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Παρασκευή 18 Αυγούστου 2017

The dual role of group V secretory phospholipase A 2 in pancreatic β-cells

Abstract

Purpose

Group X (GX) and group V (GV) secretory phospholipase A2 (sPLA2) potently release arachidonic acid (AA) from the plasma membrane of intact cells. We previously demonstrated that GX sPLA2 negatively regulates glucose-stimulated insulin secretion (GSIS) by a prostaglandin E2 (PGE2)-dependent mechanism. In this study we investigated whether GV sPLA2 similarly regulates GSIS.

Methods

GSIS and pancreatic islet-size were assessed in wild-type (WT) and GV sPLA2-knock out (GV KO) mice. GSIS was also assessed ex vivo in isolated islets and in vitro using MIN6 pancreatic beta cell lines with or without GV sPLA2 overexpression or silencing.

Results

GSIS was significantly decreased in islets isolated from GV KO mice compared to WT mice and in MIN6 cells with siRNA-mediated GV sPLA2 suppression. MIN6 cells overexpressing GV sPLA2 (MIN6-GV) showed a significant increase in GSIS compared to control cells. Though the amount of AA released into the media by MIN6-GV cells was significantly higher, PGE2 production was not enhanced or cAMP content decreased compared to control MIN6 cells. Surprisingly, GV KO mice exhibited a significant increase in plasma insulin levels following i.p. injection of glucose compared to WT mice. This increase in GSIS in GV KO mice was associated with a significant increase in pancreatic islet size and number of proliferating cells in β-islets compared to WT mice.

Conclusions

Deficiency of GV sPLA2 results in diminished GSIS in isolated pancreatic beta-cells. However, the reduced GSIS in islets lacking GV sPLA2 appears to be compensated by increased islet mass in GV KO mice.



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The dual role of group V secretory phospholipase A 2 in pancreatic β-cells

Abstract

Purpose

Group X (GX) and group V (GV) secretory phospholipase A2 (sPLA2) potently release arachidonic acid (AA) from the plasma membrane of intact cells. We previously demonstrated that GX sPLA2 negatively regulates glucose-stimulated insulin secretion (GSIS) by a prostaglandin E2 (PGE2)-dependent mechanism. In this study we investigated whether GV sPLA2 similarly regulates GSIS.

Methods

GSIS and pancreatic islet-size were assessed in wild-type (WT) and GV sPLA2-knock out (GV KO) mice. GSIS was also assessed ex vivo in isolated islets and in vitro using MIN6 pancreatic beta cell lines with or without GV sPLA2 overexpression or silencing.

Results

GSIS was significantly decreased in islets isolated from GV KO mice compared to WT mice and in MIN6 cells with siRNA-mediated GV sPLA2 suppression. MIN6 cells overexpressing GV sPLA2 (MIN6-GV) showed a significant increase in GSIS compared to control cells. Though the amount of AA released into the media by MIN6-GV cells was significantly higher, PGE2 production was not enhanced or cAMP content decreased compared to control MIN6 cells. Surprisingly, GV KO mice exhibited a significant increase in plasma insulin levels following i.p. injection of glucose compared to WT mice. This increase in GSIS in GV KO mice was associated with a significant increase in pancreatic islet size and number of proliferating cells in β-islets compared to WT mice.

Conclusions

Deficiency of GV sPLA2 results in diminished GSIS in isolated pancreatic beta-cells. However, the reduced GSIS in islets lacking GV sPLA2 appears to be compensated by increased islet mass in GV KO mice.



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Comparison of Combined Spike Detection and Clustering Using Mutual Information

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Publication date: Available online 18 August 2017
Source:Journal of Neuroscience Methods
Author(s): Peter N. Steinmetz
BackgroundSpike sorting techniques involve both detection of spike waveform events and classification of those events into clusters of similar waveform shape. The one existing method of evaluating the combined effects of both detection and classification depends on assignment of cluster correspondence. Other methods of evaluation have focused on either clustering or detection, but not both, although these two steps may interact.New methodThis paper develops an information theoretic measure of agreement between the output of two spike sorting techniques, AMIall, which can be used even when the number of waveform events detected by the two techniques differs.ResultsAMIall is shown to be a useful measure for studying variations of parameters of spike sorting techniques in two examples: comparing outputs for simulated noisy spike sorting and spike sorting of human single neuron recordings.Comparison with existing methods Computing AMIall does not require an explicit assignment of cluster correspondence, thereby eliminating a potential source of variation. By providing a single measure of performance, computing AMIall is very useful when comparing large numbers of algorithmic or parametric variations of spike sorting techniques; prior comparison techniques have often required multiple measures of performance which complicates large scale comparisons.ConclusionsThe use of AMIall to measure agreement between spike sorting techniques facilitates the comparison of the outputs of those techniques, including variations in both spike detection and waveform clustering. This measure should be useful for broad based and large scale comparisons between spike sorting techniques.



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Home-cage anxiety levels in a transgenic rat model for Spinocerebellar Ataxia type 17 measured by an approach-avoidance task: the light spot test

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Publication date: Available online 18 August 2017
Source:Journal of Neuroscience Methods
Author(s): Elisavet I. Kyriakou, Huu Phuc Nguyen, Judith R. Homberg, Johanneke E. Van der Harst
BackgroundMeasuring anxiety in a reliable manner is essential for behavioural phenotyping of rodent models such as the rat model for Spinocerebellar ataxia type 17 (SCA17) where anxiety is reported in patients. An automated tool for assessing anxiety within the home cage can minimize human intervention, stress of handling, transportation and novelty.New methodWe applied the anxiety test "light spot" (LS) (white led directed at the food-hopper) to our transgenic SCA17 rat model in the PhenoTyper 4500® to extend the knowledge of this automated tool for behavioural phenotyping and to verify an anxiety-like phenotype at three different disease stages for use in future therapeutic studies.ResultsLocomotor activity was increased in SCA17 rats at 6 and 9 months during the first 15minutes of the LS, potentially reflecting increased risk assessment. Both genotypes responded to the test with lower duration in the LS zone and higher time spent inside the shelter compared to baseline.Comparison with existing methodsWe present the first data of a rat model subjected to the LS. The LS can be considered more biologically relevant than a traditional test as it measures anxiety in a familiar situation.ConclusionsThe LS successfully evoked avoidance and shelter-seeking in rats. SCA17 rats showed a stronger approach-avoidance conflict reflected by increased activity in the area outside the LS. This home cage test, continuously monitoring pre- and post-effects, provides the opportunity for in-depth analysis, making it a potentially useful tool for detecting subtle or complex anxiety-related traits in rodents.



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Reproducibility of task activation using the Addenbrooke’s cognitive examination in healthy controls: A functional Transcranial Doppler ultrasonography study

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Publication date: Available online 19 August 2017
Source:Journal of Neuroscience Methods
Author(s): L Beishon, C.A.L Williams, R.B Panerai, T.G Robinson, V.J Haunton
IntroductionCerebral blood flow velocity (CBFv) changes occurring with cognitive stimulation can be measured by Transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the reproducibility of CBFv changes to the Addenbrooke's cognitive examination (ACE-III).New Method13 volunteers underwent bilateral TCD (middle cerebral artery), continuous heart rate (HR, 3-lead ECG, Finometer), beat-to-beat mean arterial pressure (MAP, Finometer), and end-tidal CO2 (ETCO2, capnography). After 5minutes baseline, all ACE-III tasks were performed in 3 domains (A/B/C). Data presented are population CBFv peak normalised changes and area under the curve (AUC). Statistical analysis was by 2-way repeated measures (ANOVA), intra-class correlation coefficient (ICC), standard error of measurement (SEM) and coefficient of variation (CV).Results12 bilateral data sets were obtained (10 right hand dominant, 6 female). Baseline parameters (MAP, HR, ETCO2) did not differ between visits. All tasks increased CBFv. Only domain A on AUC analysis differed significantly on ANOVA, and one task on post hoc testing (p <0.05). ICC values were poor (<0.4) for most tasks, but 3 tasks produced more consistent results on AUC and peak CBFv analysis (range ICC: 0.15-0.73, peak CV: 16.2-56.1(%), AUC CV: 23.2-60.2(%), peak SEM: 2.5–6.0 (%), AUC SEM: 21.8-135.8 (%*s).Comparison with existing methodsThis is the first study to examine reproducibility of CBFv changes to a complete cognitive assessment tool.ConclusionsReproducibility of CBFv measurements to the ACE-III was variable. AUC may provide more reliable estimates than peak CBFv responses. These data need validating in patient populations.



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Microdialysis and its use in behavioural studies: Focus on acetylcholine.

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Publication date: Available online 18 August 2017
Source:Journal of Neuroscience Methods
Author(s): Magdalena König, Anna Thinnes, Jochen Klein
Microdialysis is a technique that allows access to the extracellular space of many tissues. For behavioural studies, microdialysis probes are inserted into the brain under anesthesia, but the experiment can be done in awake and freely moving animals. Microdialysis is a sampling method (not a measuring method), therefore, the analyte(s) under study must be quantified from the dialysate using available analytical methods of high sensitivity. Neurotransmitters and energy metabolites are most commonly measured. Limitations of the microdialysis technique are poor time resolution in the minute range and large diameters of the probe which samples from many thousands of cells and millions of synapses. The article illustrates the use of microdialysis in several behavioural fields and describes uses in motor function, stress research, and novelty and habituation, with an emphasis on its use in cholinergic mechanisms.



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Method of derivation and differentiation of mouse embryonic stem cells generating synchronous neuronal networks

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Publication date: Available online 18 August 2017
Source:Journal of Neuroscience Methods
Author(s): Elena V. Gazina, Emma Morrisroe, Gunarathna D.C. Mendis, Anna E. Michalska, Joseph Chen, Christian M. Nefzger, Benjamin N. Rollo, Christopher A. Reid, Martin F. Pera, Steven Petrou
BackgroundStem cells-derived neuronal cultures hold great promise for in vitro disease modelling and drug screening. However, currently stem cells-derived neuronal cultures do not recapitulate the functional properties of primary neurons, such as network properties. Cultured primary murine neurons develop networks which are synchronised over large fractions of the culture, whereas neurons derived from mouse embryonic stem cells (ESCs) display only partly synchronised network activity and human pluripotent stem cells-derived neurons have mostly asynchronous network properties. Therefore, strategies to improve correspondence of derived neuronal cultures with primary neurons need to be developed to validate the use of stem cell-derived neuronal cultures as in vitro models.New methodBy combining serum-free derivation of ESCs from mouse blastocysts with neuronal differentiation of ESCs in morphogen-free adherent culture we generated neuronal networks with properties recapitulating those of mature primary cortical cultures.ResultsAfter 35days of differentiation ESC-derived neurons developed network activity very similar to that of mature primary cortical neurons. Importantly, ESC plating density was critical for network development.Comparison with existing method(s)Compared to the previously published methods this protocol generated more synchronous neuronal networks, with high similarity to the networks formed in mature primary cortical culture.ConclusionWe have demonstrated that ESC-derived neuronal networks recapitulating key properties of mature primary cortical networks can be generated by optimising both stem cell derivation and differentiation. This validates the approach of using ESC-derived neuronal cultures for disease modelling and in vitro drug screening.



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Hypofractionated stereotactic radiotherapy to the resection bed for intracranial metastases

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Publication date: Available online 19 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Audrey Keller, Mélanie Doré, Hélène Cebula, François Thillays, François Proust, Ioana Darié, Stéphane-André Martin, Gregory Delpon, François Lefebvre, Georges Noël, Delphine Antoni
PurposeWe retrospectively report the outcomes of a large multicenter cohort of patients treated with surgery and hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavities of brain metastases (BMs).Methods and materialsBetween March 2008 and February 2015, 181 patients with no prior whole-brain radiation therapy (WBRT) were treated by HFSRT to the surgical bed of BM at the dose of 33 Gy (3×11 Gy). The primary end-point was local control (LC). Secondary endpoints were distant brain control (DBC), overall survival (OS), risk of radionecrosis (RN) and leptomeningeal disease (LMD).ResultsOf the 189 resected lesions, 44% were metastatic from a non-small cell lung cancer (NSCLC) primary tumor, and 76% of patients had a single BM at the time of treatment. With a median follow up of 15 months, the 6-and 12-month LC rates were 93% and 88%, respectively. On multivariate analysis, PTV (p=0.005), GPA score (p=0.021) and meningeal contact of BM (p=0.032), were predictive of local failure. The 6-and 12-month DBC rates were 70% and 61%. Twenty-six patients (14%) developed signs of LMD at a median time of 3.8 months. The preoperative tumor volume was predictive of LMD (p=0.029). The median OS was 17months. The 6-,12-and 24-month OS rates were 79%, 62% and 39%, respectively. RPA Class 3 (p=0.02), piecemeal resection (p=0.017) and an increasing number of BMs (p<0.01) were independent unfavorable prognostic factors for OS. Fifty-four patients (30%) were subsequently treated with salvage WBRT at a median time of 6.5 months, and 41% were re-irradiated with SRT. RN occurred in 19% of cases at a median time of 15 months and was associated with the infratentorial location of the BM (p=0.0025).ConclusionThis study demonstrated the safety and efficacy of a 3×11 Gy HFSRT regimen for the irradiation of BMs resection cavities. It was an alternative to adjuvant WBRT.

Teaser

We retrospectively report the outcomes of a large multicenter cohort of patients treated with surgery and hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavities of brain metastases (BMs). We analyzed the local control, distant brain control, overall survival, risk of radionecrosis and leptomeningeal disease. This study demonstrated the safety and efficacy of a 3×11Gy HFSRT regimen for the irradiation of BMs resection cavities. It was an alternative to adjuvant whole-brain radiotherapy (WBRT).


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Impact of surgery, adjuvant therapy and other prognostic factors for choroid plexus carcinoma; a systematic review and individual patient data analysis

Publication date: Available online 18 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Supriya Mallick, Rony Benson, Wineeta Melgandi, G.K. Rath
ObjectiveThe optimal management of patients with choroid plexus carcinoma (CPC) is unclear. We conducted a systematic review and meta-analysis of individual patient information to find the impact of surgery, adjuvant therapy and other prognostic factors in this disease.MethodologyA comprehensive search of the PubMed and Google scholar was performed with the following MesH terms: "choroid plexus tumor; choroid plexus carcinoma; choroid plexus carcinoma AND treatment; and choroid plexus carcinoma AND survival" to find all possible publications on CPC. We performed individual patient data analysis, to assess the strength of potential association between different variables and the outcome in patients with CPC.ResultsData from 284 patients was retrieved from 89 publications. The median age of the patients was 2 years with 26% patients diagnosed in the 1st year of their life. 52.8% of patients underwent a gross total resection [GTR] or near total resection. Median follow-up for the entire cohort was 10.8 months. Median progression free survival [PFS] was 13 months [95% CI 8.14-17.8]. PFS was better for patients older than 5 years and GTR. Median overall survival [OS] was 29 months (95% CI 16.3- 41.7). OS was better for patients older than 5 years, GTR, adjuvant treatment and parenchymal site of the tumor.ConclusionCPC is an aggressive tumor, with a median PFS of 13 months and a median OS of 29 months. All patients should undergo a maximal safe resection as GTR is associated with improved survival. Adjuvant radiation and chemotherapy were also associated with improved outcomes.

Teaser

Optimal management of patients with choroid plexus carcinoma (CPC) is not clear. We conducted a systematic review and meta-analysis of individual patient observations to find the impact of surgery, adjuvant therapy and other prognostic factors for CPC. Median overall survival for the entire cohort was 29 months. The overall survival was better for patients older than 5 years, patients undergoing GTR, adjuvant treatment, and parenchymal tumor. A gross total resection and adjuvant treatment need to be advocated for all patients as it improves survival outcome.


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Duration of Adjuvant Trastuzumab in HER2 Positive Breast Cancer: Overall and Disease Free Survival Results from Meta-Analyses of Randomized Controlled Trials

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Publication date: Available online 19 August 2017
Source:Cancer Treatment Reviews
Author(s): Bishal Gyawali, Saroj Niraula
BackgroundOne year of trastuzumab, chosen empirically, improves survival of women with early-stage, HER2-positive breast cancer but also adds substantially to cost, toxicity, and inconvenience. Longer treatment does not improve outcomes, but potentiates toxicities.MethodsMedline, Embase, and major conference proceedings were searched systematically in June, 2017 to identify Randomized Controlled Trials (RCTs) comparing one year versus shorter durations of trastuzumab in adjuvant treatment of breast cancer. Reported Hazard-Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds-Ratios for cardiac events, with respective 95% Confidence Intervals (CI) from each study was weighted using generic inverse-variance, and pooled in a meta-analysis. Inter-study heterogeneity and sub-group difference (based on hormone-receptors and node-positivity) were assessed using I2, and chi2 statistics, respectively.ResultsFour studies (n=7,614) satisfied inclusion criteria. Individual RCTs had diverse pre-specified upper-limits of 95% CI for declaring non-inferiority (range: <1.15 to <1.53). Pooled results demonstrated significant improvements in OS (HR 1.28, p=0.04), and DFS (HR 1.24, p=0.005) with 1 year of trastuzumab compared to shorter durations. Absence of multiplicity argument allowed for declaring superiority of 1 year of trastuzumab based on our results despite non-inferiority designs of individual trials. No influence on overall effect by duration of trastuzumab in experimental arm (9 weeks versus 6 months) was noted. No statistical interaction by hormone-receptor status and node-positivity on overall results was noticed [p(sub-group difference) 0.73, and 0.52, respectively]. Odds-Ratio for cardiac events was 2.65(p<0.001) favoring shorter duration.ConclusionOne year of trastuzumab prolongs overall, and disease-free survivals in women with early-stage HER2 positive breast cancer compared to shorter durations and this should remain as the standard of care. Cardiotoxicity increased significantly with the 1-year treatment.



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Recent advances in signal amplification strategy based on oligonucleotide and nanomaterials for microRNA detection-a review

Publication date: Available online 18 August 2017
Source:Biosensors and Bioelectronics
Author(s): Ying-Xu Chen, Ke-Jing Huang, Ke-Xin Niu
MicroRNAs (MiRNAs) play multiple crucial regulating roles in cell which can regulate one third of protein-coding genes. MiRNAs participate in the developmental and physiological processes of human body, while their aberrant adjustment will be more likely to trigger diseases such as cancers, kidney disease, central nervous system diseases, cardiovascular diseases, diabetes, viral infections and so on. What's worse, for the detection of miRNAs, their small size, high sequence similarity, low abundance and difficult extraction from cells impose great challenges in the analysis. Hence, it's necessary to fabricate accurate and sensitive biosensing platform for miRNAs detection. Up to now, researchers have developed many signal-amplification strategies for miRNAs detection, including hybridization chain reaction, nuclease amplification, rolling circle amplification, catalyzed hairpin assembly amplification and nanomaterials based amplification. These methods are typical, feasible and frequently used. In this review, we retrospect recent advances in signal amplification strategies for detecting miRNAs and point out the pros and cons of them. Furthermore, further prospects and promising developments of the signal-amplification strategies for detecting miRNAs are proposed.



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Reduced levels of methyltransferase DNMT2 sensitize human fibroblasts to oxidative stress and DNA damage that is accompanied by changes in proliferation-related miRNA expression

Publication date: Available online 18 August 2017
Source:Redox Biology
Author(s): Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Ewelina Semik, Tomasz Zabek, Maciej Wnuk
Methyltransferase DNMT2 is suggested to be involved in the regulation of numerous processes, however its biological significance and underlying molecular mechanisms remain elusive. In the present study, we have used WI-38 and BJ human fibroblasts as an in vitro model system to investigate the effects of siRNA-based DNMT2 silencing. DNMT2-depleted cells were found to be sensitive to oxidative stress conditions as judged by increased production of reactive oxygen species and susceptible to DNA damage that resulted in the inhibition of cell proliferation. DNMT2 silencing promoted upregulation of proliferation-related and tumor suppressor miRNAs, namely miR-28-3p, miR-34a-3p, miR-30b-5p, miR-29b-3p, miR-200c-3p, miR-28-5p, miR-379-5p, miR-382-5p, miR-194-5p, miR-193b-3p and miR-409-3p. Moreover, DNMT2 silencing induced cellular senescence and DNMT2 levels were elevated in replicatively senescent cells. Taken together, we found that DNMT2 may take part in the regulation of cell proliferation and longevity in human fibroblasts and speculate that the manipulation of DNMT2 levels that limits cell proliferation may be potentially useful anticancer strategy.



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Effect of postural insoles on gait pattern in individuals with hemiparesis: A randomized controlled clinical trial

Publication date: Available online 18 August 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Luiz Alfredo Braun Ferreira, Veronica Cimolin, Hugo Pasini Neto, Luanda André Colange Grecco, Roberta Delasta Lazzari, Arislander Jonathan Lopes Dumont, Manuela Galli, Claudia Santos Oliveira
IntroductionRecovering the ability to walk is an important goal of physical therapy for patients who have survived cerebrovascular accident (stroke). Orthotics can provide a reduction in plantar flexion of the ankle, leading to greater stability in the stance phase of the gait cycle. Postural insoles can be used to reorganize the tone of muscle chains, which exerts an influence on postural control through correction reflexes. The aim of the present study was to perform kinematic and spatiotemporal analyses of gait in stroke survivors with hemiparesis during postural insole usage.Material and MethodsTwenty stroke victims were randomly divided into two groups: 12 in the experimental group, who used insoles with corrective elements specifically designed for equinovarus foot, and eight in the control group, who used placebo insoles with no corrective elements. Both groups were also submitted to conventional physical therapy. The subjects were analyzed immediately following insole placement and after three months of insole usage. The SMART-D 140® system (BTS Engineering) with eight cameras sensitive to infrared light and the 32-channel SMART-D INTEGRATED WORKSTATION® were used for the three-dimensional gait evaluation.ResultsSignificant improvements were found in kinematic range of movement in the ankle and knee as well as gains in ankle dorsiflexion and knee flexion in the experimental group in comparison to the control group after three months of using the insoles.ConclusionPostural insoles offer significant benefits to stroke survivors regarding the kinematics of gait, as evidenced by gains in ankle dorsiflexion and knee flexion after three months of usage in combination with conventional physical therapy.



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Three-dimensional kinematics of the thorax during over-ground running

Publication date: Available online 18 August 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Dominic Fisher, Quinette Louw, John Cockcroft, Nassib Tawa
BackgroundGiven the size and mass of the thoracic segment, understanding its neuromotor control demand during over ground running at different speeds is important in the rehabilitation and research setting. This study describes key kinematics characteristics as proxy measures for thoracic neuromotor control. We hypothesized that thoracic kinematics would differ significantly when running at different running speeds and that speed related thoracic kinematic changes would not differ between gender.MethodsThree-dimensional thoracic kinematics of 19 healthy runners were recorded using an optical 3D motion capture system. We compared peak kinematic angles and range of motion of the thorax in each anatomical plane, in three running speeds during the stance phase. The Wilcoxon Signed Rank Test was used to analyse thoracic kinematics differences across different speeds.ResultsThere was increased group peak kinematic angles and total range of motion during slower and faster than self-selected pace compared to self-selected pace in all three planes. There were gender differences in the changes in kinematic measures at different running speeds.ConclusionOur findings suggest that the differences in thoracic kinematics as a result of non-self-selected running speed may be due either to the increased neuromotor demands inherent to that running speed or due to the individual's adjustment to running at an unfamiliar speed. Further investigation is required to determine whether protocols that require participants to run at speeds other than self-selected pace confound the results. We therefore recommend normative data set protocols that avoid potential confounding by employing only self-selected pace. Our findings further suggest kinematic changes due to speed differed across gender, most notably in the transverse plane. Thus, we propose that gender specific normative data sets may be required.



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The effect of tactile-kinesthetic stimulation on growth indices of healthy neonates

Publication date: Available online 18 August 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Fatemeh Abedi, Neda Mirbagher Ajorpaz, Sophia Esalatmanesh, Zahra Rahemi, Hamid Reza Gilasi, Mahboobeh Kafaei Atrian, Masoumeh Hosseinian
Therapeutic touch is emphasized by healthcare professionals for improvement of neonates' growth and development. However, inconsistencies exist regarding effects and methods of massage in neonates. The purpose of this clinical trial is to assess and comprise intervention and control groups regarding the effects of tactile-kinesthetic stimulation (TKS) by mothers on growth indices of healthy term neonates. Sixty healthy term neonates were randomly assigned into intervention and control groups. Mothers of neonates in the experimental group were trained to perform TKS for their newborns at home before feeding for at least 28 consecutive days, two times a day, and 15 min each time. Neonates in the control group were not required to receive this intervention. The neonates' growth indices were measured within 24 h after birth, and then at days 14 and 28. During the study and the three consecutive measurements, no significant difference was found between the mean weights, heights, and head circumferences of the neonates in the two groups (p > 0.05).



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A critical overview of the current myofascial pain literature – October 2017

Publication date: Available online 18 August 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Jan Dommerholt, Michelle Finnegan, Todd Hooks, Li-Wei Chou
In this overview of the myofascial pain literature, we have included several original contributions ranging from a study by Bowen and colleagues of trigger points in horses to the introduction of a new clinical entity of "laryngeal muscle myofascial pain syndrome in dysphonic patients." Minerbi and colleagues described for the first time the referred pain patterns of the longus colli muscle, while Casale and associates studied the spinal modulatory action of dry needling or acupuncture stimulation. Many dry needling articles are included in this overview with several recent outcome studies. Slowly, there is increasing scientific support for using dry needling for a variety of conditions. Several researchers explored specific aspects of dry needling, such as needle placements, whether eliciting a local twitch response is desired, and the role of psychological factors in post-needling soreness. Contributions originated in Australia, Belgium, Brazil, Canada, China, Germany, Greece, India, Israel, Italy, Korea, Portugal, Spain, Switzerland, Turkey, the UK, and the USA.



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Do isometric, isotonic and/or isokinetic strength trainings produce different strength outcomes?

Publication date: Available online 19 August 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Sabrina Eun Kyung Lee, Claudio Andre Barbosa de Lira, Viviane Louise Andree Nouailhetas, Rodrigo Luiz Vancini, Marilia Santos Andrade
IntroductionSeveral studies have been developed to determine which type of muscular action (isometric, isotonic and isokinetic) elicits more gains in functional strength and muscle mass. The comparisons between training outcomes are inconclusive due to lack of exercise standardization.ObjectiveTo compare muscle strength, mass, and functional performance in response to isometric, isotonic, and isokinetic contractions, when training loads (volume and intensity) are equated.MethodData were derived from a university community-recruited sample (n = 31 men).InterventionsUntrained men were assigned to isotonic (IT), isometric (IM), or isokinetic (IK) group, and trained their dominant quadriceps muscle 3 sessions/week for 8 weeks with a dynamometer. Muscle strength was assessed using Cybex 6000 dynamometer; the triple-hop-distance test was used to assess functional performance, and dual energy x-ray absorptiometry to assess lean muscle mass.ResultsAfter training, muscle lean muscle mass increased in isometric (+3.1%, p < 0.01) and isotonic groups (+3.9%, p < 0.01); only the isokinetic group showed a significant improvement in the triple-hop-distance test (4.84%, p < 0.01).ConclusionClinicians should consider isometric training as an alternative for isotonic training to gain muscle mass, and isokinetic training to improve functional performance of daily activities and/or sports.



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Increased serum levels of fetuin B in patients with coronary artery disease

Abstract

Background

Recent evidence indicates a pivotal role for fetuin B, one of the cystatin superfamily of cysteine protease inhibitors, in the pathogenesis of metabolic diseases. This study investigated whether serum fetuin B levels are associated with the presence of coronary artery disease.

Methods

Serum fetuin B levels were assessed in 87 patients with coronary artery disease (41 with acute coronary syndromes and 46 with stable angina pectoris) and 87 healthy controls using an enzyme-linked immunosorbent assay. The association of serum fetuin B levels with cardiac risk factors was analyzed.

Results

Serum fetuin B levels were significantly higher in patients with coronary artery disease than those in healthy controls (90.7 ± 32.1 vs. 110.0 ± 32.7 μg/ml, P < 0.001), extremely elevated in group with acute coronary syndromes (115.0 ± 35.2 μg/ml). Pearson correlation analysis showed that serum fetuin B levels were positively associated with the levels of total cholesterol (r = 0.276, P < 0.001), low-density lipoprotein cholesterol (r = 0.363, P < 0.001), and fasting blood glucose (r = 0.159, P < 0.05). In addition, multiple logistic regression analyses revealed that fetuin B was independently associated with the presence of coronary artery disease (OR, 1.019; 95% CI, 1.009 to 1.029; P < 0.001) and acute coronary syndromes (OR, 1.017; 95% CI, 1.006 to 1.028; P < 0.01).

Conclusions

Our data revealed that high fetuin B levels are associated with the presence of coronary artery disease and acute coronary syndromes, and that fetuin B may serve as a potential biomarker for coronary artery disease.



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Increased serum levels of fetuin B in patients with coronary artery disease

Abstract

Background

Recent evidence indicates a pivotal role for fetuin B, one of the cystatin superfamily of cysteine protease inhibitors, in the pathogenesis of metabolic diseases. This study investigated whether serum fetuin B levels are associated with the presence of coronary artery disease.

Methods

Serum fetuin B levels were assessed in 87 patients with coronary artery disease (41 with acute coronary syndromes and 46 with stable angina pectoris) and 87 healthy controls using an enzyme-linked immunosorbent assay. The association of serum fetuin B levels with cardiac risk factors was analyzed.

Results

Serum fetuin B levels were significantly higher in patients with coronary artery disease than those in healthy controls (90.7 ± 32.1 vs. 110.0 ± 32.7 μg/ml, P < 0.001), extremely elevated in group with acute coronary syndromes (115.0 ± 35.2 μg/ml). Pearson correlation analysis showed that serum fetuin B levels were positively associated with the levels of total cholesterol (r = 0.276, P < 0.001), low-density lipoprotein cholesterol (r = 0.363, P < 0.001), and fasting blood glucose (r = 0.159, P < 0.05). In addition, multiple logistic regression analyses revealed that fetuin B was independently associated with the presence of coronary artery disease (OR, 1.019; 95% CI, 1.009 to 1.029; P < 0.001) and acute coronary syndromes (OR, 1.017; 95% CI, 1.006 to 1.028; P < 0.01).

Conclusions

Our data revealed that high fetuin B levels are associated with the presence of coronary artery disease and acute coronary syndromes, and that fetuin B may serve as a potential biomarker for coronary artery disease.



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Esthetic dermatology and emotional well-being according to gender

Summary

Introduction

There has been an increase in the demand for esthetic dermatology treatments within the general population. The purpose of this study was to analyze, within the scope of general population, the relationship between people's perception of esthetic dermatology treatments and emotional well-being, as well as for differences in gender.

Methods

The Aesthetic Dermatology and Emotional Well-Being (DEBIE) Scale, [Journal of Cosmetic Dermatology vol. 13 (2014) 336-345] was applied to 770 Spanish people over 18 years old. The scale is structured according to six factors and classified into two dimensions: (1) Emotional Well-Being and (2) Perception of Aesthetic Dermatology. Cronbach alpha for the total scale was very high (0.90). Data analysis includes the following: (1) bivariate correlations with Pearson's coefficient; (2) gender differences through Student's t test, and (3) the effect size through R2 and Cohen's d.

Results

A statistically significant relationship which is directly proportional has been identified between the degree of emotional well-being of people (self-esteem and assertiveness, optimism, and motivation) and the knowledge and attitude toward Aesthetic Dermatology. There are statistically significant differences according to gender: Women have a lower level of emotional well-being than men, as well as greater knowledge and more positive attitude toward Aesthetic Dermatology.

Conclusions

People who are familiar with Aesthetic Dermatology and have a better attitude toward it, are also more self-confident, more optimistic and more motivated; with emotional strength. Regarding gender, it is expected that women may seek more consultation and esthetic dermatology treatments than men do.



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Large enhancement in cell performance of CdSe-sensitized ZnO solar cell via ZnSe overcoating

Publication date: 15 December 2017
Source:Journal of Alloys and Compounds, Volume 727
Author(s): Jianguang Jia, Chunmei Liu, Yuan Lin, Xiaowen Zhou
Charge recombination is an important factor that limits the cell efficiency of quantum dot sensitized solar cells (QDSSCs). Herein, we report a facile way to improve the cell performance of CdSe sensitized ZnO QDSSC by overcoating a thin layer of ZnSe on CdSe/ZnO film through a successive ionic layer adsorption and reaction (SILAR) procedure. Photovoltaic investigations indicate that ZnSe overcoating can increase photocurrent and photovoltage of the cell, resulting in significant enhancement of the cell efficiency, which is much better than the widely used traditional ZnS material. The superior role of ZnSe overcoating is ascribed to its large inhibition of charge recombination loss owing to its suitable band structure, efficient passivation of ZnO and CdSe QDs as well as its small lattice mismatch with CdSe that leads to the large decrease of surface/interface defects in CdSe/ZnO photoanode. This finding provides an alternative efficient way to enhance the cell performance of ZnO based QDSSC by suppressing the charge recombination.



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Zn-Fe-CNTs catalytic in situ generation of H2O2 for Fenton-like degradation of sulfamethoxazole

Publication date: 15 January 2018
Source:Journal of Hazardous Materials, Volume 342
Author(s): Yong Liu, Qin Fan, Jianlong Wang
A novel Fenton-like catalyst (Zn-Fe-CNTs) capable of converting O2 to H2O2 and further to OH was prepared through infiltration fusion method followed by chemical replacement in argon atmosphere. The catalyst was characterized by SEM, EDS, TEM, XRD and XPS. The reaction between Zn-Fe-CNTs and O2 in aqueous solution could generate H2O2 in situ, which was further transferred to OH. The Fenton-like degradation of sulfamethoxazole (SMX) using Zn-Fe-CNTs as catalyst was evaluated. The results indicated that Zn-Fe-CNTs had a coral porous structure with a BET area of 51.67m2/g, exhibiting excellent adsorption capacity for SMX, which enhanced its degradation. The particles of Zn0 and Fe0/Fe2O3 were observed on the surface of Zn-Fe-CNTs. The mixture of Zn0 and CNTs could reduce O2 into H2O2 by micro-electrolysis and Fe0/Fe2O3 could catalyze in-situ generation of H2O2 to produce OH through Fenton-like process. When initial pH=1.5, T=25°C, O2 flow rate=400mL/min, Zn-Fe-CNTs=0.6g/L, SMX=25mg/L and reaction time=10min, the removal efficiency of SMX and TOC was 100% and 51.3%, respectively. The intermediates were detected and the possible pathway of SMX degradation and the mechanism of Zn-Fe-CNTs/O2 process were tentatively proposed.



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Effect of welding speed on microstructural evolution and mechanical properties of laser welded-brazed Al/brass dissimilar joints

Publication date: 1 January 2018
Source:Optics & Laser Technology, Volume 98
Author(s): L. Zhou, L.Y. Luo, C.W. Tan, Z.Y. Li, X.G. Song, H.Y. Zhao, Y.X. Huang, J.C. Feng
Laser welding-brazing process was developed for joining 5052 aluminum alloy and H62 brass in butt configuration with Zn-15%Al filler. Effect of welding speed on microstructural characteristics and mechanical properties of joints were investigated. Acceptable joints without obvious defect were obtained with the welding speed of 0.5–0.6m/min, while lower and higher welding speed caused excessive back reinforcement and cracking, respectively. Three reaction layers were observed at welding speed of 0.3m/min, which were Al4.2Cu3.2Zn0.7 (τ′)/Al4Cu9/CuZn from weld seam side to brass side; while at welding speed of 0.4–0.6m/min, two layers Al4.2Cu3.2Zn0.7 and CuZn formed. The thickness of interfacial reaction layers increased with the decrease of welding speed, but varied little at different interfacial positions from top to bottom in one joint. Tensile test results indicated that the maximum joint tensile strength of 128MPa was obtained at 0.5m/min, which was 55.7% of that of Al base metal. All the joints fractured along the weld seam/brass interface. Some differences were found regarding fracture locations with three and two reaction layers. The joint fractured between Al4Cu9 and τ′ IMC layer when the interface had three layers, while the crack occurred between CuZn and τ′ phase in the case of two layers.



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Design, fabrication and characterization of nanocaged 12CaO·7Al2O3:Tb3+ photostimulable phosphor for high-quality X-ray imaging

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Shengnan Li, Yuxue Liu, Chunguang Liu, Duanting Yan, Hancheng Zhu, Jian Yang, Meng Zhang, Changshan Xu, Li Ma, Xiaojun Wang
It has been a challenge to realize high-quality X-ray imaging using oxide-based phosphors for avoiding halogenide-based materials and satisfying the requirements of environmental protection. In this study, lanthanide-doped nanocaged 12CaO·7Al2O3:Tb3+ (C12A7:Tb3+) X-ray imaging phosphors with strong photostimulated luminescence (PSL) have been prepared using a combustion method. X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR) spectra, scanning electron microscopy (SEM) and transmission electron microscope (TEM) measurements suggest that single-phased C12A7:Tb3+ powders with an average grain size ranging from several hundred nanometers to several micrometers have been obtained at the ignition temperature from 700 to 900°C. PSL, thermoluminescence (TL), electron spin resonance (ESR) and photoconductivity analyses indicate that the storage time of X-ray image exceeds 48h due to the existence of deep traps in the C12A7:Tb3+ phosphor. High-quality X-ray imaging with a resolution of 15 line pairs per mm has been achieved using the phosphor. High conversion efficiency is achieved at 1.28pJ/mm2/mR, suggesting the application potential of the phosphors in X-ray imaging and medical diagnostics.

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Boron films produced by high energy Pulsed Laser Deposition

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): D. Dellasega, V. Russo, A. Pezzoli, C. Conti, N. Lecis, E. Besozzi, M. Beghi, C.E. Bottani, M. Passoni
Micron-thick boron films have been deposited by Pulsed Laser Deposition in vacuum on several substrates at room temperature. The use of high energy pulses (>700mJ) results in the deposition of smooth coatings with low oxygen uptake even at base pressures of 10−4–10−3Pa. A detailed structural analysis, by X-Ray Diffraction and Raman, allowed to assess the amorphous nature of the deposited films as well as to determine the base pressure that prevents boron oxide formation. In addition the crystallization dynamics has been characterized showing that film crystallinity already improves at relatively low temperatures (800°C). Elastic properties of the boron films have been determined by Brillouin Spectroscopy. Finally, micro-hardness tests have been used to explore cohesion and hardness of B films deposited on aluminum, silicon and alumina. The reported deposition strategy allows the growth of reliable boron coatings paving the way for their use in many technology fields.

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Investigating the internal structure and mechanical properties of graphene nanoflakes enhanced aluminum foam

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Yukun An, Siyi Yang, Hongyan Wu, Ertuan Zhao, Zongshen Wang
The manuscript focuses on analyzing the pore morphology and pore distribution of novel graphene nanoflakes reinforced aluminum foam (GNF-AF) and investigating their mechanical properties under quasi-static compressive loadings. Experimental results indicate the existence of GNFs can reduce the pore diameter, refine the pore morphology, and improve the pore distribution. Distinguish from other brittle foams, GNF-AF presents smooth stress-strain curve, wherein the local buckling deformation, shear deformation, tensile deformation combinate the whole compressive behavior. By comparing the plateau stress, energy absorption, and specific energy absorption of GNF-AF with varying content of GNFs, a notable improvement of 29.0%, 28.5%, and 27.9% was detected by adding 0.10wt% GNFs. Besides, the energy absorption efficiency of enhanced aluminum foam was slightly improved.

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Morphological and combustion study of interface effects in aluminum-poly(vinylidene fluoride) composites

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Jena McCollum, Aimee M. Morey, Scott T. Iacono
Condensed energetic composites were produced from poly(vinylidene fluoride) (PVDF) and nano-scale aluminum (Al) via injection molding. This work aimed to (1) resolve changes in PVDF decomposition as a function of composition approaching Al concentrations sufficient in producing self-propagating burns and (2) observe interface effects on combustion performance. Dynamic mechanical analysis showed that the PVDF glass transition response to Al loading was negligible indicating that Al particles were well dispersed in the composite. This finding was confirmed with scanning electron microscopy imaging. Combustion performance was assessed with open-air burns and X-ray diffraction. Coupons loaded beyond 4wt% Al burned in a linear manner and primarily produced aluminum fluoride (AlF3). Overall, results show that a condensed interface in Al-PVDF composites enhances ignition sensitivity at low Al loadings and controls reaction product species.

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Evolution of Fe–rich phases in Mg melt and a novel method for separating Al and Fe from Al–Si–Fe alloys

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Tong Gao, Zengqiang Li, Yaoxian Zhang, Jingyu Qin, Xiangfa Liu
The recycling of high Fe–contained Al–Si alloys is a green industry and how to separate Al and Fe is the key point therein. An efficient technique using Mg melt to separate Al and Fe is proposed in this study. By introducing Al–14wt% Si–4wt% Fe alloy into Mg melt and adjusting melting, holding and cooling parameters, the evolution behavior and separation performance of Fe–rich intermetallics were investigated. A separation layer with Fe–rich particles was obtained at the bottom of the cooled ingot. A meta–stable phase Fe3Al0.7Si0.3 was detected, which only exists above 699°C confirmed by a thermodynamic calculation. Making β–Al5SiFe phase from the initial Al–14wt% Si–4wt% Fe alloy transform to Fe3Al0.7Si0.3 in Mg melt is beneficial to achieve higher separation efficiency since the Fe3Al0.7Si0.3 phase is Al–poor, indicating that quantities of Al are released to the Mg matrix. Holding at 750°C for 30min followed by a further holding at 650°C for 30min is regarded most proper in this study. This work may be referred by relative study on the evolution of intermetallics by introducing one matrix alloy into another melt.

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Microstructural evolution, nanoprecipitation behavior and mechanical properties of selective laser melted high-performance grade 300 maraging steel

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Chaolin Tan, Kesong Zhou, Wenyou Ma, Panpan Zhang, Min Liu, Tongchun Kuang
High-performance grade 300 maraging steels were fabricated by selective laser melting (SLM) and different heat treatments were applied for improving their mechanical properties. The microstructural evolutions, nanoprecipitation behaviors and mechanical properties of the as-fabricated and heat-treated SLM parts were carefully characterized and analysed. The evolutions of the massive submicron sized cellular and elongated acicular microstructures are illustrated and theoretically explained. Nanoprecipitates triggered by intrinsic heat treatment and amorphous phases in as-fabricated specimens are observed by TEM. High-resolution TEM (HRTEM) images of the age hardened specimens clearly exhibit massive nanosized needle-shaped nanoprecipitates Ni3X (X=Ti, Al, Mo) and 50–60nm sized spherical core-shell structural nanoparticles embedded in amorphous matrix. XRD analyses reveal austenite reversion and probable phase transformations during heat treatments. The hardness and tensile strength of the as-fabricated and age-treated SLM specimens absolutely meet the standard wrought requirements. Furthermore, the lost ductility after aging can be compensated by preposed solution treatments. Relationships between massive nanoprecipitates and dramatically improved mechanical performances of age hardened specimens are elaborately analysed and perfectly explained by Orowan mechanism. This study demonstrates that high-performance grade 300 maraging steels, which is comparable to the standard wrought levels, can be produced by SLM additive manufacturing.

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Selective laser melting of an oxide dispersion strengthened (ODS) γ-TiAl alloy towards production of complex structures

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): C. Kenel, G. Dasargyri, T. Bauer, A. Colella, A.B. Spierings, C. Leinenbach, K. Wegener
The selective laser melting of oxide dispersion strengthened Ti-45Al-3Nb-Y2O3 with a focus on processing parameters and layer-wise re-scanning strategies is described. Smooth melt pools are observed in single line deposition for laser powers of 100 to 200W at low scanning speeds. Increased porosity is observed at energies exceeding 150W. Laser melting scans on sintered material show a common behavior of melt pool width and depth as a function of radiant exposure at 100 to 200W. Deep welding and keyhole formation is observed at 150W to 200W exceeding a radiant exposure of 20J/mm2. Re-scanning strategies in multi-layer deposits are found to reduce cracking frequency significantly. Re-scans with a 90° orientation are superior to scans with 0° and 45° with respect to the initial deposition scan and reduce the cracking frequency by a factor of 2 without preheating. In free-standing lattice structures re-scanning was found to be mostly detrimental which is explained by their low heat transport towards the base plate. The results clearly demonstrate the potential of re-scanning strategies in manufacturing of structural intermetallics at ambient temperatures, which are usually processed at high preheating temperatures.

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Ablation of facial adenoma sebaceum using the Versajet™ Hydrosurgery System

Abstract

Sebaceous adenomas, histologically facial angiofibromas, are closely associated with the tuberous sclerosis complex. The dermatologic disorder constitutes one of the main characteristics for that disease. The lesions commonly involve the central part of the face, including the cheeks, perioral region and nose with predominance in the nasolabial folds, causing a major cosmetic disfigurement. Aesthetic surgery of the face comprises different forms of ablative treatments using mechanical dermabrasion, shave excision, radiofrequency ablation, cryosurgery, laser therapy, and electrocoagulation. The use of Versajet™ Hydrosurgery System has not been previously described in the treatment of adenoma sebaceum so far. In this case report, we present the successful application of this hydrosurgical system in a patient with tuberous sclerosis and multiple facial angiofibromas indicating it as a feasible, effective, reliable, and economical treatment option.

Level of Evidence: Level V, therapeutic study.



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IFC (editorial board)

Publication date: September 2017
Source:Peptides, Volume 95





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The International Neuropeptide society pages

Publication date: September 2017
Source:Peptides, Volume 95





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Gayle & Richard Olson prize pages

Publication date: September 2017
Source:Peptides, Volume 95





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Analysis of temperature increase in swine gingiva after exposure to a Polywave® LED light curing unit

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Publication date: Available online 18 August 2017
Source:Dental Materials
Author(s): Cristiane Maucoski, Driellen Christine Zarpellon, Fabio Andre dos Santos, Leandro Cavalcante Lipinski, Eduardo Bauml Campagnoli, Frederick Allen Rueggeberg, Cesar Augusto Galvão Arrais
ObjectiveThis study evaluated the temperature increase in swine gingival temperature after exposure to light emitted by a Polywave® LED light curing unit (LCU, Bluephase 20i, Ivoclar Vivadent).MethodsAfter local Ethics Committee approval (protocol 711/2015), 40 pigs were subjected to general anesthesia and the LCU tip was placed 5mm from the buccal gingival tissue (GT) close to lower lateral incisors. A thermocouple probe (Thermes WFI, Physitemp) was inserted into the gingival sulcus before and immediately after exposure to light. Real-time temperature (°C) was measured after the following exposure modes were applied: High Power (20s-H, 40s-H, and 60s-H) or Turbo mode (5s-T), either with or without the presence of rubber dam (RD) interposed between the LCU tip and GT (n=10). The presence of gingival lesions after the exposures was also evaluated. Peak temperature (°C) and the temperature increase during exposure over that of the pre-exposure baseline value (ΔT) data were analyzed using 2-way ANOVA followed by Bonferroni's post-hoc test (α=5%). A binary logistic regression analysis determined the risk of gingival lesion development.ResultsWithout RD, no significant difference in ΔT was observed among 20s-H, 40s-H, and 60s-H groups, which showed the highest temperature values, while the 5s-T exposure showed the lowest ΔT, regardless of RD. RD reduced ΔT only for the 20s-H group (p=0.004). Gingival lesions were predominantly observed using 40s-H, with RD, and 60s-H, with and without RD.SignificanceExposure to a LCU light might be harmful to swine gingiva only when high radiant exposure values are delivered, regardless of the use of RD.



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Favorable residual stress induction by resin-cementation on dental porcelain

Publication date: Available online 16 August 2017
Source:Dental Materials
Author(s): Garry J.P. Fleming, Xu Cao, Dan L. Romanyk, Owen Addison
ObjectivesDespite developments in polycrystalline ceramics, glassy dental-ceramic materials provide the optimum cosmetic option in most clinical situations to mimic the natural dentition. The clinical success of glassy dental-ceramic materials is often attributed to resin-adhesive bonding techniques. In this study we explore whether shrinkage stresses generated on photo-polymerisation of the resin-cement are sufficient to induce ceramic surface defect stabilization, and we quantify the transient nature of the induced stresses.MethodsStress-induced changes in a feldspathic ceramic over a range of thicknesses (0.5–2.0mm: n=20 per thickness) were measured using a profilometric technique at baseline for each disc-shaped specimen (mean of the maximum deflection (δbaseline)) and again following polymerisation of a controlled resin-cement thickness on the contra-lateral surface. Measurements were repeated at 30, 60, 90 and 1440min following photo-polymerization (δ30, δ60, δ90 and δ1440, respectively) before bi-axial flexure strength (BFS) determination at 24h.ResultsA repeated measures ANOVA and post-hoc Bonferroni tests determined that δ1440 was significantly different from δbaseline (p=0.02), δ30 (p<0.01) and δ60 (p<0.01) but not δ90 (p=0.61). Data exploration revealed that there were differences in directionality of the independent variable (mean of the maximum deflection (δ)) with a proportion of specimens increasing in deflection and others reducing. The directionality of the effect strongly correlated with the BFS values. Where δ1440-δbaseline was low and/or negative, BFS values were also low. High BFS values were observed when δ1440-δbaseline was large and positive (indirectly inferring high shrinkage-stress-induced-deformation).SignificanceA link between shrinkage stresses associated with the photo-polymerization of dental resin-based cements and the reinforcement of dental porcelain has clearly been established.



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Constructing Fine-granularity Functional Brain Network Atlases via Deep Convolutional Autoencoder

Publication date: Available online 18 August 2017
Source:Medical Image Analysis
Author(s): Yu Zhao, Qinglin Dong, Hanbo Chen, Armin Iraji, Yujie Li, Milad Makkie, Zhifeng Kou, Tianming Liu
State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with fine granularities, based on fMRI data.

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Efficient and sustainable water systems management toward worth living development



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Applications of Resting State Functional MR Imaging to Traumatic Brain Injury

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Publication date: Available online 18 August 2017
Source:Neuroimaging Clinics of North America
Author(s): Thomas J. O'Neill, Elizabeth M. Davenport, Gowtham Murugesan, Albert Montillo, Joseph A. Maldjian

Teaser

Traumatic brain injury (TBI) is an important public health issue. TBI includes a broad spectrum of injury severities and abnormalities. Functional MR imaging (fMR imaging), both resting state (rs) and task, has been used often in research to study the effects of TBI. Although rs-fMR imaging is not currently applicable in clinical diagnosis of TBI, computer-aided tools are making this a possibility for the future. Specifically, graph theory is being used to study the change in networks after TBI. Machine learning methods allow researchers to build models capable of predicting injury severity and recovery trajectories.


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Ten Key Observations on the Analysis of Resting-state Functional MR Imaging Data Using Independent Component Analysis

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Publication date: Available online 18 August 2017
Source:Neuroimaging Clinics of North America
Author(s): Vince D. Calhoun, Nina de Lacy

Teaser

For more than 20 years, the powerful, flexible family of independent component analysis (ICA) techniques has been used to examine spatial, temporal, and subject variation in functional magnetic resonance (fMR) imaging data. This article provides an overview of 10 key principles in the basic and advanced application of ICA to resting-state fMR imaging. ICA's core advantages include robustness to artifact; false-positives and autocorrelation; adaptability to variant study designs; agnosticism to the temporal evolution of fMR imaging signals; and ability to extract, identify, and analyze neural networks. ICA remains in the vanguard of fMRI methods development.


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Reply: Discussion on "Intraoperative comparison of anatomical versus round implants in breast augmentation: A randomized controlled trial".

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Role of Mitomycin C in Preventing Capsular Contracture in Implant-Based Reconstructive Breast Surgery: A Randomized Controlled Trial.

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Blood Congestion Can Be Rescued by Hemodilution in a Random-Pattern Skin Flap. Letter.

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High-Resolution Magnetic Resonance Imaging of Aging Upper Face Fat Compartments.

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Reply: Role of Mitomycin C in Preventing Capsular Contracture in Implant-Based Reconstructive Breast Surgery: A Randomized Controlled Trial.

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Reply: Medial Row Perforators Are Associated with Higher Rates of Fat Necrosis in Bilateral DIEP Flap Breast Reconstruction#8232;.

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Direct-to-Implant Breast Reconstruction without the Use of an Acellular Dermal Matrix Is Cost Effective and Oncologically Safe.

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Comments on "Should Immediate Autologous Breast Reconstruction be considered in women who require Post-Mastectomy Radiation Therapy?".

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Why Women Request Labiaplasty.

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Reply: Blood Congestion Can be Rescued by Hemodilution in a Random-Pattern Skin Flap.

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Response of letter to the Editor on: High-Resolution Magnetic Resonance Imaging of Aging Upper Face Fat Compartments.

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Reply: The Impact of Two Operating Surgeons on Microsurgical Breast Reconstruction.

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Comment on: Application of Posterior Thigh Three-Dimensional Profunda Artery Perforator Perforasomes in Refining Next-Generation Flap Designs: Transverse, Vertical, and S-Shaped Profunda Artery Perforator Flaps.

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The Impact of Two Operating Surgeons on Microsurgical Breast Reconstruction.

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Response to Letter by Dr. Ciancio to PRS manuscript 170529.

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"Medial Row Perforators Are Associated with Higher Rates of Fat Necrosis in Bilateral DIEP Flap Breast Reconstruction.".

No abstract available

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Reply to Letter to the Editor: Why Women Request Labiaplasty.

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Unilateral cleft lip repair.

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response letter for "Simplifying the Forehead Flap for Nasal Reconstruction : A review of 420 consecutive cases.

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Enoxaparin Dosing and the Prevention of Venous Thromboembolism in Plastic Surgery Patients.

No abstract available

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Transition From Feature-Search to Singleton-Detection Strategies in Visual Search: The Role of Number of Target-Defining Options.

Author: Lagroix, Hayley E. P.; Yanko, Matthew R.; Spalek, Thomas M.
DOI: 10.1037/xhp0000467
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Superior Olfactory Language and Cognition in Odor-Color Synaesthesia.

Author: Speed, Laura J.; Majid, Asifa
DOI: 10.1037/xhp0000469
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Benefits of Flexible Prioritization in Working Memory Can Arise Without Costs.

Author: Myers, Nicholas E.; Chekroud, Sammi R.; Stokes, Mark G.; Nobre, Anna C.
DOI: 10.1037/xhp0000449
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Individuals' Eye Movements in Reading are Highly Consistent Across Time and Trial.

Author: Carter, Benjamin T.; Luke, Steven G.
DOI: 10.1037/xhp0000471
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Towards a Unified Model of Vision and Attention: Effects of Visual Landmarks and Identity Cues on Covert and Overt Attention Movements.

Author: Lambert, Anthony J.; Wilkie, Jaimie; Greenwood, Andrea; Ryckman, Nathan; Sciberras-Lim, Evatte; Booker, Laura-Jane; Tahara-Eckl, Lenore
DOI: 10.1037/xhp0000474
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Same-Location Costs in Peripheral Cueing: The Role of Cue Awareness and Feature Changes.

Author: Schoeberl, Tobias; Ditye, Thomas; Ansorge, Ulrich
DOI: 10.1037/xhp0000470
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Alternation Blindness in the Representation of Binary Sequences.

Author: Yu, Ru Qi; Osherson, Daniel; Zhao, Jiaying
DOI: 10.1037/xhp0000476
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Effect of Travel Speed on the Visual Control of Steering Toward a Goal.

Author: Chen, Rongrong; Niehorster, Diederick C.; Li, Li
DOI: 10.1037/xhp0000477
Publication Date: POST AUTHOR CORRECTIONS, 17 August 2017


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Acute Δ-9-tetrahydrocannabinol administration in female rats attenuates immediate responses following losses but not multi-trial reinforcement learning from wins

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Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Scott A. Wong, Sienna H. Randolph, Victorita E. Ivan, Aaron J. Gruber
Δ-9-Tetrahydrocannabinol (THC) is the main psychoactive component of marijuana and has potent effects on decision-making, including a proposed reduction in cognitive flexibility. We demonstrate here that acute THC administration differentially affects some of the processes that contribute to cognitive flexibility. Specifically, THC reduces lose-shift responding in which female rats tend to immediately shift choice responses away from options that result in reward omission on the previous trial. THC, however, did not impair the ability of rats to flexibly bias responses toward feeders with higher probability of reward in a reversal task. This response adaptation developed over several trials, suggesting that THC did not impair slower forms of reinforcement learning needed to choose among options with unequal utility. This dissociation of THC's effects on innate/rapid and learned/gradual decision-making processes was unexpected, but is supported by emerging evidence that lose-shift responding is mediated by neural mechanisms distinct from those involved in other forms of reinforcement learning. The present data suggest that, at least in some tasks, the apparent reductions in cognitive flexibility by THC may be explained by the immediate effects on loss sensitivity, rather than impairments of all processes used for choice adaptation.



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SIRT2 inhibition reverses anhedonia in the VGLUT1+/− depression model

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): I. Muñoz-Cobo, F.B. Belloch, T. Díaz-Perdigón, E. Puerta, R.M. Tordera
Some histone deacetylase (HDACs) enzymes have been proposed as epigenetic targets involved in the pathophysiology of depression and antidepressant-like action. Among them, we have recently identified SIRT2, a class III NAD+-dependent HDAC, as being oppositely regulated by stress and antidepressants. Moreover, SIRT2 inhibition has shown antianhedonic-like action in the chronic mild stress model of depression. Here we have extended the study using an alternative model of depression based in a genetic manipulation of glutamate function. Specifically, mice heterozygous for the vesicular glutamate transporter 1 (VGLUT1+/−) were used.Firstly, mRNA expression of the different members of the HDAC superfamily in the prefrontal cortex (PFC) of VGLUT1+/− mice and WT littermates were studied by RT-PCR. Secondly, the effect of repeated treatment with the selective SIRT2 inhibitor 33i and the antidepressant imipramine on anhedonic behaviour of VGLUT1+/− mice was studied by weekly monitoring of sucrose intake. Further, the interaction of 33i towards specific monoaminergic targets such as serotonin or noradrenaline transporters as well as the monoaminooxidase enzyme was studied.The mRNA occurance of the different members of HDAC superfamily was not altered in the PFC of VGLUT1+/− mice. While repeated imipramine showed an anti-anhedonic action in both VGLUT1+/− and WT, the selective SIRT2 inhibitor 33i fully reversed anhedonia of VGLUT1+/−. Further, 33i showed no interaction with the above mentioned monoaminergic molecular targets.These results confirm that SIRT2 inhibition is able to reverse anhedonia in different animal models and highlight the need to further investigate the role of SIRT2 inhibitors as new antidepressant agents.



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Neocortical prodynorphin expression is transiently increased with learning: Implications for time- and learning-dependent neocortical kappa opioid receptor activation

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Ryan Loh, Sean Collins, Roberto Galvez
There are several lines of evidence that indicate a prominent role for the opioid system in the acquisition and consolidation of learned associations. Specifically, kappa opioid receptor (KOR) modulation has been demonstrated to alter various behavioral tasks including whisker trace eyeblink conditioning (WTEB). WTEB is an associative conditioning paradigm in which a neutral conditioned stimulus (CS; Whisker stimulation) is paired following a short stimulus free trace interval with a salient unconditioned stimulus that elicits a blink response (US; Eye shock). Work from our laboratory has shown that WTEB conditioning is dependent upon and induces plasticity in primary somatosensory cortex (S1), a likely site for memory storage. Our subsequent studies have shown that WTEB acquisition or consolidation are impaired when the initial or later phase of KOR activation in S1 is respectively blocked. Interestingly, this mechanism by which KOR is activated in S1 during learning remains unexplored. Dynorphin (DYN), KOR's endogenous ligand, is synthesized from the precursor prodynorphin (PD) that is synthesized from preprodynorphin (PPD). In S1, most PPD is found in inhibitory GABAergic somatostatin interneurons (SOM), suggesting that these SOM interneurons are upstream regulators of learning induced KOR activation. Using immunofluorescence to investigate the expression of PD and SOM, the current study found that PD/SOM expression was transiently increased in S1 during learning. Interestingly, these findings have direct implications towards a time- and learning-dependent role for KOR activation in neocortical mechanisms mediating learning.



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Dynamic feet distance: A new functional assessment during treadmill locomotion in normal and thoracic spinal cord injured rats

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Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Camila Cardoso Diogo, Luís Maltez da Costa, José Eduardo Pereira, Vítor Filipe, Pedro Alexandre Couto, Luís G. Magalhães, Stefano Geuna, Paulo A. Armada-da-Silva, Ana Colette Maurício, Artur Severo Varejão
Of all the detrimental effects of spinal cord injury (SCI), one of the most devastating is the disruption of the ability to perform functional movement. Very little is known on the recovery of hindlimb joint kinematics after clinically-relevant contusive thoracic lesion in experimental animal models. A new functional assessment instrument, the dynamic feet distance (DFD) was used to describe the distance between the two feet throughout the gait cycle in normal and affected rodents. The purpose of this investigation was the evaluation and characterization of the DFD during treadmill locomotion in normal and T9 contusion injured rats, using three-dimensional (3D) instrumented gait analysis. Despite that normal and injured rats showed a similar pattern in the fifth metatarsal head joints distance excursion, we found a significantly wider distance between the feet during the entire gait cycle following spinal injury. This is the first study to quantify the distance between the two feet, throughout the gait cycle, and the biomechanical adjustments made between limbs in laboratory rodents after nervous system injury.



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Full title with Editorial board members

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Publication date: 15 September 2017
Source:Behavioural Brain Research, Volume 334





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Improved tumor tissue penetration and tumor cell uptake achieved by delayed charge reversal nanoparticles

Publication date: Available online 18 August 2017
Source:Acta Biomaterialia
Author(s): Jingxin Gou, Yuheng Liang, Linlin Miao, Wei Guo, Yanhui Chao, Haibing He, Yu Zhang, Jingyu Yang, Chunfu Wu, Tian Yin, Yanjiao Wang, Xing Tang
The high affinity of positively charged nanoparticles to biological interfaces makes them easily taken up by tumor cells but limits their tumor permeation due to non-specific electrostatic interactions. In this study, polyion complex coated nanoparticles with different charge reversal profiles were developed to study the influence of charge reversal profile on tumor penetration. The system was constructed by polyion complex coating using micelles composed of poly (lysine)-b-polycaprolactone (PLys-b-PCL) as the cationic core and poly (glutamic acid)-g- methoxyl poly (ethylene glycol) (PGlu-g-mPEG) as the anionic coating material. Manipulation of charge reversal profile was achieved by controlling the polymer chain entanglement and electrostatic interaction in the polyion complex layer through glutaraldehyde-induced shell-crosslinking. The delayed charge reversal nanoparticles (CTCL30) could maintain negatively charged in pH 6.5 PBS for at least 2 h and exhibit pH-responsive cytotoxicity and cellular uptake in an extended time scale. Compared with a faster charge reversal counterpart (CTCL70) with similar pharmacokinetic profile, CTCL30 showed deeper penetration, higher in vivo tumor cell uptake and stronger antitumor activity in vivo (tumor inhibition rate: 72.3% vs 60.2%, compared with CTCL70). These results indicate that the delayed charge reversal strategy could improve therapeutic effect via facilitating tumor penetration.Statement of SignificanceHere, the high tumor penetration capability of PEG-coated nanoparticles and the high cellular uptake of cationic nanoparticles were combined by a delayed charge reversal drug delivery system. This drug delivery system was composed of a drug-loading cationic inner core and a polyion complex coating. Manipulation of charge reversal profile was realized by varying the crosslinking degree of the shell of the cationic inner core, through which changed the strength of the polyion complex layer. Nanoparticles with delayed charge reversal profile exhibited improved tumor penetration, in vivo tumor cell uptake and in vivo tumor growth inhibition effect although they have similar pharmacokinetic and biodistribution behaviors with their instant charge reversal counterpart.

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An RGD-modified hollow silica@Au core/shell nanoplatform for tumor combination therapy

Publication date: Available online 18 August 2017
Source:Acta Biomaterialia
Author(s): Xin Li, Lingxi Xing, Yong Hu, Zhijuan Xiong, Ruizhi Wang, Xiaoying Xu, Lianfang Du, Mingwu Shen, Xiangyang Shi
The combination of chemotherapy and photothermal therapy (PTT) in multifunctional nanoplatforms to improve cancer therapeutic efficacy is of great significance while it still remains to be a challenging task. Herein, we report Au nanostar (NS)-coated hollow mesoporous silica nanocapsules (HMSs) with surface modified by arginine-glycine-aspartic acid (RGD) peptide as a drug delivery system to encapsulate doxorubicin (DOX) for targeted chemotherapy and PTT of tumors. Au NSs-coated HMSs core/shell nanocapsules (HMSs@Au NSs) synthesized previously were conjugated with RGD peptide via a spacer of polyethylene glycol (PEG). We show that the prepared HMSs@Au-PEG-RGD NSs are non-cytotxic in the given concentration range, and have a DOX encapsulation efficiency of 98.6 ± 0.7%. The designed HMSs@Au-PEG-RGD NSs/DOX system can release DOX in a pH/NIR laser dual-responsive manner. Importantly, the formed HMSs@Au-PEG-RGD NSs/DOX nanoplatform can specifically target cancer cells overexpressing αvβ3 intergrin and exert combination chemotherapy and PTT efficacy to the cells in vitro and a xenografted tumor model in vivo. Our results suggest that the designed HMSs@Au-PEG-RGD NSs/DOX nanoplatform may be used for combination chemotherapy and PTT of tumors.Statement of SignificanceWe demonstrate a convenient approach to preparing a novel RGD-targeted drug delivery system of HMSs@Au-PEG-RGD NSs/DOX that possesses pH/NIR laser dual-responsive drug delivery performance for combinational chemotherapy and PTT of tumors. The developed Au NS-coated HMS capsules have both merits of HMS capsules that can be used for high payload drug loading and Au NSs that have NIR laser-induced photothermal conversion efficiency (70.8%) and can be used for PTT of tumors.

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NanoTopoChip: High-throughput Nanotopographical Cell Instruction.

Publication date: Available online 18 August 2017
Source:Acta Biomaterialia
Author(s): Frits FB Hulshof, Yiping Zhao, Aliaksei Vasilevich, Nick RM Beijer, Meint de Boer, Bernke J Papenburg, Clemens van Blitterswijk, Dimitrios Stamatialis, Jan de Boer
Surface topography is able to influence cell phenotype in numerous ways and offers opportunities to manipulate cells and tissues. In this work, we develop the Nano-Topochip and study the cell instructive effects of nanoscale topographies. A combination of deep UV projection lithography and conventional lithography was used to fabricate a library of more than 1200 different defined nanotopographies. To illustrate the cell instructive effects of nanotopography, actin-RFP labeled U2OS osteosarcoma cells were cultured and imaged on the Nano-TopoChip. Automated image analysis shows that of many cell morphological parameters, cell spreading, cell orientation and actin morphology are mostly affected by the nanotopographies. Additionally, by using modeling, the changes of cell morphological parameters could by predicted by several feature shape parameters such as lateral size and spacing.This work overcomes the technological challenges of fabricating high quality defined nanoscale features on unprecedented large surface areas of a material relevant for tissue culture such as PS and the screening system is able to infer nanotopography - cell morphological parameter relationships. Our screening platform provides opportunities to identify and study the effect of nanotopography with beneficial properties for the culture of various cell types.Statement of SignificanceThe nanotopography of biomaterial surfaces can be modified to influence adhering cells with the aim to improve the performance of medical implants and tissue culture substrates. However, the necessary knowledge of the underlying mechanisms remains incomplete. One reason for this is the limited availability of high-resolution nanotopographies on relevant biomaterials, suitable to conduct systematic biological studies. The present study shows the fabrication of a library of nano-sized surface topographies with high fidelity. The potential of this library, called the 'Nanotopochip' is shown in a proof of principle HTS study which demonstrates how cells are affected by nanotopographies. The large dataset, acquired by quantitative high-content imaging, allowed us to use predictive modeling to describe how feature dimensions affect cell morphology.

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Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy

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Publication date: November 2017
Source:Biomaterials, Volume 144
Author(s): Xiaomin Liu, Zhongqi Fan, Li Zhang, Zheng Jin, Dongmei Yan, Youlin Zhang, Xiaodan Li, Langping Tu, Bin Xue, Yulei Chang, Hong Zhang, Xianggui Kong
Similar to many other anticancer therapies, photodynamic therapy (PDT) also suffers from the intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by various proteins, among which anti-apoptotic protein Bcl-2 plays an important role in regulation of programmed cell death and has been proved to involve in protecting against oxidative stimuli. Confronted by this challenge, we propose and validate here a novel upconversion photosensitizing nanoplatform which enables significant reduction of cancer resistance and improve PDT efficacy. The upconversion nanophotosensitizer contains the photosensitizing molecules - Zinc phthalocyanine (ZnPc) and Bcl-2 inhibitor - ABT737 small molecules, denoted as ABT737@ZnPc-UCNPs. ABT737 molecules were encapsulated, in a pH sensitive way, into the nanoplatform through Poly (ethylene glycol)-Poly (l-histidine) diblock copolymers (PEG-b-PHis). This nanosystem exhibits the superiority of sensitizing tumor cells for PDT through adjuvant intervention strategy. Upon reaching to lysosomes, the acidic environment changes the solubility of PEG-b-PHis, resulting in the burst-release of ABT737 molecules which deplete the Bcl-2 level in tumor cells and leave the tumor cells out from the protection of anti-apoptotic survival pathway in advance. Owing to the sensitization effect of ABT737@ZnPc-UCNPs, the PDT therapeutic efficiency of cancer cells can be significantly potentiated in vitro and in vivo.



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Covalent coupling of high-affinity ligands to the surface of viral vector particles by protein trans-splicing mediates cell type-specific gene transfer

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Publication date: November 2017
Source:Biomaterials, Volume 144
Author(s): Alexander Muik, Johanna Reul, Thorsten Friedel, Anke Muth, Karen Patricia Hartmann, Irene C. Schneider, Robert C. Münch, Christian J. Buchholz
We have established a novel approach for the covalent coupling of large polypeptides to the surface of fully assembled adeno-associated viral gene transfer vector (AAV) particles via split-intein mediated protein-trans-splicing (PTS). This way, we achieved selective gene transfer to distinct cell types. Single-chain variable fragments (scFvs) or designed ankyrin repeat proteins (DARPins), exhibiting high-affinity binding to cell surface receptors selectively expressed on the surface of target cells, were coupled to AAV particles harboring mutations in the capsid proteins which ablate natural receptor usage. Both, the AAV capsid protein VP2 and multiple separately produced targeting ligands recognizing Her2/neu, EpCAM, CD133 or CD30 were genetically fused with complementary split-intein domains. Optimized coupling conditions led to an effective conjugation of each targeting ligand to the universal AAV capsid and translated into specific gene transfer into target receptor-positive cell types in vitro and in vivo. Interestingly, PTS-based AAVs exhibited significantly less gene transfer into target receptor-negative cells than AAVs displaying the same targeting ligand but coupled genetically. Another important consequence of the PTS technology is the possibility to now display scFvs or other antibody-derived domain formats harboring disulfide-bonds in a functionally active form on the surface of AAV particles. Hence, the custom combination of a universal AAV vector particle and targeting ligands of various formats allows for an unprecedented flexibility in the generation of gene transfer vectors targeted to distinct cell types.



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Boldine isolated from Litsea cubeba inhibits bone resorption by suppressing the osteoclast differentiation in collagen-induced arthritis

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Hongyan Zhao, Huihui Xu, Senyan Qiao, Cheng Lu, Gui Wang, Meijie Liu, Baosheng Guo, Yong Tan, Dahong Ju, Cheng Xiao
ObjectiveTo investigate the effect of boldine isolated from Litsea cubeba on collagen-induced arthritis (CIA) rats and explore the molecular mechanism predicted by network pharmacology.Material and methodsCIA rats were orally administered with boldine. The bone destruction of paws was analyzed by histologic examination, tartrate-resistant acid phosphatase (TRACP) staining and micro-computed tomography. Prediction of signal pathway associated with boldine network molecules and CIA genes was applied by the network pharmacology analysis. The expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) in the ankle were detected by immunohistochemistry. In vitro osteoclasts were cultured in the presence of variable doses of boldine and the RANK expressions were evaluated using Real-time polymerase chain reaction and western blot.ResultsBoldine reduced ankle swelling, alleviated pathological damage and significantly prevented bone destruction in CIA rats. Consistent with this, enzyme linked immunosorbent assay revealed boldine decreased serum TRACP5b levels and osteoclast number in the ankle region by TRACP staining from CIA rats. The network pharmacology analysis indicated that RANK signaling in osteoclasts was the most significant canonical pathway associated with boldine network molecules and CIA genes, which was verified by the increased expression of OPG, reduced expression of RANK, RANKL and RANKL/OPG in boldine-treated CIA rats. The in vitro study further confirmed that boldine inhibited osteoclastogenesis by inhibiting the RANKL/RANK signaling pathway.ConclusionTaken together, our study first indicates that boldine from Litsea cubeba suppresses osteoclastogenesis, improves bone destruction by down-regulating the OPG/RANKL/RANK signal pathway and may be a potential therapeutic agent for rheumatoid arthritis.



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Potential mechanisms of calcium dependent regulation of the mammalian cell cycle revealed by comprehensive unbiased label-free nLC-MS/MS quantitative proteomics

Publication date: Available online 18 August 2017
Source:Journal of Proteomics
Author(s): Anna Kwasnik, Alex von Kriegsheim, Andrew Irving, Stephen R. Pennington
Calcium (Ca2+) controls progression through the mammalian cell cycle by engaging a diverse range of molecular pathways. While the essential role of spatio-temporal Ca2+ signalling in the cell cycle is well established, the precise mechanisms by which it regulates cell cycle entry and progression through G1 are not particularly well understood.Here, high-resolution label-free semi-quantitative nLC-MS/MS analysis has been used to support a highly reproducible unbiased analysis of Ca2+ influx dependent growth factor induced protein expression early in G1 in human fibroblasts. Using this strategy a panel of 182 proteins whose expression was Ca2+ dependent were identified. Pathway analysis has indicated that Ca2+ likely regulates cell proliferation via PI3K/AKT pathway and its downstream target mTOR. In addition to cell proliferation found proteins were involved in the regulation of cell morphology and cellular assembly and organization, the environmental clues, which are known to regulate G1 progression.Reported here data represents one of the most comprehensive proteomic datasets of growth factor and Ca2+ dependent protein expression in the mammalian cell cycle and provides a rich source of publically available data to support continued investigation of the role of Ca2+ in G1 progression at both the molecular and systems level.Biological significanceThe results of this study provide new insight into Ca2+ dependent regulation of cell cycle. This manuscript reports first to date global analysis of Ca2+ regulated protein expression changes early in G1 in non-transformed human fibroblast cell line. It also highlights canonical signalling pathways and biological processes that are regulated by the inhibition of Ca2+ influx. Importantly, it appears that Ca2+ may be the factor that links cell division with environmental cues, cell morphology and cellular assembly and organization, on which cell proliferation depends. Hence, the findings presented here provide numerous opportunities for more detailed investigations of the mechanism of Ca2+ dependent regulation of cell cycle at the molecular and systemic level.

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The effect of sources and air mass transport on the variability of trace element deposition in central Poland: a cluster-based approach

Abstract

Measurements of trace element (As, Cu, Cd, Cr, Ni, Pb, Zn) deposition fluxes were conducted simultaneously in two contrasted environments, i.e., urban and forest, between April 2013 and October 2014. This was the first such project in central Poland, aimed at long-term observations of trace elements in the atmosphere and their distribution, transport, and deposition pattern. The receptor sites were different in terms of local meteorological conditions, emission potential, and distance to major anthropogenic sources. The deposition fluxes of all trace elements showed clear seasonal variations, with relatively higher values in winter than in summer. The main factors affecting interannual differences in concentrations and deposition of trace elements in central Poland were local emission from industrial and commercial sources, and changes in atmospheric conditions (wind speed and direction, boundary layer, precipitation amount, air mass origin). In this study, the impact of regional and long-range transport on trace element deposition was determined using the air back-trajectory cluster analysis. During the summertime of 2013 and 2014, the predominant SW and E advections from regional and remote anthropogenic sources in Europe were responsible for high deposition of Cd, Cr, Pb, Cu, and Zn, whereas during the wintertime of 2013/2014, we observed a significant influence of polluted air masses from southeastern regions. Based on the Pb/Zn ratio, it was found that regional sources significantly influenced the aerosol composition and rainwater chemistry within the study domain. However, the role of a long-range transport of anthropogenic pollutants was also important. In addition, a relatively small difference in the Pb/Zn ratio between both sites (urban 0.26 ± 0.18, forest 0.23 ± 0.17) may suggest (1) very similar contribution of anthropogenic sources and (2) minor importance of atmospheric transformation processes of these metals in the aqueous phase.



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Selected Abstracts from the September Issue of the Journal of Vascular Surgery

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3





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Contents

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3





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Into the Lead: How EJVES Became the Leading Journal in Vascular Surgery

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3
Author(s): M. Björck, P. Kolh




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Editorial Board

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3





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One year on: Test your knowledge from the previous year

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3





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Forthcoming Events

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3





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EJVES vol. 54, issue 3 (September 2017) - Spanish Translated Abstracts

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3





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Long-term Outcome of Endovascular Treatment for Mycotic Aortic Aneurysm

Publication date: Available online 18 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): C.-M. Luo, C.-Y. Chan, Y.-S. Chen, S.-S. Wang, N.-H. Chi, I.-H. Wu
Objective/BackgroundEndovascular repair (EVAR) of mycotic aortic aneurysm (MAA) has become an alternative treatment for high risk patients. The aim of this study was to evaluate long-term survival and outcomes.MethodsRetrospective analysis of 40 consecutive patients with MAAs undergoing EVAR and subsequent intravenous antibiotic treatment between September 2009 and April 2015. Follow-up was truncated on 30 April 2015. Uni- and multivariate logistic regression were used to assess risk factors of adverse outcomes. Cumulative survival was calculated using the Kaplan–Meier method.ResultsMedian age at repair was 73 years (range 48–88 years) and 31 (77%) were men. Eleven (27%) patients were infected with Salmonella, 12 (30%) with non-Salmonella species, and 17 (42%) had negative cultures. Anatomical locations included the aortic arch/thoracic area in 10 (25%), the paravisceral area in seven (17%), and the infrarenal area in 23 (57%). Ten (25%) patients presented with aneurysm rupture and underwent emergency repair. Median follow-up was 25 months (range 1–69 months). Cumulative 1 and 5 year survival rates were 71% and 53%, respectively. Persistent or recurrent infection occurred in 20% (n = 8). Patients with persistent infection were treated with long-term medical therapy, but all died (75%; n = 6) within 6 months of repair. No survival difference was found between patients with or without Salmonella infections. However, there was a trend toward better survival in culture negative patients.ConclusionEVAR of MAA is an acceptable alternative treatment of MAA. However, persistent infection after endovascular treatment does occur and is often fatal without surgical treatment.



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Abnormally High Ankle–Brachial Index is Associated with All-cause and Cardiovascular Mortality: The REGICOR Study

Publication date: September 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 3
Author(s): A. Velescu, A. Clara, R. Martí, R. Ramos, S. Perez-Fernandez, L. Marcos, M. Grau, I.R. Degano, J. Marrugat, R. Elosua
IntroductionThe clinical significance of a high ankle brachial index (ABI) and its relationship to cardiovascular disease (CVD) and mortality is controversial. The aim of this study was to estimate the association between abnormally high ABI ≥ 1.4 and coronary heart disease (CHD), cerebrovascular disease, and all-cause mortality in a Mediterranean population without CVD.MethodsA prospective population based cohort study of 6352 subjects was followed up for a median 6.2 years. Subjects under 35 years, with a history of CVD or an ABI < 0.9 were excluded. All CHD events (angina, myocardial infarction, coronary revascularisation), cerebrovascular events (stroke, transient ischaemic attack), and all-cause mortality were recorded.ResultsA total of 5679 subjects fulfilled the inclusion criteria, of which 5517 (97.1%) had a normal ABI whereas 162 (2.9%) had an ABI ≥ 1.4. The profile of individuals with abnormally high ABI revealed as independent related factors age (OR = 1.0; p = .045), female sex (OR = 0.4; p < .01), diabetes (OR = 1.9; p = .02), and lower diastolic blood pressure (OR = 0.9; p < .001). During follow-up 309 (5.4%) participants presented with a CV event and 286 (5.0%) died. An ABI ≥ 1.4 was associated with a higher incidence of CV events in the univariate (HR = 1.7) but not in the multivariate survival Cox regression analysis. An ABI ≥ 1.4 was independently associated with all-cause mortality (HR = 2.0; IC 95% 1.32–2.92) and cardiovascular mortality (HR = 3.1; IC 95% 1.52–6.48).ConclusionsIn subjects without CVD, those with abnormally high ABI do not have a greater CV event rate than those with a normal ABI. However, there seems to be a trend towards higher mortality risk, supporting the guidelines that consider this subgroup to be a high risk population.



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Comparative analysis of the effects of CO 2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid

Abstract

Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.



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Is antimicrobial photodynamic therapy an effective treatment for chronic periodontitis in diabetes mellitus and cigarette smokers: a systematic review and meta-analysis

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Publication date: September 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 19
Author(s): Nawwaf Al-Hamoudi
BackgroundTo determine whether treatment with antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) improves clinical, microbiological and immunological outcomes in type 2 diabetes mellitus (T2DM) and cigarette smokers with chronic periodontitis (CP).MethodsDatabases (MEDLINE, PubMed; Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register) were searched up to and including May 2017. The addressed PICO question was: "Does aPDT as an adjunct to SRP improves clinical, microbiological and immunological outcomes in T2DM and smokers with CP?"ResultsSix randomized clinical trials were included. All studies reporting clinical periodontal, microbiological, and immunological parameters showed that aPDT was effective in the treatment of CP in T2DM and smokers at follow up. When compared with SRP alone, none of the studies showed additional benefits of aPDT at follow up. Considering the effects of adjunctive aPDT as compared to SRP on clinical signs of CP in T2DM and smokers, no difference could be observed for all evaluated parameters (PD: Z=−0.81, P=0.41; CAL: Z=−0.19, P=0.84) except IL-1β (Z=4.57, P<0.001).ConclusionDue to limited evidence, it remains debatable whether aPDT as an adjunct to SRP is effective in improving clinical, microbiological and immunological outcomes compared to SRP alone in T2DM and smokers with CP. Further well-designed, large-scale clinical trials with microbiological parameters and long follow up periods are needed in order to assess the efficacy of adjunctive aPDT in T2DM and cigarette smokers with CP.



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