBS among patients with OCD, psychiatrists, and cognitive behavioral therapists.
Methods: The study was conducted through web-based surveys for the aimed target groups -psychiatrist, patients, and cognitive behavioral therapists. The surveys contained questions regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy.
Results: The main source of information was from scientific sources among psychiatrists and psychotherapists. The patient's main source of information was the media. Common concerns among the groups included complications from surgery, anesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists, and ethical concerns among psychiatrists.
Conclusion: There are challenges for DBS in OCD as identified by the participants of this study; source and quality of information, efficacy, potential adverse effects, and eligibility. In all of which the current evidence base still is limited. A broad research agenda is needed for studies going forward.

PMID: 29285414 [PubMed]

http://ift.tt/2zPabgQ

Nontraumatic, posterior circulation pseudoaneurysm of the basilar artery summit with complete spontaneous resolution: Case Report and literature review.

Related Articles

Nontraumatic, posterior circulation pseudoaneurysm of the basilar artery summit with complete spontaneous resolution: Case Report and literature review.

Surg Neurol Int. 2017;8:296

Authors: Kozyrev DA, Hernesniemi J

PMID: 29285412 [PubMed]

http://ift.tt/2DCock3

Simple training tricks for mastering and taming bypass procedures in neurosurgery.

Related Articles

Simple training tricks for mastering and taming bypass procedures in neurosurgery.

Surg Neurol Int. 2017;8:295

Authors: Hafez A, Raj R, Lawton MT, Niemelä M

Abstract
Background: Neurosurgeons devoted to bypass neurosurgery or revascularization neurosurgery are becoming scarcer. From a practical point of view, "bypass neurosurgeons" are anastomosis makers, vessels technicians, and time-racing repairers of vessel walls. This requires understanding the key features and hidden tricks of bypass surgery. The goal of this paper is to provide simple and inexpensive tricks for taming the art of bypass neurosurgery. Most of these tricks and materials described can be borrowed, donated, or purchased inexpensively.
Methods: We performed a review of relevant training materials and recorded videos for training bypass procedures for 3 years between June 2014 and July 2017. In total, 1,300 training bypass procedures were performed, of which 200 procedures were chosen for this paper.
Results: A training laboratory bypass procedures is required to enable a neurosurgeon to develop the necessary skills. The important skills for training bypass procedures gained through meticulous practice to be as reflexes are coordination, speed, agility, flexibility, and reaction time. Bypassing requires synchronization between the surgeon's gross movements, fine motoric skills, and mental strength. The suturing rhythm must be timed in a brain-body-hand fashion.
Conclusion: Bypass-training is a critical part of neurosurgical training and not for a selected few. Diligent and meticulous training can enable every neurosurgeon to tame the art of bypass neurosurgery. This requires understanding the key features and hidden tricks of bypass surgery, as well as uncountable hours of training. In bypass neurosurgery, quality and time goes hand in hand.

PMID: 29285411 [PubMed]

http://ift.tt/2DByocC

The clinical examination in the patient with subarachnoid hemorrhage is still the most reliable parameter for predicting pathophysiological changes.

Related Articles

The clinical examination in the patient with subarachnoid hemorrhage is still the most reliable parameter for predicting pathophysiological changes.

Surg Neurol Int. 2017;8:294

Authors: Petridis AK, Beseoglu K, Steiger HJ

Abstract
Background: Macrovasospasms and delayed cerebral injury are factors which correlate with high morbidity in patients suffering a subarachnoid hemorrhage. Transcranial Doppler (TCD) ultrasonography and perfusion computed tomography (PCT) are diagnostic tools used to diagnose such pathologies. However, TCD is not very reliable and PCT exposes patients to radiation and cannot be performed daily.
Case Description: We present the case of a 47-year-old female with subarachnoid hemorrhage caused by rupture of an intracranial aneurysm. The aneurysm was coil embolized, and the clinical course of the patient was uncomplicated. She was writing notes about her stay in the intensive care unit. Without having any other complaints, she noticed that her writing became abruptly unrecognizable. TCD failed to show pathological signs, although PCT revealed decreased brain perfusion.
Conclusion: We rely more and more on our technical tools in medicine. However, clinical examination is and will stay the the first sign indicating cerebral pathologies and should remain the first priority to have an awake patient who can be examined routinely. In addition, we emphasize on the need of seeing the patient and not only the images. More than anything else, the patient is the first who shows signs of pathology and not the instruments (CT, TCD, etc.). The sentence "a fool with a tool is still a fool" should be present in every doctor's mind to avoid mistakes and react appropriately.

PMID: 29285410 [PubMed]

http://ift.tt/2DCAjxU

Massive lumbar spine hematoma post-spinal tap.

Related Articles

Massive lumbar spine hematoma post-spinal tap.

Surg Neurol Int. 2017;8:293

Authors: Al Jishi A, Murty N

Abstract
Background: Lumbar puncture is a well-known procedure. The indications for lumbar puncture vary among different medical and surgical disciplines, though obtaining a sample for cerebrospinal fluid analysis is the most common one. A normal coagulation profile is crucial prior to pursing the procedure. Occasionally, an urgent sample is needed to guide an appropriate treatment while the patient's coagulation status is suboptimum. In those specific critical situations, some may accept suboptimal correction owing to the urgency of the case.
Case Description: We report a case for a patient with Burkitt lymphoma who presented with mild neuroaxial symptoms. An urgent cerebrospinal fluid sample was required which was taken after correcting his platelets count to 53.4 × 109/L. He developed a massive multi-compartmental thoracolumbar hematoma with acute cauda equine syndrome requiring surgical intervention. Despite aggressive management, he remained permanently paraplegic with functional status that negatively affected his overall outcome.
Conclusion: Lumbar puncture is a useful diagnostic and treatment tool. Although serious events are seldom, they can be detrimental. A precaution not to underestimate such events in practicing lumbar, especially in patients with suboptimum coagulation state. Image-guided procedure can be useful and should be considered in appropriately selected patients.

PMID: 29285409 [PubMed]

http://ift.tt/2DzHmqT

A technique for sequential, progressive clipping for a giant thrombosed distal anterior cerebral artery aneurysm: Technical note.

Related Articles

A technique for sequential, progressive clipping for a giant thrombosed distal anterior cerebral artery aneurysm: Technical note.

Surg Neurol Int. 2017;8:292

Authors: Sato Y, Samii M

Abstract
Background: Giant thrombosed aneurysms often present with thickened walls and a hard thrombus, including in the near-neck aneurysmal sac. These usually make it difficult to achieve complete neck clipping with preservation of local branch patency. Here, we demonstrate a simple but safe and effective technique to overcome these problems in a patient with a 6-cm giant thrombosed distal anterior cerebral artery aneurysm.
Case Description: A 77-year-old-man suffered from loss of volitional activity due to the frontal mass effect. The aneurysm was exposed with unilateral paramedian craniotomy and an interhemispheric approach. The clip was applied to the aneurysmal neck but it slipped onto the parent artery, which caused branch artery occlusion. Intra-aneurysmal thrombectomy was immediately performed near the aneurysmal neck with ultrasonic aspiration. The next clip was added along the aneurysm side of the preceding clip, which was then removed. This procedure was repeated twice so that complete neck clipping was achieved while preserving the branch patency. All the residual thrombus and aneurysmal wall were subsequently removed. Postoperatively, there was no additional neurological deficit. The patient's mental function was significantly improved.
Conclusions: We conclude that the sequential, progressive clipping technique is a robust option for successful neck clipping of giant thrombosed aneurysms.

PMID: 29285408 [PubMed]

http://ift.tt/2DAoZ56

Designing a pain management protocol for craniotomy: A narrative review and consideration of promising practices.

Related Articles

Designing a pain management protocol for craniotomy: A narrative review and consideration of promising practices.

Surg Neurol Int. 2017;8:291

Authors: Vacas S, Van de Wiele B

Abstract
Background: Craniotomy is a relatively common surgical procedure with a high incidence of postoperative pain. Development of standardized pain management and enhanced recovery after surgery (ERAS) protocols are necessary and crucial to optimize outcomes and patient satisfaction and reduce health care costs.
Methods: This work is based upon a literature search of published manuscripts (between 1996 and 2017) from Pubmed, Cochrane Central Register, and Google Scholar. It seeks to both synthesize and review our current scientific understanding of postcraniotomy pain and its part in neurosurgical ERAS protocols.
Results: Strategies to ameliorate craniotomy pain demand interventions during all phases of patient care: preoperative, intraoperative, and postoperative interventions. Pain management should begin in the perioperative period with risk assessment, patient education, and premedication. In the intraoperative period, modifications in anesthesia technique, choice of opioids, acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), regional techniques, dexmedetomidine, ketamine, lidocaine, corticosteroids, and interdisciplinary communication are all strategies to consider and possibly deploy. Opioids remain the mainstay for pain relief, but patient-controlled analgesia, NSAIDs, standardization of pain management, bio/behavioral interventions, modification of head dressings as well as patient-centric management are useful opportunities that potentially improve patient care.
Conclusions: Future research on mechanisms, predictors, treatments, and pain management pathways will help define the combinations of interventions that optimize pain outcomes.

PMID: 29285407 [PubMed]

http://ift.tt/2BUZMSt

Virtual autopsy to assess sacral anatomy: Conditions for a minimal invasive approach to the spinal canal through the hiatus sacralis.

Related Articles

Virtual autopsy to assess sacral anatomy: Conditions for a minimal invasive approach to the spinal canal through the hiatus sacralis.

Surg Neurol Int. 2017;8:290

Authors: Bodmer A, Ross S, Raabe A, Beck J, Ulrich CT, Schucht P

Abstract
Background: Despite multiple advantages of minimally invasive techniques in spinal surgery, the currently used approaches may lead to postoperative pain and spinal instability. As a natural orifice, the hiatus sacralis offers a nontransmuscular alternative entry point for endoscopic approaches. In this study, we collected data about the complex anatomical conditions of the sacral canal as a basis for the development of a sacral endoscope.
Methods: We retrospectively evaluated 192 postmortem human cadaveric specimens with computed tomography (CT). The anatomical conditions of the sacrum and lumbar spine were analyzed, including assessment of the lateral and anteroposterior diameters, measurement of the cross-sectional area of the sacral canal at the lumbosacral transition, hiatus sacralis, and the narrowest point of the sacral canal.
Results: The narrowest anteroposterior diameter was >2.3 mm in 95% of the cases; the width was >13 mm in 95% of the cases. The narrowest point was located at the hiatus in 72% of the cases. The angle of sacral kyphosis was less than 30° and less than 50° in lumbar lordosis in 95% of the cases. A length shorter than 288 mm was measured in 95% of the cases. Anatomical conditions in male and female sacra were comparable.
Conclusions: The narrow anteroposterior diameter is the key limiting feature for using the canalis sacralis as a natural entry point into the spinal canal. Sacroscopy will require endoscopes with a flattened shape, with parallel arrangement of instruments and flexibility to accommodate the varied dorsal and ventral curvatures.

PMID: 29285406 [PubMed]

http://ift.tt/2CsaIrR

Cervicothoracic syringomyelia caused by cervical spinal stenosis: Case report and literature review.

Related Articles

Cervicothoracic syringomyelia caused by cervical spinal stenosis: Case report and literature review.

Surg Neurol Int. 2017;8:288

Authors: Badri M, Gader G, Bahri K, Zammel I

Abstract
Background: Syringomyelia is commonly associated with Chiari malformations, spinal trauma, arachnoiditis, or tumors. However, rarely, cervical canal stenosis is implicated in intramedullary cavitations.
Case Discription: Here, we report the case of a 60-year-old male patient who presented with loss of pain and temperature sensation in upper extremities associated with a spastic tetraparesis. On magnetic resonance imaging, the patient was found to have syringomyelia extending from C1 to Th3. Following posterior decompressive surgery, the syrinx resolved along with the patient's neurological complaints.
Conclusion: Here, the authors presented a case and reviewed the literature regarding how cervical spinal stenosis may contribute to cervical or thoracic syringomyelia.

PMID: 29285404 [PubMed]

http://ift.tt/2CoQsax

Sacroiliac stabilization for sacral metastasis: A case series.

Related Articles

Sacroiliac stabilization for sacral metastasis: A case series.

Surg Neurol Int. 2017;8:287

Authors: Buraimoh MA, Yu CC, Mott MP, Graziano GP

Abstract
Background: The sacrum is a rare location for spinal metastasis. These lesions are typically large and destructive by the time of diagnosis, making treatment difficult. When indicated, surgical stabilization offers pain relief and preserves independence in patients with impending and acute pathological sacral fractures.
Case Description: Three consecutive patients presented with sacral metastases. After either failing radiation therapy or presenting with acute fracture and instability, the patients underwent intralesional excision, bilateral L4 to ilium fusion with instrumentation, and sacroiliac (SI) screw fixation. Pain improved after surgery, and there were no wound healing complications. Two patients could continue walking without any assistive device, while one patient required a walker.
Conclusion: Stabilization with combined modified Galveston fixation and SI screw fixation relieves pain and allows maintenance of independence in patients with sacral metastasis.

PMID: 29285403 [PubMed]

http://ift.tt/2Cs7XXG

In reply to recent letter to editor regarding: Towards consensus reporting of radiation induced liver toxicity in the treatment of primary liver malignancies: defining clinically relevant endpoints

Publication date: Available online 30 December 2017
Source:Practical Radiation Oncology
Author(s): Tobias R. Chapman, Stephen R. Bowen, Smith Apisarnthanarax




http://ift.tt/2lrHhiD

Stereotactic radiosurgery for multiple brain metastases: Results of multi-centre benchmark planning studies

Publication date: Available online 30 December 2017
Source:Practical Radiation Oncology
Author(s): David J. Eaton, Jonathan Lee, Ian Paddick
PurposeStereotactic radiosurgery is indicated for treatment of multiple brain metastases. Various treatment platforms are available, but most comparisons are limited to single centre studies. As part of a national commissioning programme, benchmark planning cases were completed by 21 clinical centres, providing a unique dataset of current practice across a large number of providers and equipment platforms.Methods and MaterialsTwo brain metastases cases were provided, with images and structures pre-drawn, involving three and seven lesions. Centres produced plans according to their local practice, which were reviewed centrally using metrics for target coverage, selectivity, gradient fall-off and normal tissue sparing.Results50 plans were submitted, using 24 treatment platforms. 11 plans were revised following feedback, including two centres who acquired a new platform; and one other centre accepted a restriction of service. All centres prioritised coverage, with the prescription isodose covering ≥95% of 233/235 target volumes. Selectivity was much more variable, especially for smaller lesions, and when combined with poor gradient indices resulted in large volumes of normal tissue being irradiated. Tomotherapy submissions were outliers for either selectivity or gradient index, but other platforms could produce plans with relatively low gradient indices for larger lesion volumes. There was more variation among Varian and Elekta linac plans than for Gamma Knife and Cyberknife, and larger differences for smaller targets, both inter- and intra-treatment-platform. Doses to normal brain and brainstem were highest when margins were applied, but improvements were possible by re-planning alone.ConclusionsMulti-centre benchmarking exercises have highlighted some variation in clinical practice and priorities, with a few outliers. Most platforms are able to achieve comparable plans, except for the smallest volumes and when larger planning margins are used. The data will be used to progress standardisation and quality improvement of national services, and can provide useful guidance for centres worldwide.



http://ift.tt/2lxJLLA

Regarding: “Towards consensus reporting of radiation-induced liver toxicity in the treatment of primary liver malignancies: defining clinically relevant endpoints”

Publication date: Available online 29 December 2017
Source:Practical Radiation Oncology
Author(s): Naoko Sanuki




http://ift.tt/2lnSgJP

Optimal imaging surveillance after stereotactic ablative radiation therapy for early-stage non-small cell lung cancer: Findings of an International Delphi Consensus Study

Publication date: Available online 30 December 2017
Source:Practical Radiation Oncology
Author(s): Timothy K. Nguyen, Suresh Senan, Jeffery D. Bradley, Kevin Franks, Meredith Giuliani, Matthias Guckenberger, Mark Landis, Billy W. Loo, Alexander V. Louie, Hiroshi Onishi, Heidi Schmidt, Robert Timmerman, Gregory M.M. Videtic, David A. Palma
PurposeImaging after stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer can detect recurrences and second primary lung cancers; however, the optimal follow-up practice of these patients remains unclear. We sought to establish consensus recommendations for surveillance after SABR.Methods and materialsInternational opinion leaders in thoracic radiation oncology and radiology were invited to participate (n = 31), with 11 accepting (9 radiation oncologists, 2 radiologists). Consensus-building was achieved using a 3-round Delphi process. Participants rated their agreement/disagreement with statements using a 5-point Likert scale. An a priori threshold of ≥75% agreement/disagreement was required for consensus.ResultsA 100% response rate was achieved and final consensus statements were approved by all participants. The consensus statements were: (1.1) thoracic computed tomography (CT) scans should be ordered routinely in follow-up; (1.2) if there is a suspicion for local recurrence (LR), fludeoxyglucose positron emission tomography/CT scans are strongly recommended. Otherwise, there is limited evidence to guide routine use of fludeoxyglucose positron emission tomography /CT; (1.3) CT imaging is not recommended at 6 weeks, but is recommended at months 3, 6, and 12 in year 1 and then every 6 months in year 2 and annually in years 3 through 5; (1.4) after 5 years, CT imaging should continue, although no consensus was reached regarding the frequency. (2.1) Response Evaluation Criteria in Solid Tumors 1.1 criteria are not sufficient for detecting LR; (2.2) a formal scoring system, informed by validated data, should be used to classify high-risk imaging features predictive of LR; (2.3) CT findings suspicious for LR include: infiltration into adjacent structures, bulging margins, sustained growth, mass-like growth, spherical growth, craniocaudal growth, and loss of air bronchograms. (3) Salvage therapy without pathologic confirmation of recurrence is acceptable if imaging findings are highly suspicious and a biopsy is not safe/feasible or if an attempted biopsy was nondiagnostic.ConclusionsThese guidelines provide international expert consensus on areas of uncertainty in the management of early-stage non-small cell lung cancer patients after SABR.



http://ift.tt/2luSDRS

Potential role of NDRG2 in reprogramming cancer metabolism and epithelial -to-mesenchymal transition.

Related Articles

Potential role of NDRG2 in reprogramming cancer metabolism and epithelial -to-mesenchymal transition.

Histol Histopathol. 2017 Dec 29;:11957

Authors: Chen XL, Lei L, Hong LL, Ling LL

Abstract
Epithelial-to-mesenchymal transition (EMT) allows a cell with epithelial characteristics to transdifferentiate into a cell with mesenchymal characteristics, which is recognized as a key priming event for the initiation and evolvement of cancer metastasis. Accumulating data have shown that aberrant cancer metabolism contributes to the execution of EMT and cancer metastasis through multiple pathological pathways. Recently, the N-MYC downstream-regulated gene 2 (NDRG2), as a tumor suppressor and metabolism-related gene in various cancers, has been widely noted. NDGR2 is associated with energy metabolism, especially glycose metabolism. Hence, we propose a hypothesis that EMT is repressed by NDRG2 via cancer metabolic reprogramming, and summarize the pathological processes and molecular pathways related to the regulation of NDRG2.

PMID: 29285747 [PubMed - as supplied by publisher]

http://ift.tt/2lnqpcE

Systematic review of low-level laser therapy for adult androgenic alopecia.

Related Articles

Systematic review of low-level laser therapy for adult androgenic alopecia.

J Cosmet Laser Ther. 2017 Dec 29;:1-8

Authors: Delaney SW, Zhang P

Abstract
Alopecia is a common disorder affecting over half of the world's population. Within this condition, androgenic alopecia (AA) is the most common type, affecting 50% of males over 40 and 75% of females over 65. Anecdotal paradoxical hypertrichosis noted during laser epilation has generated interest in the possibility of using laser to stimulate hair growth. In this study, we aimed to critically appraise the application of low-level laser therapy for the treatment of AA in adults. A systematic review was performed on studies identified on Medline, EMBASE, Cochrane database, and clinicaltrials.org. Double-blinded randomized controlled trials were selected and analyzed quantitatively (meta-analysis) and qualitatively (quality of evidence, risk of bias). Low-level laser therapy appears to be a promising noninvasive treatment for AA in adults that is safe for self-administration in the home setting. Although shown to effectively stimulate hair growth when compared to sham devices, these results must be interpreted with caution. Further studies with larger samples, longer follow-up, and independent funding sources are necessary to determine the clinical effectiveness of this novel therapy.

PMID: 29286826 [PubMed - as supplied by publisher]

http://ift.tt/2DyAlGQ

Editorial Board

Publication date: January 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 1





http://ift.tt/2CfddRK

Potential role of NDRG2 in reprogramming cancer metabolism and epithelial -to-mesenchymal transition.

Related Articles

Potential role of NDRG2 in reprogramming cancer metabolism and epithelial -to-mesenchymal transition.

Histol Histopathol. 2017 Dec 29;:11957

Authors: Chen XL, Lei L, Hong LL, Ling LL

Abstract
Epithelial-to-mesenchymal transition (EMT) allows a cell with epithelial characteristics to transdifferentiate into a cell with mesenchymal characteristics, which is recognized as a key priming event for the initiation and evolvement of cancer metastasis. Accumulating data have shown that aberrant cancer metabolism contributes to the execution of EMT and cancer metastasis through multiple pathological pathways. Recently, the N-MYC downstream-regulated gene 2 (NDRG2), as a tumor suppressor and metabolism-related gene in various cancers, has been widely noted. NDGR2 is associated with energy metabolism, especially glycose metabolism. Hence, we propose a hypothesis that EMT is repressed by NDRG2 via cancer metabolic reprogramming, and summarize the pathological processes and molecular pathways related to the regulation of NDRG2.

PMID: 29285747 [PubMed - as supplied by publisher]

http://ift.tt/2lnqpcE

"Asian Pac J Cancer Prev"[jour]; +34 new citations

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Asian Pac J Cancer Prev"[jour]

These pubmed results were generated on 2017/12/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2ElIGPy

"J Vis Exp"[jour]; +133 new citations

133 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"J Vis Exp"[jour]

These pubmed results were generated on 2017/12/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2DBc7M2

Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: Formulation development and in vivo therapeutic efficacy in rats

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Salwa Salah, Ghada E.A. Awad, Amal I.A. Makhlouf
Traditional azole antifungal formulations suffer from poor retention in the vaginal cavity, irritation and burning of the vaginal area. In the present work, we aim at the development of a novel miconazole (MCZ) microsponges gel as an attractive dosage form for vaginal candidiasis. The proposed formula has the potential to minimize the local side effects of the drug due to the controlled release characteristic, which increases patient compliance. Moreover, the mucosal retention effect of the microsponges in addition to the bioadhesion property of Carbopol gel prolongs the retention of the dosage form in the vagina and consequently improves the therapeutic efficiency. MCZ microsponges were prepared applying Quasi emulsion method using Eudragit RS100. The effect of formulation factors, namely, drug:polymer ratio (1:1, 2:1 and 4:1), the amount of poly vinyl alcohol (PVA) (25, 50 and 75mg) and the volume of organic solvent (2.5, 5, 10mL) on the characteristics of MCZ microsponges has been investigated. The microsponges were optimized regarding the production yield (68.8±6.4%), particle size (78.2±2.1μm), entrapment efficiency (92.9±1.9%) and release rate (Q150 51.8±2.5%). The selected formula was further evaluated for its, flowability, porosity and surface morphology. MCZ microsponges were incorporated into Carbopol gel, then the viscosity and bioadhesion were examined. The in vitro antifungal activity of MCZ microsponges gel was comparable to the market product. In vivo, MCZ microsponges vaginal gel was more effective than the market product (p<0.05) in eradicating Candida infection in rats, which was supported by the histopathological findings.

Graphical abstract

http://ift.tt/2Cd9bcd

Acta Awards 2018

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66





http://ift.tt/2CdGDj9

Editorial Board

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66





http://ift.tt/2zQA4Na

Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66
Author(s): Yan Huang, Chengtie Wu, Xiaoling Zhang, Jiang Chang, Kerong Dai
Silicate bioceramics have been considered to possess a wide prospect of clinical application for orthopedic tissue regeneration due to their excellent osteogenesis and angiogenesis. However, the mechanism for silicate bioceramics stimulating bone formation is not fully understood. The host immune defense to implants is proved to greatly influence the osteogenesis and new bone formation, but up to now, few studies are focused on the silicate bioceramics modulated host immune responses. In our present study, two representative silicate bioceramics, akermanite (AKT) and nagelschmidtite (NAGEL) were used as model materials to investigate the inflammation responses in vitro and in vivo, and β-tricalcium phosphate (β-TCP) bioceramics were used as a control. It was found that the mouse macrophage cell RAW264.7 that cultured on AKT and NAGEL bioceramics displayed not only less viability and proliferation, but also a significant less inflammatory cytokine secretion than those on β-TCP in vitro. The formation of foreign body giant cells and fibrous capsules, the invasion of macrophages, as well as the detected inflammatory cytokines around the implanted materials were much lower in both AKT and NAGEL bioceramic groups as compared with those in the β-TCP controls in vivo. Furthermore, it was found that not just the certain concentration of extracellular Si-containing ionic products released from the silicate bioceramics, but also the separate Si, Mg and Ca ions revealed the activity to inhibit the macrophage inflammatory responses by the way of suppressing the activated inflammatory MAPK and NF-κB signaling pathway and promoting the caspase-dependent apoptosis of macrophages. In general, our study suggests that the silicate bioceramics could regulate immune responses by altering the ionic microenvironment between the implants and hosts, which may offer new insight about the mechanism of the bioactivity of silicate bioceramics in bone regeneration and provide profitable guidance for designing new biomaterials for bone tissue engineering.Statement of SignificanceSilicate bioceramics have been widely used for orthopedic tissue regeneration because of their excellent characteristics in bone formation. However, there are few studies concerning their interrelationships with the host immune defense that has been proved to greatly influence osteogenesis. In our present study, the akermanite and nagelschmidtite were used as two representative silicate bioceramics to investigate the inflammation responses in vitro and in vivo; and for the first time, the bioactive ions released from the silicate bioceramics were discovered to regulate the macrophage immune responses through both inhibiting the inflammatory signaling and activating apoptosis of macrophages. Our findings in this study may not only increase the understanding in osteogenic activity of silicate bioceramics, but also provide profitable guidance for designing and manufacturing new biomaterials for bone tissue engineering.

Graphical abstract

http://ift.tt/2Cenygq

Effects of nanofeatures induced by severe shot peening (SSP) on mechanical, corrosion and cytocompatibility properties of magnesium alloy AZ31

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66
Author(s): Sara Bagherifard, Daniel J. Hickey, Stanislava Fintová, Filip Pastorek, Ines Fernandez-Pariente, Michele Bandini, Thomas J. Webster, Mario Guagliano
The application of biodegradable magnesium-based materials in the biomedical field is highly restricted by their low fatigue strength and high corrosion rate in biological environments. Herein, we treated the surface of a biocompatible magnesium alloy AZ31 by severe shot peening in order to evaluate the potential of surface grain refinement to enhance this alloy's functionality in a biological environment. The AZ31 samples were studied in terms of micro/nanostructural, mechanical, and chemical characteristics in addition to cytocompatibility properties. The evolution of surface grain structure and surface morphology were investigated using optical, scanning and transmission electron microscopy. Surface roughness, wettability, and chemical composition, as well as in depth-microhardness and residual stress distribution, fatigue behaviour and corrosion resistance were investigated. Cytocompatibility tests with osteoblasts (bone forming cells) were performed using sample extracts. The results revealed for the first time that severe shot peening can significantly enhance mechanical properties of AZ31 without causing adverse effects on the growth of surrounding osteoblasts. The corrosion behavior, on the other hand, was not improved; nevertheless, removing the rough surface layer with a high density of crystallographic lattice defects, without removing the entire nanocrystallized layer, provided a good potential for improving corrosion characteristics after severe shot peening and thus, this method should be studied for a wide range of orthopedic applications in which biodegradable magnesium is used.Statement of SignificanceA major challenge for most commonly used metals for bio-implants is their non-biodegradability that necessitates revision surgery for implant retrieval when used as fixation plates, screws, etc. Magnesium is reported among the most biocompatible metals that resorb over time without adverse tissue reactions and is indispensable for many biochemical processes in human body. However, fast and uncontrolled degradation of magnesium alloys in the physiological environment in addition to their inadequate mechanical properties especially under repeated loading have limited their application in the biomedical field. The present study providesdata on the effect of a relatively simple surface nanocrystallziation method with high potential to tailor the mechanical and chemical behavior of magnesium based material while maintaining its cytocompatibility.

Graphical abstract

http://ift.tt/2CfHtvq

The influence of biodegradable magnesium implants on the growth plate

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66
Author(s): Tanja Kraus, Stefan Fischerauer, Stefan Treichler, Elisabeth Martinelli, Johannes Eichler, Anastasia Myrissa, Silvia Zötsch, Peter J. Uggowitzer, Jörg F. Löffler, Annelie M. Weinberg
Mg-based biodegradable materials are considered promising candidates in the paediatric field due to their favourable mechanical and biological properties and their biodegrading potential that makes a second surgery for implant removal unnecessary. In many cases the surgical fixation technique requires a crossing of the growth plate by the implant in order to achieve an adequate fragment replacement or fracture stabilisation. This study investigates the kinetics of slowly and rapidly degrading Mg alloys in a transphyseal rat model, and also reports on their dynamics in the context of the physis and consecutive bone growth. Twenty-six male Sprague–Dawley rats received either a rapidly degrading (ZX50; n = 13) or a slowly degrading (WZ21; n = 13) Mg alloy, implanted transphyseal into the distal femur. The contralateral leg was drilled in the same manner and served as a direct sham specimen. Degradation behaviour, gas formation, and leg length were measured by continuous in vivo micro CT for up to 52 weeks, and additional high-resolution µCT (HRS) scans and histomorphological analyses of the growth plate were performed. The growth plate was locally destroyed and bone growth was significantly diminished by the fast degradation of ZX50 implants and the accompanying release of large amounts of hydrogen gas. In contrast, WZ21 implants showed homogenous and moderate degradation performance, and the effect on bone growth did not differ significantly from a single drill-hole defect.Statement of SignificanceThis study is the first that reports on the effects of degrading magnesium implants on the growth plate in a living animal model. The results show that high evolution of hydrogen gas due to rapid Mg degradation can damage the growth plate substantially. Slow degradation, however, such as seen for WZ21 alloys, does not affect the growth plate more than drilling alone, thus meeting one important prerequisite for deployment in paediatric osteosynthesis.

Graphical abstract

http://ift.tt/2CeD7oE

An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66
Author(s): Can Zhang, Xianliu Wang, Erchen Zhang, Long Yang, Huihua Yuan, Wenjing Tu, Huilan Zhang, Zi Yin, Weiliang Shen, Xiao Chen, Yanzhong Zhang, Hongwei Ouyang
Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. Here, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), an HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. We found that TSA incorporated aligned fibers of PLLA had an additive effect in directing tenogenic differentiation. Moreover, the in situ implantation study in rat model further confirmed that A-TSA scaffold promoted the structural and mechanical properties of the regenerated Achilles tendon. This study demonstrated that HDAC was involved in the teno-differentiation with aligned fiber topography, and the combination of HDAC with aligned topography might be a more efficient strategy to promote tenogenesis of stem cells.Statement of SignificanceElectrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. The uniqueness of our studies are as follows, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), a HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. The incorporation and subsequent release of bioactive small molecule TSA into electrospun aligned fibers allows a controllable manner for both biochemical and physical regulation of tenogenesis of stem cells both in vitro and in vivo. Collectively, the present study provides a model of "translating the biological knowledge learned from cell-material interaction into optimizing biomaterials (from Biomat-to-Biomat)".

Graphical abstract

http://ift.tt/2CfHq2I

Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments to promote regeneration after spinal cord injury

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66
Author(s): Liudmila N. Novikova, Mallappa K. Kolar, Paul J. Kingham, Andreas Ullrich, Sven Oberhoffner, Monika Renardy, Michael Doser, Erhard Müller, Mikael Wiberg, Lev N. Novikov
Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and ε-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material. For in vivo experiments, the TC/PDO conduit was implanted into a small 2–3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2–5 months after initial surgery (chronic SCI). At 8 weeks after implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons and sensory CGRP-positive axons regenerated across the conduit and were often associated with PDO microfilaments and migrated host cells. Implantation into chronically injured SCI induced regeneration mainly of the sensory CGRP-positive axons. Although the conduit had no effect on the density of OX42-positive microglial cells when compared with SCI control, the activity of GFAP-positive astrocytes was reduced. The results suggest that a TC/PDO conduit can support axonal regeneration after acute and chronic SCI even without addition of exogenous glial or stem cells.Statement of SignificanceBiosynthetic conduits can support regeneration after spinal cord injury but often require addition of cell therapy and neurotrophic factors. This study demonstrates that biodegradable conduits made from trimethylene carbonate and ε-caprolactone with poly-p-dioxanone microfilaments alone can promote migration of different host cells and stimulate axonal regeneration after implantation into acute and chronic spinal cord injury. These results can be used to develop biosynthetic conduits for future clinical applications.

Graphical abstract

http://ift.tt/2CfHlvW

Focal adhesion signaling affects regeneration by human nucleus pulposus cells in collagen- but not carbohydrate-based hydrogels

Publication date: 15 January 2018
Source:Acta Biomaterialia, Volume 66
Author(s): Anita Krouwels, Ferry P.W. Melchels, Mattie H.P. van Rijen, Corlinda B.M. Ten Brink, Wouter J.A. Dhert, F. Cumhur Öner, Marianna A. Tryfonidou, Laura B. Creemers
Hydrogel-based 3D cell cultures are an emerging strategy for the regeneration of cartilage. In an attempt to regenerate dysfunctional intervertebral discs, nucleus pulposus (NP) cells can be cultured in hydrogels of various kinds and physical properties. Stiffness sensing through focal adhesions is believed to direct chondrogenesis, but the mechanisms by which this works are largely unknown. In this study we compared focal adhesion formation and glycosaminoglycan (GAG) deposition by NP cells in a range of hydrogels. Using a focal adhesion kinase (FAK) inhibitor, we demonstrated that focal adhesion signaling is involved in the response of NP cells in hydrogels that contain integrin binding sites (i.e. methacrylated gelatin (gelMA) and type II collagen), but not in hydrogels deplete from integrin binding sites such as alginate and agarose, or CD44-binding hydrogels based on hyaluronic acid. As a result of FAK inhibition we observedenhanced proteoglycan production in gelMA, but decreased production in type II collagen hydrogels, which could be explained by alteration in cell fate as supported by the increase in the adipogenic marker peroxisome proliferator-activated receptor gamma (PPARy). Furthermore, GAG deposition was inversely proportional to polymer concentration in integrin-binding gelMA, while no direct relationship was found for the non-integrin binding gels alginate and agarose. This corroborates our finding that focal adhesion formation plays an important role in NP cell response to its surrounding matrix.Statement of SignificanceBiomaterials are increasingly being investigated for regenerative medicine applications, including regeneration of the nucleus pulposus. Cells interact with their environment and are influenced by extracellular matrix or polymer properties. Insight in these interactions can improve regeneration and helps to understand degeneration processes. The role of focal adhesion formation in the regenerative response of nucleus pulposus cells is largely unknown. Therefore, the relation between materials, stiffness and focal adhesion formation is studied here.

Graphical abstract

http://ift.tt/2Cd0LS9