PROTON PUMP INHIBITION AND CANCER THERAPEUTICS; A SPECIFIC TUMOR TARGETING OR IT IS A PHENOMENON SECONDARY TO A SYSTEMIC BUFFERING?

Publication date: Available online 11 January 2017
Source:Seminars in Cancer Biology
Author(s): Enrico Spugnini, Stefano Fais
One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu. Proton exchangers do not allow intracellular acidification through a continuous elimination of H+ either outside the cells or within the internal vacuoles. This article wants to comment a translational process through that led to the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed powerful chemosensitizers as well. In this process we achieved the clinical proof of concept that PPI may well be included in new anti-cancer strategies with a solid background and rationale.



http://ift.tt/2ifL2YD

Environmental carcinogenesis and pH homeostasis: not only a matter of dysregulated metabolism

Publication date: Available online 11 January 2017
Source:Seminars in Cancer Biology
Author(s): Kévin Hardonniere, Laurence Huc, Odile Sergent, Jørn A. Holme, Dominique Lagadic-Gossmann
According to the World Health Organization, around 20% of all cancers would be due to environmental factors. Among these factors, several chemicals are indeed well recognized carcinogens. The widespread contaminant benzo[a]pyrene (B[a]P), an often used model carcinogen of the polycyclic aromatic hydrocarbons' family, has been suggested to target most, if not all, cancer hallmarks described by Hanahan and Weinberg. It is classified as a group I carcinogen by the International Agency for Research on Cancer; however, the precise intracellular mechanisms underlying its carcinogenic properties remain yet to be thoroughly defined. Recently, the pH homeostasis, a well known regulator of carcinogenic processes, was suggested to be a key actor in both cell death and Warburg-like metabolic reprogramming induced upon B[a]P exposure. The present review will highlight those data with the aim of favoring research on the role of H⁺ dynamics in environmental carcinogenesis.



http://ift.tt/2ifztk5

Long term neurobehavioral symptoms and return to productivity in Operation Enduring Freedom/Operation Iraqi Freedom Veterans with and without traumatic brain injury

Publication date: Available online 11 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Marianne H. Mortera, Stacy A. Kinirons, Jessie Simantov, Heidi Klingbeil
ObjectivesTo describe Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans who underwent the Comprehensive Traumatic Brain Injury Evaluation (CTBIE), differences between the traumatic brain injury (TBI) and non- traumatic brain injury (non-TBI) subgroups, and factors associated with return to productivity (RTP).DesignRetrospective medical record review.SettingVeterans Affairs Medical Center, Polytrauma/TBI Network Site.ParticipantsMedical records of 236 OEF/OIF Veterans who underwent the CTBIE between 2009-2013.InterventionsNot applicable.Main Outcome MeasuresDemographic characteristics, injury history, clinical presentation, and factors associated with RTP.ResultsVeterans (n=236) were male (90.7%), White (45.3%) or Black (34.7%), with half of Hispanic origin, and a mean age of 33 years. The mean time since injury was approximately 4 years. Reported symptoms were high, with greater than 90% reporting anxiousness, irritability, sleep difficulty, forgetfulness, and headaches.TBI diagnosis was found in 163 (69%) Veterans. The TBI subgroup was younger (TBI 32.5 years versus non-TBI 34.9 years, p=0.02), reported a greater number of injuries (p= 0.000), and had significantly higher rates of half of the reported symptoms. Greatest differences were noted with forgetfulness (TBI 95.7% versus non-TBI 79.5%, p=0.000), poor concentration (TBI 90.2% versus non-TBI 76.7%, p=0.007), and headaches (TBI 93.9% versus non-TBI 83.6%, p=0.014).RTP was 60.6% for the total Veteran population. Factors associated with RTP were race (white) (OR=2.00; 95%CI:1.13-3.55, p=0.018), sensitivity to light (OR=2.58; 95%CI:1.17-5.66, p=0.018), and fatigue (OR=3.68; 95%CI:1.51-8.95, p=0.004). Veterans that did RTP wessre three times less likely to report depression (OR=0.323; 95%CI:0.12-.85, p=0.022).ConclusionsVeterans reported a substantial number of lingering symptoms, with a higher prevalence in Veterans with TBI. Veterans with reported depression were less likely to RTP. Future research should focus on the relationship between depression and non-RTP and the effectiveness of VA services.



http://ift.tt/2j9wIA6

Functional Electrical Stimulation for foot drop in Multiple Sclerosis: A Systematic Review and Meta-Analysis of the impact on gait speed

Publication date: Available online 11 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Linda Miller, Angus McFadyen, Anna C. Lord, Rebecca Hunter, Lorna Paul, Danny Rafferty, Roy Bowers, Paul Mattison
ObjectiveTo review the efficacy of functional electrical stimulation (FES) used for foot drop in people with multiple sclerosis (pwMS) on gait speed in short and long walking performance tests.Data sourcesFive databases (Cochrane Library, CINAHL, Embase, MEDLINE, Pubmed) and reference lists were searched.Study selectionStudies of both observational and experimental design where gait speed data in pwMS could be extracted were included.Data extractionData were independently extracted and recorded. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) tool.Data synthesisNineteen studies (described in 20 articles) recruiting 490 pwMS were identified and rated moderate or weak, with none gaining a strong rating. All studies rated weak for blinding. Initial and ongoing orthotic and therapeutic effects were assessed with regards to the impact of FES on gait speed in short and long walking tests. Meta-analyses of the short walk tests revealed a significant initial orthotic effect (t = 2.14, p = 0.016) with a mean increase in gait speed of 0.05 meters per second (m/s) and ongoing orthotic effect (t = 2.81, p = 0.003) with a mean increase of 0.08m/s. There were no initial or ongoing effect on gait speed in long walk tests and no therapeutic effect on gait speed in either short or long walk tests.ConclusionsFES used for foot drop has a positive initial and ongoing effect on gait speed in short walking tests. Further fully-powered randomized controlled trials comparing FES with alternative treatments are required.



http://ift.tt/2jlZsDz

Aquatic Exercise Therapy for People with Parkinson’s disease: a Randomized Controlled Trial

Publication date: Available online 12 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Louise M. Carroll, Daniele Volpe, Meg E. Morris, Jean Saunders, Amanda M. Clifford
ObjectiveTo evaluate the effects of aquatic exercise therapy on gait variability and disability compared to usual care for people with Parkinson's disease (PD).DesignSingle-blind randomized control trial (RCT).SettingA community based hydrotherapy pool in Ireland.ParticipantsTwenty one individuals with PD (Hoehn-Yahr Stages I-III).InterventionsParticipants were randomly assigned to either an aquatic exercise therapy group (45 minutes, twice a week for 6 weeks) or a control group that received usual care.Main Outcome Measure(s)The primary outcome measure was gait variability as measured using a Coda CX1 motion capture system. Secondary outcomes were quality of life measured on the Parkinson's Disease Questionnaire-39, freezing of gait and motor disability quantified by the Unified Parkinson Disease Rating Scale (UPDRS III). Feasibility was evaluated by measuring safety, adverse events and participant satisfaction.ResultsPeople in the aquatic therapy group and control group showed similar small improvements in gait variability. The aquatic therapy group showed greater improvements in disability than the control group (P<0.01). No differences between groups or over time were identified for freezing of gait or quality of life. Aquatic therapy sessions were safe and enjoyable with no adverse events.ConclusionsAquatic therapy appears feasible and safe for some people in the early stages of Parkinson's disease.



http://ift.tt/2j9LvLg

LN2, CD10, and Ezrin Do Not Distinguish Between Atypical Fibroxanthoma and Undifferentiated Pleomorphic Sarcoma or Predict Clinical Outcome.

BACKGROUND: Atypical fibroxanthoma (AFX) is a rare cutaneous spindled cell neoplasm. For both diagnostic and therapeutic purposes, it is important to distinguish AFX from other poorly differentiated tumors, including undifferentiated pleomorphic sarcoma (UPS). OBJECTIVE: The authors aimed to identify the clinical, histologic, and immunohistochemical expression of LN2, ezrin, and CD10 in AFX and UPS tumors. METHODS AND MATERIALS: The authors retrospectively examined the charts of patients with AFX and UPS treated with Mohs micrographic surgery (MMS) at 2 academic institutions. Patient demographics, tumor characteristics, and clinical course data were collected. Immunohistochemical stains were performed on primary and recurrent AFX and UPS tumors with monoclonal antibodies against the B-cell marker LN2 (CD74), CD10, and ezrin. RESULTS: In the series of 169 patients with AFX included in this study, local recurrence was rare at 3%. In contrast, the seven patients with UPS had an aggressive clinical course with 1 local recurrence and 2 distant metastases. Immunohistochemistry staining for ezrin, LN2, and CD10 were similar in AFX and UPS tumors. CONCLUSION: AFX can be treated with MMS with rare instances of recurrence. Undifferentiated pleomorphic sarcoma has a more aggressive clinical course with increased risk for recurrence and metastasis. Staining with ezrin, LN2, and CD10 did not differentiate AFX or UPS tumors. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2iJi7sl

The Effect of Waxing Versus Shaving on the Efficacy of Laser Hair Removal.

BACKGROUND: Excessive hair is undesirable and represents both a social and emotional burden, especially among females. Laser hair removal (LHR) has gained popularity in the past 2 decades. It is a common practice to instruct patients not to pluck or wax their hair before undergoing LHR; only shaving is allowed to improve the efficacy of the LHR. OBJECTIVE: To compare the percentage of hair reduction in preshaved versus prewax epilated axillae after LHR in healthy adult Saudi females. METHODS AND MATERIALS: This study is a quantitative experimental pilot clinical trial. Twenty female volunteers were enrolled into this study; all underwent 3 laser sessions using a long-pulsed alexandrite laser. Their left axilla was prewaxed and right axilla was preshaved immediately before laser treatment. Hair was counted manually before and 6 months after the third laser session. RESULTS: The right and left axillae both showed significant hair reduction, between the first session and the hair count 6 months after the third laser session. However, there was no statistically significant difference between these 2 means (p = .44). CONCLUSION: There is no statistical difference in hair reduction after LHR whether the area is preshaved or prewax epilated. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2jGwvWm

Batten Stitch: A Tissue-Sparing Technique for Correction of an Inverted Dog-Ear.

No abstract available

http://ift.tt/2iJoAmM

Comparison of the American Joint Committee on Cancer Seventh Edition and Brigham and Women's Hospital Cutaneous Squamous Cell Carcinoma Tumor Staging in Immunosuppressed Patients.

BACKGROUND: The American Joint Committee on Cancer 7th edition (AJCC-7) and Brigham and Women's Hospital (BWH) staging criteria for cutaneous squamous cell carcinoma (cSCC) have not been validated in immunosuppressed patients. OBJECTIVE: To compare the AJCC-7 and BWH staging systems for cSCCs in immunosuppressed patients. METHODS AND MATERIALS: A single-institution retrospective cohort study of cSCCs in immunosuppressed patients. Risks of local recurrence (LR), nodal metastasis (NM), in-transit metastasis, and any poor outcome (PO) were compared among AJCC-7 and BWH tumor T stages. RESULTS: One hundred six patients had 412 primary invasive cSCCs. Eighty-five percent were AJCC-7 T1, and 15% T2. Risks of NM and PO for AJCC-7 T1 versus T2 were 0.9% versus 5% and 12.8% versus 23.3%, respectively, p

http://ift.tt/2jGz1fb

Reconstruction of a Postoperative Mohs Defect of the Upper Cutaneous and Vermilion Lip Involving Cupid's Bow.

No abstract available

http://ift.tt/2iJo9cj

The emotive nature of conflict monitoring in the medial prefrontal cortex

Publication date: Available online 11 January 2017
Source:International Journal of Psychophysiology
Author(s): Blair Saunders, Hause Lin, Marina Milyavskaya, Michael Inzlicht
The detection of conflict between incompatible impulses, thoughts, and actions is a ubiquitous source of motivation across theories of goal-directed action. In this overview, we explore the hypothesis that conflict is emotive, integrating perspectives from affective science and cognitive neuroscience. Initially, we review evidence suggesting that the mental and biological processes that monitor for information processing conflict—particularly those generated by the anterior midcingulate cortex—track the affective significance of conflict and use this signal to motivate increased control. In this sense, variation in control resembles a form of affect regulation in which control implementation counteracts the aversive experience of conflict. We also highlight emerging evidence proposing that states and dispositions associated with acceptance facilitate control by tuning individuals to the emotive nature of conflict, before proposing avenues for future research, including investigating the role of affect in reinforcement learning and decision making.



http://ift.tt/2j3mwat

A current perspective on the oncopreventive and oncolytic properties of selective serotonin reuptake inhibitors

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Daniel P. Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers. In the current work, we discuss how the secondary mechanisms of action associated with these drugs mediate their oncolytic effect. In particular, sertraline limits tumor growth by abrogating the PI3K/akt signaling pathway, a growth pathway shown to be constitutively active in multiple cancers. Fluoxetine has been shown to activate the AMPA-type glutamate receptor, induce massive calcium influx and mitochondrial calcium overload and induce caspase-9-dependent apoptosis. This receptor being highly overexpressed in cancer stem cells may explain why SSRIs lower the risk of multiple types of cancer. Fluoxetine has also been shown to inhibit multidrug resistance pumps, increasing the efficacy of several standard chemotherapies. Given the vast potential of SSRIs in treating cancer, these drugs should be more heavily used not only in treating cancer-related depression, but in combating cancer and increasing the efficacy of standard of care chemotherapies.



http://ift.tt/2iJ7JAL

Editorial board

Publication date: March 2017
Source:Biomaterials, Volume 120





http://ift.tt/2iceqyY

Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Eunee Koh, Eun Jung Lee, Gi-Hoon Nam, Yeonsun Hong, Eunji Cho, Yoosoo Yang, In-San Kim
CD47, a "don't eat me" signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein α (SIRPα) on phagocytic cells. By engaging SIRPα, CD47 limits the ability of macrophages to engulf tumor cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. Disruption of CD47-SIRPα interaction by SIRPα-exosomes leads to an increase in cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Moreover, SIRPα-exosomes therapy promotes an intensive T cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. Note that very small amount of exosomal SIRPα proteins could effectively lead to phagocytic elimination of tumor cells both in vitro and in vivo. Our results suggest that superlative exosome-based platform has broad potential to maximize the therapeutic efficacy of membrane-associated protein therapeutics.



http://ift.tt/2j0urFe

Engineered gadolinium-doped carbon dots for magnetic resonance imaging-guided radiotherapy of tumors

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Fengyi Du, Lirong Zhang, Li Zhang, Miaomiao Zhang, Aihua Gong, Youwen Tan, Jiawen Miao, Yuhua Gong, Mingzhong Sun, Huixiang Ju, Chaoyang Wu, Shenqiang Zou
The effectiveness of radiotherapy can decrease due to inaccurate positioning of machinery and inherent radioresistance of tumors. To address this issue, we present a novel theranostic nanoplatform based on gadolinium-doped carbon dots (Gd-doped CDs) designed specifically for magnetic resonance imaging (MRI)-guided radiotherapy of tumors. The Gd-doped CDs (∼18 nm) with dispersibility in water and stable photoluminescence were synthesized via a one-step hydrothermal approach. After tail vein injection of the Gd-doped CDs, they exhibited a relatively long circulation time (∼6 h), enabled efficient passive tumor targeting. Gd-doped CDs accumulate in the kidney and could be cleared out of the body from bladder. Importantly, they exhibited favorable biocompatibility with excellent performance in longitudinal relaxivity rate (r1) of 6.45 mM⁻¹S⁻¹ and radiosensitization enhancements. These results show that Gd-doped CDs are excellent T1 contrast agents and radiosensitizers, possessing great promise for MRI-guided radiotherapy of tumors.



http://ift.tt/2izxOlE

Central nervous system vasculitis in adults: An update

Publication date: Available online 11 January 2017
Source:Autoimmunity Reviews
Author(s): Lívia Almeida Dutra, Alexandre Wagner Silva de Souza, Gabriela Grinberg-Dias, Orlando Graziani Povoas Barsottini, Simone Appenzeller
Primary central nervous system vasculitis (PCNSV) is a challenging diagnosis due to broad clinical manifestations and variable specificity and sensitivity of laboratory and imaging diagnostic tools. Differential diagnosis include reversible cerebral vasoconstriction syndrome (RCVS), secondary vasculitis of the CNS and other noninflammatory vasculopathies. Brain biopsy is essential for definitive diagnosis and to exclude mimickers. Recent data show data large-vessel PCNSV present worse prognosis when compared to small-vessel PCNSV. Herein we review diagnosis and management of PCNSV, secondary vasculitis of CNS and RCVS.



http://ift.tt/2if881y

Syntheses, structures, luminescent and photocatalytic properties of two Zn(II) coordination polymers assembled with mixed bridging N-donors and 2-(4-carboxyphenyl)-4,5-imidazole dicarboxylic acid ligand

Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Gang Yuan, Kui-Zhan Shao, Xiang-Rong Hao, Pei-Ying Zhan, Zhong-Min Su
Two new Zn(II) coordination polymers with the formulas of {[Zn3(HCpIDC)2(4,4′-bipy)(H2O)]·4H2O}n (1) and {[Zn2(CpIDC)(BIMB)]·H2O}n (2) [H4CpIDC = 2-(4-carboxyphenyl)-4,5-imidazole dicarboxylic acid, 4,4′-bipy = 4,4′-bipyridine, and BIMB = 1,4-bis(1-imidazolyl)benzene] have been successfully synthesized. Both complexes 1 and 2 feature 3D frameworks in which the IDC groups of HCpIDC^3- and CpIDC⁴⁻ ligands link metal nodes leading to infinite 21 helical chains. The HCpIDC^3- and CpIDC⁴⁻ anions exhibit two coordination modes (μ4–kN,O: kN′,O′: kO″,O‴: kO″″ and μ5–kN,O: kN′,O′: kO″,O‴: kO″″: kO) in different coordination environments. Further structural analyses show that 1 and 2 are topologically bimodal 4-connected net and trinodal (3,4,6)-connected net, respectively. As is expected, two complexes with good thermal stability displayed strong fluorescence emissions in the solid state at the room temperature. Moreover, complex 1 has some extent of photocatalytic activities for RhB.

Graphical abstract

http://ift.tt/2iIUShV

Histidine-functionalized carbon-based dot-Zinc(II) nanoparticles as a novel stabilizer for Pickering emulsion synthesis of polystyrene microspheres

Publication date: 1 May 2017
Source:Journal of Colloid and Interface Science, Volume 493
Author(s): Li Ruiyi, Li Zaijun, Liu Junkang
Carbon-based dots (CDs) are nanoparticles with size-dependent optical and electronic properties that have been widely applied in energy-efficient displays and lighting, photovoltaic devices and biological markers. However, conventional CDs are difficult to be used as ideal stabilizer for Pickering emulsion due to its irrational amphiphilic structure. The study designed and synthesized a new histidine-functionalized carbon dot-Zinc(II) nanoparticles, which is termed as His-CD-Zn. The His-CD was made via one-step hydrothermal treatment of histidine and maleic acid. The His-CD reacted with Zn²⁺ to form His-CD-Zn. The as-prepared His-CD-Zn was used as a solid particle surfactant for stabilizing styrene-in-water emulsion. The Pickering emulsion exhibits high stability and sensitive pH-switching behaviour. The introduction of S2O8²⁻ triggers the emulsion polymerization of styrene. The resulted polystyrene microsphere was well coated with His-CDs on the surface. It was successfully used as an ideal adsorbent for removal of heavy metallic ions from water with high adsorption capacity. The study also provides a prominent approach for fabrication of amphiphilic carbon-based nanoparticles for stabilizing Pickering emulsion.

Graphical abstract

http://ift.tt/2iIUIax

Liquid-liquid extraction studies on Zn(II) and Cd(II) using phosphonium ionic liquid (Cyphos IL 104) and recovery of zinc from zinc plating mud

Publication date: 28 April 2017
Source:Separation and Purification Technology, Volume 177
Author(s): Harshit Mahandra, Rashmi Singh, Bina Gupta
The present study describes partition behavior of Zn(II) and Cd(II) from acidic chloride medium using Cyphos IL 104 [trihexyl(tetradecyl)phosphonium bis 2,4,4-(trimethylpentyl)phosphinate] diluted in toluene. Factors affecting the extraction such as concentration of extractant and H⁺, nature of diluent, equilibration time and temperature have been evaluated. Loading and regeneration capacity along with the stability of extractant have also been assessed. The data obtained have been used to determine the stoichiometry of the extracted complex that was found to be 1:2 i.e., two moles of extractant per mole of Zn(II)/Cd(II). Effect of temperature on distribution suggested the process to be exothermic and spontaneous with ΔG° values of −39.63±4.27kJ/mol and −65.91±0.4kJ/mol for zinc and cadmium, respectively. The extraction behavior of associated metal ions namely Cu(II), Ni(II), Co(II), Fe(II)/(III) and Mn(II) has been studied and conditions for their separation from zinc and cadmium have been optimized. Based on the extraction data a separation scheme was designed and applied to a synthetic multi element mixture for the recovery of zinc and cadmium. The potential of the extractant for the recovery of zinc from zinc plating mud is assessed.



http://ift.tt/2iIRVxM

Supramolecular architectures in luminescent Zn(II) and Cd(II) complexes containing imidazole derivatives: Crystal structures, vibrational and thermal properties, Hirshfeld surface analysis and electrostatic potentials

Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Alejandro Di Santo, Gustavo A. Echeverría, Oscar E. Piro, Hiram Pérez, Aida Ben Altabef, Diego M. Gil
Three novel zinc and cadmium complexes with 1-methylimidazole and 2-methylimidazole as ligands, mono-nuclear dichloro-bis(1-methylimidazole) zinc(II) and dibromo-bis(2-methylimidazole)cadmium(II) monohydrate complexes, and poly-nuclear bis(1-methylimidazole)-di-(μ2-bromo)cadmium(II) complex, namely, compounds 1–3, respectively, have been synthesized. The complexes were characterized by IR and Raman spectroscopies, thermal analysis and fluorescence. All the compounds exhibit interesting luminescent properties in solid state originated from intra-ligand (π→π*) transitions. Crystal structures of 1–3 were determined by single-crystal X-ray diffraction. Compound 1 crystallizes in P21/n space group, the Zn(II) ion lies at a crystal general position in a tetrahedral environment, and the mono-nuclear units are weakly bonded to one another by CH⋯Cl hydrogen bonds. Compound 2 crystallizes in Pnma space group, and mirror-related tetrahedral units around Cd(II) ion are H-bonded through a water molecule. Compound 3 crystallizes in P21/c space group, and the Cd(II) ion presents a centrosymmetric octahedral coordination. Neighboring and equatorial edge-sharing octahedra conform a polymeric arrangement that extends along the crystal a-axis. Weak hydrogen bonds are the major driving forces in the crystal packing of the three complexes. Hirshfeld surface analysis reveals a detailed scrutiny of intermolecular interactions experienced by each complex. The surfaces mapped over dnorm property highlight the X···H (X = Cl, Br) as the main intermolecular contacts for the three complexes, being also relevant the presence of O⋯H contacts for complex 2. The surfaces mapped over Shape index and curvedness properties for the two Cd complexes allow identify π ^… π stacking interactions which are absent in the Zn complex. 2D fingerprint plots have been used to quantify the relative contribution of the intermolecular contacts to crystal stability of compounds, showing the crucial importance of weak interactions in building different supramolecular architectures. Furthermore, molecular electrostatic potentials for visualizing and quantifying the attractive character of interactions were calculated.

Graphical abstract

http://ift.tt/2jGepUp

Microstructural, mechanical and corrosion characteristics of heat-treated Mg-1.2Zn-0.5Ca (wt%) alloy for use as resorbable bone fixation material

Publication date: May 2017
Source:Journal of the Mechanical Behavior of Biomedical Materials, Volume 69
Author(s): Hamdy Ibrahim, Andrew D. Klarner, Behrang Poorganji, David Dean, Alan A. Luo, Mohammad Elahinia
Mg-Zn-Ca alloys have grabbed most of the recent attention in research attempting to develop an Mg alloy for bone fixation devices due to their superior biocompatibility. However, early resorption and insufficient strength remain the main problems that hinder their use. Heat treatment has previously been thoroughly studied as a post-shaping process, especially after the fabrication of complex parts (e.g. porous structures) by 3D-printing or powder metallurgy. In this work, the effect of heat treatment on Mg-1.2Zn-0.5Ca (wt%) alloy's microstructural, mechanical and corrosion properties was studied. The surface morphology of samples was characterized by optical microscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and x-ray diffraction (XRD). Hardness, compression and tensile tests were conducted, while the in vitro corrosion characteristics of the prepared samples were determined using potentiodynamic polarization (PDP) and immersion tests. It was found that increasing the age hardening duration up to 2–5h increased the heat-treated Mg-1.2Zn-0.5Ca alloy's mechanical properties. Further increase in the age hardening duration did not result in further enhancement in mechanical properties. Similarly, heat treatment significantly altered the Mg-1.2Zn-0.5Ca alloy's in vitro corrosion properties. The corrosion rate of the Mg-1.2Zn-0.5Ca alloy after the heat treatment process was reduced to half of that for the as-cast alloy. XRD results showed the formation of biocompatible agglomerations of hydroxyapatite (HA) and magnesium hydroxide (Mg(OH)2) on the corroded surface of the heat-treated Mg-1.2Zn-0.5Ca alloy samples. The performed heat treatment process had a significant effect on both mechanical and corrosion properties of the prepared Mg-1.2Zn-0.5Ca alloy. The age hardening duration which caused the greatest increase in mechanical and the most slowed corrosion rate for Mg-1.2Zn-0.5Ca alloy material was between 2 and 5h.

Graphical abstract

http://ift.tt/2jGi1pu

Lead(II) extraction from aqueous solutions by pyridine extractants

Publication date: 28 April 2017
Source:Separation and Purification Technology, Volume 177
Author(s): Aleksandra Wojciechowska, Karolina Wieszczycka, Irmina Wojciechowska, Andrzej Olszanowski
In this work, the Pb(II) extraction from chloride and chloride/nitrate solution with novel hydrophobic extractants: 1-(3-pyridyl)undecan-1-one oxime and its pyridinium salts (3-[1-(hydroxyimine)undecyl]-1-propylpyridinium bromide and 3-[1-(hydroxyimine)undecyl]-1-propylpyridinium chloride) was discussed. The extraction efficiency strongly depended on chloride and extractant concentration, as well as the extractant structure. The conducted calculations indicated that lead(II) was extracted as PbCl3⁻ and PbCl4²⁻ without the mineral acid participation in the complex structure. The most efficient extractant of lead(II) from the concentrated chloride solutions was 3-[1-(hydroxyimine)undecyl]-1-propylpyridinium chloride. Laboratory-scale experiments indicated that 3-[1-(hydroxyimine)undecyl]-1-propylpyridinium chloride can be proposed as a selective Pb(II) extractant from the Pb-Zn-Cu and Pb-Zn-Fe mixtures.

Graphical abstract

http://ift.tt/2jG1v8L

Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes

Publication date: Available online 11 January 2017
Source:Brain Research Bulletin
Author(s): Peng Fang, Jie An, Xin Tan, Ling-Li Zeng, Hui Shen, Shijun Qiu, Dewen Hu
Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits.



http://ift.tt/2jlJFor

Intraoperative Hypotonie: Pathophysiologie und klinische Relevanz

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 16-27
DOI: 10.1055/s-0042-106052

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  CME online  |  Full text

http://ift.tt/2jxxnsc

Mechanische Reanimationshilfen innerklinisch genutzt

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 6-6
DOI: 10.1055/s-0042-121862

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if1VTa

Praxisbuch Beatmung

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 13-13
DOI: 10.1055/s-0042-103729

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieZKzc

Muss Metformin wegen der Gefahr der Laktatazidose 48 h vor OP abgesetzt werden?

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 66-69
DOI: 10.1055/s-0042-121635

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if4dSm

Eine Geschichte von Nervenblockaden und Ergebnissen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 6-7
DOI: 10.1055/s-0042-121865

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if1WGI

Infektionen: Molekulargenetischer Test statt Blutkulturen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 7-8
DOI: 10.1055/s-0042-121861

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieSLGv

Medikamente im Rettungsdienst

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 13-13
DOI: 10.1055/s-0042-109764

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if1W9Y

Stark überlastete Notaufnahmen und Rettungsdienste

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 12-12
DOI: 10.1055/s-0042-122174

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if6QDN

Schlaganfall: Anästhesie bei endovaskulärer Therapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 8-9
DOI: 10.1055/s-0042-121863

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieU2xe

Intraoperative Hypotonie: Therapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 45-54
DOI: 10.1055/s-0042-106074

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieVeAU

Personalisierte Antibiotikatherapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 10-10
DOI: 10.1055/s-0042-122171

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieSROu

Notfalldaten auf elektronischer Gesundheitskarte

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 10-11
DOI: 10.1055/s-0042-122172

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieTZS4

Weiterbildung Schmerzmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 13-13
DOI: 10.1055/s-0042-104432

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieXtE6

DIVI unterstützt Bundesmedikationsplan für mehr Patientensicherheit

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 10-10
DOI: 10.1055/s-0042-122175

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if4SU7

Intraoperative Hypotonie: Werden Sie Homöostatiker!

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 14-15
DOI: 10.1055/s-0042-121853

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2ieS4ga

Europaweite Studie zu Antibiotikaresistenz in Krankenhäusern

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 11-12
DOI: 10.1055/s-0042-122176

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2if3nVG

Intraoperative Hypotonie: Bedeutung und Monitoring in der klinischen Praxis

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 29-44
DOI: 10.1055/s-0042-107915

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  CME online  |  Full text

http://ift.tt/2ieXYOp

Reform der Notfallambulanzen bedroht Kliniken

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 12-12
DOI: 10.1055/s-0042-122173

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2jxv5sY

Notfälle im Rettungsdienst und in der Klinik: Gefäßzugänge bei Kindern

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 55-64
DOI: 10.1055/s-0042-104853

Der i. v. Gefäßzugang ist im Notfall zwingend notwendig, um Medikamente und/oder Flüssigkeiten zuführen zu können. Gerade aber bei kleinen Kindern oder Säuglingen ist die Punktion peripherer Venen mitunter schwierig und in einer zeitkritischen Situation häufig auch sehr stressbelastet. In solchen Situationen muss der Anwender Alternativen zur etablierten Venenpunktion kennen und Hilfsmittel beherrschen können. Im Rettungsdienst sind die intraossären (i. o.) Gefäßzugänge ohne Verzögerung anzuwenden, falls die peripheren Venenpunktion nicht zügig garantiert werden kann. Obwohl inzwischen zahlreiche transportable Ultraschallgeräte auf dem Markt sind, die auch im Rettungsdienst eingesetzt werden können, sind diese zurzeit noch nicht flächendeckend im außerklinischen Alltag verfügbar. Nach Stabilisierung der Vitalfunktionen und Transport ins Krankenhaus kann die Anlage eines periphervenösen (PVK) oder zentralvenösen Katheters (ZVK) erwogen werden, um einen bereits liegenden i. o. Zugang zu ersetzen. In dieser Übersicht sollen die gängigen Gefäßzugänge bei Kindern und Säuglingen besprochen, Alternativen diskutiert und zentrale Punktionstechniken beschrieben werden. Die Anwendung des Ultraschalls zu Gefäßpunktion nimmt einen immer größeren Stellenwert ein. Daher werden auch ultraschallbasierte Techniken vorgestellt. Die Sonografie kann die Anlage von peripheren Verweilkanülen und/oder zentralvenösen Kathetern beim pädiatrischen Patienten in innerklinischen Notfallsituationen oder bei schwierigen Venenverhältnissen erheblich erleichtern.Abstract: Vascular access is necessary for the administration of medication and for the collection of blood samples in an emergency. Peripheral venous access is occasionally difficult in infants and younger children, particularly during emergencies. However, reliable vascular access and prompt treatment are required in these circumstances to successfully treat the patient. During the rescue service, immediate establishment of the intraosseous vascular access is very important, in case peripheral vascular access cannot be established rapidly. Although numerous transportable ultrasound machines have been developed, which may be utilized during rescue service, relatively difficult access hampers their application during the rescue service. After stabilizing vital functions and transportation to the hospital, peripheral venous access or central venous access can be attempted again in order to replace intraosseous vascular access. In this manuscript, we first discuss intraosseous vascular access as an alternative vascular access technique, which can be attempted during the rescue service. Next, we introduce ultrasound-guided and other techniques for peripheral and central vascular access as potential alternatives for pediatric patients with difficult vascular access or in-hospital emergency situations. Timely decision-making and prompt utilization of alternative procedures to achieve unimpeded vascular access is essential for the treatment and survival of pediatric patients in an emergency.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2jxCCbj

Pssst … AINS-Secrets: Heute aus der Gynäkologie

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 70-74
DOI: 10.1055/s-0042-101637

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2jxv5cD

Medial Prefrontal Cortex-Pontine Nuclei Projections Modulate Suboptimal Cue-Induced Associative Motor Learning

Diverse and powerful mechanisms have evolved to enable organisms to modulate learning and memory under a variety of survival conditions. Cumulative evidence has shown that the prefrontal cortex (PFC) is closely involved in many higher-order cognitive functions. However, when and how the medial PFC (mPFC) modulates associative motor learning remains largely unknown. Here, we show that delay eyeblink conditioning (DEC) with the weak conditioned stimulus (wCS) but not the strong CS (sCS) elicited a significant increase in the levels of c-Fos expression in caudal mPFC. Both optogenetic inhibition and activation of the bilateral caudal mPFC, or its axon terminals at the pontine nucleus (PN) contralateral to the training eye, significantly impaired the acquisition, recent and remote retrieval of DEC with the wCS but not the sCS. However, direct optogenetic activation of the contralateral PN had no significant effect on the acquisition, recent and remote retrieval of DEC. These results are of great importance in understanding the elusive role of the mPFC and its projection to PN in subserving the associative motor learning under suboptimal learning cue.

http://ift.tt/2jxfKbO

Representational Similarity Mapping of Distributional Semantics in Left Inferior Frontal, Middle Temporal, and Motor Cortex

Language comprehension engages a distributed network of frontotemporal, parietal, and sensorimotor regions, but it is still unclear how meaning of words and their semantic relationships are represented and processed within these regions and to which degrees lexico-semantic representations differ between regions and semantic types. We used fMRI and representational similarity analysis to relate word-elicited multivoxel patterns to semantic similarity between action and object words. In left inferior frontal (BA 44-45-47), left posterior middle temporal and left precentral cortex, the similarity of brain response patterns reflected semantic similarity among action-related verbs, as well as across lexical classes-between action verbs and tool-related nouns and, to a degree, between action verbs and food nouns, but not between action verbs and animal nouns. Instead, posterior inferior temporal cortex exhibited a reverse response pattern, which reflected the semantic similarity among object-related nouns, but not action-related words. These results show that semantic similarity is encoded by a range of cortical areas, including multimodal association (e.g., anterior inferior frontal, posterior middle temporal) and modality-preferential (premotor) cortex and that the representational geometries in these regions are partly dependent on semantic type, with semantic similarity among action-related words crossing lexical-semantic category boundaries.

http://ift.tt/2j9Fdvs

Cognitive Control Structures in the Imitation Learning of Spatial Sequences and Rhythms--An fMRI Study

Imitation learning involves the acquisition of novel motor patterns based on action observation (AO). We used event-related functional magnetic resonance imaging to study the imitation learning of spatial sequences and rhythms during AO, motor imagery (MI), and imitative execution in nonmusicians and musicians. While both tasks engaged the fronto-parietal mirror circuit, the spatial sequence task recruited posterior parietal and dorsal premotor regions more strongly. The rhythm task involved an additional network for auditory working memory. This partial dissociation supports the concept of task-specific mirror mechanisms. Two regions of cognitive control were identified: 1) dorsolateral prefrontal cortex (DLPFC) was found to be more strongly activated during MI of novel spatial sequences, which allowed us to extend the 2-level model of imitation learning by Buccino et al. (2004) to spatial sequences. 2) During imitative execution of both tasks, the posterior medial frontal cortex was robustly activated, along with the DLPFC, which suggests that both regions are involved in the cognitive control of imitation learning. The musicians' selective behavioral advantage for rhythm imitation was reflected cortically in enhanced sensory-motor processing during AO and by the absence of practice-related activation differences in DLPFC during rhythm execution.

http://ift.tt/2jxfdqu

Altered Connectivity and Synapse Maturation of the Hippocampal Mossy Fiber Pathway in a Mouse Model of the Fragile X Syndrome

The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (fmr1 knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons. This phenotype is accompanied by increased activity of fmr1 KO animals in the marble burying task, detecting repetitive and obsessive compulsive behavior. Spine apparatus development and insertion of AMPA receptors is enhanced at postsynaptic thorny excrescences (TEs) in fmr1 KO mice. We report age-dependent alterations in TE morphology and in the underlying actin dynamics possibly linked to a dysregulation in profilin1 expression. TEs form detonator synapses guiding CA3 network activity. Thus, alterations described here are likely to contribute substantially to the impairment in hippocampal function and therefore to the pathogenesis of FXS.

http://ift.tt/2j9yS3g

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans

Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans.

http://ift.tt/2jxmTJv

Marijuana use disorder symptoms among recent onset marijuana users

Publication date: May 2017
Source:Addictive Behaviors, Volume 68
Author(s): Lisa Dierker, William Mendoza, Renee Goodwin, Arielle Selya, Jennifer Rose
BackgroundWith recreational marijuana having recently been legalized in a growing number of U.S. states, as well as the increasing support for its legalization among substantial segments of the American public, an understanding of the development of symptoms associated with marijuana use disorders will assist in guiding both education and policy.MethodsThis study examined the prevalence of marijuana use disorder symptoms among a nationally representative sample of recent onset marijuana users ages 12–21 drawn from the National Survey of Drug Use and Health (N=9697).ResultsThe most frequently reported marijuana use symptoms were "tolerance", and "time occupied acquiring, using or recovering from the effects of marijuana". Logistic regression analyses indicated an expected positive association between marijuana use frequency and each marijuana use disorder symptom. In many cases the positive trend was quadratic or cubic, with greater increases between rates among low and moderate frequency marijuana users (i.e. 1–10days per month) than among those using at a higher frequency (i.e. >10days per month). Relationships between marijuana use frequency and marijuana use symptoms were largely consistent according to age, gender and ethnicity.ConclusionsRecognizing symptoms of marijuana use disorders among adolescents and young adults using marijuana infrequently may assist in early identification and intervention for those at risk for problem use.



http://ift.tt/2jlgHF4

Medicinal versus recreational cannabis use: Patterns of cannabis use, alcohol use, and cued-arousal among veterans who screen positive for PTSD

Publication date: May 2017
Source:Addictive Behaviors, Volume 68
Author(s): Mallory Loflin, Mitch Earleywine, Marcel Bonn-Miller
IntroductionThe present study is the first to test whether veterans who use cannabis specifically for the purposes of self-medication for their reported PTSD symptoms differ from veterans who use cannabis medicinally for other reasons, or recreationally, in terms of patterns of cannabis use, use of alcohol, and reactivity to written combat trauma reminders.MethodsAssessment measures were administered online to a sample of veterans with a history of cannabis use (n=1971). Cued arousal was assessed pre/post via a prompt about combat experiences. Hypotheses were tested using a series of Bonferroni corrected one-way analyses of variance, t-tests, bivariate and partial correlations, and a Chi-square test.ResultsCompared to recreational users, veterans who identify as medicinal cannabis users reported greater combat exposure (d=0.56), PTSD symptoms (d=1.02), subjective arousal when cued (d=0.25), and cannabis use (dfrequency=0.40; ddensity=0.42), but less alcohol use (d=0.28). Few differences were observed between medicinal users who reported using for PTSD versus those who reported using for other reasons.ConclusionsCompared to those who use cannabis recreationally, veterans who report that they use cannabis medicinally use more cannabis and endorse significantly more symptoms of arousal following a prompt about combat trauma experiences.



http://ift.tt/2j8v2H4

Sensitivity and specificity of the gain short-screener for predicting substance use disorders in a large national sample of emerging adults

Publication date: May 2017
Source:Addictive Behaviors, Volume 68
Author(s): Douglas C. Smith, Kyle M. Bennett, Michael L. Dennis, Rodney R. Funk
Background and objectivesEmerging Adults (ages 18–25) have the highest prevalence of substance use disorders and rarely receive treatment from the specialty care system. Thus, it is important to have screening instruments specifically developed for emerging adults for use in Screening, Brief Intervention and Referral to Treatment (SBIRT) models. Optimal cutoffs for the widely-used GAIN Short-Screener's (GAIN-SS) Substance Disorder Screener (SDScrY) are not established specifically for emerging adults. Therefore, this study examined the sensitivity and specificity of the SDScrY in predicting emerging adult (ages 18–25) substance use disorders.MethodsWe analyzed data from emerging adults in a large clinical sample (n=9,808) who completed both the five-item SDScrY (α=0.85) and the full criteria set for DSM-IV Substance Use Disorders. We estimated the sensitivity, specificity and area under the curve to determine optimal cutoffs.ResultsAnalyses revealed a high correlation between the SDScrY screener and its longer parent scale (r=0.95, p<0.001). Sensitivity (83%) and specificity (95%) were highest at a cutoff score of two (AUC=94%) on the SDScrY for any past year substance use disorder. Sensitivity (85%) was also high at a cutoff score of two on the SDScrY for any past year alcohol disorder.ConclusionsThe five-item Substance Use Disorder Screener is a sensitive and specific screener for emerging adults, and could be used to identify emerging adults who may benefit from SBIRT interventions.



http://ift.tt/2jlkUZk

Thermometers for monitoring cellular temperature

Publication date: Available online 11 January 2017
Source:Journal of Photochemistry and Photobiology C: Photochemistry Reviews
Author(s): Masahiro Nakano, Takeharu Nagai
Temperature is a critical parameter that influences various biological events and reactions in homeotherms (including mammals), poikilotherms, and plants. However, the spatiotemporal patterns of temperature at the single-cell level remain largely unknown. Various kinds of thermometers have been developed for monitoring temperature at the single-cell level. We introduce some cellular thermometers based on Europium (III) thenoyltrifluoroacetonate trihydrate, gold nanoclusters, nanodiamonds, synthetic polymers, quantum dots, green fluorescent protein, and bimaterial microcantilevers. We also discuss a critique of these thermometric methods and provide some responses to this critique.

Graphical abstract

http://ift.tt/2jFVNUE

The natural history of streptozotocin-stimulated non-alcoholic steatohepatitis mice followed by Gd-EOB-DTPA-enhanced MRI: Comparison with simple steatosis mice

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Hiroyuki Akai, Shigeru Kiryu, Yasunori Ohta, Koichiro Yasaka, Yoshiyasu Nakano, Yusuke Inoue, Kuni Ohtomo
PurposeTo clarify the development of HCC, temporal change of steatosis and Gd-EOB-DTPA enhancement of non-alcoholic steatohepatitis (NASH) model mice by magnetic resonance imaging (MRI).Materials and methodsAll animal experiments were approved by the institution's Animal Research Committee. MRI was performed on six NASH and six simple steatosis (SS) model mice every 2weeks from the ages of 8weeks to 16weeks. The sequential changes in the number and size of the focal liver lesions detected on Gd-EOB-DTPA-enhanced MRI were evaluated. Additionally, the hepatic fat fraction (HFF), contrast-to-noise ratio (CNR) and relative enhancement (RE) were calculated at each time point. The temporal changes and correlations in these parameters were evaluated.ResultsAll alive NASH model mice demonstrated focal liver lesions from week 10, at the latest. Number of the lesions increased with time, and all the lesion enlarged with time. All the lesions larger than 1mm were confirmed as hepatocellular carcinoma (HCC) pathologically. While the HFF remained constant in NASH model mice, HFF in SS model mice dramatically increased with time. CNR of the NASH model mice remained constant through the study period, while CNR in SS model mice decreased with time. Although no correlation was seen in NASH model mice, the HFF showed a negative correlation against CNR and RE in SS model mice.ConclusionDevelopment of HCC was observed using Gd-EOB-DTPA-enhanced MRI only in NASH model mice. Degree of steatosis and hepatic enhancement by Gd-EOB-DTPA was both constant in NASH model mice, while steatosis increased and hepatic enhancement decreased with time in SS model mice.



http://ift.tt/2jxn9rL

Multiple sclerosis and air pollution exposure: mechanisms toward brain autoimmunity

Publication date: Available online 11 January 2017
Source:Medical Hypotheses
Author(s): Sayed Esmaeil Mousavi, Pouria Heydarpour, Jacques Reis, Masoud Amiri, Mohammad Ali Sahraian
The association between neurodegenerative diseases and environmental exposures, in particular air pollution, has been noticed in the last two decades, but the importance of this environmental factor in Multiple Sclerosis (MS) pathogenesis has not been considered extensively. However, recent evidence suggests that major mechanisms involved in MS pathogenesis, such as inflammatory factors expression, free radicals overproduction, the blood brain barrier (BBB) breakdown, neuroinflammation, vitamin D deficiency and mitochondrial dysfunction could also occur due to exposure to air pollutants. A prospective hypothesis is suggested here in which exposure to air pollutants may initiate destructive mechanisms inducing inflammatory-oxidative cascades, reduction of immunological self-tolerance and neurodegeneration leading to brain autoimmunity.



http://ift.tt/2jFL5xm

Rhizoma smilacis glabrae protects rats with gentamicin-induced kidney injury from oxidative stress-induced apoptosis by inhibiting caspase-3 activation

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Cuiyan Liu, Youxi Kang, Xiuhong Zhou, Zisheng Yang, Jingang Gu, Chunyang Han
Ethnopharmacological relevanceRhizoma smilacis glabrae (RSG), which is mild-natured and tastes sweet or bland, has pharmacological action of eliminating dampness, detoxifying, and ensuring that joints were healthy and supple in traditional Chinese medicine.Aim of the studyTo discuss the protective effect of RSG on gentamicin (GM)-induced kidney injury in rats and its regulatory mechanisms of oxidative stress-induced apoptosis by inhibiting caspase-3 activation.Materials and methodsA total of 40 Sprague–Dawley (SD) rats were randomly divided into 5 groups: control group, model group, and RSG low, middle, and high dose groups (0.75，1.5，3gkg⁻¹). Six hours after intramuscular GM injections, rats in the model group were given distilled water by intragastric administration, and rats in the 3 RSG intervention groups were given different dosages of RSG water-extracts. Twenty-four hours after the last administration, blood and kidney samples were collected to test for biochemical indexes of kidney injury, oxidative stress, histopathological defects, apoptosis rate, and caspase-3 protein expression to assess the protective effect of RSG water-extracts against GM-induced kidney injury.ResultsCompared with the model group, serum TP and ALB levels were significantly higher (P<0.05), and BUN, CRE, and UA levels were significantly lower (P<0.05) in the 3 RSG intervention groups. In kidney tissues, SOD, CAT, and GSH levels increased significantly (P<0.05), while MDA level decreased significantly (P<0.05). Total apoptosis rate dropped markedly (P<0.01), and the protein expressions of caspase-3 increased, while expressions of activated caspase-3 decreased. Histopathological analysis showed shrinkage of kidney cells reduced with appearance of complete kidney structure and decrease in activated caspase-3 expressions in impaired renal tubules decreased. Among the 3 RSG intervention groups, the middle dose group (1.5gkg⁻¹) showed the best protective effect.ConclusionsRSG water-extracts had protective effects against GM-induced kidney injury in rats, and its mechanism of action was related to oxidative stress-induced apoptosis by inhibiting caspase-3 activation.

Graphical abstract

http://ift.tt/2jl1KCO

Network pharmacology-based study on the mechanism of action for herbal medicines in Alzheimer treatment

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Jiansong Fang, Ling Wang, Tian Wu, Cong Yang, Li Gao, Haobin Cai, Junhui Liu, Shuhuan Fang, Yunbo Chen, Wen Tan, Qi Wang
Ethnopharmacological relevanceAlzheimer's disease (AD), as the most common type of dementia, has brought a heavy economic burden to healthcare system around the world. However, currently there is still lack of effective treatment for AD patients. Herbal medicines, featured as multiple herbs, ingredients and targets, have accumulated a great deal of valuable experience in treating AD although the exact molecular mechanisms are still unclear.Materials and methodsIn this investigation, we proposed a network pharmacology-based method, which combined large-scale text-mining, drug-likeness filtering, target prediction and network analysis to decipher the mechanisms of action for the most widely studied medicinal herbs in AD treatment.ResultsThe text mining of PubMed resulted in 10 herbs exhibiting significant correlations with AD. Subsequently, after drug-likeness filtering, 1016 compounds were remaining for 10 herbs, followed by structure clustering to sum up chemical scaffolds of herb ingredients. Based on target prediction results performed by our in-house protocol named AlzhCPI, compound-target (C-T) and target-pathway (T-P) networks were constructed to decipher the mechanism of action for anti-AD herbs.ConclusionsOverall, this approach provided a novel strategy to explore the mechanisms of herbal medicine from a holistic perspective.

Graphical abstract

http://ift.tt/2jl14gV

Pikuni-Blackfeet traditional medicine: Neuroprotective activities of medicinal plants used to treat Parkinson’s disease-related symptoms

Publication date: Available online 11 January 2017
Source:Journal of Ethnopharmacology
Author(s): Aurélie de Rus Jacquet, Mitali Arun Tambe, Sin Ying Ma, George P. McCabe, Jay Hansford C. Vest, Jean-Christophe Rochet
Ethnopharmacological relevanceParkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations.Aim of the studyThe aims of this study were to (i) identify medicinal plants used by the Pikuni-Blackfeet tribe to treat individuals with symptoms related to PD or other CNS disorders, and (ii) characterize a subset of the identified plants in terms of antioxidant and neuroprotective activities in cellular models of PD.Materials and MethodsInterviews of healers and local people were carried out on the Blackfeet Indian reservation. Plant samples were collected, and water extracts were produced for subsequent analysis. A subset of botanical extracts was tested for the ability to induce activation of the Nrf2-mediated transcriptional response and to protect against neurotoxicity elicited by the PD-related toxins rotenone and paraquat.ResultsThe ethnopharmacological interviews resulted in the documentation of 19 medicinal plants used to treat various ailments and diseases, including symptoms related to PD. Seven botanical extracts (out of a total of 10 extracts tested) showed activation of Nrf2-mediated transcriptional activity in primary cortical astrocytes. Extracts prepared from Allium sativum cloves, Trifolium pratense flowers, and Amelanchier arborea berries exhibited neuroprotective activity against toxicity elicited by rotenone, whereas only the extracts prepared from Allium sativum and Amelanchier arborea alleviated PQ-induced dopaminergic cell death.ConclusionsOur findings highlight the potential clinical utility of plants used for medicinal purposes over generations by the Pikuni-Blackfeet people, and they shed light on mechanisms by which the plant extracts could slow neurodegeneration in PD.

Graphical abstract

http://ift.tt/2jlao4c

IFC (Journal of Ethnopharmacology)

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196





http://ift.tt/2jl5ioQ

Traditional medicine among people of Pakistani descent in the capital region of Copenhagen

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Sara Ramzan, Jens Soelberg, Anna K. Jäger, Lourdes Cantarero-Arévalo
Ethnopharmacological relevanceStudies show that ethnic minorities continue to use their cultural traditional medicines also after migration to the West. Research in this field is necessary, given that little is known about traditional medicines' impact on health-related problems. This study sheds light on the issue through a qualitative study among ethnic Pakistanis residing in Denmark.Aim of the studyThe study addresses perception, knowledge and attitudes regarding the use of medicinal plants among Pakistanis living in Copenhagen. We furthermore document and identify the medicinal plants used in households.Materials and methodsData were collected through in-depth, semi-structured interviews with sixteen ethnic Pakistanis aged 30–80 years. Interviews were transcribed verbatim and analysed through Emerson's two-phased analysis method. Medicinal plant products in the interviewees' households were collected, photographed, identified and deposited at Museum of Natural Medicine at University of Copenhagen.ResultsA total number of 121 Pakistani traditional medicines were identified, and found to represent both medicinal plants and foods. The average number of quoted Pakistani Traditional Medicines was 18 (N=16). Interviewees independently reported the same traditions for preparation and consumption of Pakistani traditional medicines. Factors that play a role in choosing to use Pakistani traditional medicines are frequent visits to Pakistan, belief in the healing power of totkas (homemade medicinal preparation), religious knowledge and the occurrence of recent illness within the family. Further, the upkeep of traditional use depends on the availability of Pakistani traditional medicines.ConclusionThe study enhanced understanding of ethnic Pakistanis' perception and continued use of traditional medicines within the household after migration to the West. In the context of Western biomedicine, little is known of the potential toxicity and side-effects of many of the Pakistani traditional medicines found to be used in households in Copenhagen.

Graphical abstract

http://ift.tt/2j8mfoF

The N-butyl alcohol extract from Hibiscus rosa-sinensis L. flowers enhances healing potential on rat excisional wounds

Publication date: Available online 11 January 2017
Source:Journal of Ethnopharmacology
Author(s): Hui-Min Shen, Chun Chen, Ji-Yang Jiang, Yi-Lin Zheng, Wen-Feng Cai, Bin Wang, Zhen Ling, Liu Tang, Yuan-Hang Wang, Gang-Gang Shi
Ethno-pharmacological relevanceHibiscus rosa-sinensis L. (HRS), a folk medicine named Zhujin in China, possess anti-tumor, antioxidant, antibacterial, low density lipoprotein oxidation prevention and macrophage death prevention effects. The leaves and red flowers of HRS have been traditionally used to treat with furuncle and ulceration.Aim of the studyTo investigate the efficacy and possible mechanism of the N-butyl alcohol extract of HRS (NHRS) red flowers in wound healing by analyzing the collagen fiber deposition, angiogenic activity and macrophages action of the NHRS.Materials and methodsIn an excisional wound healing model in rats, different concentrations of NHRS, or recombinant bovine basic fibroblast growth factor (rbFGF), were respectively applied twice daily for 9 days. Histopathology was assessed on day 9 via hematoxylin and eosin (HE) and Masson's trichrome (MT) staining, and immunohistochemistry for vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and CD68. Immunomodulation by NHRS was evaluated by a carbon clearance test in mice.ResultsWound healing post-surgery was greater in the rbFGF-control, NHRS-M and MHRS-H groups than in the model and 5% dimethylsulfoxide (DMSO)-control groups after the third day. By the sixth day the wound contraction of NHRS-M and MHRS-H groups was much higher than the rbFGF-control group. HE and MT staining revealed that epithelialization, fibroblast distribution, collagen deposition of NHRS-M- and NHRS-H-control groups were significantly higher than the model group. Moreover, immunohistochemistry showed more intense staining of VEGF, TGF-β1 and CD68 in the rbFGF- and NHRS-control groups, compared to that in model and 5% DMSO-control groups. The clearance and phagocytic indices of NHRS-M- and NHRS-H-control groups were significantly higher than that of the carboxyl methyl cellulose (CMC) group in mice.ConclusionNHRS accelerates wound repair via enhancing the macrophages activity, accelerating angiogenesis and collagen fiber deposition response mediated by VEGF and TGF-β1.

Graphical abstract

http://ift.tt/2j8uXU5

Temporal plasticity in auditory cortex improves neural discrimination of speech sounds

Publication date: Available online 11 January 2017
Source:Brain Stimulation
Author(s): Crystal T. Engineer, Jai A. Shetake, Navzer D. Engineer, Will A. Vrana, Jordan T. Wolf, Michael P. Kilgard
BackgroundMany individuals with language learning impairments exhibit temporal processing deficits and degraded neural responses to speech sounds. Auditory training can improve both the neural and behavioral deficits, though significant deficits remain. Recent evidence suggests that vagus nerve stimulation (VNS) paired with rehabilitative therapies enhances both cortical plasticity and recovery of normal function.Objective/HypothesisWe predicted that pairing VNS with rapid tone trains would enhance the primary auditory cortex (A1) response to unpaired novel speech sounds.MethodsVNS was paired with tone trains 300 times per day for 20 days in adult rats. Responses to isolated speech sounds, compressed speech sounds, word sequences, and compressed word sequences were recorded in A1 following the completion of VNS-tone train pairing.ResultsPairing VNS with rapid tone trains resulted in stronger, faster, and more discriminable A1 responses to speech sounds presented at conversational rates.ConclusionThis study extends previous findings by documenting that VNS paired with rapid tone trains altered the neural response to novel unpaired speech sounds. Future studies are necessary to determine whether pairing VNS with appropriate auditory stimuli could potentially be used to improve both neural responses to speech sounds and speech perception in individuals with receptive language disorders.



http://ift.tt/2j2Cv8E

Targeting interhemispheric inhibition with neuromodulation to enhance stroke rehabilitation

Publication date: Available online 11 January 2017
Source:Brain Stimulation
Author(s): L.J. Boddington, J.N.J. Reynolds
Background/ObjectivesInterhemispheric inhibition in the brain plays a dynamic role in the production of voluntary unimanual actions. In stroke, the interhemispheric imbalance model predicts the presence of asymmetry in interhemispheric inhibition, with excessive inhibition from the contralesional hemisphere limiting maximal recovery. Stimulation methods to reduce this asymmetry in the brain may be promising as a stroke therapy, however determining how to best measure and modulate interhemispheric inhibition and who is likely to benefit, remain important questions.MethodsThis review addresses current understanding of interhemispheric inhibition in the healthy and stroke lesioned brain. We present a review of studies that have measured interhemispheric inhibition using different paradigms in the clinic, as well as results from recent animal studies investigating stimulation methods to target abnormal inhibition after stroke.Main findings/DiscussionThe degree to which asymmetric interhemispheric inhibition impacts on stroke recovery is controversial, and we consider sources of variation between studies which may contribute to this debate. We suggest that interhemispheric inhibition is not static following stroke in terms of the movement phase in which it is aberrantly engaged. Instead it may be dynamically increased onto perilesional areas during early movement, thus impairing motor initiation. Hence, its effect on stroke recovery may differ between studies depending on the technique and movement phase of eliciting the measurement. Finally, we propose how modulating excitability in the brain through more specific targeting of neural elements underlying interhemispheric inhibition via stimulation type, location and intensity may raise the ceiling of recovery following stroke and enhance functional return.



http://ift.tt/2j2wwka

On the handling of stimulation artifacts during simultaneous electroencephalography (EEG) and transcranial low field strength magnetic stimulation (LFMS)

Publication date: Available online 11 January 2017
Source:Brain Stimulation
Author(s): Vladimir Miskovic, Karl Kuntzelman, C. Alex Goddard




http://ift.tt/2ieDGVo

Reactive oxygen species and cancer paradox: to promote or to suppress?

Publication date: Available online 11 January 2017
Source:Free Radical Biology and Medicine
Author(s): Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy. Therefore, increased ROS in cancer cells may provide a unique opportunity to eliminate cancer cells via elevating ROS to highly toxic levels intracellularly, thereby, activating various ROS-induced cell death pathways, or inhibiting cancer cell resistance to chemotherapy. Such results can be achieved by using agents that either increase ROS generation, or inhibit antioxidant defense, or even a combination of both. In fact, a large variety of anticancer drugs, and some of those currently under clinical trials, effectively kill cancer cells and overcome drug resistance via enhancing ROS generation and/or impeding the antioxidant defense mechanism. This review focuses on our current understanding of the tumor promoting (tumorigenesis, angiogenesis, invasion and metastasis, and chemoresistance) and the tumor suppressive (apoptosis, autophagy, and necroptosis) functions of ROS, and highlights the potential mechanism(s) involved. It also sheds light on a very novel and an actively growing field of ROS-dependent cell death mechanism referred to as ferroptosis.

Graphical abstract

http://ift.tt/2iltKrJ

Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia

Publication date: Available online 11 January 2017
Source:Free Radical Biology and Medicine
Author(s): Joohwan Kim, Kyu-Sun Lee, Ji-Hee Kim, Dong-Keon Lee, Minsik Park, Seunghwan Choi, Wonjin Park, Suji Kim, Yoon Kyoung Choi, Jong Yun Hwang, Jongseon Choe, Moo-Ho Won, Dooil Jeoung, Hansoo Lee, Sungwoo Ryoo, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, microRNA (miR)−155, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia. Aspirin prevented the TNF-α-mediated increase in miR-155 biogenesis and decreases in eNOS expression and NO/cGMP production in cultured human umbilical vein endothelial cells (HUVECs). Similar effects of aspirin were also observed in HUVECs treated with H2O2. The preventive effects of aspirin was associated with the inhibition of nuclear factor-κB (NF-κB)-dependent MIR155HG (miR-155 host gene) expression. Aspirin recovered the TNF-α-mediated decrease in wild-type, but not mutant, eNOS 3′-untranslated region reporter activity, whose effect was blocked by miR-155 mimic. Moreover, aspirin prevented TNF-α-mediated endothelial cell dysfunction associated with impaired vasorelaxation, angiogenesis, and trophoblast invasion, and the preventive effects were blocked by miR-155 mimic or an eNOS inhibitor. Aspirin rescued TNF-α-mediated eNOS downregulation coupled with endothelial dysfunction by inhibiting NF-κB-dependent transcriptional miR-155 biogenesis. Thus, the redox-sensitive NF-κB/miR-155/eNOS axis may be crucial in the pathogenesis of vascular disorders including preeclampsia.

Graphical abstract

http://ift.tt/2ilhqaW

Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress

Publication date: Available online 11 January 2017
Source:Free Radical Biology and Medicine
Author(s): Vera L. Bonilha, Brent A. Bell, Mary E. Rayborn, Ivy S. Samuels, Anna King, Joe G. Hollyfield, Chengsong Xie, Huaibin Cai
Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed. To this end we evaluated photoreceptor and RPE changes in mice deficient DJ-1, a protein that is thought to be important in protecting cells from oxidative stress.Young (3 months) and aged (18 months) DJ-1 knockout (DJ-1 KO) and age-matched wild-type mice were examined. In both aged mice scanning laser ophthalmoscopy (SLO) showed the presence of a few autofluorescent foci. The 18 month-old DJ-1 KO retinas were also characterized by a noticeable increase in RPE fluorescence to wild-type. Optical coherence tomography (OCT) imaging demonstrated that all retinal layers were present in the eyes of both DJ-1 KO groups. ERG comparisons showed that older DJ-1 KO mice had reduced sensitivity under dark- and light-adapted conditions compared to age-matched control. Histologically, the RPE contained prominent vacuoles in young DJ-1 KO group with the appearance of enlarged irregularly shaped RPE cells in the older group. These were also evident in OCT and in whole mount RPE/choroid preparations labeled with phalloidin. Photoreceptors in the older DJ-1 KO mice displayed decreased immunoreactivity to rhodopsin and localized reduction in cone markers compared to the wild-type control group. Lower levels of activated Nrf2 were evident in retina/RPE lysates in both young and old DJ-1 KO mouse groups compared to wild-type control levels. Conversely, higher levels of protein carbonyl derivatives and iNOS immunoreactivity were detected in retina/RPE lysates from both young and old DJ-1 KO mice.These results demonstrate that DJ-1 KO mice display progressive signs of retinal/RPE degeneration in association with higher levels of oxidative stress markers. Collectively this analysis indicates that DJ-1 plays an important role in protecting photoreceptors and RPE from oxidative damage during aging.

Graphical abstract

http://ift.tt/2ilsp3W

Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis

Publication date: April 2017
Source:Current Opinion in Immunology, Volume 45
Author(s): Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype. Concomitantly, galectins can trigger vascular signaling programs, serving as bifunctional messengers that couple tumor immunity and angiogenesis. Thus, targeting galectin–glycan interactions may halt tumor progression by simultaneously augmenting antitumor immunity and suppressing aberrant angiogenesis.



http://ift.tt/2ihDSOP

REVIEWERS ACKNOWLEDGEMENT

Publication date: 30 January 2017
Source:Journal of Neuroscience Methods, Volume 276





http://ift.tt/2jFrQUp

Near-infrared light triggered drug delivery system for higher efficacy of combined chemo-photothermal treatment

Publication date: Available online 11 January 2017
Source:Acta Biomaterialia
Author(s): Yi Chen, Haohuan Li, Yueyang Deng, Haifeng Sun, Xue Ke, Tianyuan Ci
The combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. In the present study, indocyanine green (ICG), a widely used near-infrared (NIR) dye in photothermal therapy, and chemotherapeutic drug-doxorubicin (DOX) were loaded within the nanoparticles of novel designed arylboronic ester and cholesterol modified hyaluronic acid (PPE-Chol1-HA), denoted as PCH-DI. We take advantage of reactive oxygen species (ROS) production capability of ICG and ROS-sensitivity of arylboronic ester to realize controllable drug release. It was confirmed that PCH-DI exhibited remarkable photothermal effect and light-triggered faster release of DOX with NIR laser irradiation. DOX in PCH-DI/Laser group exhibited the most efficient nucleus binding toward HCT-116 colon cells in vitro. Furthermore, enhanced cytotoxicity and promoted tumor growth suppression effect of PCH-DI on HCT-116 tumor xenograft nude mice and AOM-induced murine orthotopic colorectal cancer model was achieved under NIR laser irradiation. Thus, the co-delivery system based on PCH appears to be a promising platform for the combined chemo-photothermal therapy in tumor treatment.Statement of SignificanceIn case of chemo-photothermal combination therapy, the synchronism of treatments plays an important role in achieving expected antitumor efficiency. In this study, a light triggered ROS mediated drug delivery system was developed with the help of ROS-sensitive moieties of arylboronic ester and ROS producer of ICG. We innovatively make use of the ROS production capability of ICG under NIR laser irradiation to promote a faster release of DOX resulting from swelling of PCH-DI due to the presence of arylboronic ester. Intracellular ROS detection demonstrated that ROS level of PCH-I increased under irradiation. Moreover, the faster release behavior of DOX from PCH-DI with NIR laser irradiation was confirmed by the in vitro drug release and cellular uptake study. Meanwhile, local hyperthermia was verified by photothermal effect tests. Therefore, the synchronism of the combination therapy was achieved via light triggered faster release of DOX (chemo-therapy) and local hyperthermia (thermal-therapy) using PCH-DI under irradiation. It was reasonable to attribute the efficient anti-tumor efficiency of PCH-DI both in vitro and in vivo to the enhanced synergistic effect of chemo-photothermal combination therapy with realization of synchronism. To this end, this novel co-delivery system has provided a promising solution for achieving the synchronism of treatment to strengthen the efficiency of combination therapy.

Graphical abstract

http://ift.tt/2j8ib7U

Stepwise targeted drug delivery to liver cancer cells for enhanced therapeutic efficacy by galactose-grafted, ultra-pH-sensitive micelles

Publication date: Available online 11 January 2017
Source:Acta Biomaterialia
Author(s): Guoqing Yan, Jun Wang, Liefeng Hu, Xin Wang, Guanqing Yang, Shengxiang Fu, Xu Cheng, Panpan Zhang, Rupei Tang
To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7.4; (ii) responding to tumoral extracellular pH following gradually larger nanoparticles (NPs); (iii) conjugating receptors in the cell membrane of liver cancer through surface galactose-ligands of micelles; (iv) being sensitive to tumoral intracellular pH following further swelling for rapid drug release. In vitro cytotoxicity and cellular uptake measurement showed that POEAd-g-LA20-DOX micelle was more easily internalized and more toxic effect on tumor cells than free DOX. Moreover, in vivo biodistribution and tumor inhibition examinations demonstrated that POEAd-g-LA20-DOX formulation had more superior efficacy to significantly enhance drug accumulation in tumor, and then restrain tumor growth while decreasing drug concentration in heart.Statement of SignificanceChemotherapeutic efficacy is limited by poor tumor selectivity, which also causes severe toxicity in normal tussues and organs, although many targeted drug delivery systems have been developed by passive targeting strategies or active targeting strategies with specific targeting ligands in recent years. Herein, galactose-grafted, ultra-pH-sensitive, ortho ester-based drug carriers, which can respond to both extracellular and intracellular pH, and target to galactose-receptors in cell membrane, have been successfully constructed by facile method, therefore achieving stepwise targeting to microenvironment of liver cancer and then enhancing drug accumulation and tumor inhibition. The strategy of designing dual-stimuli-responsive copolymers can be potentially useful,and extrapolated to synthesizing other categories of highly labile drug carriers in a range of biomedical applications.

Graphical abstract

http://ift.tt/2j8qHUj

Cellular transcriptional response to zirconia-based implant materials

Publication date: Available online 10 January 2017
Source:Dental Materials
Author(s): Brigitte Altmann, Kerstin Rabel, Ralf J. Kohal, Susanne Proksch, Pascal Tomakidi, Erik Adolfsson, Falk Bernsmann, Paola Palmero, Tobias Fürderer, Thorsten Steinberg
ObjectiveTo adequately address clinically important issues such as osseointegration and soft tissue integration, we screened for the direct biological cell response by culturing human osteoblasts and gingival fibroblasts on novel zirconia-based dental implant biomaterials and subjecting them to transcriptional analysis.MethodsBiomaterials used for osteoblasts involved micro-roughened surfaces made of a new type of ceria-stabilized zirconia composite with two different topographies, zirconium dioxide, and yttria-stabilized zirconia (control). For fibroblasts smooth ceria- and yttria-stabilized zirconia surface were used. The expression of 90 issue-relevant genes was determined on mRNA transcription level by real-time PCR Array technology after growth periods of 1 and 7 days.ResultsGenerally, modulation of gene transcription exhibited a dual dependence, first by time and second by the biomaterial, whereas biomaterial-triggered changes were predominantly caused by the biomaterials' chemistry rather than surface topography. Per se, modulated genes assigned to regenerative tissue processes such as fracture healing and wound healing and in detail included colony stimulating factors (CSF2 and CSF3), growth factors, which regulate bone matrix properties (e.g. BMP3 and TGFB1), osteogenic BMPs (BMP2/4/6/7) and transcription factors (RUNX2 and SP7), matrix collagens and osteocalcin, laminins as well as integrin ß1 and MMP-2.SignificanceWith respect to the biomaterials under study, the screening showed that a new zirconia-based composite stabilized with ceria may be promising to provide clinically desired periodontal tissue integration. Moreover, by detecting biomarkers modulated in a time- and/or biomaterial-dependent manner, we identified candidate genes for the targeted analysis of cell-implant bioresponse during biomaterial research and development.



http://ift.tt/2jFizfk

Host-to-Host Transmission of the Pneumococcus—New Victims of a Toxic Relationship

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Claudia Trappetti, James C. Paton
Host-to-host transmission is critical for survival of the human-adapted bacterium Streptococcus pneumoniae. In this issue of Cell Host & Microbe, Zafar et al. (2017) show that transmission is dependent on nasopharyngeal inflammation elicited by the toxin pneumolysin, causing increased shedding and enhanced survival of the bacterium in the environment.

Teaser

Host-to-host transmission is critical for survival of the human-adapted bacterium Streptococcus pneumoniae. In this issue of Cell Host & Microbe, Zafar et al. (2017) show that transmission is dependent on nasopharyngeal inflammation elicited by the toxin pneumolysin, causing increased shedding and enhanced survival of the bacterium in the environment.


http://ift.tt/2jFfJXx

Warfare between Host Immunity and Bacterial Weapons

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Manda Yu, Erh-Min Lai
Bacterial pathogens deploy protein secretion systems to facilitate infection and colonization of their hosts. In this issue of Cell Host & Microbe, Chen et al. (2017) report a new role for a type VI secretion effector in promoting bacterial colonization by preventing inflammasome activation induced by a type III secretion system.

Teaser

Bacterial pathogens deploy protein secretion systems to facilitate infection and colonization of their hosts. In this issue of Cell Host & Microbe, Chen et al. (2017) report a new role for a type VI secretion effector in promoting bacterial colonization by preventing inflammasome activation induced by a type III secretion system.


http://ift.tt/2iHJkeV

Bringing the Dynamic Microbiome to Life with Animations

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Yoshiki Vázquez-Baeza, Antonio Gonzalez, Larry Smarr, Daniel McDonald, James T. Morton, Jose A. Navas-Molina, Rob Knight
Our bodies and natural environment contain complex microbial communities, colloquially termed microbiomes. We previously created a web-based application, EMPeror, for visualizing ordinations derived from comparisons of these microbiome communities. We have now improved EMPeror to create interactive animations that connect successive samples to highlight patterns over time.

Teaser

Our bodies and natural environment contain complex microbial communities, colloquially termed microbiomes. We previously created a web-based application, EMPeror, for visualizing ordinations derived from comparisons of these microbiome communities. We have now improved EMPeror to create interactive animations that connect successive samples to highlight patterns over time.


http://ift.tt/2iHHsCK

A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Katarzyna Modrzynska, Claudia Pfander, Lia Chappell, Lu Yu, Catherine Suarez, Kirsten Dundas, Ana Rita Gomes, David Goulding, Julian C. Rayner, Jyoti Choudhary, Oliver Billker
A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle.

Graphical abstract

Teaser

Modrzynska et al. investigate 25 putative transcriptional regulators of the apiAP2 family in a malaria parasite using a systematic knockout screen. Cellular and molecular phenotyping of the 11 viable mutants obtained reveals complex interactions between positive and negative regulators controlling the Plasmodium life cycle at different stages.


http://ift.tt/2iHKK8Y

Knotty Zika Virus Blocks Exonuclease to Produce Subgenomic Flaviviral RNAs

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Nandan S. Gokhale, Stacy M. Horner
In a recent issue of Science, Akiyama et al. (2016) prove the existence of a pseudoknot that stabilizes a nuclease-resistant RNA structure in the 3′ untranslated region of Zika virus. This reinforced structure blocks the 5′→3′ exonuclease Xrn1 for the production of pathogenic subgenomic flaviviral RNAs.

Teaser

In a recent issue of Science, Akiyama et al. (2016) prove the existence of a pseudoknot that stabilizes a nuclease-resistant RNA structure in the 3′ untranslated region of Zika virus. This reinforced structure blocks the 5′→3′ exonuclease Xrn1 for the production of pathogenic subgenomic flaviviral RNAs.


http://ift.tt/2iHEmig

Mapping and Role of the CD8+ T Cell Response During Primary Zika Virus Infection in Mice

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Annie Elong Ngono, Edward A. Vizcarra, William W. Tang, Nicholas Sheets, Yunichel Joo, Kenneth Kim, Matthew J. Gorman, Michael S. Diamond, Sujan Shresta
CD8⁺ T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8⁺ T cell response in ZIKV-infected LysMCre⁺IFNAR^fl/fl C57BL/6 (H-2^b) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8⁺ T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated. CD8⁺ T cells from infected mice were polyfunctional and mediated cytotoxicity. Adoptive transfer of ZIKV-immune CD8⁺ T cells reduced viral burdens, whereas their depletion led to higher tissue burdens, and CD8^−/− mice displayed higher mortality with ZIKV infection. Collectively, these results demonstrate that CD8⁺ T cells protect against ZIKV infection. Further, this study provides a T cell competent mouse model for investigating ZIKV-specific T cell responses.

Graphical abstract

Teaser

The nature and role of CD8+ T cell responses during Zika virus (ZIKV) infection is unknown. Elong Ngono et al. develop a mouse model to identify, characterize, and validate the H-2^b-restricted CD8⁺ T cell response to ZIKV and demonstrate a protective role for CD8⁺ T cells during primary ZIKV infection.


http://ift.tt/2jFj8px

The Bacterial T6SS Effector EvpP Prevents NLRP3 Inflammasome Activation by Inhibiting the Ca2+-Dependent MAPK-Jnk Pathway

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Hao Chen, Dahai Yang, Fajun Han, Jinchao Tan, Lingzhi Zhang, Jingfan Xiao, Yuanxing Zhang, Qin Liu
Inflammasome activation is an important innate immune defense mechanism against bacterial infection, and in return, bacteria express virulence determinants that counteract inflammasome activation. Many such effectors are secreted into host cells via specialized bacterial secretion systems. Here, the intracellular pathogenic bacterium Edwardsiella tarda was demonstrated to activate NLRC4 and NLRP3 inflammasomes via a type III secretion system (T3SS), and to inhibit NLRP3 inflammasome via a type VI secretion system (T6SS), indicating the antagonistic roles of these systems in inflammasome signaling. Furthermore, a non-VgrG T6SS effector, EvpP, was identified that significantly inhibited NLRP3 inflammasome activation. Subsequent studies revealed that EvpP significantly suppressed Jnk activation, thus impairing oligomerization of the inflammasome adaptor ASC. Moreover, EvpP counteracted cytoplasmic Ca²⁺ increase, which works upstream of Jnk activation to regulate the NLRP3 inflammasome. Finally, EvpP-mediated inflammasome inhibition promoted bacterial colonization in vivo. This work expands our understanding of bacterial T6SS in counteracting host immune responses.

Graphical abstract

Teaser

Edwardsiella tarda is an important pathogenic bacterium infecting a wide range of hosts from fish to humans. Chen et al. identify a novel T6SS effector, EvpP, in E. tarda that targets intracellular Ca²⁺ signaling to impair Jnk activation and subsequent ASC oligomerization, which promotes bacterial colonization in mice.


http://ift.tt/2jFjOeo