Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca²⁺ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca²⁺ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca²⁺ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-<span style="font-style:italic;">N</span>,<span style="font-style:italic;">N</span>,<span style="font-style:italic;">N</span>,<span style="font-style:italic;">N</span>′-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.</span>

http://ift.tt/2mrvu5Q

Characterization of White Matter Tracts by Diffusion MR Tractography in Cat and Ferret that Have Similar Gyral Patterns

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The developmental relationships between gyral structures and white matter tracts have long been debated, but it is still difficult to discern whether they influence each other's development or are causally related. To explore this topic, this study used cats and ferrets as models for species that share similar gyral folding patterns and imaged with diffusion magnetic resonance imaging to compare white matter innervations in homologous gyri and other brain regions. Adult cat and ferret brains were analyzed via diffusion spectrum imaging tractography and homologous regions of interest were compared. Although similar genetic lineage and gyral structures would suggest analogous white matter tracts, tractography reveals significantly differing white matter connectivity in both the visual and auditory cortices. Similarities in connectivity were concentrated primarily in the highly conserved cerebellar region. These results correlate well with existing histological and functional studies of both species. Our results indicate that, while the 2 species may share similar gyral structures, they utilize different white matter connectivity; suggesting that while species may share similar gyral structures, they can develop different underlying white matter connectivity.</span>

http://ift.tt/2lxnWup

Variations in Acetylcholinesterase Activity within Human Cortical Pyramidal Neurons Across Age and Cognitive Trajectories

<span class="paragraphSection"><div class="boxTitle">Abstract</div>We described an extensive network of cortical pyramidal neurons in the human brain with abundant acetylcholinesterase (AChE) activity. Emergence of these neurons during childhood/adolescence, attainment of highest density in early adulthood, and virtual absence in other species led us to hypothesize involvement of AChE within these neurons in higher cortical functions. The current study quantified the density and staining intensity of these neurons using histochemical procedures. Few faintly stained AChE-positive cortical pyramidal neurons were observed in children/adolescents. These neurons attained their highest density and staining intensity in young adulthood. Compared with the young adult group, brains of cognitively normal elderly displayed no significant change in numerical density but a significant decrease in staining intensity of AChE-positive cortical pyramidal neurons. Brains of elderly above age 80 with unusually preserved memory performance (SuperAgers) showed significantly lower staining intensity and density of these neurons when compared with same-age peers. Conceivably, low levels of AChE activity could enhance the impact of acetylcholine on pyramidal neurons to counterbalance other involutional factors that mediate the decline of memory capacity during average aging. We cannot yet tell if elderly with superior memory capacity have constitutively low neuronal AChE levels or if this feature reflects adaptive neuroplasticity.</span>

http://ift.tt/2mryoHF

Mirroring the Social Aspects of Speech and Actions: The Role of the Insula

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Action and speech may take different forms, being expressed, for example, gently or rudely. These aspects of social communication, named vitality forms, have been little studied in neuroscience. In the present functional magnetic resonance imaging study, we investigated the role of insula in processing action and speech vitality forms. In speech runs, participants were asked to listen or imaging themselves to pronounce action verbs gently or rudely. In action runs, they were asked to observe or imaging themselves to perform actions gently or rudely. The results showed that, relative to controls, there was an activation of the dorso-central insula in both tasks of speech and action runs. The insula sector specific for action vitality form was located slightly more dorsally than that of speech with a large overlap of their activations. The psycho-physiological interaction analysis showed that the insular sector involved in action vitality forms processing is connected with the left hemisphere areas controlling arm actions, whereas the sector involved in speech vitality forms processing is linked with right hemisphere areas related to speech prosody. We conclude that the central part of the insula is a key region for vitality forms processing regardless of the modality by which they are conveyed or expressed.</span>

http://ift.tt/2lxjfk2

A Critical Role of Inhibition in Temporal Processing Maturation in the Primary Auditory Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.</span>

http://ift.tt/2mrJa0P

Relapsing bullous amyloidosis of the oral mucosa and acquired cutis laxa in a patient with multiple myeloma: a rare triple association

Summary

It is well known that primary systemic amyloidosis [light chain (AL) amyloidosis] is associated with hidden dyscrasia or multiple myeloma. Acquired cutis laxa (cutis laxa acquisita; CLA) has also been described in patients with plasma cell dyscrasias, including multiple myeloma. We report a case in which haemorrhagic oral bullae were the first sign of an undiagnosed primary systemic amyloidosis related to multiple myeloma IgG-λ and previously diagnosed CLA. There is only one report in literature of this rare triple association; however, in that case the patient did not have oral mucosal involvement or bullous amyloidosis.

http://ift.tt/2lVaC3E

A novel mutation in the RSPO4 gene in a patient with autosomal recessive anonychia

Summary

The Wnt signalling pathway is a major pathway involved in the embryogenic development of the various organs of the body. Appropriate signalling in this pathway relies on the proper functioning of several proteins including the R-spondin family of proteins. Deactivating mutations in R-spondin 4 are associated with anonychia. We present the case of a 26-year-old man presenting with anonychia of the 20 nails, which had been present since birth. Using genetic studies, we identified a novel nonsense mutation, c.164-165TC>AA, characterized by two consecutive mismatch bases. To our knowledge, this mutation is the first to be reported in R-spondin 4 in a Lebanese population. Evaluating new patients with anonychia provides fruitful clinical and molecular findings.

http://ift.tt/2lStbav

Otophyma in Morbihan disease

http://ift.tt/2lV2noz

Lentigo maligna successfully treated with combination therapy of topical tazarotene and imiquimod

http://ift.tt/2lolx48

Effectiveness of omalizumab in a case of urticarial vasculitis

Summary

Urticarial vasculitis (UV) is a mainly leucocytoclastic vasculitis with urticarial plaques. Treating these patients is challenging as the available treatments have poor efficacy. Oral corticosteroids are considered the first-line treatment, but H1 antihistamines, dapsone, colchicine, antimalarials, ciclosporin and antileucotrienes have all been tried also. However, because of their adverse effects and/or lack of efficacy, new agents are still needed. Omalizumab, an anti-IgE antibody, shows efficacy in chronic spontaneous urticaria, and might also be a good treatment for angio-oedema and urticarial vasculitis. To our knowledge, there have been only seven relevant case reports published in the English literature. We add a new case of severe chronic recurrent urticarial vasculitis refractory to all of the drugs mentioned above. We started the patient on subcutaneous omalizumab 300 mg every 4 weeks, which produced clinical improvement within the first month and total remission in the fifth month. The patient has remained stable for 23 months, and follow-up is ongoing.

http://ift.tt/2lSgqwJ

Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer’s Disease: Results from a Double-Blind, Placebo-Controlled Trial

Introduction: To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. <p></p> Methods: This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. <p></p> Results: A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. <p></p> Conclusion: This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. <p></p>

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Follicular lymphoma transforming into diffuse large B-cell lymphoma in spleen: Simultaneous appearance of both on 18F-FDG PET/CT and histology

Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): William Makis, Anthony Ciarallo, Tina Petrogiannis-Haliotis, Arthur Rosenberg, Stephan Probst
Low grade lymphoma may transform into a more aggressive lymphoma and this transformation is usually associated with a poor outcome. A 65year old man presented with two metabolically active splenic lesions on a staging [18F] fluoro-2-deoxy-d-glucose (¹⁸F–FDG) positron emission tomography/computed tomography (PET/CT). Histologic evaluation post splenectomy confirmed the presence of two clonally related lymphomas: a follicular lymphoma (FL) and a diffuse large B-cell lymphoma (DLBCL). Molecular genetic studies confirmed that the DLBCL lesions arose from a pre-existing FL. We present the ¹⁸F–FDG PET/CT imaging characteristics of both lymphoma types which were simultaneously present in the spleen.



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Direct resin composite restorations for fractured maxillary teeth and diastema closure: A 7 years retrospective evaluation of survival and influencing factors

Publication date: Available online 28 February 2017
Source:Dental Materials
Author(s): Edina Lempel, Bálint Viktor Lovász, Réka Meszarics, Sára Jeges, Ákos Tóth, József Szalma
ObjectivesThis retrospective study evaluated the survival rate of anterior direct resin based composite (RBC) build-ups in vital teeth made of microhybrid and nanofill RBC materials and the influence of bruxism, beverage consumption and smoking on the long-term performance of restorations.MethodsPatients receiving anterior restoration between 2006 and 2011, with the diagnosis of fracture or diastema, were selected. A total of 65 adult patients (mean age: 25.2) with 163 restorations (78 Filtek Supreme XT and 85 Enamel Plus HFO) were evaluated using the USPHS criteria. Data were analyzed with Fisher's Exact Test, Extended Cox-regression analysis and Kaplan–Meier method.ResultsMean observation period was 7.2 (±1.4) years and the mean annual failure rate for this period was 1.43%. The reasons of failures included restoration fracture and color mismatch. Nanofill restorations had significantly higher rate of color mismatch (p=0.002), microhybrids more frequently failed in fracture of restoration (p=0.034). The overall difference in potential hazard of using Enamel Plus HFO or Filtek Supreme XT was not significant (p=0.704). Chipping or fracture of the restoration was more frequent in the first year after placement (p=0.036), while beverage consumption was significantly correlated with discoloration of the restorations (p=0.005).SignificanceThe application of direct RBC restorations provides an excellent treatment option for fractured teeth and for closing diastemas. The overall survival rate was 88.34% up to 10 years. Microhybrid and nanofill RBC restorations showed similar survival rates, however nanofills discolored at a higher rate, meanwhile chipping of the restoration occurred frequently with microhybrids.



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Cytotoxicity and genotoxicity of a low-shrinkage monomer and monoacylphosphine oxide photoinitiator: Comparative analyses of individual toxicity and combination effects in mixtures

Publication date: Available online 28 February 2017
Source:Dental Materials
Author(s): Dragica Manojlovic, Miroslav D. Dramićanin, Vesna Miletic, Dragana Mitić-Ćulafić, Bojana Jovanović, Biljana Nikolić
ObjectiveTo compare cytotoxicity and genotoxicity of novel urethane-based monomer FIT-852 and monoacylphosphine oxide photoinitiator (Lucirin TPO) with conventional Bisphenol A-glycidyl-methacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) monomers and camphorquinone (CQ)/amine photoinitiator system, respectively. Moreover, we quantified and analyzed the combinatorial effects of individual substances in resin-based mixtures concerning the nature of the combinatorial effects.MethodsCytotoxic and genotoxic effects of BisGMA, FIT, TEGDMA, CQ, DMAEMA and TPO and their combined toxicity in four clinically relevant mixtures (FIT/TPO, FIT/CQ, BisGMA/TPO, BisGMA/CQ) were tested on human fetal lung fibroblasts MRC-5 using MTT and Comet assays. We assessed combination effects of monomers and photoinitiators on overall toxicity from the measured concentration-effect relationships. Combination index (CI) was calculated on the basis of the median-effect equation derived from the mass-action law principle.ResultsIndividual substances showed decreasing cytotoxic effects in the following order: BisGMA>TPO>FIT>CQ>DMAEMA>TEGDMA. Experimental mixtures showed decreasing cytotoxic effects in the order BisGMA/TPO>BisGMA/CQ>FIT/CQ>FIT/TPO. FIT-based mixtures exhibited antagonistic cytotoxic effects between components while BisGMA-based mixtures demonstrated synergistic effects at ED50. TPO amplified both antagonistic and synergistic cytotoxic effects in mixtures. Pure substances showed genotoxicity in the following order: TPO>BisGMA>FIT>CQ>TEGDMA. We did not detect the genotoxic potential of DMAEMA. The rank of genotoxic concentrations of the mixtures was: BisGMA/TPO>BisGMA/CQ>FIT/CQ>FIT/TPO.SignificanceLower cytotoxicity and genotoxicity of FIT than BisGMA suggests its greater biocompatibility. Conversely, photoinitiator TPO was significantly more cytotoxic and genotoxic than both CQ and DMAEMA. CI values showed that components of FIT-based mixtures exhibit an antagonistic cytotoxic effect, while compontents of BisGMA-based mixtures show synergism.



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Evaluation of dental adhesive systems incorporating an antibacterial monomer eugenyl methacrylate (EgMA) for endodontic restorations

Publication date: Available online 27 February 2017
Source:Dental Materials
Author(s): A. Almaroof, S.A. Niazi, L. Rojo, F. Mannocci, S. Deb
ObjectiveThe purpose of this study was to incorporate EgMA, an antibacterial monomer into two commercial dental adhesive systems for their application in endodontic restoration with the aim to disinfect the root canal space before curing and to inhibit bacterial growth on their surfaces after being cured.MethodsEgMA monomer was added at 20%wt. into the formulation of the single-component self-etch, Clearfil Universal Bond™ (CUB) and into the catalyst and the adhesive components of the total-etch Adper Scotchbond-multipurpose™ (SBMP) adhesive systems. The degree of conversion (DC) was calculated from FTIR spectra, glass transition temperature (Tg) determined by DSC, water sorption and solubility were measured gravimetrically, and surface free energy (SFE) via contact angle measurements. The bonding performance to coronal and middle root canal dentin was assessed through push-out bond strength after filling the canals with a composite core material and the surface integrity was observed using SEM and confocal laser scanning microscopy (CLSM). The standard agar diffusion test (ADT) was used to identify the sensitivity of three endodontically pathogenic bacteria, Enterococcus faecalis, Streptococcus mutans and Propionibacterium acnes to uncured EgMA modified adhesives. Multispecies biofilm model from these strains was grown on the disc surface of cured adhesives and investigated using quantitative microbial culture and CLSM with live/dead staining. MTT assay was also used to determine the cytotoxicity of these adhesives.ResultsThe incorporation of EgMA lowered polymerization exotherm and enhanced the hydrophobic character of these adhesives, without changing the DC and Tg in comparison to the controls (without EgMA). The total push-out bond strengths of the EgMA-containing adhesives were not significantly different from those of the controls (p>0.05). The modification of self-etch adhesive system enhanced the bond strength in the middle region of the roots canal. SEM of debonded specimens and CLSM examination showed the integrity of the resin-dentin interfaces. For all three bacteria tested, the sizes of the inhibition zones produced by uncured EgMA modified adhesives were significantly greater (p<0.05) than those of the controls. The results of biofilm inhibition tests showed less CFU for total bacteria on bonding agents with EgMA compared to the control materials (p<0.05). The modification at 20% monomer concentration had no adverse effects on cytocompatibility of both adhesives tested.SignificanceThe inclusion of EgMA endows dental adhesives with effective antibacterial effects without influencing their curing properties, bonding ability to root canal dentin, and cytotoxicity against human gingival fibroblasts, indicating the usefulness of their application in endodontic restorations.



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Effect of monomer type on the CC degree of conversion, water sorption and solubility, and color stability of model dental composites

Publication date: Available online 27 February 2017
Source:Dental Materials
Author(s): Andrea Soares Q.S. Fonseca, Allana Dutra Labruna Moreira, Pedro Paulo A.C. de Albuquerque, Lívia Rodrigues de Menezes, Carmem S. Pfeifer, Luis Felipe J. Schneider
ObjectiveThis study has investigated the influence of BisGMA, BisEMA, BisEMA 30, and two UDMA-based monomers (UDMA and Fit 852), with TEGDMA as co-monomer, on the degree of conversion, water sorption, water solubility, and optical properties of experimental dental composites.MethodsMaterials were formulated at 70/30 molar rations using BisGMA, BisEMA, BisEMA 30, UDMA or FIT 852, as base monomers, combined with TEGDMA. 60wt% of silanated-glass particles was added. Degree of conversion (DC) and polymerization kinetics were monitored using Fourier-transformed infrared spectroscopy in the near-IR range. Water sorption (Wsp) and solubility (Wsl) were assessed using mass variation after 60days water storage. Color was evaluated using a digital spectrophotometer, applying the CIELab parameters 24h after dry storage and 60days after water immersion to calculate ΔE values. All data were analyzed using ANOVA and Tukey's test (pre-set alpha=0.05).ResultsThe BisGMA-based co-monomer mixture presented the lowest DC (62±1%), whereas BisEMA 30 had the highest DC value (95±2%). The highest Wsp was observed for BisEMA 30 (12.2±0.8%), and the lowest for BisEMA (0.4±0.1%). BisEMA has shown the lowest Wsl (0.03±0.01%) and BisEMA 30 the highest one (0.97±0.1%). The ΔE values showed that BisEMA 30 (7.3 color units) and Fit 852 (3.8 color units) altered the color stability providing ΔE>3.3, which is considered clinically unacceptable.ConclusionsThe chemical composition and structure of the base monomer influenced the degree of conversion, water sorption, water solubility, and color stability. Considering the overall results, it is possible to state that the base monomer BisEMA mixed with the co-monomer TEGDMA presented the best performance in terms of all the parameters tested.SignificanceThe resin matrix composition might influence physical property degradation processes and color stability of dental resin composites. Formulations based on BisEMA seem most promising for materials' development.



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Laryngopharyngeal Reflux in Children with Chronic Otitis Media with Effusion

http://sfaki.blogspot.com/2017/02/laryngopharyngeal-reflux-in-children.html

Children aged 7-10 years of age with OME underwent 24-hour multichannel intraluminal impedance pH-metry. The upper pH sensor was situated 1 cm above the upper esophageal sphincter, and the lower pH sensor was placed 3-5 cm above the lower esophageal sphincter. Parents were asked to complete the gastroesophageal reflux assessment of symptoms in a pediatrics questionnaire.

Twenty-eight children were enrolled; LPR was detected in 19 (67.9%) children. The criteria of the LPR diagnosis was the presence of at least one supraesophageal episode with a pH < 5.0 and a change in the pH value measured from the initial level at the upper sensor of > 0.2. In total, 64 episodes were observed. Assessment of all LPR episodes showed the presence of 246 episodes in the entire study. A considerable predominance of weakly acidic episodes (87.8%) was noted; there were 6.5% acidic episodes, and weakly alkaline episodes reached 5.7%. Pathological GER was noted in 10 (35.7%) subjects. Acid GER was detected in 8 children, 2 of whom demonstrated non-acidic reflux. In the LPR-negative patients, no pathological GER was confirmed with the exception of a single case of non-acidic reflux.

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

6948891480

alsfakia@gmail.com

Low-grade intraductal carcinoma (low-grade cribriform cystadenocarcinoma) with tumor-associated lymphoid proliferation of parotid gland

Publication date: Available online 28 February 2017
Source:Pathology - Research and Practice
Author(s): Toshimitsu Nishijima, Hidetaka Yamamoto, Takafumi Nakano, Yui Hatanaka, Ken-ichi Taguchi, Muneyuki Masuda, Yoshinao Oda
We report a rare case of low-grade intraductal carcinoma with tumor-associated lymphoid proliferation (TALP) in the parotid gland of a 75-year-old woman. Grossly, the tumor was solid and cystic. Histologically, the tumor consisted of a papillary-cystic, micropapillary, or focally cribriform proliferations of epithelial cells with low-grade cytological atypia. The interspaces between the epithelial components were filled with prominent lymphoid stroma and lymphoid follicles, superficially mimicking Warthin tumor. The neoplastic epithelial cells were positive for S100 protein by immunohistochemical staining. There was an attenuated layer of myoepithelial cells all around the epithelial components, indicating a non-invasive (in situ) nature. Although TALP is a rare finding in intraductal carcinoma, it should be considered as a histological variation of this kind of tumor. The relationship between intraductal carcinoma, low-grade cribriform cystadenocarcinoma, low-grade salivary duct carcinoma, and salivary duct carcinoma in situ is also discussed in this report.



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Genomic profiling of esophageal squamous cell carcinoma (ESCC) − basis for precision medicine

Publication date: Available online 28 February 2017
Source:Pathology - Research and Practice
Author(s): Jung Wook Yang, Yoon-La Choi
PurposePreparing for precision medicine, we surveyed genomic alterations in esophageal squamous cell carcinoma (ESCC) and identified candidate therapeutic targets by genomic profiling using next-generation sequencing (NGS).Materials and methodsSingle-nucleotide variations, indels, and copy number variations in 80 genes were evaluated by targeted deep sequencing in 24 surgically resected ESCC specimens. Immunohistochemistry analyses and silver in situ hybridization for ERBB2 (HER2) were conducted to verify the NGS results. Associations between clinicopathological factors and detected genomic alterations were estimated.ResultsThe mean coverage of sequencing of the tumor tissues from 24 patients was 464.8X with 85.1% over 100X. We detected a total of 115 genetic alterations and more than one genetic alteration was detected in most patients (23/24, 95.8%). Genes with genetic alterations detected in more than 20% of cases included TP53 (20/24, 83%), NOTCH1 (7/24, 29%), and MTOR (6/24, 25%). Amplification of 7 genes was detected in 8 cases. Genes showing amplification included AKT2 (1/24, 4.2%), EGFR (2/24, 8.3%), ERBB2 (HER2; 1/24, 4.2%), FGFR1 (1/24, 4.2%), KRAS (1/24, 4.2%), MDM2 (1/24, 4.2%), and PIK3CA (1/24, 4.2%). The ERBB2 alteration was confirmed by immunohistochemistry and silver in situ hybridization. Patients with NF1 and ARID1A mutations were younger than the patients without the mutations. (p=0.024 and 0.014, respectively). NOTCH1 mutation and EGFR genetic alteration were associated with a larger tumor size (p=0.019) and lesser invasion depth (p=0.005), respectively.ConclusionThis study revealed the genetic profiles of ESCC, which may provide a foundation for the development of novel targeted therapy and precision medicine.



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Organic contaminants and heavy metals in indoor dust from e-waste recycling, rural, and urban areas in South China: Spatial characteristics and implications for human exposure

Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Chun-Tao He, Xiao-Bo Zheng, Xiao Yan, Jing Zheng, Mei-Huan Wang, Xiao Tan, Lin Qiao, She-Jun Chen, Zhong-Yi Yang, Bi-Xian Mai
The concentrations of several organic contaminants (OCs) and heavy metals were measured in indoor dust from e-waste recycling, rural, and urban areas in South China to illustrate the spatial characteristics of these pollutants and to further evaluate human exposure risks. The median concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), and dechlorane plus (DPs) were 38.6–3560, 2360–30,100, 665–2720, and 19.5–1860ng/g, while the median concentrations of Cd, Pb, Cu, Cr, and Zn were 2.46–40.4, 206–1380, 217- 1200, 25.3–134, and 176–212μg/g in indoor dust. The levels of all pollutants, except Zn, in dust from the e-waste recycling area were significantly higher than those from the other areas. Cd, Pb, and most OCs exhibited similar pollution patterns in the three areas, indicating that e-waste recycling activities are the major pollution source. In contrast, Cu, Cr, Zn, and penta-BDE are likely derived from household products in the rural and urban areas. The highest estimated daily intakes (EDIs) of PCBs, PBDEs, DBDPE, and DPs were 0.15–163, 3.97–1470, 1.26–169, and 0.11–134ng/kg bw/day for toddlers and adults. The highest EDIs of BDE 209 and Pb in toddlers in the e-waste recycling area were 16% and 18 times higher than the reference doses, indicating the high exposure risk of these pollutants in the e-waste recycling area.

Graphical abstract

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Two 3D Zinc(II) coordination frameworks constructed from pyrazine-2,3-dicarboxylate and 1,2-bis(4-pyridyl)ethylene

Publication date: 5 June 2017
Source:Journal of Molecular Structure, Volume 1137
Author(s): Güneş Günay Sezer, Okan Zafer Yeşilel, Orhan Büyükgüngör
Two 3D coordination polymers, {[Zn(μ3-pzdc)(μ-dpeten)0.5]∙3H2O}n (1) and [Zn(μ3-pzdc)(μ-dpeten)0.5]n (2) (H2pzdc = pyrazine-2,3-dicarboxylic acid and dpeten = 1,2-bis(4-pyridyl)ethylene) have been synthesized by hydrothermal methods and structurally characterized by elemental analysis, IR spectroscopy, single-crystal and powder X-ray diffraction. In complex 1, each pzdc ligand bridges three Zn(II) ions through forming two-dimensional layers. The adjacent 2D layers are further connected by dpeten ligand to generate a novel 3D framework containing one-dimensional large porous channel. It displays a 5-connected bnn hexagonal topology with point symbol {4⁶.6⁴}. Although the complex 2 was obtained under the same reaction conditions together with complex 1, it exhibits 3D→3D a 2-fold interpenetration network with 6-connected pcu α-Po primitive cubic topology with point symbol {4¹².6³}. The adjacent three Zn(II) ions are linked by tridentate bridging pzdc ligands to form a 2D layer structure. The 2D layers are further bridged by dpeten ligand to form a 3D pillar-layered network. Moreover, thermal and photoluminescent properties of complexes 1 and 2 have also been studied.



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Game-based combined cognitive and neurofeedback training using focus pocus reduces symptom severity in children with diagnosed AD/HD and subclinical AD/HD

Publication date: Available online 28 February 2017
Source:International Journal of Psychophysiology
Author(s): Stuart J. Johnstone, Steven J. Roodenrys, Kirsten Johnson, Rebecca Bonfield, Susan J. Bennett
Previous studies report reductions in symptom severity after combined working memory (WM) and inhibitory control (IC) training in children with AD/HD. Based on theoretical accounts of the role of arousal/attention modulation problems in AD/HD, the current study examined the efficacy of combined WM, IC, and neurofeedback training in children with AD/HD and subclinical AD/HD. Using a randomized waitlist control design, 85 children were randomly allocated to a training or waitlist condition and completed pre- and post-training assessments of overt behavior, trained and untrained cognitive task performance, and resting and task-related EEG activity. The training group completed twenty-five sessions of training using Focus Pocus software at home over a 7 to 8-week period. Trainees improved at the trained tasks, while enjoyment and engagement declined across sessions. After training, AD/HD symptom severity was reduced in the AD/HD and subclinical groups according to parents, and in the former group only according to blinded teachers and significant-others. There were minor improvements in two of six near-transfer tasks, and evidence of far-transfer of training effects in four of five far-transfer tasks. Frontal region changes indicated normalization of atypical EEG features with reduced delta and increased alpha activity. It is concluded that technology developments provide an interesting a vehicle for delivering interventions and that, while further research is needed, combined WM, IC, and neurofeedback training can reduce AD/HD symptom severity in children with AD/HD and may also be beneficial to children with subclinical AD/HD.



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Enzymatic extraction and characterization of polysaccharide from Tuber aestivum

Publication date: Available online 28 February 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Devshri Bhotmange, Janne H. Wallenius, Rekha S. Singhal, Salem S. Shamekh
Tuber aestivum is one of the important edible mycorrhizal truffle having unique flavor and texture. It is known to contain approximately 5.23% of polysaccharide. The present work was focused on extraction and characterization of the polysaccharide from fruiting body of T. aestivum. The polysaccharide was extracted using complex enzymes viz. papain, trypsin and pectinase. Taguchi orthogonal array experimental design and response surface methodology were employed to optimize the factors involved in the extraction process. The optimal factors for the extraction of polysaccharide from T. aestivum were 1.0% trypsin, 2.0% pectinase, 1.0% papain, temperature 50°C, pH 6.0 and extraction time 90min. Under these optimum conditions the polysaccharide extraction yield was found to be 46.93% of total polysaccharide. Polysaccharide so obtained was characterized for its structure, chemical composition, thermal analysis and bioactivity. The monosaccharides present in the extracted polysaccharides were glucose (>90%), rhamnose, galactose and mannose. The polysaccharide extracted from T. aestivum possessed the significant in vitro antioxidant capability.

Graphical abstract

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Brusterhaltende Therapie mit adjuvanter Radiotherapie des Mammakarzinoms besser als die Mastektomie?

http://ift.tt/2mrlCsX

Clinical relevance of the M1b and M1c descriptors from the proposed TNM 8 classification of lung cancer

Abstract

Objective

The TNM 8 lung cancer staging system reclassifies patients with a solitary extrathoracic metastasis as M1b and two or more extrathoracic metastases as M1c. This study investigates the clinical relevance of this change.

Methods

Advanced lung cancer patients were retrospectively restaged according to the TNM8 M1b and M1c classifiers. Overall survival was compared in M1b and M1c patients staged with and without PET-CT. We then summarized the TNM 8 staging classification and the relevant literature on the treatment of oligometastatic lung cancer.

Results

In all, 82 patients with metastatic lung cancer were reclassified according to the TNM 8: 14 had M1b and 58 had M1c disease. Those with M1b disease lived significantly longer than those with M1c disease (15.2 vs. 7.3 months, p = 0.0029). Among those with M1b disease, survival was the highest when M1b status was confirmed by PET-CT (21.4 vs. 7 months). M1c patients with 4 or less distant metastases had a trend to longer survival vs. M1c patients with 5 or more metastases (9.4 vs. 7.3 months), especially when PET-CT staging was used (13.9 months).

Conclusions

We confirmed the prognostic value of the M1b and M1c descriptors in a Western European tertiary care population. The use of PET-CT seems to increase the prognostic value of the M descriptor and may define an additional oligometastatic subgroup of M1c patients. Clinical trials investigating the treatment of patients with varying degrees of metastatic disease are needed and should be based on PET-CT staging.

http://ift.tt/2lxbTgt

A 2-bp insertion (c.67_68insCC) in MC1R causes recessive white coat color in Bama miniature pigs

Publication date: Available online 28 February 2017
Source:Journal of Genetics and Genomics
Author(s): Qitao Jia, Chunwei Cao, Hai Tang, Ying Zhang, Qiantao Zheng, Xiao Wang, Rui Zhang, Xianlong Wang, Ailing Luo, Hong Wei, Anming Meng, Qi Zhou, Hongmei Wang, Jianguo Zhao




http://ift.tt/2lnwkvs

Surveillance culture for multidrug-resistant gram-negative bacteria: Performance in liver transplant recipients

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3
Author(s): Maristela Pinheiro Freire, Isabel Cristina Villela Soares Oshiro, Patrícia Rodrigues Bonazzi, Ligia Câmera Pierrotti, Larissa Marques de Oliveira, Anna Silva Machado, Inneke Marie Van Der Heijdenn, Flavia Rossi, Silvia Figueiredo Costa, Luiz Augusto Carneiro D'Albuquerque, Edson Abdala
BackgroundThe prevalence of infection with multidrug-resistant gram-negative bacteria (MDR-GNB) after solid-organ transplantation is increasing. Surveillance culture (SC) seems to be an important tool for MDR-GNB control. The goal of this study was to analyze the performance of SC for MDR-GNB among liver transplant (LT) recipients.MethodsThis was a prospective cohort study involving patients who underwent LT between November 2009 and November 2011. We screened patients for extended spectrum β-lactamase-producing Escherichia coli, extended spectrum β-lactamase-producing Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB). We collected SC samples immediately before LT and weekly thereafter, until hospital discharge. Samples were collected from the inguinal-rectal area, axilla, and throat. The performance of SC was evaluated through analysis of its sensitivity, negative predictive value, and accuracy.ResultsDuring the study period, 181 patients were evaluated and 4,110 SC samples were collected. The GNB most often identified was CRAB, in 45.9% of patients, followed by CRKP in 40.3%. For all microorganisms, the positivity rate was highest among the inguinal-rectal samples. If only samples collected from this area were considered, the SC would fail to identify 34.9% of the cases of CRAB colonization. The sensitivity of SC for CRKP was 92.5%. The performance of SC was poorest for CRAB (sensitivity, 80.6%).ConclusionsOur data indicate that SC is a sensitive tool to identify LT recipients colonized by MDR-GNB.



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Editorial Board

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3





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Improvement in the diagnosis of catheter-related bloodstream infections in a tertiary cancer center

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3
Author(s): Patrick Chaftari, Anne-Marie Chaftari, Javier Adachi, Ray Hachem, Sammy Raad, Elizabeth Natividad, Nora Oliver, Bena Ellickalputhenpura, Ying Jiang, Jeffrey Tarrand, Issam Raad
BackgroundIdentifying a central venous catheter (CVC) as the source of bacteremia requires drawing simultaneous blood cultures (BCs) from the CVC and peripheral site and correct labeling of the BC source. In our emergency center (EC), 52% of BCs collected from febrile cancer patients lacked source information, making the diagnosis and management of catheter-related bloodstream infections (CRBSIs) challenging.MethodsBetween January 2015 and June 2015, we conducted a quality improvement project in our EC aiming to increase the occurrence of simultaneous BC drawing with accurate source labeling by 10%.ResultsStaff education and monitoring increased average BC source labeling from a baseline of 48% to a much better rate of 70%. Label introduction led to increased source labeling to 94% by June 2015. This project had a significant influence in patients with a CVC and a positive BC because the physician is now able to determine whether the CVC is the source of the bacteremia in 88% of cases compared with 36% at baseline (P = .0003).ConclusionsEducation without an active intervention is usually not enough. Simple solutions such as label introduction can have significant influence on patient safety and care. Accurate diagnosis may guide clinicians at the bedside to appropriately manage CVCs in the setting of bacteremia, remove a CVC when indicated, and prevent unnecessary CVC removal with its potential safety and cost-effectiveness implications.



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APIC Masthead

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3





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Information for Readers

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3





http://ift.tt/2lwXIIq

Information for Authors

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3





http://ift.tt/2lRHpbN

Foam soap is not as effective as liquid soap in eliminating hand microbial flora

Publication date: Available online 28 February 2017
Source:American Journal of Infection Control
Author(s): Nicolette Dixon, Margie Morgan, Ozlem Equils
Foam soaps are aerosolized liquid soaps dispensed through a special pump mechanism. Currently there are no studies comparing liquid soap with foam soap in regard to efficacy of reducing hand microbial burden. In 3 separate experiments and with 2 different brands of foam soap, it was observed that nonantimicrobial foam soap was not as effective in reducing hand bacterial load as the liquid soap.



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Long-term care certificate program prepares facilities for regulatory changes

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3





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Table of Contents

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3





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National survey of practices to prevent health care-associated infections in Thailand: The role of prevention bundles

Publication date: Available online 28 February 2017
Source:American Journal of Infection Control
Author(s): Anucha Apisarnthanarak, David Ratz, M. Todd Greene, Thana Khawcharoenporn, David J. Weber, Sanjay Saint
BackgroundWe evaluated the practices used in Thai hospitals to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated pneumonia (VAP).MethodsFrom January 1, 2014-November 30, 2014, we surveyed all Thai hospitals with an intensive care unit and at least 250 beds. The use of prevention practices for CAUTI, CLABSI, and VAP was assessed. High compliance (≥75%) with all components of the CLABSI and VAP prevention bundles were determined. CAUTI, CLABSI, and VAP infection rates before and after implementing infection control practices are reported. Multivariable regression was used to examine associations between infection prevention bundle compliance and infection rate changes.ResultsOut of 245 eligible hospitals, 212 (86.5%) responded. A total of 120 (56.6%) and 115 hospitals (54.2%) reported ≥75% compliance for all components of the CLABSI and VAP prevention bundles, respectively, and 91 hospitals (42.9%) reported using ≥ 4 recommended CAUTI-prevention practices. High compliance with all of the CLABSI and VAP bundle components was associated with significant infection rate reductions (CLABSI, 38.3%; P < .001; VAP, 32.0%; P < .001). Hospitals regularly using ≥ 4 CAUTI-prevention practices did not have greater reductions in CAUTI (0.02%; P = .99).ConclusionsCompliance with practices to prevent hospital infections was suboptimal. Policies and interventions promoting bundled approaches may help reduce hospital infections for Thai hospitals.



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Are hospital floors an underappreciated reservoir for transmission of health care-associated pathogens?

Publication date: 1 March 2017
Source:American Journal of Infection Control, Volume 45, Issue 3
Author(s): Abhishek Deshpande, Jennifer L. Cadnum, Dennis Fertelli, Brett Sitzlar, Priyaleela Thota, Thriveen S. Mana, Annette Jencson, Heba Alhmidi, Sreelatha Koganti, Curtis J. Donskey
In a survey of 5 hospitals, we found that floors in patient rooms were frequently contaminated with pathogens and high-touch objects such as blood pressure cuffs and call buttons were often in contact with the floor. Contact with objects on floors frequently resulted in transfer of pathogens to hands.

Graphical abstract

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Reasons for influenza vaccination underuse: A case-control study

Publication date: Available online 28 February 2017
Source:American Journal of Infection Control
Author(s): Scott S. Field




http://ift.tt/2lRF68E

The importance of nano-porosity in the stalk-derived biochar to the sorption of 17β-estradiol and retention of it in the greenhouse soil

Abstract

Natural estrogens in greenhouse soils with long-term manure application are becoming a potential threat to adjacent aquatic environment. Porous stalk biochar as a cost-effective adsorbent of estrogen has a strong potential to reduce their transportation from soil to waters. But the dominant adsorption mechanism of estrogen to stalk biochars and retention of estrogen by greenhouse soils amended with biochar are less well known. Element, function groups, total surface area (SA_total), nano-pores of stalk biochars, and chemical structure of 17β-estradiol (E2, length 1.20 nm, width 0.56 nm, thickness 0.48 nm) are integrated in research on E2 sorption behavior in three stalk-derived biochars produced from wheat straw (WS), rice straw (RS), and corn straw (CS), and greenhouse soils amended with optimal biochar. The three biochars had comparable H/C and (O + N)/C, while their aromatic carbon contents and total surface areas (SA_total) both varied as CS > WS > RS. However, WS had the highest sorption capacity (logK _oc), sorption affinity (K _f ), and strongest nonlinearity (n). Additionally, the variation of Langmuir maximum adsorption capacity (Q ⁰) was consistent with the trend for SA_1.2-20 (WS > RS > CS) but contrary to the trend for SA_total and SA_<1.2 (CS > WS > RS). These results indicate that pore-filling dominates the sorption of E2 by biochars and exhibits "sieving effect" and length-directionality-specific via H-bonding between –OH groups on the both ends of E2 in the length direction and polar groups on the inner surface of pores. After the addition of wheat straw biochar, the extent of increase in the sorption affinity for E2 in the soil with low OC content was higher than those in the soil with high OC content. Therefore, the effectiveness for the wheat straw biochar mitigating the risk of E2 in greenhouse soil depended on the compositions of soil, especially organic matter.

http://ift.tt/2mIMWia

Self-assembly of mesoporous Bi-S-TiO 2 composites for degradation of industrial dinitrotoluene solution under UV light

Abstract

Mesoporous Bi-S-TiO₂ composites were synthesized by the method combining evaporation-induced self-assembly (EISA) method with impregnation process. Characterization shows mesoporous Bi-S-TiO₂ was a highly crystalline anatase, with relatively high thermal stability, large surface area (75–120 m²/g), and large mesopore (10–20 nm). The results also revealed that Bi and S species existed in Bi⁴⁺, S²⁻, S and S⁶⁺ forms in the mesoporous TiO₂, which allow the mesoporous Bi-S-TiO₂ illustrating strong absorption in the ultraviolet region, and the absorption edge shifts to the visible-light region. Photodegradation tests shown that, about 92.3% industrial aqueous dinitrotoluene (DNT) solution could be degraded by 1.5%Bi-S-TiO₂ under UV irradiation for 5 h. Concentration of Bi ions and calcination temperature were found to play important roles in its mesoporous properties and photocatalytic activity.

http://ift.tt/2lacjxf

Evaluation of Coronary Artery Disease Using Myocardial Elastography with Diverging Wave Imaging: Validation against Myocardial Perfusion Imaging and Coronary Angiography

Publication date: Available online 28 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Julien Grondin, Marc Waase, Alok Gambhir, Ethan Bunting, Vincent Sayseng, Elisa E. Konofagou
Myocardial elastography (ME) is an ultrasound-based technique that can image 2-D myocardial strains. The objectives of this study were to illustrate that 2-D myocardial strains can be imaged with diverging wave imaging and differ, on average, between normal and coronary artery disease (CAD) patients. In this study, 66 patients with symptoms of CAD were imaged with myocardial elastography before a nuclear stress test or an invasive coronary angiography. Radial cumulative strains were estimated in all patients. The end-systolic radial strain in the total cross section of the myocardium was significantly higher in normal patients (17.9 ± 8.7%) than in patients with reversible perfusion defect (6.2 ± 9.3%, p < 0.001) and patients with significant (−0.9 ± 7.4%, p < 0.001) and non-significant (3.7 ± 5.7%, p < 0.01) lesions. End-systolic radial strain in the left anterior descending, left circumflex and right coronary artery territory was found to be significantly higher in normal patients than in CAD patients. These preliminary findings indicate that end-systolic radial strain measured with ME is higher on average in healthy persons than in CAD patients and that ME has the potential to be used for non-invasive, radiation-free early detection of CAD.



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TLR4/MD2 specific peptides stalled in vivo LPS-induced immune exacerbation

Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Seolhee Park, Hyeon-Jun Shin, Masaud Shah, Hey-Young Cho, Muhammad Ayaz Anwar, Asma Achek, Hyuk-Kwon Kwon, Byugsung Lee, Tae Hyeon Yoo, Sangdun Choi
Negative regulation of Toll-like receptor-4 (TLR4) is anticipated to control the pathogen-induced exaggerated immune response. However, effective TLR4 antagonists with scarce off-target effects are yet to be developed. To fill this void, we sought to design small peptide-inhibitors of the TLR4/MD2−LPS interaction. Here we report novel TLR4-antagonistic peptides (TAP), identified through phage display, endowed with the LPS-induced proinflammation inhibition, and confirmed in mice. TAPs-attributed TLR4-antagonism were initially evaluated through NF-κB inhibition in HEK-blue hTLR4 and RAW264.7 cells, and further reinforced by the downregulation of MAPKs (mitogen-activated protein kinases), NF-κB, interleukin 6, and suppression of the oxidative-stress products and iNOS in macrophages and human peripheral blood mononuclear cells (hPBMCs). Among these, TAP2 specifically halted the TLR4, but not other TLRs signaling, which was further confirmed by the biophysical kinetic assay. Finally, TAP2 diminished LPS-elicited systemic cytokine response in vivo, suggesting that TAPs, specifically TAP2, have the potential to treat TLR4-mediated immune ailments.



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Editorial board

Publication date: May 2017
Source:Biomaterials, Volume 125





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Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Joshua R. Gershlak, Sarah Hernandez, Gianluca Fontana, Luke R. Perreault, Katrina J. Hansen, Sara A. Larson, Bernard Y.K. Binder, David M. Dolivo, Tianhong Yang, Tanja Dominko, Marsha W. Rolle, Pamela J. Weathers, Fabricio Medina-Bolivar, Carole L. Cramer, William L. Murphy, Glenn R. Gaudette
Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass.

Graphical abstract

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New Classification System for Tear Trough Deformity.

BACKGROUND: Tear trough deformities (TTD) refer to a set of conditions leading to different shapes in the junction between the lower eyelid and the cheek. Tear trough deformity is a major aesthetic concern for a lot of individuals seeking periorbital rejuvenation and is one of the most discussed landmarks in facial aesthetic surgery. OBJECTIVE: To describe a new morphologically related classification system, providing an objective means to evaluating the deformity. METHODS: The article proposes a new classification system exhibiting 5 different forms of a TTD based on the author's clinical experience and review of medical literature. CONCLUSION: Five forms of a TTD include a "hill" due to the superficial infraorbital fat pad herniation; a "valley" caused by fat reduction and skin changes; a "hill-valley" resulting from the weakening of the orbital portion of the orbicularis oculi muscle and its retaining ligaments, followed by fat reduction and skin changes; a "hill-valley-hill-valley" formed by a series of changes in portions of the orbicularis oculi muscle and its retaining ligaments; and a "mixed" form depicting a range of any of the 4 deformities. Classification of TTD is of great value to aid the treating physician in choosing the appropriate treating options. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2lx0Dk0

Vibration Anesthesia for Pain Reduction During Intralesional Steroid Injection for Keloid Treatment.

BACKGROUND: Patients suffer significant pain during intralesional steroid injection treatment for keloids and hypertrophic scars. Vibration anesthesia has been shown to effectively and safely alleviate pain sensations, likely by reducing pain transmission from peripheral receptors to the brain. OBJECTIVE: The objective was to evaluate the efficacy, safety, and patient satisfaction associated with vibration anesthesia for reducing pain during intralesional corticosteroid injection. METHODS: The authors recruited 40 patients with 58 keloids who were scheduled to undergo intralesional triamcinolone acetonide (TA) injections. Half of each keloid was injected with concomitant vibration anesthesia, whereas the other half was injected without vibration anesthesia. Pain experienced by patients during both procedures was assessed according to visual analog scale (VAS) score. The authors also assessed procedure safety. RESULTS: The mean VAS score during intralesional TA injection therapy without vibration was 5.88 +/- 2.34. By contrast, the same patients yielded a mean VAS score during intralesional TA injection therapy with vibration of 3.28 +/- 1.85; the difference between the mean scores was significant (p

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Reply to Blood Aspiration Test for Cosmetic Fillers to Prevent Accidental Intravascular Injection in the Face.

No abstract available

http://ift.tt/2lwRLey

Deoxycholic Acid.

No abstract available

http://ift.tt/2lUrTKv

Clinical Characteristics of Arteriovenous Malformations of the Head and Neck.

BACKGROUND: Arteriovenous malformation (AVM) of the head and neck regions show low incidence; hence, studies regarding the causative factors of onset, diagnostic criteria, clinical aspects, treatment methods, and outcomes remain lacking. OBJECTIVE: To share the diagnostic and treatment experiences at the center and to understand the treatments' effect through a retrospective analysis of cases in the past 15 years. MATERIALS AND METHODS: The authors included 60 patients with AVM in the head and neck area between January 1999 and September 2014 to investigate diagnostic methods, distributions and locations of lesions, clinical stage, and treatment methods by retrospective evaluation. RESULTS: In all, 3.7% were diagnosed with AVMs of the head and neck. No sex-related differences were observed, and the mean age at diagnosis was 27.6 +/- 14.24 years. The left (26 patients, 43%) and V2 sections (33 patients, 55%) of the head and neck were the most frequent locations. Stage II (28 patients, 47%) had the largest distribution. Forty-four patients (73%) showed improvement after sclerotherapy, embolization, and surgical resection. CONCLUSION: The diagnosis and treatment of AVMs should be approached on a case-by-case basis by gathering opinions from specialists in each department using medical history, physical examination, and imaging results. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2lUIDkC

Different Glabellar Contraction Patterns in Chinese and Efficacy of Botulinum Toxin Type A for Treating Glabellar Lines: A Pilot Study.

BACKGROUND: Published research studies have described the existence of 5 glabellar contraction patterns. Botulinum toxin A (BoNTA) has been an approved and effective treatment of glabellar lines. OBJECTIVE: To study the pattern and frequency of glabellar contraction patterns in the Chinese population. To compare injection patterns and doses of BoNTA in Westerners within China. METHODS: Four hundred fifty-six healthy volunteers were randomly recruited. Photographs both in static and in frown state were taken and classified based on the method of 5 glabellar line patterns. The severity of the glabellar lines both at repose and during forced contraction was assessed by the Facial Wrinkle Scale (FWS). Subsequently, 75 of them were treated with BoNTA. RESULTS: The frequency of the various glabellar line patterns differs greatly between Chinese and Westerners with the "Converging arrows" pattern being the most common type and the "V" pattern being the least common when compared with the Westerners. Lower doses of BoNTA significantly improved the static and dynamic glabellar lines in the Chinese. CONCLUSION: The classification of 5 glabellar patterns is compatible for the Chinese population despite different proportions. The dosage of BoNTA should be less than 20 U during treatment in China with lowered incidence of complications. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2lwZpW1

Actinic Granuloma Annulare With Scarring and Open Comedones.

Actinic granuloma and annular elastolytic giant cell granuloma are variants of granuloma annulare affecting, respectively, sun-exposed and sun-covered skin sites on where, besides classical findings, abundant elastophagocytosis is observed. Here, we report a case of exuberant actinic granuloma annulare that, in addition to extensive scarring, showed multiple overlying open comedones. Markedly dilated follicular infundibula filled with compact masses of laminated keratinous material were observed in proximity to dermal inflammation composed of many histiocytes and multinucleated giant cells in close association with degenerated elastic fibers and abundant elastophagocytosis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2mqWVg6

Benign Atrophic Papulosis (Degos Disease) With Lymphocytic Vasculitis and Lichen Sclerosus-Like Features.

Degos disease manifests as 2 distinct clinical variants, malignant atrophic papulosis and benign atrophic papulosis, which are distinguished by the presence or absence of systemic disease. Both forms feature cutaneous involvement typified by erythematous papules with scar-like centers, and the classic histologic picture is described as wedge-shaped dermal necrosis overlying thrombotic vasculopathy. However, the histopathology of early lesions is distinct and more variable. A case of benign atrophic papulosis with lymphocytic vasculitis and lichen sclerosus-like features is described, and the spectrum of histologic findings in Degos disease is reviewed. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2mrc0OL

Metastatic Cellular Blue Nevus: A Rare Case With Metastasis Beyond Regional Nodes.

In this study, we present a rare case of a 35-year-old man with a long-standing blue-black lesion on his left hand with subsequent infraclavicular and axillary lymph node tumor deposits. The hand lesion and lymph nodes were excised revealing histological, immunohistochemical, and molecular findings consistent with cellular blue nevus. Despite nonregional lymph node involvement, there has been no progression at 12-months follow-up. This is an index case of a cellular blue nevus with metastasis to both regional and nonregional lymph nodes. The lack of atypical/malignant features in this lesion makes the metastatic behavior extraordinary, and hence the prognosis of lesions of this type is indeterminate. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Practical strategy to realistically measure the swelling ratio of poly(dimethylsiloxane) without underestimation due to the solvent volatility

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Maura Cesaria, Valentina Arima, Maria Grazia Manera, Roberto Rella
We present an experimental method for measuring "realistically" the swelling ratio in terms of weight (SRW) of PDMS, where "realistically" means without the underestimation involved by the standard protocol (weight-measurements in open environment with time-delay incompatible with fast solvent evaporation rate). Comparison with the literature demonstrates that misleading conclusions can result under application of the standard protocol to very volatile solvents. To discuss this point, we develop a mathematical expression of SRW including solvent properties and the effective amount of sorbed solvent determining a weight gain, consider two solvents with different volatility that severely swell PDMS (i.e., toluene and dichloromethane), check that the results of our measurements are consistent with theoretical predictions, demonstrate that our protocol rules out any dependence of SRW on the solvent volatility and its reliability to measure and compare SRW values of PDMS (or any swelling polymer/soft material) in the case of solvents with very different volatility.

Graphical abstract

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Distyrylbenzene-based segmented conjugated polymers: Synthesis, thin film morphology and chemosensing of hydrophobic and hydrophilic nitroaromatics in aqueous media

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Marcela F. Almassio, Maria J. Romagnoli, Pablo G. Del Rosso, Ana Belén Schvval, Raúl O. Garay
Two new segmented conjugated polymers bearing distyrylbenzene chromophoric units and their model compounds were synthesized. The tendency of the model compounds to form H- and J-type aggregates in the amorphous matrix was greatly diminished by the twisted polymeric architecture. Fluorescence anisotropy measurements indicated good exciton mobilities in condensed phase. Fluorescence quenching by nitroaromatic aqueous solutions was fast, complete, selective and reversible pointing to a rapid diffusion of analytes into the films. The quenching response to nitrophenols was superior to that against nitrotoluenes. The increase of the electron-donating capabilities by diethoxy-substitution was detrimental to the amorphous morphology and it did not increase sensitivity to NACs. Quenching efficiencies of polymers were not modified when MeOH was used instead of water. The solubility parameter distances, Ra. indicate that the sensing materials show higher responses when their affinity with the analytes is lower. This observation could help in the designing of fluorescent sensors.

Graphical abstract

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Congenital erosive and vesicular dermatosis with reticulated supple scarring

Abstract

Congenital erosive and vesicular dermatosis with reticulated supple scarring is a rare cutaneous disorder of unknown aetiology first described by Cohen and colleagues in 1985. It classically presents in the neonate as erosions and vesicles that heal within the first months of life, with supple scarring of a reticulated pattern. Along with a review of the literature, this article presents two atypical cases of congenital erosive and vesicular dermatosis with reticulated supple scarring. Patient one presented with neither erosions nor vesicles at birth, yet continued to experience sporadic blistering at the age of 15 months and patient two is the second documented case to develop congenital erosive and vesicular dermatosis after birth.

http://ift.tt/2lmZsD4

Smartphone use in dermatology for clinical photography and consultation: Current practice and the law

Abstract

Background

Smartphones are rapidly changing the way doctors capture and communicate clinical information, particularly in highly visual specialties such as dermatology. An understanding of how and why smartphones are currently used in clinical practice is critical in order to evaluate professional and legal risks, and to formulate policies that enable safe use of mobile technologies for the maximal benefit of practitioners and patients.

Methods

Australian dermatologists and dermatology trainees were surveyed on their current practices relating to clinical smartphone use.

Results

Of the 105 respondents, 101 provided useable results. The data show clinical smartphone use is common and frequent, with more than 50% of respondents sending and receiving images on their smartphones at least weekly. Clinical photographs were usually sent via multimedia message or email and were commonly stored on smartphones (46%). Security measures adopted to protect data were limited. There was inadequate documentation of consent for transmission of photographs and advice provided. Only 22% of respondents were aware of clear policies in their workplace regarding smartphone use, and a majority desired further education on digital image management.

Conclusions

Given the frequency of use and the degree of importance placed on the ability to send and receive clinical images, clinical smartphone use will persist and will likely increase over time. Current practices are insufficient to comply with professional and legal obligations, and increase practitioners' vulnerability to civil and disciplinary proceedings. Further education, realistic policies and adequate software resources are critical to ensure protection of patients, practitioners and the reputation of the dermatological profession.

http://ift.tt/2m5WFlD

Age-Related Differences in Face Recognition: Neural Correlates of Repetition and Semantic Priming in Young and Older Adults.

Author: Wiese, Holger; Komes, Jessica; Tuttenberg, Simone; Leidinger, Jana; Schweinberger, Stefan R.

DOI: 10.1037/xlm0000380

Publication Date: POST AUTHOR CORRECTIONS, 27 February 2017

http://ift.tt/2lmQ6XZ

The Semantic Distance Task: Quantifying Semantic Distance With Semantic Network Path Length.

Author: Kenett, Yoed N.; Levi, Effi; Anaki, David; Faust, Miriam

DOI: 10.1037/xlm0000391

Publication Date: POST AUTHOR CORRECTIONS, 27 February 2017

http://ift.tt/2m5AFaD

TLR4/MD2 specific peptides stalled in vivo LPS-induced immune exacerbation

Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Seolhee Park, Hyeon-Jun Shin, Masaud Shah, Hey-Young Cho, Muhammad Ayaz Anwar, Asma Achek, Hyuk-Kwon Kwon, Byugsung Lee, Tae Hyeon Yoo, Sangdun Choi
Negative regulation of Toll-like receptor-4 (TLR4) is anticipated to control the pathogen-induced exaggerated immune response. However, effective TLR4 antagonists with scarce off-target effects are yet to be developed. To fill this void, we sought to design small peptide-inhibitors of the TLR4/MD2−LPS interaction. Here we report novel TLR4-antagonistic peptides (TAP), identified through phage display, endowed with the LPS-induced proinflammation inhibition, and confirmed in mice. TAPs-attributed TLR4-antagonism were initially evaluated through NF-κB inhibition in HEK-blue hTLR4 and RAW264.7 cells, and further reinforced by the downregulation of MAPKs (mitogen-activated protein kinases), NF-κB, interleukin 6, and suppression of the oxidative-stress products and iNOS in macrophages and human peripheral blood mononuclear cells (hPBMCs). Among these, TAP2 specifically halted the TLR4, but not other TLRs signaling, which was further confirmed by the biophysical kinetic assay. Finally, TAP2 diminished LPS-elicited systemic cytokine response in vivo, suggesting that TAPs, specifically TAP2, have the potential to treat TLR4-mediated immune ailments.



http://ift.tt/2l9vlDH

Effect of shear stress on structure and function of polyplex micelles from poly(ethylene glycol)-poly(l-lysine) block copolymers as systemic gene delivery carrier

Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Kaori M. Takeda, Yuichi Yamasaki, Anjaneyulu Dirisala, Sorato Ikeda, Theofilus A. Tockary, Kazuko Toh, Kensuke Osada, Kazunori Kataoka
Structural stability of polyplex micelles (PMs), prepared from plasmid DNA (pDNA) and poly(ethylene glycol)-b-poly(l-lysine) block catiomer (PEG−PLys), was evaluated in terms of their resistance against shear stress. When exposed to shear stress at magnitudes typically present in the blood stream, structural deterioration was observed in PMs owing to the partial removal of PEG−PLys strands. Eventually, impaired PEG coverage of the polyplex core led to accelerated degradation by nucleases, implying that structural deterioration by shear stress in blood stream may be a major cause of rapid clearance of PMs from blood circulation. To address this issue, introduction of disulfide crosslinking into the PM core was shown to be an efficient strategy, which successfully mitigated unfavorable effects of shear stress. Furthermore, improved in vivo blood retention profile and subsequently enhanced antitumor efficacy in systemic treatment of pancreatic adenocarcinoma were confirmed for the crosslinked PMs loaded with pDNA encoding an anti-angiogenic protein, suggesting that high stability under the shear stress during blood circulation may be a critical factor in systemically applicable gene delivery systems.



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Editorial board

Publication date: May 2017
Source:Biomaterials, Volume 125





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Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Joshua R. Gershlak, Sarah Hernandez, Gianluca Fontana, Luke R. Perreault, Katrina J. Hansen, Sara A. Larson, Bernard Y.K. Binder, David M. Dolivo, Tianhong Yang, Tanja Dominko, Marsha W. Rolle, Pamela J. Weathers, Fabricio Medina-Bolivar, Carole L. Cramer, William L. Murphy, Glenn R. Gaudette
Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass.

Graphical abstract

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The cancer-immunity cycle as rational design for synthetic cancer drugs: Novel DC vaccines and CAR T-cells

Publication date: Available online 28 February 2017
Source:Seminars in Cancer Biology
Author(s): Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas. Although encouraging, CAR T-cells have not yet proven clinically effective for solid tumors. This is mainly due to the lack of specific and homogenously expressed targets to direct the T-cells against and a hostile immunosuppressive tumor microenvironment in solid tumors. Cancer vaccines based on dendritic cells (DC) are also making progress although clinical efficacy is still lacking. The likelihood of success is however increasing now when individual tumors can be sequences and patient-specific neoepitopes identified. Neoepitopes and/or neoantigens can then be included in patient-based DC vaccines. This review discusses recent advancements of DC vaccines and CAR T-cells with emphasis on the cancer-immunity cycle, and current efforts to design novel cell therapies.



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Cancer stem cells: the root of tumor recurrence and metastasis

Publication date: Available online 28 February 2017
Source:Seminars in Cancer Biology
Author(s): Claudia Peitzsch, Anna Tyutyunnykova, Klaus Pantel, Anna Dubrovska
Metastatic tumors are the cause of more than 90% of cancer related deaths. The metastasis formation can be considered as a culmination of the Darwinian evolutionary process within the tumor, when competing of multiple subclones results in the development of the cell inherent traits that favor tumor dissemination. The unit of tumor evolution is cancer stem cell (CSC) defined by the self-renewal potential, clonogenic properties and genomic instability. The cancer cells which have the capacity to colonize distant organs have the features of CSC but also exert their tumor-initiating capacity under adverse microenvironmental conditions. Recent studies support an idea that metastases can be driven by the evolved and selected subpopulations of CSC. In this review we discuss the common hallmarks of CSC and metastasis initiating cells (MIC) and the perspectives for implication of CSC concept for the development of anti-metastatic therapy.



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“The new pH-centric anticancer paradigm in Oncology and Medicine”; SCB, 2017

Publication date: Available online 27 February 2017
Source:Seminars in Cancer Biology
Author(s): Salvador Harguindey, Stephan J. Reshkin




http://ift.tt/2lRmbuB

Population pharmacokinetics of ABT-767 in BRCA1 or BRCA2 mutation carriers with advanced solid tumors or in subjects with high grade serous ovarian, primary peritoneal or fallopian tube cancer

Abstract

Purpose

The objective of the manuscript is to describe the development of a population pharmacokinetic model for ABT-767, a potent and orally bioavailable inhibitor of poly (ADP-ribose) polymerase enzyme, and to evaluate the potential influence of patient demographics and baseline covariates on the pharmacokinetics of ABT-767.

Methods

A total of 1809 plasma ABT-767 concentrations from 90 subjects were used for population pharmacokinetic modeling. Covariates screened for influence on pharmacokinetic parameters were body weight, lean body weight, body surface area, albumin, creatinine clearance, serum creatinine, liver function tests, and age. The effect of food on absorption and bioavailability were also evaluated. Model validation was performed using bootstrap analysis and visual predictive check.

Results

A two-compartment model with firstorder absorption adequately described the pharmacokinetics of ABT-767. The population estimates of apparent clearance from central compartment (CL/F), volume of central compartment (V _c/F), and absorption rate constant (k _a) were 7.34 L/h, 25.8 L, 1.45 h⁻¹, respectively. The estimates of interindividual variabilities (%CV) in CL/F, V _c/F, and k _a were 40.4, 40.5, and 53.8%, respectively. The k _a was influenced by food. Albumin on CL/F was a statistically significant covariate; however, it explained only 8% of the variability in the pharmacokinetics of ABT-767.

Conclusions

Albumin on CL/F was the only statistically significant baseline covariate affecting ABT-767 pharmacokinetics, but it only explained a fraction of the pharmacokinetic variability. Dosage adjustments based on body size, age, or mild renal impairment are not needed for ABT-767. The developed model will be used to evaluate ABT-767 exposure–response analyses and to perform simulations for different dose and dosing regimens.

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From ancient herb to versatile, modern drug: Artemisia annua and artemisinin for cancer therapy

Publication date: Available online 28 February 2017
Source:Seminars in Cancer Biology
Author(s): Thomas Efferth
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteether) towards cancer cells include oxidative stress response by reactive oxygen species and nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis, necrosis, necroptosis, oncosis), inhibition of angiogenesis and tumor-related signal transduction pathways (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.



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Idiopathic or Secondary?.

No abstract available

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Diagnosing Chronic Lymphocytic Leukemia With Temporal Artery Biopsy.

No abstract available

http://ift.tt/2mozSTd

Small-Molecule RORγt Antagonists: One Stone Kills Two Birds

Publication date: Available online 28 February 2017
Source:Trends in Immunology
Author(s): Chao Zhong, Jinfang Zhu
Although small-molecule thymus-specific isoform of retinoic acid receptor-related orphan nuclear receptor γ (RORγt) antagonists suppressing interleukin (IL)-17-producing T helper (Th17) cells are widely reported, the effect of these molecules on other RORγt-expressing cells is unknown. However, a new study reports that RORγt inhibition in CD4⁺CD8⁺ thymocytes resulted in skewed T cell repertoire, contributing to a reduction in the frequency of self-reactive T cells and resistance to autoimmunity.



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Estimating direction in brain-behavior interactions: Proactive and reactive brain states in driving

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Javier O. Garcia, Justin Brooks, Scott Kerick, Tony Johnson, Tim R. Mullen, Jean M. Vettel
Conventional neuroimaging analyses have ascribed function to particular brain regions, exploiting the power of the subtraction technique in fMRI and event-related potential analyses in EEG. Moving beyond this convention, many researchers have begun exploring network-based neurodynamics and coordination between brain regions as a function of behavioral parameters or environmental statistics; however, most approaches average evoked activity across the experimental session to study task-dependent networks. Here, we examined on-going oscillatory activity as measured with EEG and use a methodology to estimate directionality in brain-behavior interactions. After source reconstruction, activity within specific frequency bands (delta: 2–3Hz; theta: 4–7Hz; alpha: 8–12Hz; beta: 13–25Hz) in a priori regions of interest was linked to continuous behavioral measurements, and we used a predictive filtering scheme to estimate the asymmetry between brain-to-behavior and behavior-to-brain prediction using a variant of Granger causality. We applied this approach to a simulated driving task and examined directed relationships between brain activity and continuous driving performance (steering behavior or vehicle heading error). Our results indicated that two neuro-behavioral states may be explored with this methodology: a Proactive brain state that actively plans the response to the sensory information and is characterized by delta-beta activity, and a Reactive brain state that processes incoming information and reacts to environmental statistics primarily within the alpha band.

Graphical abstract

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Mapping visual dominance in human sleep

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Mark McAvoy, Anish Mitra, Enzo Tagliazucchi, Helmut Laufs, Marcus E. Raichle
Sleep is a universal behavior, essential for humans and animals alike to survive. Its importance to a person's physical and mental health cannot be overstated. Although lateralization of function is well established in the lesion, split-brain and task based neuroimaging literature, and more recently in functional imaging studies of spontaneous fluctuations of the fMRI BOLD signal during wakeful rest, it is unknown if these asymmetries are present during sleep. We investigated hemispheric asymmetries in the global brain signal during non-REM sleep. Here we show that increasing sleep depth is accompanied by an increasing rightward asymmetry of regions in visual cortex including primary bilaterally and in the right hemisphere along the lingual gyrus and middle temporal cortex. In addition, left hemisphere language regions largely maintained their leftward asymmetry during sleep. Right hemisphere attention related regions expressed a more complicated relation with some regions maintaining a rightward asymmetry while this was lost in others. These results suggest that asymmetries in the human brain are state dependent.



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High-sensitivity TMS/fMRI of the Human Motor Cortex Using a Dedicated Multichannel MR Coil

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Lucia I. Navarro de Lara, Martin Tik, Michael Woletz, Roberta Frass-Kriegl, Ewald Moser, Elmar Laistler, Christian Windischberger
PurposeTo validate a novel setup for concurrent TMS/fMRI in the human motor cortex based on a dedicated, ultra-thin, multichannel receive MR coil positioned between scalp and TMS system providing greatly enhanced sensitivity compared to the standard birdcage coil setting.MethodsA combined TMS/fMRI design was applied over the primary motor cortex based on 1Hz stimulation with stimulation levels of 80%, 90%, 100%, and 110% of the individual active motor threshold, respectively. Due to the use of a multichannel receive coil we were able to use multiband-accelerated (MB=2) EPI sequences for the acquisition of functional images. Data were analysed with SPM12 and BOLD-weighted signal intensity time courses were extracted in each subject from two local maxima (individual functional finger tapping localiser, fixed MNI coordinate of the hand knob) next to the hand area of the primary motor cortex (M1) and from the global maximum.ResultsWe report excellent image quality without noticeable signal dropouts or image distortions. Parameter estimates in the three peak voxels showed monotonically ascending activation levels over increasing stimulation intensities. Across all subjects, mean BOLD signal changes for 80%, 90%, 100%, 110% of the individual active motor threshold were 0.43%, 0.63%, 1.01%, 2.01% next to the individual functional finger tapping maximum, 0.73%, 0.91%, 1.34%, 2.21% next to the MNI-defined hand knob and 0.88%, 1.09%, 1.65%, 2.77% for the global maximum, respectively.ConclusionOur results show that the new setup for concurrent TMS/fMRI experiments using a dedicated MR coil array allows for high-sensitivity fMRI particularly at the site of stimulation. Contrary to the standard birdcage approach, the results also demonstrate that the new coil can be successfully used for multiband-accelerated EPI acquisition. The gain in flexibility due to the new coil can be easily combined with neuronavigation within the MR scanner to allow for accurate targeting in TMS/fMRI experiments.



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Neural signatures of adaptive post-error adjustments in visual search

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Robert Steinhauser, Martin E. Maier, Marco Steinhauser
Errors in speeded choice tasks can lead to post-error adjustments both on the behavioral and on the neural level. There is an ongoing debate whether such adjustments result from adaptive processes that serve to optimize performance or whether they reflect interference from error monitoring or attentional orientation. The present study aimed at identifying adaptive adjustments in a two-stage visual search task, in which participants had to select and subsequently identify a target stimulus presented to the left or right visual hemifield. Target selection and identification can be measured by two distinct event-related potentials, the N2pc and the SPCN. Using a decoder analysis based on multivariate pattern analysis, we were able to isolate the processing stages related to error sources and post-error adjustments. Whereas errors were linked to deviations in the N2pc and the SPCN, only for the N2pc we identified a post-error adjustment, which exhibits key features of source-specific adaptivity. While errors were associated with an increased N2pc, post-error adjustments consisted in an N2pc decrease. We interpret this as an adaptive adjustment of target selection to prevent errors due to disproportionate processing of the task-irrelevant target location. Our study thus provides evidence for adaptive post-error adjustments in visual search.



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Is still there a place for orteronel in management of prostate cancer?: Data from a literature based meta-analysis of randomized trials

Publication date: Available online 28 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Giandomenico Roviello, Chiara Pacifico, Giorgio Chiriacò, Daniele Generali
Orteronel (TAK-700) is an oral, non-steroidal 17,20-lyase inhibitor with higher specificity for 17,20 lyase over 17 hydroxylase. The first phase III studies showed an advantage with orteronel compared with placebo in terms of progression free survival and response of PSA. Unfortunately orteronel did not significantly prolong the overall survival. In order to assess the efficacy of orteronel in prostate cancer, we evaluated all available data on orteronel in the management of prostate cancer. A total of 2716 patients were evaluated from 3 randomized trials. We showed orteronel improved the progression free survival, time to PSA progression and PSA response compared with the placebo. In conclusion, given the limitations a literature rather than on individual patients' data meta-analysis, our data show a clinical efficacy of orteronel in prostate cancer, therefore we deem that orteronel may be investigated in combination with the other approved agents for CRPC or be tested in prior setting of disease such as the hormone sensitive prostate cancer.



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β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): Emily L. Goldberg, Jennifer L. Asher, Ryan D. Molony, Albert C. Shaw, Caroline J. Zeiss, Chao Wang, Ludmilla A. Morozova-Roche, Raimund I. Herzog, Akiko Iwasaki, Vishwa Deep Dixit
Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1β (IL-1β) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases β-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1β in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.

Graphical abstract

Teaser

NLRP3 inflammasome activation in macrophages and neutrophils drives painful inflammation during gout. Goldberg et al. report that ketogenic diet prevents systemic inflammation and joint damage in a rat model of gouty flare. Mechanistically, the ketone body β-hydroxybutyrate, the most abundant ketone in vivo, inhibits NLRP3/caspase-1-dependent IL-1β secretion from neutrophils.


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Pharmacologic Targeting of S6K1 in PTEN-Deficient Neoplasia

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): Hongqi Liu, Xizhi Feng, Kelli N. Ennis, Catherine A. Behrmann, Pranjal Sarma, Tony T. Jiang, Satoshi Kofuji, Liang Niu, Yiwen Stratton, Hala Elnakat Thomas, Sang-Oh Yoon, Atsuo T. Sasaki, David R. Plas
Genetic S6K1 inactivation can induce apoptosis in PTEN-deficient cells. We analyzed the therapeutic potential of S6K1 inhibitors in PTEN-deficient T cell leukemia and glioblastoma. Results revealed that the S6K1 inhibitor LY-2779964 was relatively ineffective as a single agent, while S6K1-targeting AD80 induced cytotoxicity selectively in PTEN-deficient cells. In vivo, AD80 rescued 50% of mice transplanted with PTEN-deficient leukemia cells. Cells surviving LY-2779964 treatment exhibited inhibitor-induced S6K1 phosphorylation due to increased mTOR-S6K1 co-association, which primed the rapid recovery of S6K1 signaling. In contrast, AD80 avoided S6K1 phosphorylation and mTOR co-association, resulting in durable suppression of S6K1-induced signaling and protein synthesis. Kinome analysis revealed that AD80 coordinately inhibits S6K1 together with the TAM family tyrosine kinase AXL. TAM suppression by BMS-777607 or genetic knockdown potentiated cytotoxic responses to LY-2779964 in PTEN-deficient glioblastoma cells. These results reveal that combination targeting of S6K1 and TAMs is a potential strategy for treatment of PTEN-deficient malignancy.

Graphical abstract

Teaser

Liu et al. find that the S6K1 inhibitor, AD80, is selectively cytotoxic for PTEN-deficient cancer cells, while LY-2779964 is ineffective as a single agent. AD80 avoids S6K1 priming and co-targets TAM tyrosine kinases. Combining LY-2779964 with the TAM kinase inhibitor BMS-777607 is selectively cytotoxic for PTEN-deficient cells.


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Non-enzymatic N-acetylation of Lysine Residues by AcetylCoA Often Occurs via a Proximal S-acetylated Thiol Intermediate Sensitive to Glyoxalase II

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): Andrew M. James, Kurt Hoogewijs, Angela Logan, Andrew R. Hall, Shujing Ding, Ian M. Fearnley, Michael P. Murphy
Acetyl coenzyme A (AcCoA), a key intermediate in mitochondrial metabolism, N-acetylates lysine residues, disrupting and, in some cases, regulating protein function. The mitochondrial lysine deacetylase Sirtuin 3 (Sirt3) reverses this modification with benefits reported in diabetes, obesity, and aging. We show that non-enzymatic lysine N-acetylation by AcCoA is greatly enhanced by initial acetylation of a cysteine residue, followed by SN-transfer of the acetyl moiety to a nearby lysine on mitochondrial proteins and synthetic peptides. The frequent occurrence of an S-acetyl intermediate before lysine N-acetylation suggests that proximity to a thioester is a key determinant of lysine susceptibility to acetylation. The thioesterase glyoxalase II (Glo2) can limit protein S-acetylation, thereby preventing subsequent lysine N-acetylation. This suggests that the hitherto obscure role of Glo2 in mitochondria is to act upstream of Sirt3 in minimizing protein N-acetylation, thus limiting protein dysfunction when AcCoA accumulates.

Graphical abstract

Teaser

James et al. show that the non-enzymatic N-acetylation of lysine residues in mitochondrial proteins frequently occurs via a proximal S-acetylated thiol intermediate. Glutathione equilibrates with this intermediate, allowing the thioesterase glyoxalase II to limit protein lysine N-acetylation. These findings expand our understanding of how protein acetylation arises.


http://ift.tt/2lmbHj2

Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): Michael W. Gramlich, Vitaly A. Klyachko
Vesicle sharing between synaptic boutons is an important component of the recycling process that synapses employ to maintain vesicle pools. However, the mechanisms supporting and regulating vesicle transport during the inter-synaptic exchange remain poorly understood. Using nanometer-resolution tracking of individual synaptic vesicles and advanced computational algorithms, we find that long-distance axonal transport of synaptic vesicles between hippocampal boutons is partially mediated by the actin network, with myosin V as the primary actin-dependent motor that drives this vesicle transport. Furthermore, we find that vesicle exit from the synapse to the axon and long-distance vesicle transport are both rapidly and dynamically regulated by activity. We corroborated these findings with two complementary modeling approaches of vesicle exit, which closely reproduced experimental observations. These findings uncover the roles of actin and myosin V in supporting the inter-synaptic vesicle exchange and reveal that this process is dynamically modulated in an activity-dependent manner.

Graphical abstract

Teaser

Gramlich and Klyachko uncover the roles of actin and myosin V in supporting vesicle transport during inter-synaptic exchange (ISVE). They also reveal that this process is rapidly and dynamically modulated in an activity-dependent manner.


http://ift.tt/2lm8sby

Ultrastructural Characterization of Zika Virus Replication Factories

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): Mirko Cortese, Sarah Goellner, Eliana Gisela Acosta, Christopher John Neufeldt, Olga Oleksiuk, Marko Lampe, Uta Haselmann, Charlotta Funaya, Nicole Schieber, Paolo Ronchi, Martin Schorb, Priit Pruunsild, Yannick Schwab, Laurent Chatel-Chaix, Alessia Ruggieri, Ralf Bartenschlager
A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.

Graphical abstract

Teaser

Cortese et al. show that ZIKV infection in both human hepatoma and neuronal progenitor cells induces drastic structural modification of the cellular architecture. Microtubules and intermediate filaments surround the viral replication factory composed of vesicles corresponding to ER membrane invagination toward the ER lumen. Importantly, alteration of microtubule flexibility impairs ZIKV replication.


http://ift.tt/2lm4gbL