Publication date: Available online 31 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): M.F. Reneman, M. Roelofs, H.R. Schiphorst Preuper
ObjectiveTo analyze test-retest reliability and agreement, and to explore safety of Neck Functional Capacity Evaluation tests (Neck-FCE) in patients with chronic multifactorial neck pain.Designtest-retest; 2 FCE sessions were held with a 2 week interval.Settinguniversity based outpatient rehabilitation center.Participantsn=18 participants, 14 females, mean age of 34 years.Interventionsnot applicable.Main Outcome MeasureThe Neck-FCE protocol consists of 6 tests: lifting waist to overhead (kg), two-handed carrying (kg), overhead working (s), bending and overhead reaching (s), and repetitive side reaching (left and right) (s). Intraclass Correlation Coefficients (ICCs) and limits of agreement (LoA). ICC point estimates between 0.75 and 0.90 was considered as good and >0.90 was considered as excellent reliability.ResultsICC point estimates ranged between 0.39 and 0.96. Ratios of the LoA ranged between 32.0% and 56.5%. Mean NRS pain scores in neck and shoulder 24-hours after the test were respectively 6.7 (SD 2.6) and 6.3 (SD 3.0).ConclusionBased on ICC point estimates and 95%CI, it was concluded that that 3 tests had excellent reliability and 3 had poor reliability. LoA were substantial in all 6 tests. Safety was confirmed.
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Κυριακή 1 Ιανουαρίου 2017
Reliability and agreement of Neck Functional Capacity Evaluation tests in patients with chronic multifactorial neck pain
Microcirculatory Assessment of Arterial Below-Knee Stumps: Near-Infrared Spectroscopy vs. Transcutaneous Oxygen Tension. A Preliminary Study in Prosthesis Users
Publication date: Available online 31 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Davy Laroche, José-Luis Barnay, Bastien Tourlonias, Cyril Orta, Christine Obert, Jean-Marie Casillas
ObjectivesTo examine metrological properties of near-infrared spectroscopy (NIRS) vs. transcutaneous oxygen tension (TcPO2) for microcirculatory assessment of vascular transtibial stumps at the stabilized period of prosthesis fitting, as a preliminary step before exploring its ability to predict stump healing, considering the previously identified limits of TcPO2 (borderline area between 15 and 35 mmHg).DesignProspective single-centre observational study.SettingUniversity-based rehabilitation center.ParticipantsIndividuals with unilateral transtibial amputation for peripheral artery disease, at the definitive stage of prosthesis fitting, able to perform a two-minute walk test (30).InterventionNot applicable.Main Outcome MeasuresTest-retest, the stump being evaluated in supine and inclined position, first by NIRS (Tissue Saturation Index (TSI), oxy-haemoglobin, deoxy-haemoglobin, total haemoglobin) and second by TcPO2. Subjects carried out a 2-minute walk test and visual analogue scales (wound healing, pain).ResultsFeasibility and tolerance of NIRS were satisfactory. The reliability of NIRS and TcPO2 values was good (ICC>0.7, p<0.05). No significant relationship was found between NIRS and TcPO2. No responsiveness (inclined vs. supine) was reported (p>0.05). Significant relationship between TSI and the 2-minute walk test (r>0.49, p<0.05) was found.ConclusionsNIRS is painless, complication-free and feasible, with good reliability. NIRS evaluate other domain than TcPO2, more linked to metabolic adaptation. Its capacity to predict the stump healing and tolerance to early prosthesis fitting is thus interesting to estimate in future studies.
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Cognitive motor interference on upper extremity motor performance in a robot-assisted planar reaching task among patients with stroke
Publication date: Available online 31 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Joon-Ho Shin, Gyulee Park, Duk Youn Cho
ObjectiveTo explore motor performance on two different cognitive tasks during robotic rehabilitation in which motor performance was longitudinally assessed.DesignProspective studySettingRehabilitation hospitalParticipantsPatients with chronic stroke and upper extremity impairment (N=22)InterventionA total of 640 repetitions of robot-assisted planar reaching, five times a week for 4 weeksMain Outcome MeasuresLongitudinal robotic evaluations regarding motor performance included smoothness, mean velocity, path error, and reach error by the type of cognitive task. Dual-task effects (DTE) of motor performance were computed in order to analyze the effect of the cognitive task on dual-task interference.ResultsCognitive task type influenced smoothness (p = 0.006), the DTE of smoothness (p = 0.002), and the DTE of reach error (p = 0.052). Robotic rehabilitation improved smoothness (p = 0.007) and reach error (p = 0.078), while stroke severity affected smoothness (p = 0.01), reach error (p < 0.001), and path error (p = 0.01). Robotic rehabilitation or severity did not affect the DTE of motor performance.ConclusionsThe present results provide evidence for the effect of cognitive-motor interference on upper extremity performance among participants with stroke using a robotic-guided rehabilitation system.
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May the year be brighter than the one gone by; enveloped in goodness, well being, bliss and wealth. Happy New Year!
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Carotid artery aneurysm associated with Marfan Syndrome: A case report
Publication date: Available online 31 December 2016
Source:Alexandria Journal of Medicine
Author(s): Paolo Re, Simone Collura, Cristiano Saronni, Giacomo Pata, Andrea Battistella, Federico Ghidinelli, Gianluca Abrami, Maurizio Giovanetti
http://ift.tt/2inPQtT
Caudal Regression Syndrome/neurogenic bladder presented as recurrent urinary tract infection
Publication date: Available online 31 December 2016
Source:Alexandria Journal of Medicine
Author(s): Burhan M. Edrees
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Proliferaton index in pituitary adenomas from a black African population
Publication date: Available online 31 December 2016
Source:Alexandria Journal of Medicine
Author(s): Ayodeji Salami, Mustapha Ajani, Augustine Adeolu, Olufunmi Ogun, Amos Adeleye, Olabiyi Ogun, Clement Okolo, Adefolarin Malomo, Effiong Akang
BackgroundThe WHO has recognized a variant of pituitary adenomas with potential aggressive behaviour which have been termed atypical pituitary adenomas. This group of tumours are recognized by their mitotic rate of more than >3%, p53 expression and invasion of surrounding structures. There has however been no study of the occurrence of these tumours in a black African population. This study is a preliminary attempt to examine this group of tumours in blacks.MethodsThis study retrospectively reviewed fifty-seven histologically diagnosed and immunohistochemically characterized pituitary adenomas received in our department over a twenty-one year period. Specimens were stained with ki67, a nuclear marker of cell proliferation which has been identified as the single best predictor of atypical pituitary adenoma.ResultsTwelve of the tumours showed atypical features with eight (67%) of these tumours being prolactinomas. Two of the tumours were gonadotrophs and two were null cell adenomas. There was no correlation with age or gender. Two of the tumours required neurosurgical re-exploration with one of these showing a higher mitotic index in the second biopsy.ConclusionThe study suggests similarity in the rate of occurrence of pituitary adenomas with atypical features in a black African population with what is seen in Caucasians. Prolactinomas constitute a significant percentage of the tumours with this feature.
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Subclinical hypothyroidism ups the risk of vascular complications in type 2 diabetes
Publication date: Available online 31 December 2016
Source:Alexandria Journal of Medicine
Author(s): Ghada A. Mohamed, Amira M Elsayed
The incidence of thyroid dysfunction in diabetic patients is higher than that of the general population. Undiagnosed thyroid dysfunction may affect the metabolic control and enhance cardiovascular, and other chronic complication risks in diabetic patients. Few studies have examined the relationship between subclinical hypothyroidism (SCH) and vascular complications of type 2 diabetes. Objectives: To find out the relationship between SCH and vascular complications in patients with Type 2 diabetes. Subjects and Methods: Our cross sectional study included 110 patients with type 2DM (45 males and 65 females) who were followed at the Diabetes outpatient Clinics in the state of Kuwait during 6months period. All patients subjected to complete clinical and laboratory data, including thyroid function tests, total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, urinary albumin, fundus examination, ECG, and Glycosylated hemoglobin. Results: Among 110 patients, 21 (19.1%) Patients had SCH. Patients with SCH were more significantly older, with longer duration of diabetes, higher HbA1c, total cholesterol and LDL-C than euthyroid group. However, gender (p=0.076), BMI (p=0.092), and smoking (P=0.715) were not significantly different between the SCH and euthyroid groups. The SCH group had a higher prevalence of dyslipidemia (p=0.017), diabetic nephropathy (p=0.003) diabetic retinopathy (p=0.004) and IHD (p=0.011) than the euthyroid group while no significant difference in the prevalence of diabetic neuropathy (p=0.420). Conclusions: SCH is a common endocrine disorder in patients with Type 2 diabetes. It could be associated with a higher prevalence of vascular complications in type 2 diabetes. We could not prove a relation between SCH and diabetic neuropathy.
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Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis
Source:Biomaterials, Volume 120
Author(s): Jaewoo Lee, Jennifer G. Jackman, Jean Kwun, Miriam Manook, Angelo Moreno, Eric A. Elster, Allan D. Kirk, Kam W. Leong, Bruce A. Sullenger
Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma.
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Nanoparticles for multi-modality cancer diagnosis: Simple protocol for self-assembly of gold nanoclusters mediated by gadolinium ions
Source:Biomaterials, Volume 120
Author(s): Wenxiu Hou, Fangfang Xia, Gabriel Alfranca, Hao Yan, Xiao Zhi, Yanlei Liu, Chen Peng, Chunlei Zhang, Jesus Martinez de la Fuente, Daxiang Cui
It is essential to develop a simple synthetic strategy to improve the quality of multifunctional contrast agents for cancer diagnosis. Herein, we report a time-saving method for gadolinium (Gd3+) ions-mediated self-assembly of gold nanoclusters (GNCs) into monodisperse spherical nanoparticles (GNCNs) under mild conditions. The monodisperse, regular and colloidal stable GNCNs were formed via selectively inducing electrostatic interactions between negatively-charged carboxylic groups of gold nanoclusters and trivalent cations of gadolinium in aqueous solution. In this way, the Gd3+ ions were chelated into GNCNs without the use of molecular gadolinium chelates. With the co-existence of GNCs and Gd3+ ions, the formed GNCNs exhibit significant luminescence intensity enhancement for near-infrared fluorescence (NIRF) imaging, high X-ray attenuation for computed tomography (CT) imaging and reasonable r1 relaxivity for magnetic resonance (MR) imaging. The excellent biocompatibility of the GNCNs was proved both in vitro and in vivo. Meanwhile, the GNCNs also possess unique NIRF/CT/MR imaging ability in A549 tumor-bearing mice. In a nutshell, the simple and safe GNCNs hold great potential for tumor multi-modality clinical diagnosis.
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Thermal diffusion in polymer solutions: Approaching spinodal
Publication date: 27 January 2017
Source:Polymer, Volume 109
Author(s): S. Shams Es-haghi, M. Cakmak
This paper aims to theoretically explain the behavior of thermal diffusion coefficient in polymer solutions; specifically, in the vicinity of the unstable regions of phase diagrams. Based on an equation that was derived in the framework of classical irreversible thermodynamics, a dimensionless number was introduced that plays a crucial role in determining the thermal diffusion in polymer solutions. The behavior of thermal diffusion coefficient in various phase diagrams was investigated by changing the Flory-Huggins interaction parameter to include concentration and temperature dependencies using Koningsveld interaction factor. It was shown that irrespective of the types of phase diagrams, the proposed equation for thermal diffusion becomes zero at infinite dilution and takes finite values on the spinodal line. Moreover, it was illustrated that in a binary polymer solution the Soret coefficient (the ratio of the thermal diffusion coefficient to the mutual diffusion coefficient) diverges at the critical point, and more importantly it was predicted that the divergent behavior of the Soret coefficient is observed at all the points of the spinodal line.
Graphical abstract
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In vivo anti-arthritic efficacy of Camellia sinensis (L.) in collagen induced arthritis model
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Ankit Tanwar, Raman Chawla, Md. Meraj Ansari, Neha, Pallavi Thakur, Ankita Singh Chakotiya, Rajeev Goel, Himanshu Ojha, M. Asif, Mitra Basu, Rajesh Arora, Haider Ali Khan
BackgroundRheumatoid arthritis (RA), an autoimmune inflammatory disorder with synovial hyperplasia, destruction of cartilage, bone damage is often associated with risk of infections. Such risk could be attributed towards usage of immunosuppressive agents. Thus, the present study was undertaken to evaluate the anti-arthritic efficacy of aquo-alcoholic extract of Camellia sinensis (L.).Material and methodsDried leaves of Camellia sinensis (L.) or Cs were filtered and extracted in 1:1 aqueous: ethanol by Soxhlet apparatus followed by lyophilization and spray drying to develop amorphous powder. Four different oral doses (50, 100, 200, 400mg/kg/body wt.) of aquo-alcoholic extract were evaluated for anti-edematogenic effect in collagen induced arthritis model. The selected anti-arthritic doses of Cs were evaluated for the oxidative stress markers like Glutathione [5-5'dithio-bis-2-nitrobenzoicacid (DTNB)], Superoxide dismutase [Epinephrine], Catalase [Hydrogen peroxide], Lipid peroxidation [Thiobarbituric acid reactive substance (TBARS)], Nitric oxide [Griess reagents:Nitrobluetetrazolium], Articular elastase [N-methoxysuccinyl-Ala-Ala-Pro- Val p-nitroanilide] in joints followed by haematological evaluation including RBC, WBC, Haemoglobin, platelets and haematocrit. To validate these biochemical changes, the radiological and histopathological (Haematoxylin & Eosin) evaluation was also conducted.ResultsThe selected anti-arthritic dose of Cs i.e. 400mg/kg/body wt. (∼60% anti-arthritic efficacy on 35th day) could be attributed towards significant (p<0.05) increase in the levels of enzymatic (Superoxide dismutase and Catalase) and non-enzymatic (Glutathione) antioxidants by 34%, 59% and 50% respectively. Simultaneously, the significant (p<0.05) reduction of lipid peroxides, nitrite radical and elastase activity by 32%, 45% & 32% respectively as compare to control indicated overall decrease in oxidative stress. Haematological evaluation revealed restoration of RBC, WBC and platelets level in treatment group. The confirmatory analysis utilizing radiological and histological assessment showed alleviation of joint deformity, tissue swelling, pannus formation and neutrophils infiltration in treatment group as compared to collagen induced arthritis.ConclusionThe analysis showed that Cs can play an effective role in reduction of oxidative stress by modulating levels of antioxidants, reducing levels of free radicals while restoring normal haematopoietic cascade as observed in collagen induced arthritis model. Thus, the cumulative dose impact of 400mg/kg body wt., over a period of 14days also found extremely effective in terms of safeguarding their structural conformity against such auto-immune disorder.
Graphical abstract
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Taspine derivative 12k suppressed A549 cell migration through the Wnt/β-catenin and EphrinB2 signaling pathway
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Bingling Dai, Yujiao Ma, Tianfeng Yang, Wenjie Wang, Yanmin Zhang
12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells. In addition, 12k repressed the EphrinB2 and its PDZ protein, impairing the VEGFR2 and VEGFR3 expression in A549 cells, as well as inhibited the downstream of VEGFR2 included PI3K/AKT/mTOR and ERK/MAPK signaling pathways. Taken together, our findings revealed that 12k suppressed migration of A549 cells through the Wnt/β-catenin signaling pathway and EphrinB2 related signaling pathway.
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Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Aifeng Zhang, Yuqing Sheng, Mingchang Zou
Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis.
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Regulation of different components from Ophiopogon japonicus on autophagy in human lung adenocarcinoma A549Cells through PI3K/Akt/mTOR signaling pathway
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Juan Chen, Jiarui Yuan, Liqiang Zhou, Maomao Zhu, Ziqi Shi, Jie Song, Qingyu Xu, Guowen Yin, You Lv, Yi Luo, Xiaobin Jia, Liang Feng
Autophagy plays a dual role in the development of cancer, acting as both a tumor suppressor and a cell survival inducer. Ophiopogon japonicus (L.f) Ker-Gawl (OJ), as a traditional Chinese medicine, specially possesses remarkable anti-cancer activity in the clinical. Previously, studies have indicated that flavonoids (FOJ) and steroidal saponins (SSOJ) are the main active substances of OJ. However, the effects of FOJ and SSOJ on autophagy of A549 cells have not been fully elucidated. In this study, we found that the expressions of autophagy-related mediators (LC3-II/LC3-I ratio, Atg-3, Atg-7 and Beclin-1) were increased in A549 cells by the treatment with FOJ (7.9mg crude drug/mL) and SSOJ (12.2mg crude drug/mL). Meanwhile, FOJ or SSOJ could induce the up-regulation of LC3-II at both protein and mRNA levels. Moreover, we observed the cytoplasmic vaculoes which formed double-layered membranes and only some cytoplasmic organelles or myelin figures remained in FOJ or SSOJ-treated A549 cells for 24h by Transmission Electron Microscopy (TEM). Further detection about the PI3K/Akt/mTOR signaling pathway showed that the levels of PI3K, Akt and mTOR were significantly suppressed with the FOJ or SSOJ treatment. The 3-MA (an autophagy inhibitor) and LY294002 (a PI3K inhibitor) further confirmed the underlying mechanism in the FOJ or SSOJ-induced autophagy of A549 cells. Additionally, the pretreatment with FOJ and SSOJ increased the level of p53, whereas decreased the expression of Ki67. These findings suggested that FOJ or SSOJ could activate the autophagy of A549 cells, wherein the mechanism might be associated with their inhibition of PI3K/Akt/mTOR signaling pathway. Thus, FOJ or SSOJ could be a potential autophagy inducer to prevent the process of lung cancer.
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Aryl hydrocarbon receptor activation modulates CD8αα+TCRαβ+ IELs and suppression of colitis manifestations in mice
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Weigang Chen, Aimin Pu, Baifa Sheng, Zhicao Zhang, Liangzi Li, Zhongze Liu, Qimeng Wang, Xiang Li, Yuanhang Ma, Min Yu, Lihua Sun, Yuan Qiu, Hua Yang
BackgroundThis research is dedicated to investigating the effects and potential mechanism of action of the aryl hydrocarbon receptor on the intestinal mucosal immune system in dextran sulfate sodium (DSS)-induced colitis.MethodsColitis was induced by the administration of 3% DSS to wild-type C57BL/6J mice for 7days. 6-formylindolo(3, 2-b)carbazole (FICZ), an endogenous agonist of the aryl hydrocarbon receptor (AhR), was given intraperitoneally on a daily basis beginning 2days after the start of DSS administration. The mice were weighed and assessed, and colon tissues were measured. Intraepithelial lymphocytes (IELs) were isolated from the colon and examined by flow cytometry and quantitative real-time PCR.ResultsFICZ ameliorated DSS-induced colitis, resulting in a reduced disease activity index and improvement in the histology and length of the colon. Colitis reduced the percentage and number of CD8αα+TCRαβ+ IELs. FICZ prevented the reduction in the numbers of CD8αα+TCRαβ+ IELs by upregulating the expression of the IL-15 receptor and the aryl hydrocarbon receptor (AhR), and attenuating the apoptotic rate of CD8αα+TCRαβ+ IELs. Finally, IL-10 was increased and IFN-γ was decreased in CD8αα+TCRαβ+ IELs by FICZ administration in DSS-induced colitis.ConclusionsThe results suggest that AhR activation ameliorated DSS-induced acute colitis, in a manner that is associated with the local expansion and functions of CD8αα+TCRαβ+ IELs in acute colitis. The findings indicate that AhR-related ligands might be targeted as novel drug targets for IBD.
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Riluzole ameliorates learning and memory deficits in Aβ25-35-induced rat model of Alzheimer’s disease and is independent of cholinoceptor activation
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Zahra Mokhtari, Tourandokht Baluchnejadmojarad, Farnaz Nikbakht, Monireh Mansouri, Mehrdad Roghani
Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ25-35-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists. Further biochemical analysis showed that riluzole pretreatment of intrahippocampal Aβ-microinjected rats is able to attenuate hippocampal AChE activity and lower some oxidative stress markers, i.e. MDA and nitrite, with no significant change of the defensive enzyme catalase. Furthermore, riluzole prevented hippocampal CA1 neuronal loss and reduced 3-nitrotyrosine immunoreactivity. It is concluded that riluzole could exert a protective effect against memory decline induced by intrahippocampal Aβ25-35 through anti-oxidative, anti-cholinesterase, and neuroprotective potential and its beneficial effect is possibly independent of cholinoceptor activation.
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Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Dan Tang, Qi-Bin Chen, Xue-Lei Xin, Haji-Akber Aisa
Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A–C (compounds A–C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A–C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A–C. The results suggested that compounds A–C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A–C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A-C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) were also suppressed by wortmannin. Western blot results indicated that compounds A–C-induced IRS-1/Akt activation was likely a consequence of PTP1B inhibition. Compounds A–C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the anti-diabetic effect of compounds A–C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.
Graphical abstract
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Interaction of ozone and carbon dioxide with polycrystalline potassium bromide and its atmospheric implication
Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Alexander V. Levanov, Oksana Ya. Isaikina, Ivan B. Maksimov, Valerii V. Lunin
It has been discovered for the first time that gaseous ozone in the presence of carbon dioxide and water vapor interacts with crystalline potassium bromide giving gaseous Br2 and solid salts KHCO3 and KBrO3. Molecular bromine and hydrocarbonate ion are the products of one and the same reaction described by the stoichiometric equation 2KBr(cr.) + O3(gas) + 2CO2(gas) + H2O(gas) → 2KHCO3(cr.) + Br2(gas) + O2(gas). The dependencies of Br2, KHCO3 and KBrO3 formation rates on the concentrations of O3 and CO2, humidity of initial gas mixture, and temperature have been investigated. A kinetic scheme has been proposed that explains the experimental regularities found in this work on the quantitative level. According to the scheme, the formation of molecular bromine and hydrocarbonate is due to the reaction between hypobromite BrO−, the primary product of bromide oxidation by ozone, with carbon dioxide and water; bromate results from consecutive oxidation of bromide ion by ozone Br−→+O3,−O2BrO−→+O3,−O2BrO2−→+O3,−O2BrO3−.
Graphical abstract
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Relative impact of on-road vehicular and point-source industrial emissions of air pollutants in a medium-sized Andean city
Source:Atmospheric Environment, Volume 152
Author(s): C.M. González, C.D. Gómez, N.Y. Rojas, H. Acevedo, B.H. Aristizábal
Cities in emerging countries are facing a fast growth and urbanization; however, the study of air pollutant emissions and its dynamics is scarce, making their populations vulnerable to potential effects of air pollution. This situation is critical in medium-sized urban areas built along the tropical Andean mountains. This work assesses the contribution of on-road vehicular and point-source industrial activities in the medium-sized Andean city of Manizales, Colombia. Annual fluxes of criteria pollutants, NMVOC, and greenhouse gases were estimated. Emissions were dominated by vehicular activity, with more than 90% of total estimated releases for the majority of air pollutants. On-road vehicular emissions for CO (43.4 Gg/yr) and NMVOC (9.6 Gg/yr) were mainly associated with the use of motorcycles (50% and 81% of total CO and NMVOC emissions respectively). Public transit buses were the main source of PM10 (47%) and NOx (48%). The per-capita emission index was significantly higher in Manizales than in other medium-sized cities, especially for NMVOC, CO, NOx and CO2. The unique mountainous terrain of Andean cities suggest that a methodology based on VSP model could give more realistic emission estimates, with additional model components that include slope and acceleration. Food and beverage facilities were the main contributors of point-source industrial emissions for PM10 (63%), SOx (55%) and NOx (45%), whereas scrap metal recycling had high emissions of CO (73%) and NMVOC (47%). Results provide the baseline for ongoing research in atmospheric modeling and urban air quality, in order to improve the understanding of air pollutant fluxes, transport and transformation in the atmosphere. In addition, this emission inventory could be used as a tool to identify areas of public health exposure and provide information for future decision makers.
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The impact of atmospheric dust deposition and trace elements levels on the villages surrounding the former mining areas in a semi-arid environment (SE Spain)
Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): David Sánchez Bisquert, José Matías Peñas Castejón, Gregorio García Fernández
It is understood that particulate matter in the atmosphere from metallic mining waste has adverse health effects on populations living nearby. Atmospheric deposition is a process connecting the mining wasteswith nearby ecosystems. Unfortunately, very limited information is available about atmospheric deposition surrounding rural metallic mining areas. This article will focus on the deposition from mining areas, combined with its impact on nearby rural built areas and populations. Particle samples were collected between June 2011 and March 2013. They were collected according to Spanish legislation in ten specialised dust collectors. They were located near populations close to a former Mediterranean mining area, plus a control, to assess the impact of mining waste on these villages. This article and its results have been made through an analysis of atmospheric deposition of these trace elements (Mn, Zn, As, Cd and Pb). It also includes an analysis of total dust flux. Within this analysis it has considered the spatial variations of atmospheric deposition flux in these locations. The average annual level of total bulk deposition registered was 42.0 g m-2 per year. This was higher than most of the areas affected by a Mediterranean climate or in semi-arid conditions around the world. Regarding the overall analysis of trace elements, the annual bulk deposition fluxes of total Zn far exceeded the values of other areas. While Mn, Cd and Pb showed similar or lower values, and in part much lower than those described in other Mediterranean mining areas. This study confirmed some spatial variability of dust and trace elements, contained within the atmospheric deposition. From both an environmental and a public health perspective, environmental managers must take into account the cumulative effect of the deposition of trace elements on the soil and air quality around and within the villages surrounding metallic mining areas.
Graphical abstract
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Sulfur, arsenic, fluorine and mercury emissions resulting from coal-washing byproducts: A critical component of China's emission inventory
Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Chao Zhao, Kunli Luo
The coal-washing rate in China increased from 1991 to 2014 and shows a particular increase from ∼22% to ∼60% since 2002. However, few studies pay attention to the use and disposal of the coal-washing byproducts (CWBs). A preliminary estimate of the likely S, As, F and Hg contents and emissions from the combustion of CWBs in China was determined in this work. About 632 million tons of CWBs, including middling coal, flotation tailing coal and coal slime, were produced in China in 2014. About 4.03%, 20.80%, 1.48%, and 73.25% CWBs were used for thermal power, industry, domestic and discard. The mean S, As, F and Hg contents of CWBs are 1.52%, 14.04 mg/kg, 216.31 mg/kg and 0.27 mg/kg, respectively. SO2 emissions in 2014 from the combustion of CWBs were ∼5.76 million tons, similar to that released into the atmosphere by China's coal-fired power plants, accounting for ∼29% of the country's total SO2 emissions. Arsenic, F and Hg emissions from CWBs were 1 599.54, 61 575.07 and 77.16 tons, respectively. These emissions have become a critical component of air pollution in China.
Graphical abstract
http://ift.tt/2hEeanv
Gradenigo syndrome and primitive sphenoid sinus cancer
Publication date: Available online 31 December 2016
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Jbali Souheil, Dhaha Mohamed, Dhambri Sawssen, Kedous Skander, Hedhili Farah, Yazid Delia, Abidi Rim, Attia Zied, Touati Slim, Gritli Said
First described in 1907, Gradenigo's syndrome associates the following triad: acute otitis media as a causative infection of petrous apicitis, ipsilateral abducens nerve palsy and trigeminal neuralgia. This entity is becoming rare because of the wide use of antibiotics. The above definition can be extended as the fifth and sixth cranial nerves are intimately related near the apex of the petrous bone. Thus, any adjacent process may cause petrositis and palsies of these nerves.Paranasal sinus adenocarcinomas are common. But primitive sphenoid bone localization is exceptional and manifest usually with a deep retro orbital headache.1Gardenigo's syndrome is a rare revelation mode of sphenoid tumors.We report the case of a 55-years old female with a history of Budd Chiari syndrome, who presented with a typical Gradenigo's Syndrome. The imaging showed an invasive process of sphenoid sinus. trans-sphenoidal biopsy concluded to adenocarcinoma. As the patient was inoperable, palliative radiotherapy was indicated.
http://ift.tt/2it5Qca
Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report
Source:European Journal of Cancer, Volume 72
Author(s): M.M. de Jonge, A.L. Mooyaart, M.P.G. Vreeswijk, C.D. de Kroon, T. van Wezel, C.J. van Asperen, V.T.H.B.M. Smit, O.M. Dekkers, T. Bosse
BackgroundUterine serous carcinoma (USC) shows greater morphological, clinical and molecular similarities to high-grade ovarian tubal serous carcinoma than to other types of endometrial cancer. As high-grade ovarian tubal serous carcinoma is known to be associated with BRCA1/2 pathogenic germline mutations (PMs), we aimed to explore whether USC is also a constituent of hereditary breast and ovarian cancer syndrome.MethodsPubmed, EMBASE and Web of Science were searched in July 2016 for articles assessing the association between USC and germline BRCA1/2-PMs. Pooled analysis and comparisons were performed using a random effects logistic model, stratifying for ethnicity (Ashkenazi versus non-Ashkenazi). In addition, tumour tissue from an USC case with a hereditary BRCA1-PM was analysed for loss of heterozygosity at the BRCA1 locus and was functionally analysed for homologous recombination proficiency.ResultsThe search yielded 1893 citations, 10 studies were included describing 345 USC patients. For Ashkenazi Jews, the pooled odds ratio of having a germline BRCA1/2-PM was increased in USC patients compared with the general Ashkenazi population: odds ratio 5.4 (95%confidence interval: 2.2–13.1). In the patient with USC, we identified the known germline BRCA1-PM in the tumour DNA. Furthermore, we showed both loss of heterozygosity of the wild-type allele and a deficiency of homologous recombination.ConclusionThis study suggests that USC may be an overlooked component of BRCA1/2-associated hereditary breast and ovarian cancer syndrome. Screening for germline BRCA1/2-PMs should be considered in patients diagnosed with USC, especially in cases with a positive first-degree family history for breast and/or ovarian cancer.
http://ift.tt/2incTF6
Gradenigo syndrome and primitive sphenoid sinus cancer
Publication date: Available online 31 December 2016
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Jbali Souheil, Dhaha Mohamed, Dhambri Sawssen, Kedous Skander, Hedhili Farah, Yazid Delia, Abidi Rim, Attia Zied, Touati Slim, Gritli Said
First described in 1907, Gradenigo's syndrome associates the following triad: acute otitis media as a causative infection of petrous apicitis, ipsilateral abducens nerve palsy and trigeminal neuralgia. This entity is becoming rare because of the wide use of antibiotics. The above definition can be extended as the fifth and sixth cranial nerves are intimately related near the apex of the petrous bone. Thus, any adjacent process may cause petrositis and palsies of these nerves.Paranasal sinus adenocarcinomas are common. But primitive sphenoid bone localization is exceptional and manifest usually with a deep retro orbital headache.1Gardenigo's syndrome is a rare revelation mode of sphenoid tumors.We report the case of a 55-years old female with a history of Budd Chiari syndrome, who presented with a typical Gradenigo's Syndrome. The imaging showed an invasive process of sphenoid sinus. trans-sphenoidal biopsy concluded to adenocarcinoma. As the patient was inoperable, palliative radiotherapy was indicated.
http://ift.tt/2it5Qca
Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis
Source:Biomaterials, Volume 120
Author(s): Jaewoo Lee, Jennifer G. Jackman, Jean Kwun, Miriam Manook, Angelo Moreno, Eric A. Elster, Allan D. Kirk, Kam W. Leong, Bruce A. Sullenger
Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma.
http://ift.tt/2iTA333
The efficacy of Dynorphin fragments at the κ, μ and δ opioid receptor in transfected HEK cells and in an animal model of unilateral peripheral inflammation.
Source:Peptides
Author(s): M. Morgan, A. Heffernan, F. Benhabib, S. Wagner, A.K. Hewavitharana, P.N. Shaw, P.J. Cabot
BackgroundDynorphin 1-17 is an endogenous peptide that is released at sites of inflammation by leukocytes, binding preferentially to κ-opioid receptors (KOP) to mediate nociception. We have previously shown that dynorphin 1-17 is rapidly biotransformed to smaller peptide fragments in inflamed tissue homogenate. This study aimed to determine the efficacy and potency of selected dynorphin fragments produced in an inflamed environment at the KOP, μ and δ-opioid receptors (MOP and DOP respectively) and in a model of inflammatory pain. Functional activity of Dynorphin 1-17 and fragments (1-6, 1-7 and 1-9) were screened over a range of concentrations against forskolin stimulated human embryonic kidney 293 (HEK) cells stably transfected with one of KOP, MOP or DOP. The analgesic activity of dynorphin 1-7 in a unilateral model of inflammatory pain was subsequently tested. Rats received unilateral intraplantar injections of Freund's Complete Adjuvant to induce inflammation. After six days rats received either dynorphin 1-7, 1-17 or the selective KOP agonist U50488H and mechanical allodynia determined. Dynorphin 1-7 and 1-9 displayed the greatest activity across all receptor subtypes, while dynorphin 1-7, 1-9 and 1-17 displaying a potent activation of both KOP and DOP evidenced by cAMP inihibition. Administration of dynorphin 1-7 and U50488H, but not dynorphin 1-17 resulted in a significant increase in paw pressure threshold at an equimolar dose suggesting the small peptide dynorphin 1-7 mediates analgesia. These results show that dynorphin fragments produced in an inflamed tissue homogenate have changed activity at the opioid receptors and that dynorphin 1-7 mediates analgesia.
http://ift.tt/2iV3zcD
pH–value-controlled assembly of photoluminescent zinc coordination polymers in the mixed-ligand system
Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Kang Liu, Hanbin Hu, Jing Sun, Yiheng Zhang, Jishu Han, Lei Wang
Three novel coordination polymers, [Zn(sdi)2(NO3)(H2O)]·NO3 (1), [Zn(sdi)2(H2O)2]·2NO3 (2) and [Zn(sdi)0.5(H2C3O4)(H2O)] (3), (sdi = N,N′-sulfuryldiimidazole) have been synthesized and characterized by elemental analysis, IR spectroscopy, single crystal X-ray diffraction, powder X-ray diffraction and thermogravimetric analyses. These compounds have abundant structural chemistry ranging from zero-dimensional (0D) (1), one-dimensional (1D) (2), to three-dimensional (3D) (3) networks. Compound 1 displays a 0D structure which formed by [Zn(sdi)2]2 dimers. Compound 2 possesses 1D chain with closed loops. Notably, compound 3 exhibits a 3D (3,4)-connected net with a (63)(65·8) topology. Interestingly, compounds 1–3 were obtained under similar reaction conditions and the structural diversity of these coordination polymers illustrate the remarkable effect of pH on the self-assembling process. Moreover, the fluorescent properties of these compounds have been investigated.
Graphical abstract
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Eradication ofPseudomonas aeruginosacells by cathodic electrochemical currents delivered with graphite electrodes
Publication date: Available online 31 December 2016
Source:Acta Biomaterialia
Author(s): Tagbo H.R. Niepa, Hao Wang, Jeremy L. Gilbert, Dacheng Ren
Antibiotic resistance is a major challenge to the treatment of bacterial infections associated with medical devices and biomaterials. One important intrinsic mechanism of such resistance is the formation of persister cells that are phenotypic variants of microorganisms and highly tolerant to antibiotics. Recently, we reported a new approach to eradicating persister cells of Pseudomonas aeruginosa using low-level direct electrochemical current (DC) and synergy with the antibiotic tobramycin. To further understand the underlying mechanism and develop this technology toward possible medical applications, we investigated the electricidal activities of non-metallic biomaterial on persister and biofilm cells of P. aeruginosa using graphite-based TGON™ 805 electrodes. We employed both single and dual chamber systems to compare electrochemical factors of TGON and stainless steel 304 electrodes. The results revealed that TGON-based treatments were highly effective against P. aeruginosa persister cells. In the single chamber system, complete eradication of planktonic persister cells (corresponding to a 7-log killing) was achieved with 70 μA/cm2 DC using TGON electrodes within 40 min of treatment, while cell viability in biofilms was reduced by 2 logs within 1 h. The killing effects were dose and time dependent with higher current densities requiring less time. Moreover, reduction reactions were found more effective than oxidation reactions, confirming that metal cations are not indispensable, although they may facilitate cell killing. The findings of this study can help develop electrochemical technologies to eradicate persister and biofilm cells for more effective treatment of medical device and biomaterial related infections.[Significance Statement]Infections associated with medical devices and biomaterials present a major challenge due to high-level tolerance of microbes to conventional antibiotics. It is well established that such tolerance is due to the formation of dormant persister cells and multicellular structures known as biofilms. Recent studies have demonstrated electrochemical treatment as a promising alternative to eradicate bacterial infections, since the killing mechanism is independent of the growth phase of bacterial cells, but relies on the various electrochemical species interplaying during the treatment. The current study investigated major bactericidal properties of the electrochemical currents mediated via TGON, a carbon-based electrode material. Up to total eradication of Pseudomonas aeruginosa persister cells was achieved. The new knowledge of electrochemical properties and the bioactivity of TGON may help develop new methods/devices to eradicate bacterial infections by delivering safe levels of electrochemical currents.
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Neonatal Sacrococcygeal Neuroblastoma Mimicking a Teratoma
We reported the first case of a congenital intrapelvic presacral neuroblastoma in Puerto Rico managed in the early neonatal period. The preoperative diagnosis was a sacrococcygeal teratoma Altman stage IV classification. This case confirms the importance of a comprehensive physical examination and observation of low-risk newborn infants with a history of adequate prenatal care and an unremarkable fetal ultrasonogram during pregnancy.
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Mixed Botryoid and Spindle Cell Bladder Rhabdomyosarcoma: An Outstanding Pediatric Case
We report a case of a 3-year-old North African child, initially assessed for nonspecific urinary symptoms such as haematuria and burning urination. The ultrasound evaluation showed a vegetating mass occupying the lumen with weak vascular signs at the Colour-Doppler evaluation. An explorative cystoscopy was performed and it revealed a nonbleeding lesion, white in colour, pedunculated, projecting into the lumen, and associated with a brown satellite formation. Histological examination showed a mixed Botryoid and Spindle Cell Rhabdomyosarcoma. This mixed histology has not been described before and no statistical data are reported in literature so far. Despite the Embryonal Rhabdomyosarcoma variant being the most common, the association characterized by two histological Rhabdomyosarcoma subtypes such as Botryoid and Spindle Cell is rarely observed and it is important to get an accurate histological diagnosis in order to immediately start the correct treatment protocol.
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IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis
Publication date: Available online 31 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Andrew Johnston, Xianying Xing, Liza Wolterink, Drew H. Barnes, ZhiQiang Yin, Laura Reingold, J. Michelle Kahlenberg, Paul W. Harms, Johann E. Gudjonsson
BackgroundGeneralized pustular psoriasis (GPP) is a rare, debilitating, and often life-threatening inflammatory disease characterized by episodic infiltration of neutrophils into the skin, pustule development, and systemic inflammation, which can manifest in the presence or absence of chronic plaque psoriasis (PV). Current treatments are unsatisfactory warranting a better understanding of GPP pathogenesis.ObjectiveTo understand better the disease mechanism of GPP to allow improved targeted therapies.MethodsWe performed a gene expression study on formalin-fixed paraffin-embedded GPP (n=28) and PV (n=12) lesional biopsies and healthy control (n=20) skin. Differential gene expression was analyzed using gene ontology and enrichment analysis. Gene expression was validated with qRT-PCR and immunohistochemistry, and a potential disease mechanism investigated using primary human cell culture.ResultsCompared with healthy skin, GPP lesions yielded 479 and PV 854 differentially expressed genes respectively, with 184 upregulated in both diseases. We detected significant contributions of IL-17A, TNF, IL-1, IL-36 and interferons in both diseases; although GPP lesions furnished higher IL-1 and IL-36 and lower IL-17A and interferon-γ mRNA expression than PV. We detected prominent IL-36 expression by keratinocytes proximal to neutrophilic pustules and show that both neutrophils and neutrophil proteases activate IL-36. Suggesting another mechanism regulating IL-36 activity, the protease inhibitors serpin A1 and A3, which inhibit elastase and cathepsin G respectively, were upregulated in both diseases and inhibited activation of IL-36.ConclusionsOur data indicate sustained activation of IL-1 and IL-36 in GPP, inducing neutrophil chemokine expression, infiltration and pustule formation, suggesting that the IL-1/IL-36 inflammatory axis is a potent driver of disease pathology in GPP.
Graphical abstract
Teaser
Current treatments for generalized pustular psoriasis are unsatisfactory. We applied recently-developed techniques for transcriptomic analysis of archived FFPE biopsies revealing pro-inflammatory IL-1, IL-17, TNF and IL-36 activity, which provides a rationale for biologic targeting of these cytokines.http://ift.tt/2hGzMTr
Bcl-2 Inhibitors Reduce Steroid-insensitive Airway Inflammation
Source:Journal of Allergy and Clinical Immunology
Author(s): Bao-ping Tian, Li-xia Xia, Zheng-qiang Bao, Hao Zhang, Zhi-wei Xu, Yuan-yuan Mao, Chao Cao, Luan-qing Che, Jin-kai Liu, Wen Li, Zhi-hua Chen, Songmin Ying, Hua-hao Shen
BackgroundAsthmatic inflammation is dominated either by eosinophil and/or neutrophil accumulation in airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, while neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies.ObjectiveWe thought to explore the underlying mechanisms of airway inflammation persistence as well as corticosteroid resistance, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma.MethodsMouse models of either eosinophils-dominated or neutrophils-dominated airway inflammation were used in this study to test corticosteroid sensitivity in vivo and in vitro. We also used vav-Bcl-2 transgenic mice to confirm the importance of granulocytes apoptosis in the clearance of airway inflammation. Finally, Bcl-2 inhibitors ABT-737 or ABT-199 –were tested for their therapeutic effects against eosinophilic or neutrophilic airway inflammation and airway hyperresponsiveness.ResultsOverexpression of Bcl-2 protein was found to be responsible for persistence of granulocytes in bronchoalveolar lavage fluid following allergic challenge. This was important as allergen-induced airway inflammation aggravated and persisted in vav-Bcl-2 transgenic mice, where nucleated hematopoietic cells were over-expressed with Bcl-2 and resistant to apoptosis. Bcl-2 inhibitors, ABT-737 or ABT-199, play efficient roles in alleviation of either eosinophilic or corticosteroid resistant-neutrophilic airway inflammation, by inducing apoptosis of immune cell, such as eosinophils, neutrophils, Th2, Th17 and dendritic cells. Moreover, these inhibitors were found to be more efficient than steroid to induce granulocytes apoptosis ex vivo from severe asthma patients.ConclusionApoptosis of inflammatory cells is essential for the clearance of allergen-induced airway inflammation. Bcl-2 inhibitors ABT-737 or ABT-199 may be promising drugs for the treatment against airway inflammation, especially for corticosteroid-insensitive neutrophilic airway inflammation.
Teaser
Bcl-2 inhibitors may be promising drugs for the treatment against corticosteroid-insensitive neutrophilic airway inflammation.http://ift.tt/2hGolv0
Adaptation is mandatory for intensity modulated proton therapy of advanced lung cancer to ensure target coverage
Source:Radiotherapy and Oncology
Author(s): Lone Hoffmann, Markus Alber, Maria Fuglsang Jensen, Marianne Ingerslev Holt, Ditte Sloth Møller
Background and purposeLarge anatomical changes during radiotherapy are seen for a large proportion of lung cancer patients. We investigate the applicability of a decision support protocol for photon therapy in a proton therapy setting.Material and methodsTwenty-three consecutive NSCLC patients treated with adaptive photon therapy were retrospectively planned using IMPT. The adaptive protocol was based on geometrical measures of target positioning and large anatomical changes as shown on daily CBCT scans. Two surveillance CT-scans were acquired during the treatment course. The consequences of anatomical changes were evaluated by recalculating the proton plans on the surveillance scans. The CTV receiving 95% of the prescribed dose was analysed.ResultsFourteen (61%) patients needed adaptations when treated with protons, given that 95% of the CTV must be covered by 95% of the dose. In comparison, no patients needed adaptation when treated with photons using this criterion. The adaptive protocol was found to identify patients with large target under-dosage for proton therapy (six patients). Additionally, target under-dosage was observed for eight patients with non-rigid changes up to 15mm in the positioning of the bones.ConclusionsProton therapy for loco-regional lung cancer demands daily imaging and therapy adaptation for a high proportion of patients.
http://ift.tt/2ivROZH
The fate of the free flap pedicle after free tissue transfer to the head and neck area
Source:Oral Oncology, Volume 65
Author(s): Maarten L.V. Van Genechten, Martin D. Batstone
ObjectivesLittle is understood about what happens to the vascular pedicle following free tissue transfer in the head and neck region. The viability of a free flap completely depends on the vascular supply by its vascular pedicle until neovascularization occurs from surrounding tissues. The aim of this study is to find out how long a vascular pedicle lasts following free tissue transfer in the head and neck region.Materials and methodsPatients were recruited from the Maxillofacial Unit at the Royal Brisbane & Women's Hospital. A Doppler ultrasound was used to map the vascular pedicle immediately postoperatively, at 2weeks, 6weeks, 3months and 6months.ResultsFifty-seven consecutive free flaps underwent colour Doppler ultrasonography at the timepoints described demonstrating the status of the vascular pedicle. All the patients underwent reconstructive head and neck surgery with a wide variety of soft tissue and composite free flaps.ConclusionThis study is the first to document the fate of the vascular pedicle over a long time period for a wide variety of head and neck free flaps. This information is important when undertaking revision surgery to the free flap, or planning the vascular supply for a second or third free flap to the head and neck region.
http://ift.tt/2ivUR4h
Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma
Source:Oral Oncology, Volume 65
Author(s): Aswini R. Krishnan, Avinaash Korrapati, Angela E. Zou, Yuanhao Qu, Xiao Qi Wang, Joseph A. Califano, Jessica Wang-Rodriguez, Scott M. Lippman, Melbourne F. Hovell, Weg M. Ongkeko
ObjectiveSmoking remains a primary etiological factor in head and neck squamous cell carcinoma (HNSCC). Given that non-coding RNAs (ncRNAs), including PIWI-interacting RNAs (piRNAs), have emerged as mediators of initiation and progression in head and neck malignancies, we undertook a global study of piRNA expression patterns in smoking-associated HNSCC.Materials and methodsUsing RNA-sequencing data from 256 current smoker and lifelong nonsmoker samples in The Cancer Genome Atlas (TCGA), we analyzed the differential expression patterns of 27,127 piRNAs across patient cohorts stratified by tobacco use, with HPV16 status and tumor status taken into account. We correlated their expression to clinical characteristics and to smoking-induced alterations of PIWI proteins, the functional counterparts of piRNAs. Finally, we correlated our identified piRNAs and PIWI proteins to known chromosomal aberrations in HNSCC to understand their wider-ranging genomic effects.Results and conclusionOur analyses implicated a 13-member piRNA panel in smoking-related HNSCC, among which NONHSAT123636 and NONHSAT113708 associated with tumor stage, NONHSAT067200 with patient survival, and NONHSAT081250 with smoking-altered PIWIL1 protein expression. 6 piRNAs as well as PIWIL1 correlated with genomic alterations common to HNSCC, including TP53 mutation, TP53-3p co-occurrence, and 3q26, 8q24, and 11q13 amplification. Collectively, our findings provide novel insights into the etiology-specific piRNA landscape of smoking-induced HNSCC.
http://ift.tt/2iSTaKx
QuEChERS extraction for multi-residue analysis of PCBs, PAHs, PBDEs and PCDD/Fs in biological samples
Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Pierre-Luc Cloutier, Frédérik Fortin, Paule Emilie Groleau, Pauline Brousseau, Michel Fournier, Mélanie Desrosiers
In this study, a fast and rugged method is presented for the analysis of PCBs, PAHs, PBDEs and PCDD/Fs in biological tissues using a simple Quick, Easy, Cheap, Efficient, Rugged and Safe (QuEChERS) extraction and a clean-up by Gel Permeation Chromatography (GPC) and silica Solid Phase Extraction (SPE). Development was performed on blue mussels (Mytilus edulis) and Atlantic salmon (Salmo salar) for evaluation of two ranges of lipid and water content of biological tissues. Statistical validation was performed with Atlantic salmon samples. Forty-five PAHs were analyzed including the priority list of the US EPA and the European Union with 41 PCBs, 24 PBDEs and 17 PCDD/Fs. Instrumental analyses were performed on Gas Chromatography – High Resolution Mass Spectrometry (GC-HRMS). Accuracy was evaluated for PCBs and PCDD/Fs with a certified reference material furnished by the National Research Council Canada (NRCC) and also compared with results obtained by the conventional Soxhlet extraction. Statistical validation showed recoveries for PCBs, PAHs, PBDEs and PCDD/Fs close to 100% with average Relative Standard Deviation (RSD) lower than 10% and internal standard recoveries in the range of 70% with average RSD ranging from 5–15%. Average calculated Method Detection Limits (MDLs) were lower than 0.05μg/Kg for PCBs, 0.2μg/Kg for PAHs and PBDEs and 1ng/Kg for PCDD/Fs. The method is a faster and cheaper alternative to the time-consuming conventional method that has been used in most environmental laboratories.
Graphical abstract
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Shared orthographic neuronal representations for spelling and reading
Source:NeuroImage, Volume 147
Author(s): Jeremy J. Purcell, Xiong Jiang, Guinevere F. Eden
A central question in the study of the neural basis of written language is whether reading and spelling utilize shared orthographic representations. While recent studies employing fMRI to test this question report that the left inferior frontal gyrus (IFG) and ventral occipitotemporal cortex (vOTC) are active during both spelling and reading in the same subjects (Purcell et al., 2011a; Rapp and Lipka, 2011), the spatial resolution of fMRI limits the interpretation of these findings. Specifically, it is unknown if the neurons which encode orthography for reading are also involved in spelling of the same words. Here we address this question by employing an event-related functional magnetic resonance imaging-adaptation (fMRI-A) paradigm designed to examine shared orthographic representations across spelling and reading. First, we identified areas that independently showed adaptation to reading, and adaptation to spelling. Then we identified spatial convergence for these two separate maps via a conjunction analysis. Consistent with previous studies (Purcell et al., 2011a; Rapp and Lipka, 2011), this analysis revealed the left dorsal IFG, vOTC and supplementary motor area. To further validate these observations, we then interrogated these regions using an across-task adaptation technique, and found adaptation across reading and spelling in the left dorsal IFG (BA 44/9). Our final analysis focused specifically on the Visual Word Form Area (VWFA) in the vOTC, whose variability in location among subjects requires the use of subject-specific identification mechanisms (Glezer and Riesenhuber, 2013). Using a functional localizer for reading, we defined the VWFA in each subject, and found adaptation effects for both within the spelling and reading conditions, respectively, as well as across spelling and reading. Because none of these effects were observed during a phonological/semantic control condition, we conclude that the left dorsal IFG and VWFA are involved in accessing the same orthography-specific representations for spelling and reading.
http://ift.tt/2iDlQIg
The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus
Source:Clinical Immunology
Author(s): Robert J. Ragotte, Anita Dhanrajani, Julian Pleydell-Pearce, Kate L. Del Bel, Maja Tarailo-Graovac, Clara van Karnebeek, Jefferson Terry, Christof Senger, Margaret L. McKinnon, Michael Seear, Julie S. Prendiville, Lori B. Tucker, Kristin Houghton, David A. Cabral, Jaime Guzman, Ross E. Petty, Kelly L. Brown, Jenny Tekano, John Wu, Kimberly A. Morishita, Stuart E. Turvey
ObjectivesClinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life.Methods and resultsBy harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosis (SLE).ConclusionsThis case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.
http://ift.tt/2iDd2Sx
The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus
Source:Clinical Immunology
Author(s): Robert J. Ragotte, Anita Dhanrajani, Julian Pleydell-Pearce, Kate L. Del Bel, Maja Tarailo-Graovac, Clara van Karnebeek, Jefferson Terry, Christof Senger, Margaret L. McKinnon, Michael Seear, Julie S. Prendiville, Lori B. Tucker, Kristin Houghton, David A. Cabral, Jaime Guzman, Ross E. Petty, Kelly L. Brown, Jenny Tekano, John Wu, Kimberly A. Morishita, Stuart E. Turvey
ObjectivesClinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life.Methods and resultsBy harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosis (SLE).ConclusionsThis case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.
http://ift.tt/2iDd2Sx
Effect of full helmet systems on human head responses under blast loading
Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): M. Rodríguez-Millán, L.B Tan, K.M. Tse, H.P. Lee, M.H Miguélez
This paper focuses on helmet design for head protection under blast threats. It is presented a numerical investigation of the head response accruing to blast loads on helmet protective systems. Various combinations of the helmet, visor and mandible guard were numerically analyzed for a given mass of TNT at a distance to the target representing an anti-vehicle buried mine threat. Limited published articles on the subject are available in the scientific literature. In this paper, a 3D head–helmet numerical model for blast analyses is developed in the finite element code ABAQUS/Explicit. The results showed that individual protective systems are not effective enough to mitigate the damage caused by blast loading. The complete protective equipment reduces the pressures on the brain by up to 5 times and ensures that no fracture in the skull appears. This numerical study aims to provide helmet manufacturers and users with some insight in what possible brain injuries are to be expected in various blast scenarios so as to help in better diagnosis of unsuspected brain injury.
Graphical abstract
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Global Updates on the Future Directions of Neurotoxins and Fillers
http://ift.tt/2iD7g3p
Technical Considerations for Filler and Neuromodulator Refinements
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