Publication date: Available online 20 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Cristina Amaral, Tiago Vieira Augusto, Elisiário Tavares-da-Silva, Fernanda M.F. Roleira, Georgina Correia-da-Silva, Natércia Teixeira
The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered a first-line treatment for estrogen receptor-positive (ER+) breast tumors, in postmenopausal women. Exemestane (Exe) is a powerful steroidal AI, however, despite its therapeutic success, Exe-acquired resistance may occur leading to tumor relapse. Our group previously demonstrated that autophagy acts as a pro-survival process in Exe-induced cell death of ER+ sensitive breast cancer cells. In this work, the role of autophagy and its relationship with the PI3K/AKT/mTOR pathway in Exe-acquired resistance was explored. In that way, the mechanism behind the effects of the combination of Exe with pan-PI3K, or autophagic inhibitors, was studied in a long-term estrogen deprived ER+ breast cancer cell line (LTEDaro cells). Our results indicate that Exe induces autophagy as a cytoprotective mechanism linked to acquired resistance. Moreover, it was demonstrated that by inhibiting autophagy and/or PI3K pathway it is possible to revert Exe-resistance through apoptosis promotion, disruption of cell cycle, and inhibition of cell survival pathways. This work provides new insights into the mechanisms involved in Exe-acquired resistance, pointing autophagy as an attractive therapeutic target to surpass it. Thus, it highlights new targets that together with aromatase inhibition may improve ER+ breast cancer therapy, overcoming AIs-acquired resistance.
https://ift.tt/2Izz2yr
Κυριακή 20 Μαΐου 2018
Hormone-dependent breast cancer: Targeting autophagy and PI3K overcomes Exemestane-acquired resistance
Methylmercury and diphenyl diselenide interactions in Drosophila melanogaster: effects on development, behavior, and Hg levels
Abstract
Methylmercury (MeHg) is a highly toxic environmental pollutant which binds with a high affinity to selenol groups. In view of this, seleno-compounds have been investigated as MeHg antidotes. In the present study, we evaluated the effects of the co-exposure to MeHg and the seleno-compound diphenyl diselenide (PhSe)2 on Drosophila melanogaster. We measured the survival rate, developmental survival, locomotor ability, reactive oxygen species (ROS) production, and Hg levels in D. melanogaster exposed to MeHg and/or (PhSe)2 in the food. Exposure to MeHg caused a reduction in the survival rate, developmental survival, and locomotion in D. melanogaster. In addition, MeHg increased the ROS production and mercury levels in flies. The co-exposure to MeHg and (PhSe)2 did not prevent the toxic effects of MeHg in D. melanogaster. On the contrary, the co-exposure enhanced the toxic effects on the locomotor ability and developmental survival. This effect may be explained by the fact that the co-exposure increased the Hg levels in body when compared to flies exposed only to MeHg, suggesting that MeHg and (PhSe)2 interaction may increase Hg body burden in D. melanogaster which could contribute for the increased toxicity observed in the co-exposure.
https://ift.tt/2IAqzqx
Lipid-modified Cell-Penetrating Peptide-Based Self-assembly Micelles for Co-delivery of Narciclasine and siULK1 in Hepatocellular Carcinoma Therapy
Publication date: Available online 19 May 2018
Source:Acta Biomaterialia
Author(s): Xiaoyun Wang, Fengbo Wu, Guoyou Li, Nan Zhang, Xiangrong Song, Yu Zheng, Changyang Gong, Bo Han, Gu He
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and one therapeutic approach is to target both the AMPK and autophagy pathways in order to synergistically promote programmed cell death. Here, a series of amphiphilic, lipid-modified cell-penetrating peptides were synthesized and allowed to self-assemble into micelles loaded with the AMPK activator narciclasine (Narc) and short interfering RNA targeting the unc-51-like kinase 1 (siULK1). The size of these micelles, their efficiency of transfection into cells, and their ability to release drug or siRNA cargo in vitro were pH-sensitive, such that drug release was facilitated in the acidic microenvironment of the tumor. Transfecting the micelles into HCC cells significantly inhibited protective autophagy within tumor cells, and delivering the micelles into mice carrying HCC xenografts induced apoptosis, slowed tumor growth, and inhibited autophagy. Our results indicate that co-delivering Narc and siULK1 in biocompatible micelles can safely inhibit tumor growth and protective autophagy, justifying further studies into this promising therapeutic approach against HCC.Statement of SignificanceWe have focused on the targeted therapy of HCC via synergistically inhibiting the autophagy and inducing apoptosis. The lipid-modified cell-penetrating peptide can not only aggregate into micelles to load natural product narciclasine and ULK1 siRNA simultaneously, but also facilitate uptake and endosome escape with a pH-sensitive manner in HepG2 cells. HepG2 cell treated with siULK1-M-Narc has increased apoptotic levels and declined autophagy via the targeted regulation of AMPK-ULK1 signaling axis. The in vivo studies have confirmed that siULK1-M-Narc efficiently reduce the growth of tumor on HCC xenograft models with good safety. Thus, we suppose the lipid-modified cell-penetrating peptide has good application prospects in the targeted combinational therapy of HCC.
Graphical abstract
https://ift.tt/2x0nEWW
Junior temperament character inventory together with quantitative EEG discriminate children with attention deficit hyperactivity disorder combined subtype from children with attention deficit hyperactivity disorder combined subtype plus oppositional defiant disorder
Publication date: Available online 19 May 2018
Source:International Journal of Psychophysiology
Author(s): Giuseppe A. Chiarenza, Stefania Villa, Lidice Galan, Pedro Valdes-Sosa, Jorge Bosch-Bayard
Oppositional defiant disorder (ODD) is frequently associated with Attention Deficit Hyperactivity Disorder (ADHD) but no clear neurophysiological evidence exists that distinguishes the two groups. Our aim was to identify biomarkers that distinguish children with Attention Deficit Hyperactivity Disorder combined subtype (ADHD_C) from children with ADHD_C + ODD, by combining the results of quantitative EEG (qEEG) and the Junior Temperament Character Inventory (JTCI).28 ADHD_C and 22 ADHD_C + ODD children who met the DSMV criteria participated in the study. JTCI and EEG were analyzed. Stability based Biomarkers identification methodology was applied to the JTCI and the qEEG separately and combined. The qEEG was tested at the scalp and the sources levels. The classification power of the selected biomarkers was tested with a robust ROC technique. The best discriminant power was obtained when TCI and qEEG were analyzed together. Novelty seeking, self-directedness and cooperativeness were selected as biomarkers together with F4 and Cz in Delta; Fz and F4 in Theta and F7 and F8 in Beta, with a robust AUC of 0.95 for the ROC. At sources level: the regions were the right lateral and medial orbito-frontal cortex, cingular region, angular gyrus, right inferior occipital gyrus, occipital pole and the left insula in Theta, Alpha and Beta. The robust estimate of the total AUC was 0.91. These structures are part of extensive networks of novelty seeking, self-directedness and cooperativeness systems that seem dysregulated in these children. These methods represent an original approach to associate differences of personality and behavior to specific neuronal systems and subsystems.
https://ift.tt/2GzRAJ8
Performance of Bi 2 O 3 /TiO 2 prepared by sol-gel on p-Cresol degradation under solar and visible light
Abstract
Photocatalytic degradation of p-Cresol was evaluated using the mixed oxide Bi2O3/TiO2 (containing 2 and 20% wt. Bi2O3 referred as TB2 and TB20) and was compared with bare TiO2 under simulated solar radiation. Materials were prepared by the classic sol-gel method. All solids exhibited the anatase phase by X-ray diffraction (XRD) and Raman spectroscopy. The synthesized materials presented lower crystallite size and Eg value, and also higher surface area as Bi2O3 amount was increased. Bi content was quantified showing near to 70% of theoretical values in TB2 and TB20. Bi2O3 incorporation also was demonstrated by X-ray photoelectron spectroscopy (XPS). Characterization of mixed oxides suggests a homogeneous distribution of Bi2O3 on TiO2 surface. Photocatalytic tests were carried out using a catalyst loading of 1 g L−1 under simulated solar light and visible light. The incorporation of Bi2O3 in TiO2 improved the photocatalytic properties of the synthesized materials obtaining better results with TB20 than the unmodified TiO2 under both radiation sources.
https://ift.tt/2GAC9Af
Follicle stimulating hormone receptor protein is expressed in ovine uterus during the estrous cycle and utero-placenta during early pregnancy: An immunohistochemical study
Publication date: Available online 11 May 2018
Source:Acta Histochemica
Author(s): Anna T. Grazul-Bilska, Arshi Reyaz, Veselina Valkov, Sheri T. Dorsam, Dale A. Redmer
Follicle stimulating hormone (FSH) is a well characterized gonadotropin that controls primarily development and functions of ovarian follicles in mammalian species. FSH binds to a specific G protein-coupled receptor (FSHR) belonging to the glycoprotein hormone receptor family that plays an essential role in reproduction. Although the primary location of FSHR is in the gonads (mainly in ovarian follicles), FSHR protein and/or mRNA have also been detected in extragonadal female reproductive tissues including embryo, placenta, endometrium, cervix, ovarian cancer tissues, and/or endometriotic lesions in several species. To determine the pattern of FSHR expression in the uterus and placenta, uterine tissues were collected at the early, mid- and/or late luteal phases of the estrous cycle from non-treated or FSH-treated ewes, and utero-placental tissues were collected during early pregnancy followed by immunohistochemistry and image generation. FSHR was immunolocalized to several uterine and utero-placental compartments including luminal epithelium, endometrial glands and surrounding stroma, myometrium, and endothelium and vascular smooth muscle cells in endometrium, myometrium and mesometrium. Intensity of staining and distribution of FSHR in selected compartments differed and seems to depend on the stage of the estrous cycle or pregnancy, and FSH-treatment. These novel data demonstrate differential expression of FSHR protein indicating that FSH plays a specific role in regulation of uterine and utero-placenta functions in sheep.
https://ift.tt/2wUIVS0
Ameliorative effects of bone marrow derived pancreatic progenitor cells on hyperglycemia and oxidative stress in diabetic rats
Publication date: Available online 8 May 2018
Source:Acta Histochemica
Author(s): Hamdy Rizk, A.F. Tohamy, Walaa Mohamed Sayed, Abdelbary Prince
The present study aimed to investigate the effects of Bone marrow derived pancreatic progenitor cells (BM- PPCs) in diabetic rats. It was conducted on 30 adult male Sprague-Dawley rats weighing 200–220 g. They were divided into three groups: (a) Group 1 was the control group; (b) Group 2 was the diabetic (induced diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/kg) and (c) Group 3 was the treated (received injection of 2.5 X 106 BM- PPCs via the tail vein twice with a 21-day time interval). The blood glucose level was estimated weekly, the oxidative stress and insulin gene expression were evaluated at the end of the experiment. Pancreatic tissue histopathology was performed. The insulin immuno-histochemical reaction was applied to the islets. The blood glucose level was reduced in the treated group over time till reaching its acceptable level whereas it was increased in the diabetic group. The oxidative stress was decreased in the treated group compared to the diabetic one. The treated group showed increased expression of the insulin gene compared to the diabetic group. The immune-histochemical analysis of insulin showed an increased number and size of pancreatic islets in the treated group compared to the diabetic one. Thus, the twofold injection of BM- PPCs could restore the normal beta-cell morphology and function.
https://ift.tt/2IYbenq
Multiple immunolabeling with antibodies from the same host species in combination with tyramide signal amplification
Publication date: Available online 5 May 2018
Source:Acta Histochemica
Author(s): Igor Buchwalow, Vera Samoilova, Werner Boecker, Markus Tiemann
A general problem in immunocytochemistry is the development of a reliable multiple immunolabeling method with primary antibodies originating from the same host species. When primary antibodies are raised in the same host species, the secondary species-specific antibodies can cross-react with each of the primary antibodies. This obstacle can however be avoided with the use of striping buffers eluting the primary/secondary antibody complex. After elution of the previous primary/secondary antibody complex, the next primary antibody from the same host species can be applied. Recently, a group from VENTANA (Tucson, AZ, USA) presented a fully automated multiplex protocol for fluorescent immunohistochemistry on the platform of VENTANA's BenchMark ULTRA slide stainer using the same species antibodies in combination with tyramide signal amplification. We adapted the automated protocol of VENTANA for the use in a routine histochemical laboratory and present here a standard procedure with a manual mode of operation for simultaneously detecting two or more antigens from the same host species.
https://ift.tt/2KIlM7b
Editorial Board
Publication date: May 2018
Source:Acta Histochemica, Volume 120, Issue 4
https://ift.tt/2IQYQp9
Nandrolone decanoate and physical activity affect quadriceps in peripubertal rats
Publication date: Available online 11 May 2018
Source:Acta Histochemica
Author(s): Jasmina Sretenovic, Vladimir Ajdzanovic, Vladimir Zivkovic, Ivan Srejovic, Milena Corbic, Verica Milosevic, Vladimir Jakovljevic, Zoran Milosavljevic
Anabolic androgenic steroids (AASs) are synthetic analogs of testosterone often used by athletes to increase the skeletal muscle mass. Our goal was to examine the effects of physical activity and physical activity combined with supraphysiological doses of nandrolone on functional morphology of the quadriceps muscle. The study included 32 peripubertal Wistar rats, divided into 4 groups: control (T-N-), nandrolone (T-N+), physical activity (T+N-) and physical activity plus nandrolone (T+N+) groups. The T+N- and T+N+ group swam for 4 weeks, 1 h/day, 5 days/week. The T-N+ and T+N+ groups received nandolone decanoate (20 mg/kg b.w.) once per week, subcutaneously. Subsequently, the rats were sacrificed and muscle specimens were prepared for the processing. Tissue sections were histochemically and immunohistochemically stained, while the image analysis was used for quantification. Longitudinal diameter of quadriceps muscle cells was increased for 21% in T-N+, for 57% in T+N- and for 64% in T+N+ group while cross section muscle cell area was increased in T-N+ for 19%, in T+N- for 47% and in T+N+ group for 59%, compared to the control. Collagen fibers covered area was increased in T-N+ group for 36%, in T+N- for 109% and in T+N+ group for 159%, compared to the control. Erythrocyte depots were decreased in T-N+ group and increased in T+N- and T+N+ group, in comparison with T-N-. VEGF depots were increased in all treated groups. Chronic administration of supraphysiological doses of AASs alone or in combination with physical activity induces hypertrophy and significant changes in the quadriceps muscle tissue structure.
https://ift.tt/2KIMtc7
Immunohistochemical expression of apoptosis-related biomarkers in normal tissues of camel (Camelus dromedarius): A survey in a desert-dwelling mammalian model
Publication date: May 2018
Source:Acta Histochemica, Volume 120, Issue 4
Author(s): Abdel-Hamid K. Osman, Thomas Caceci, Mitchiko Shintani
Programmed cell death is a fundamental event that takes place during organ development and plays an important role in cellular homeostasis. Since various body organs of the camel are under high ecological and physiological stress during food and water deprivation, desiccation, and the long exposure to solar radiation in these desert nomads, we aimed to examine the immunohistochemical expression of apoptosis-related biomarkers in some of its normal body organs to illustrate a basic track for further pathological investigation. Regarding apoptosis, the present study has revealed that the higher expression of cleaved caspase-9 (CC9) [initiator of the intrinsic pathway] and CC3 (effector caspase), and the scanty expression of CC8 (initiator of the extrinsic pathway), highlight the role of the caspase-dependent, intrinsic apoptotic pathway particularly in the intestines and lymphoid organs. The apoptosis- inducing factor (AIF)-immunoexpression was completely missing in the cell nuclei of the examined tissues, indicating the absence of the caspase-independent pathway. The nuclear overexpression of the phospho-histone H2AX (γ H2AX) and the occasional expression of single-stranded DNA, particularly among the CNS neurons, suggest an efficient, protective DNA-repair mechanism in such cells. Thus, despite efficient anti-apoptotic mechanisms intrinsic apoptotic pathways exists in brain, intestine and lymph organs of adult desert camels.
https://ift.tt/2IR2NKx
Erratum to “The possible protective role of pumpkin seed oil in an animal model of acid aspiration pneumonia: Light and electron microscopic study Acta Histochemica 119 (2017) 161–171”
Publication date: May 2018
Source:Acta Histochemica, Volume 120, Issue 4
Author(s): Nesreen Moustafa Omar, Nahla Reda Sarhan
https://ift.tt/2wW7A8L
Telocytes in human fetal skeletal muscle interstitium during early myogenesis
Publication date: Available online 1 May 2018
Source:Acta Histochemica
Author(s): Mirca Marini, Mirko Manetti, Irene Rosa, Lidia Ibba-Manneschi, Eleonora Sgambati
A new peculiar stromal cell type called telocyte (TC)/CD34-positive stromal cell (i.e. cell with distinctive prolongations named telopodes) has recently been described in various tissues and organs, including the adult skeletal muscle interstitium of mammals. By forming a resident stromal three-dimensional network, TCs have been suggested to participate in different physiological processes within the skeletal muscle tissue, including homeostasis maintenance, intercellular signaling, tissue regeneration/repair and angiogenesis. Since a continuous interplay between the stromal compartment and skeletal muscle fibers seems to take place from organogenesis to aging, the present study was undertaken to investigate for the first time the presence of TCs in the human skeletal muscle during early myogenesis. In particular, we describe the morphological distribution of TCs in human fetal lower limb skeletal muscle during early stages of myogenesis (9–12 weeks of gestation). TCs were studied on tissue sections subjected to immunoperoxidase-based immunohistochemistry for CD34. Double immunofluorescence was further performed to unequivocally differentiate TCs (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). Our findings provide evidence that stromal cells with typical morphological features and immunophenotype of TCs are present in the human skeletal muscle during early myogenesis, revealing differences in either CD34 immunopositivity or TC numbers among different gestation ages. Specifically, few TCs weakly positive for CD34 were found between 9 and 9.5 weeks. From 10 to 11.5 weeks, TCs were more numerous and strongly reactive and their telopodes formed a reticular network in close relationship with blood vessels and primary and secondary myotubes undergoing separation. On the contrary, a strong reduction in the number and immunopositivity of TCs was observed in fetal muscle sections from 12 weeks of gestation, where mature myotubes were evident. The muscle stroma showed parallel changes in amount, density and organization from 9 to 12 weeks. Moreover, blood vessels appeared particularly numerous between 10 and 11.5 weeks. Taken together, our findings suggest that TCs might play a fundamental role in the early myogenetic period, possibly guiding tissue organization and compartmentalization, as well as angiogenesis and maturation of myotubes.
https://ift.tt/2IULgB2
Executive and arousal vigilance decrement in the context of the attentional networks: The ANTI-Vea task
Publication date: Available online 20 May 2018
Source:Journal of Neuroscience Methods
Author(s): Fernando Gabriel Luna, Julián Marino, Javier Roca, Juan Lupiáñez
BackgroundVigilance is generally understood as the ability to detect infrequent critical events through long time periods. In tasks like the Sustained Attention to Response Task (SART), participants tend to detect fewer events across time, a phenomenon known as "vigilance decrement". However, vigilance might also involve sustaining a tonic arousal level. In the Psychomotor Vigilance Test (PVT), the vigilance decrement corresponds to an increment across time in both mean and variability of reaction time.New MethodThe present study aimed to develop a single task –Attentional Networks Test for Interactions and Vigilance – executive and arousal components (ANTI-Vea)– to simultaneously assess both components of vigilance (i.e., the executive vigilance as in the SART, and the arousal vigilance as in the PVT), while measuring the classic attentional functions (phasic alertness, orienting, and executive control).ResultsIn Experiment #1, the executive vigilance decrement was found as an increment in response bias. In Experiment #2, this result was replicated, and the arousal vigilance decrement was simultaneously observed as an increment in reaction time.Comparison with Existing MethodThe ANTI-Vea solves some issues observed in the previous ANTI-V task with the executive vigilance measure (e.g., a low hit rate and no vigilance decrement). Furthermore, the new ANTI-Vea task assesses both components of vigilance together with others typical attentional functions.ConclusionsThe new attentional networks test developed here may be useful to provide a better understanding of the human attentional system. The role of sensitivity and response bias in the executive vigilance decrement are discussed.
https://ift.tt/2rW979S
Autophagy and MHC-restricted antigen presentation
Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Jan Valečka, Catarina R. Almeida, Bing Su, Philippe Pierre, Evelina Gatti
Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle trafficking, and autophagy, play critical roles in presentation of these antigens. We discuss the role of autophagy, a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. We propose the new term "Type 2 cross-presentation" (CP2) to define the autophagy-dependent processes leading to MHC II-restricted presentation of intracellular antigens by professional antigen presenting cells. A better understanding of Type 2 cross-presentation may guide future efforts to control the immune system through autophagy manipulation.
https://ift.tt/2IAUI9p
The expanding role of murine class Ib MHC in the development and activation of Natural Killer cells
Publication date: Available online 20 May 2018
Source:Molecular Immunology
Author(s): Katharine J. Goodall, Angela Nguyen, Lucy C. Sullivan, Daniel M. Andrews
Major Histocompatibility Complex-I (MHC-I) molecules can be divided into class Ia and class Ib, with three distinct class Ib families found in the mouse. These families are designated as Q, T and M and are largely unexplored in terms of their immunological function. Among the class Ib MHC, H2-T23 (Qa-1b) has been a significant target for Natural Killer (NK) cell research, owing to its homology with the human class Ib human leukocyte antigen (HLA)-E. However, recent data has indicated that members of the Q and M family of class Ib MHC also play a critical role in the development and regulation NK cells. Here we discuss the recent advances in the control of NK cells by murine class Ib MHC as a means to stimulate further exploration of these molecules.
https://ift.tt/2LgOltI
Autophagy and MHC-restricted antigen presentation
Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Jan Valečka, Catarina R. Almeida, Bing Su, Philippe Pierre, Evelina Gatti
Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle trafficking, and autophagy, play critical roles in presentation of these antigens. We discuss the role of autophagy, a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. We propose the new term "Type 2 cross-presentation" (CP2) to define the autophagy-dependent processes leading to MHC II-restricted presentation of intracellular antigens by professional antigen presenting cells. A better understanding of Type 2 cross-presentation may guide future efforts to control the immune system through autophagy manipulation.
https://ift.tt/2IAUI9p
The expanding role of murine class Ib MHC in the development and activation of Natural Killer cells
Publication date: Available online 20 May 2018
Source:Molecular Immunology
Author(s): Katharine J. Goodall, Angela Nguyen, Lucy C. Sullivan, Daniel M. Andrews
Major Histocompatibility Complex-I (MHC-I) molecules can be divided into class Ia and class Ib, with three distinct class Ib families found in the mouse. These families are designated as Q, T and M and are largely unexplored in terms of their immunological function. Among the class Ib MHC, H2-T23 (Qa-1b) has been a significant target for Natural Killer (NK) cell research, owing to its homology with the human class Ib human leukocyte antigen (HLA)-E. However, recent data has indicated that members of the Q and M family of class Ib MHC also play a critical role in the development and regulation NK cells. Here we discuss the recent advances in the control of NK cells by murine class Ib MHC as a means to stimulate further exploration of these molecules.
https://ift.tt/2LgOltI
Hydrochlorothiazide and risk of hearing disorder: a case series
Hydrochlorothiazide is not known to cause hearing disorder. The Eritrean Pharmacovigilance Centre, however, has received cases of hearing disorder, including irreversible deafness, associated with hydrochlorot...
https://ift.tt/2kchfys
Vaccines, inspiring innovation in health
Publication date: Available online 19 May 2018
Source:Vaccine
Author(s): Sonia Pagliusi, Maureen Dennehy, Hun Kim
This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of vaccine supply in developing countries.
https://ift.tt/2kcs1F0
Mandatory influenza vaccination and religious accommodation for healthcare workers: Lessons from recent legal challenges
Publication date: Available online 19 May 2018
Source:Vaccine
Author(s): Y. Tony Yang, Ross D. Silverman
https://ift.tt/2rYiYLj
‘What have you HEARD about the HERD?’ Does education about local influenza vaccination coverage and herd immunity affect willingness to vaccinate?
Publication date: Available online 19 May 2018
Source:Vaccine
Author(s): Jacqueline Logan, Dawn Nederhoff, Brandon Koch, Bridget Griffith, Julian Wolfson, Fareed A. Awan, Nicole E. Basta
BackgroundVaccination protects individuals directly and communities indirectly by reducing transmission. We aimed to determine whether information about herd immunity and local vaccination coverage could change an individual's vaccination plans and concern about influenza.MethodsWe surveyed Minnesota residents ≥18 years during the 2016 Minnesota State Fair. Participants were asked to identify the definition of herd immunity, to report their history of and plans to receive influenza vaccine, to report their concern about influenza, and to estimate the reported influenza vaccination coverage in their county. After providing educational information about herd immunity and local vaccination rates, we reassessed vaccination plans and concerns. We used logistic regression to estimate predicted percentages for those willing to be vaccinated, for concern about influenza, and for changes in these outcomes after the intervention. We then compared those individuals with and without prior knowledge of herd immunity, accounting for other characteristics.ResultsAmong 554 participants, the median age was 57 years; most were female (65.9%), white (91.0%), and non-Hispanic/Latino (93.9%). Overall, 37.2% of participants did not know about herd immunity and 75.6% thought that the influenza vaccination coverage in their county was higher than it was reported. Those not knowledgeable about herd immunity were significantly less likely than those knowledgeable about the concept to report plans to be vaccinated at baseline (67.8% versus 78.9%; p = 0.004). After learning about herd immunity and influenza vaccination coverage, the proportion of those not knowledgeable about herd immunity who were willing to be vaccinated increased significantly by 7.3 percentage points (p = 0.001). Educating participants eliminated the significant difference in the proportion planning to be vaccinated between these two groups (80.1% of those knowledgeable and 75.1% of those who were not initially knowledgeable became willing; p = 0.148).ConclusionsEducation about herd immunity and local vaccination coverage could be a useful tool for increasing willingness to vaccinate, generating benefits both to individuals and communities.
https://ift.tt/2k9uP5T
A phase 1 study of safety and immunogenicity following intradermal administration of a tetravalent dengue vaccine candidate
Publication date: Available online 19 May 2018
Source:Vaccine
Author(s): Lisa A. Jackson, Richard Rupp, Athanasia Papadimitriou, Derek Wallace, Marsha Raanan, Kelley J. Moss
BackgroundAs part of the ongoing search for an effective dengue vaccine, Takeda performed a phase 1b study to investigate the safety and immunogenicity of an early low-dose tetravalent dengue vaccine candidate formulation (LD-TDV), based on an attenuated serotype 2 backbone, when administered intradermally with an injector device (PharmaJet®), or needle-syringe.MethodsThe study was performed in two centers in the US, in healthy 18–45 year old subjects with no history of dengue vaccination or disease. One or two vaccine doses were given on Day 0, and another dose or placebo on Day 90. Neutralizing antibodies were measured up to Day 270; safety was assessed as laboratory measurements and solicited and unsolicited adverse events on diary cards.ResultsChanges in World Health Organization prequalification guidance for new vaccines concerning storage conditions favored the use of lyophilized preparations, and led to the early cessation of enrolment, but not before 67 subjects were enrolled in four treatment groups. Sixty-five subjects completed the planned schedule. There were no safety signals or serious adverse events. All vaccination regimens elicited neutralizing antibodies. Titers of neutralizing antibodies against serotypes 1 and 2 were higher than those against serotypes 3 and 4. There were no consistent increases in responses with two doses given either concomitantly or 90 days apart.ConclusionsSimultaneous injection of two LD-TDV doses was shown to have the potential to improve seroconversion rates to serotypes 1 and 2, and to increase serotype 2 antibody titers. A primary dose of LD-TDV administered by PharmaJet was shown to induce more rapid seroconversion to serotypes 1, 2, and 3 compared with administration by needle-syringe (ClinicalTrials.gov: NCT01765426).
https://ift.tt/2rVTmPn
Effect of maternal immunization against pertussis in Medellin and the metropolitan area, Colombia, 2016–2017
Publication date: Available online 19 May 2018
Source:Vaccine
Author(s): Doracelly Hincapié-Palacio, María Cristina Hoyos, Jesus Ochoa, Nilton Montoya, Diego García, Elkin Osorio
BackgroundIn 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence.ObjectiveTo assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life.MethodsA cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015–2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed.ResultsWe observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16–21%]; umbilical cord: 23.1% [95% CI 19.2–27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000).ConclusionThe expected effect of Tdap maternal vaccination against pertussis was observed.
https://ift.tt/2kcrN0C
MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial
Publication date: Available online 19 May 2018
Source:Vaccine
Author(s): Luis Rivera, Pornthep Chanthavanich, Airi Põder, P.V. Suryakiran, Archana Jastorff, Marie Van der Wielen
BackgroundCo-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women.MethodsIn this phase IIIb study (NCT01755689), 1300 healthy 9–25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6. Immunogenicity, safety and reactogenicity were evaluated.ResultsImmunogenicity of MenACWY-TT and AS04-HPV16/18 when co-administered was non-inferior to that of the 2 vaccines given separately. Co-administration of MenACWY-TT, AS04-HPV16/18 and Tdap was non-inferior to MenACWY-TT administered alone or to Tdap co-administered with AS04-HPV16/18 in terms of immunogenicity for all vaccine components, except pertussis antigens. Post-vaccination, ≥89.5% of participants reached antibody levels above the pre-specified threshold for all antigens. No safety concerns were identified.ConclusionOur data support co-administration of MenACWY-TT with Tdap and AS04-HPV16/18 vaccines in adolescents.
https://ift.tt/2rYiYeh
Hyperostotic esthesioneuroblastoma as a fibrous dysplasia mimicker
Publication date: Available online 19 May 2018
Source:Acta Otorrinolaringológica Española
Author(s): Christian Calvo-Henríquez, Gabriel Martínez-Capoccioni, Aldo Rosario-Ortiz
https://ift.tt/2GC0eqi
Editorial Board
Publication date: May–June 2018
Source:Journal of Communication Disorders, Volume 73
https://ift.tt/2k8sbNI
The gist and details of sex differences in cognition and the brain: How parallels in sex differences across domains are shaped by the locus coeruleus and catecholamine systems
Publication date: Available online 19 May 2018
Source:Progress in Neurobiology
Author(s): Alexandra Ycaza Herrera, Jiaxi Wang, Mara Mather
Across three different domains, there are similar sex differences in how men and women process information. There tends to be a male advantage in attending to and remembering the gist (essential central information of a scene or situation), but a female advantage in attending to and remembering the details (non-essential peripheral information of a scene or situation). This is seen in emotional memory, where emotion enhances gist memory more for males than for females, but enhances detail memory more for females than for males. It also occurs in spatial memory, where men tend to notice and remember the gist of where they or objects are in space, allowing them to more flexibly manipulate themselves or objects within that space, whereas women tend to recall the details of the space around them, allowing them to accurately remember the locations of objects. Finally, such sex differences have also been noted in perception of stimuli such that men attend to global aspects of stimuli (such as a large letter E) more than women, whereas women attend more to the local aspects (such as the many smaller letter Ts making up the E). We review the parallel sex differences seen across these domains in this paper and how they relate to the different brain systems involved in each of these task domains. In addition, we discuss how sex differences in evolutionary pressures and in the locus coeruleus and norepinephrine system may account for why parallel sex differences occur across these different task domains.
https://ift.tt/2rTaypE
High-gamma activity in the human hippocampus and parahippocampus during inter-trial rest periods of a virtual navigation task
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Yi Pu, Brian R. Cornwell, Douglas Cheyne, Blake W. Johnson
In rodents, hippocampal cell assemblies formed during learning of a navigation task are observed to re-emerge during resting (offline) periods, accompanied by high-frequency oscillations (HFOs). This phenomenon is believed to reflect mechanisms for strengthening newly-formed memory traces. Using magnetoencephalography recordings and a beamforming source location algorithm (synthetic aperture magnetometry), we investigated high-gamma (80–140 Hz) oscillations in the hippocampal region in 18 human participants during inter-trial rest periods in a virtual navigation task. We found right hippocampal gamma oscillations mirrored the pattern of theta power in the same region during navigation, varying as a function of environmental novelty. Gamma power during inter-trial rest periods was positively correlated with theta power during navigation in the first task set when the environment was new and predicted greater performance improvement in the subsequent task set two where the environment became familiar. These findings provide evidence for human hippocampal reactivation accompanied by high-gamma activities immediately after learning and establish a link between hippocampal high-gamma activities and subsequent memory performance.
https://ift.tt/2GygCrW
Front Matter 1 - Full Title Page (regular issues)/Special Issue Title page (special issues)
Publication date: 15 August 2018
Source:Talanta, Volume 186
https://ift.tt/2KBE5Lh
Inter-comparison of the Regional Atmospheric Chemistry Mechanism (RACM2) and Master Chemical Mechanism (MCM) on the simulation of acetaldehyde
Publication date: August 2018
Source:Atmospheric Environment, Volume 186
Author(s): Ruihan Zong, Likun Xue, Tao Wang, Wenxing Wang
Acetaldehyde (CH3CHO) is a key player of atmospheric chemistry, an important air pollutant, and hence a major target of air quality modeling and management. The Regional Atmospheric Chemistry Mechanism (RACM) is a highly lumped gas-phase chemical mechanism that has been widely applied in atmospheric chemistry modeling studies. A significant update of the latest version of RACM (RACM2) is the addition of CH3CHO as an explicit aldehyde species, facilitating the direct simulation of CH3CHO. In this study, we compared the performances of RACM2 and Master Chemical Mechanism (MCM; v3.3.1) on the simulation of CH3CHO. Zero-dimensional chemical box models based on these two independent mechanisms were prescribed to a polluted scenario to simulate the evolution of ozone (O3), hydroxyl radical (OH), C2H5O2 (ETHP) and CH3CHO, as well as their detailed chemical budgets. Overall, both mechanisms agreed with the simulation of O3 and OH, but the RACM2 model simulated significantly higher levels of ETHP and CH3CHO than the MCM model. The difference in the chemical kinetic data in both mechanisms is not the reason for this discrepancy. The oversimplification of the lumped peroxy acyl radicals (RCO3) and ≥C3 aldehydes chemistry of RACM2 should be responsible for its higher simulated ETHP and CH3CHO. We caution the use of RACM2 or any other highly aggregated chemical mechanism for the simulation of C2H5O2 and CH3CHO. Better methods are needed to represent the chemistry of peroxy acyl radicals and ≥C3 aldehydes for aggregated chemical mechanisms. More experiments are required to directly validate and further improve the current chemistry mechanisms.
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Discovery and synthesis of 6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-one-based novel chemotype CCR2 antagonists via scaffold hopping strategy
Publication date: Available online 19 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Li-Huai Qin, Zhi-Long Wang, Xin Xie, Ya-Qiu Long
The chemokine CC receptor subtype 2 (CCR2) has attracted intensive interest for drug development in diverse therapeutic areas, including chronic inflammatory diseases, diabetes, neuropathic pain, atherogenesis and cancer. By employing a cut-and-sew scaffold hopping strategy, we identified an active scaffold of 3,4-dihydro-2,6-naphthyridin-1(2H)-one as the central pharmacophore to derive novel CCR2 antagonists. Systematic structure-activity relationship study with respect to the ring size and the substitution on the naphthyridinone ring gave birth to 1-arylamino-6-alkylheterocycle-6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-ones as a brand new chemotype of CCR2 antagonists with nanomolar inhibitory activity. The best antagonism activity in this series was exemplified by compound 13a, which combined the optimal substitutions of 3,4-dichlorophenylamino at C-1 and 3-(4-(N-methylmethylsulfonamido)piperidin-1-yl)propyl at N-6 position, leading to an IC50 value of 61 nM and 10-fold selectivity for CCR2 over CCR5. Efficient and general synthesis was established to construct the innovative core structure and derivethe compound collections. This is the first report on our designed 6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-one as novel CCR2 antagonist scaffold and its synthesis.
Graphical abstract
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Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics
Publication date: Available online 19 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Napon Nilchan, Wanida Phetsang, Taechin Nowwarat, Soraya Chaturongakul, Chutima Jiarpinitnun
Incorporation of halogen atoms to drug molecule has been shown to improve its properties such as enhanced in membrane permeability and increased hydrophobic interactions to its target. To investigate the effect of halogen substitutions on the antibacterial activity of trimethoprim (TMP), we synthesized a series of halogen substituted TMP and tested for their antibacterial activities against global predominant methicillin resistant Staphylococcus aureus (MRSA) strains. Structure-activity relationship analysis suggested a trend in potency that correlated with the ability of the halogen atom to facilitate in hydrophobic interaction to saDHFR. The most potent derivative, iodinated trimethoprim (TMP-I), inhibited pathogenic bacterial growth with MIC as low as 1.25 μg/mL while the clinically used TMP derivative, diaveridine, showed resistance. Similar to TMP, synergistic studies indicated that TMP-I functioned synergistically with sulfamethoxazole. The simplicity in the synthesis from an inexpensive starting material, vanillin, highlighted the potential of TMP-I as antibacterial agent for MRSA infections.
Graphical abstract
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Anthranilic diamides derivatives as potential ryanodine receptor modulators: synthesis, biological evaluation and structure activity relationship
Publication date: Available online 19 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Jing-Bo Liu, Feng-Yun Li, Jing-Yue Dong, Yu-Xin Li, Xiu-Lan Zhang, Yuan-Hong Wang, Li-Xia Xiong, Zheng-Ming Li
A series of novel anthranilic diamides derivatives (7a-s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1H NMR, 13C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental armywarm (Mythimna separata) and diamondback moth (Plutella xylostella). Above all, the larvicidal activity of 7o against oriental armywarm was 100% and 40% at 0.25 and 0.1 mg L-1, comparable to that of the standard chlorantraniliprole (100%, 0.25 mg L-1 and 20 %, 0.1 mg L-1). What is more, 7o against diamondback moth displayed 90% insecticidal activity at 0.01 mg L-1, superior to chlorantraniliprole (45%, 0.01 mg L-1). The experiments 7o on the American cockroach (Periplaneta Americana) heart beating rates (Dorsal vessel) and contractile force were compared with chlorantraniliprole. In addition, 7o could affect the calcium homeostasis in the central neurons of the third larvae of oriental armyworm, which revealed that the ryanodine receptor is the potential target of 7o. The density functional theory (DFT) calculation results revealed the amide bridge, the benzene ring of anthraniloyl moiety and pyrazole ring might play an important role in the insecticidal activity through hydrophobic interactions and π-π conjugations.
Graphical abstract
https://ift.tt/2LgI9Sv
Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair
Publication date: Available online 19 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): B. Prabha, S. Neethu, S. Lekshmy Krishnan, D.R. Sherin, M. Madhukrishnan, R. Ananthakrishnan, K.B. Rameshkumar, T.K. Manojkumar, P. Jayamurthy, K.V. Radhakrishnan
Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2–7). All the compounds displayed moderate inhibitory activity on α-amylase and significant activity on α-glucosidase; however malabaricone B (6) and C (7) were identified as potent α-glucosidase inhibitors with IC50 values of 63.70 ± 0.546, and 43.61 ± 0.620 µM respectively. Acylphenols (compounds 3–7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus.
Graphical abstract
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Novel carbamate-linked quaternary ammonium lipids containing unsaturated hydrophobic chains for gene delivery
Publication date: Available online 19 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Hengjun Zhou, Jian Yang, Yanyan Du, Shuang Fu, Chenxi Song, Defu Zhi, Yinan Zhao, Huiying Chen, Shubiao Zhang, Shufen Zhang
In this paper, two novel carbamate-linked quaternary ammonium lipids (MU18: a lipid with a mono-ammonium head; GU18: a lipid with a Gemini-ammonium head) containing unsaturated hydrophobic chains were designed and synthesized. The chemical structures of the synthetic lipids were characterized by infrared spectrum, ESI-MS, 1H NMR, 13C NMR, and HPLC. For investigating the effect of unsaturation on gene delivery, the previous reported saturated cationic liposomes (MS18 and GS18) were used as comparison. Cationic liposomes were prepared by using these cationic lipids and neutral lipid DOPE at the molar ratio of 1:1. Particle sizes and zeta potentials of the cationic liposomes were studied to show that they were suitable for gene transfection. The binding abilities of the cationic liposomes were investigated by gel electrophoresis at various N/P ratios from 0.5/1 to 8/1. The results indicated that the binding ability of GU18 was much better than MU18 and the saturated cationic liposomes (MS18 and GS18). DNA transfection of these liposomes comparable to commercially available reagent (DOTAP) was achieved in vitro against Hela, HepG-2 and NCI-H460 cell lines. GU18 showed higher transfection at the N/P ratio of 3/1 than other cationic liposomes and the positive control, DOTAP. All of the liposomes presented a relatively low cytotoxicity, which was measured by MTT. Therefore, the synthetic lipids bearing unsaturated hydrophobic chains and Gemini-head could be promising candidates for gene delivery.
Graphical abstract
https://ift.tt/2LgHZun
Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent
Publication date: Available online 19 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Madoka E. Hazemi, Kazumitsu Onizuka, Tomohito Kobayashi, Akira Usami, Norihiro Sato, Fumi Nagatsugi
Higher-order structures of nucleic acids have become widely noted for their biological consequences and the discovery of an alkylating small molecule for these structures has been of interest due to its therapeutic potential. We previously developed the vinyldiaminotriazine (VDAT)-acridine conjugate as a T-T mismatch alkylating agent. In this report, we focused on the finding of the alkylation to the G-quadruplex (G4) DNA with VDAT-acridine conjugates. The VDAT-acridine conjugates exhibited a considerable alkylation ability to G4 under mild conditions. Moreover, the investigation of properties with the alkylated G4 revealed that alkylation by this conjugate significantly increased the stability of the G4 structure. This study provides a starting point in the further development of selective G4 alkylating small molecules.
Graphical abstract
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Drug efficacy of novel 3-O-methoxy-4-halo disubstituted 5,7-dimethoxy chromans; evaluated via DNA gyrase inhibition, bacterial cell wall lesion and antibacterial prospective
Publication date: Available online 18 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Thangarasu Ponnusamy, Manikandan Alagumuthu, S. Thamaraiselvi
In this study, novel 3-O-methoxy-4-halo, disubstituted-5,7-dimethoxy chromans with bacterial cell wall degrading potentials were synthesized, characterized and evaluated as DNA gyrase inhibitors and antibacterial agents. Compounds were showed a broad spectrum of antimicrobial activity against both Gram+ve bacteria (S. aureus (MTCC 3160), C. diphtheriae (MTCC 116), S. pyogenes (MTCC 442)) and Gram-ve bacteria (E. coli (MTCC 443), P. aeruginosa (MTCC 424), K. pneumoniae (MTCC 530)). Further, a molecular docking study was carried out to get more insight into the binding mode of present study compounds to target proteins (PDB ID: 2XCT (S. aureus DNA gyrase A), PDB ID: 3G75 (S. aureus DNA gyrase B), PDB ID: 3L7L (Teichoic acid polymerase). In the results, 14 > 20 > 24 > 12 > 18 > 17 were found as the most active against almost all executed activities in this study. The predicted Lipinski's filter scores, SAR, pharmacokinetic/pharmacodynamics, and ADMET properties of these compounds envisioned the druggability prospects and the necessity of further animal model evaluations of 3-O-methoxy-4-halo disubstituted 5,7-dimethoxy chromans to establish them as an effective and future antibiotics.
Graphical abstract
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Analysis of hepatitis B virus infection in blood sera using Raman spectroscopy and machine learning
Publication date: Available online 19 May 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Saranjam Khan, Rahat Ullah, Asifullah Khan, Ruby Ashraf, Hina Ali, Muhammad Bilal, Muhammad Saleem
This study presents the analysis of hepatitis B virus (HBV) infection in human blood serum using Raman spectroscopy combined with pattern recognition technique. In total 119 confirmed samples of HBV infected sera, collected from Pakistan Atomic Energy Commission (PAEC) general hospital have been used for the current analysis. The differences between normal and HBV infected samples have been evaluated using support vector machine (SVM) algorithm. SVM model with two different kernels i.e. polynomial function and Gaussian radial basis function (RBF) have been investigated for the classification of normal blood sera from HBV infected sera based on Raman spectral features. Furthermore, the performance of the model with each kernel function has also been analyzed with two different implementations of optimization problem i.e. Quadratic programming and least square. 5-fold cross validation method has been used for the evaluation of the model. In the current study, best classification performance has been achieved for polynomial kernel of order-2. A diagnostic accuracy of about 98% with the precision of 97%, sensitivity of 100% and specificity of 95% has been achieved under these conditions.
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Neuroimaging findings of extensive sphenoethmoidal dysplasia in NF1
Publication date: September–October 2018
Source:Clinical Imaging, Volume 51
Author(s): Allison Tam, Joseph M. Sliepka, Sunil Bellur, Collin Douglas Bray, Christie M. Lincoln, Sandesh C.S. Nagamani
Whereas isolated sphenoid wing dysplasia (SWD) is a well-known clinical feature in neurofibromatosis 1 (NF1), extensive cranial defects involving multiple bones have been rarely reported in this disorder. In this report, we describe the clinical course of a 20-year-old male with NF1 and an extensive cranial bone dysplasia. The large sphenoethmoidal defect was associated with transethmoidal and orbital cephalocele as well as inferolateral herniation of the frontal lobe. In spite of the large defect, the individual did not have any symptoms or complications resulting from the osteopathy. We review the current knowledge of the pathogenesis and management of cranial bone dysplasia in NF1.
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Corrigendum to “Left hemisphere specialization for word reading potentially causes, rather than results from, a left lateralized bias for high spatial frequency visual information” [Cortex 72 (2015) 27–39]
Publication date: Available online 19 May 2018
Source:Cortex
Author(s): Alexandra Ossowski, Marlene Behrmann
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Quantification of the ω5- and γ-gliadin content in wheat flour and rat plasma with an enzyme-linked immunosorbent assay using antibodies specific to their IgE-binding epitopes
Publication date: Available online 19 May 2018
Source:Allergology International
Author(s): Tomoharu Yokooji, Hitomi Nouma, Ryohei Ogino, Takanori Taogoshi, Eishin Morita, Hiroaki Matsuo
https://ift.tt/2wVigUS