Combining advantages of homogeneous organocatalysis and heterogeneous catalysis with thermosensitive single-chain nanoparticles in a representative tetrahydropyranilation of alcohols

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Misha Rumyantsev, Sergey Rumyantsev
A significant scientific problem solved in this work is the development of effective polymer catalysts that allow carrying out organic reactions under homogeneous conditions with high rates and to remove catalyst from the system as a heterophase without the use of special treatment, thus combining the advantages of both homogeneous and heterogeneous catalysis. Kinetic experiments show high catalytic activity of the synthesized catalyst in homogeneous regime even at low dosage of the catalyst. Thus, it was demonstrated that tetrahydropyranilation of methanol was completed in nearly quantitative yield of the corresponding ether in 80 min at 60 °C with a dosage of the polymeric catalyst as low as 0.2 mol%. On the other hand anomalous decrease in the values of the effective rate constant was observed when the reaction was run at temperatures below the phase transition temperature. Kinetic data were used along with thermodynamic calculations to discuss the effect of the synthesized polymeric catalyst on the stabilization of the transition state. The high activity of the catalyst is complemented by its high sedimentation ability; thus, it usually takes a few minutes for the polymer to precipitate from the alcohol solution when cooled below the phase-transition temperature after the completion of the reaction. It was also revealed via dynamic light scattering that catalytic polymers adopt a thermodynamically stable conformation of the single-chain nanoparticles with average hydrodynamic radius in the range 2–2.5 nm.

Graphical abstract

http://ift.tt/2CqbcRK

Selective synthesis of highly soluble cyclic olefin copolymers with pendant vinyl groups using 1,5-hexadiene as a comonomer

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Ryo Tanaka, Akane Sasaki, Takuma Takenaka, Yuushou Nakayama, Takeshi Shiono
Copolymerization of norbornene (NB) and 1,5-hexadiene (HD) was performed using a fluorenylamido-ligated titanium catalyst which conducts copolymerization of NB and 1-alkene. The obtained copolymers possessed pendant vinyl groups, of which content was varied from 0 to 9.4% by the initial feed ratio of the monomers. The copolymers were soluble in various solvents even at high conversion (>85%), showing that the crosslinking of pendant vinyl groups was negligible. The glass transition temperature of the copolymer was changed from 79 °C to over 300 °C, depending on the comonomer composition. Post-functionalization of the pendant vinyl groups with 3,3,4,4,5,5,6,6,6-nonafluoro-1-hexene via ruthenium-catalyzed metathesis reaction was also performed and fluoroalkyl-functionalized cyclic olefin copolymer was successfully obtained. The fluorinated copolymer film showed higher contact angle than the unfunctionalized copolymer.

Graphical abstract

http://ift.tt/2CpEMH1

Effects of pH on the photophysics of conjugated polyelectrolyte complexes

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Pamela Schleissner, Alexander L. Ayzner
We have previously reported the formation of complexes between oppositely charged, conjugated polyelectrolytes (CPECs), resulting in electronic energy transfer between the donor and acceptor components. The ionic self-assembly process that forms CPECs is heavily influenced by environmental circumstances including solvent composition, temperature, and pH. In this article, we report the effect of polyelectrolyte chain protonation on complex formation and resulting energy transfer. The particular polyelectrolytes used in this study were a pH inactive energy donor and an acceptor polymer with protonatable sidechains. We find that over a large range of acidic pH, the optical properties do not change appreciably up to precipitation (pH 3). Surprisingly in the basic regime where the acceptor polymer is fully deprotonated, complex formation is hindered. However, at pH 11, which corresponds to an excess ion concentration of 0.001 M, the photophysical properties of the complex begin to once again resemble that of the neutral or acidic environments. Our results show that the CPEC displays impressive stability over a relatively broad range of proton concentrations, which may have implications for the construction of supramolecular light-harvesting assemblies.

Graphical abstract

http://ift.tt/2Ctk60M

Stakeholders’ Perspectives on Postmastectomy Breast Reconstruction: Recognizing Ways to Improve Shared Decision Making

Background: Postmastectomy breast reconstruction (PMBR) is an elective, preference-sensitive decision made during a stressful, time-pressured period after a cancer diagnosis. Shared decision making (SDM) can improve decision quality about preference-sensitive choices. Stakeholders’ perspectives on ways to support PMBR decision-making were explored. Methods: Forty semi-structured interviews with stakeholders (20 postmastectomy patients, 10 PMBR surgeons, 10 PMBR nurses) were conducted. Clinicians were recruited from diverse practices across the United States. Patients were recruited using purposive sampling with varying PMBR experiences, including no reconstruction. The interview guide was based on an implementation research framework. Themes were identified using grounded theory approach, based on frequency and emotive force conveyed. Results: Engagement in SDM was variable. Some patients wanted more information about PMBR from clinicians, particularly about risks. Some clinicians acknowledged highlighting benefits and downplaying risks. Many patients felt pressured to make a choice by their clinicians. Clinicians who successfully engaged patients through decisions often used outside resources to supplement conversations. Conclusions: Patient–clinician trust was critical to high-quality decisions, and many patients expressed decision regret when they were not engaged in PMBR discussions. Patients often perceived a race- or age-related bias in clinician information sharing. Interventions to support SDM may enhance decision quality and reduce decision regret about PMBR, ultimately improving patient-centered care for women with breast cancer.

http://ift.tt/2j17g27

Creation of Nepal’s First Skin Bank: Challenges and Outcomes

Background: In Nepal, burn trauma causes more than 55,000 injuries each year. Burn-related mortality is high in Nepal, in part due to lack of allograft, leading to high infection rates. To address this challenge, our collaboration between Kirtipur Hospital, America Nepal Medical Foundation, Stanford University, and ReSurge International established Nepal’s first skin bank. Methods: We identified 3 major tasks to create a sustainable skin banking program: 1) identify and acquire the equipment and personnel needed to collect, process, store, and graft cadaveric skin for burn injuries; 2) develop safe donation protocols and documentation tools that remain feasible for low-resource settings; and 3) develop a long-term awareness program to educate the Nepali people on skin donation, a previously foreign concept. Results: Kirtipur Hospital acquired the necessary equipment and materials for the skin bank through a combination of local and international fundraising efforts. Existing U.S. skin banking protocols were adapted for the Nepali setting and piloted on potential patients, donors, and physicians. For the first time in the hospital’s history, patients with > 40% total body surface area burns were successfully treated with extensive allografts. Conclusions: It is feasible to create a skin bank in a country with no tradition of allograft skin use. Long-term sustainability now depends on spreading awareness and education in the Kathmandu Valley to overcome religious and cultural barriers that have hindered donor recruitment. Our low-cost and high-impact skin bank provides a model to expand this system to other hospitals both within Nepal and beyond.

http://ift.tt/2CvviYm

Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis

Background: Hypertrophic scar formation is unpredictable and poorly understood, afflicting both the pediatric and adult populations. Treatment methods with conservative and invasive approaches have low rates of compliance and high rates of morbidity. The purpose of this study was to test a reproducible scar model and investigate a new technique of scar modification through the use of adipose- derived progenitor stromal cells (ASCs). Methods: Twenty thermal deep-partial thickness contact burns were created on the dorsum of three 8-week-old domestic swine and allowed to mature for 10 weeks. Scars were then injected with 2 cc saline, expanded autologous ASCs, or 2 cc fresh lipoaspirate and sampled at 2 week intervals up to 10 weeks postinjection. Volumetric analysis with a 3-D scanner, mechanical elasticity testing through negative pressure transduction, and standardized photography evaluation with Image J was performed. RNA sequencing was performed on scar tissue samples, cultured cells, and fresh lipoaspirate to determine relevant gene transcription regulation. Immunohistochemistry was used to verify expression level changes within the scars. Results: Volumetric analysis demonstrates a reduction in average scar thickness at 6 weeks when injected with ASCs (−1.6 cc3) and autologous fat (−1.95 cc3) relative to controls (−0.121 cc3; P

http://ift.tt/2Cvv7wa

Stakeholders’ Perspectives on Postmastectomy Breast Reconstruction: Recognizing Ways to Improve Shared Decision Making

Background: Postmastectomy breast reconstruction (PMBR) is an elective, preference-sensitive decision made during a stressful, time-pressured period after a cancer diagnosis. Shared decision making (SDM) can improve decision quality about preference-sensitive choices. Stakeholders' perspectives on ways to support PMBR decision-making were explored. Methods: Forty semi-structured interviews with stakeholders (20 postmastectomy patients, 10 PMBR surgeons, 10 PMBR nurses) were conducted. Clinicians were recruited from diverse practices across the United States. Patients were recruited using purposive sampling with varying PMBR experiences, including no reconstruction. The interview guide was based on an implementation research framework. Themes were identified using grounded theory approach, based on frequency and emotive force conveyed. Results: Engagement in SDM was variable. Some patients wanted more information about PMBR from clinicians, particularly about risks. Some clinicians acknowledged highlighting benefits and downplaying risks. Many patients felt pressured to make a choice by their clinicians. Clinicians who successfully engaged patients through decisions often used outside resources to supplement conversations. Conclusions: Patient–clinician trust was critical to high-quality decisions, and many patients expressed decision regret when they were not engaged in PMBR discussions. Patients often perceived a race- or age-related bias in clinician information sharing. Interventions to support SDM may enhance decision quality and reduce decision regret about PMBR, ultimately improving patient-centered care for women with breast cancer.

http://ift.tt/2j17g27

Creation of Nepal’s First Skin Bank: Challenges and Outcomes

Background: In Nepal, burn trauma causes more than 55,000 injuries each year. Burn-related mortality is high in Nepal, in part due to lack of allograft, leading to high infection rates. To address this challenge, our collaboration between Kirtipur Hospital, America Nepal Medical Foundation, Stanford University, and ReSurge International established Nepal's first skin bank. Methods: We identified 3 major tasks to create a sustainable skin banking program: 1) identify and acquire the equipment and personnel needed to collect, process, store, and graft cadaveric skin for burn injuries; 2) develop safe donation protocols and documentation tools that remain feasible for low-resource settings; and 3) develop a long-term awareness program to educate the Nepali people on skin donation, a previously foreign concept. Results: Kirtipur Hospital acquired the necessary equipment and materials for the skin bank through a combination of local and international fundraising efforts. Existing U.S. skin banking protocols were adapted for the Nepali setting and piloted on potential patients, donors, and physicians. For the first time in the hospital's history, patients with > 40% total body surface area burns were successfully treated with extensive allografts. Conclusions: It is feasible to create a skin bank in a country with no tradition of allograft skin use. Long-term sustainability now depends on spreading awareness and education in the Kathmandu Valley to overcome religious and cultural barriers that have hindered donor recruitment. Our low-cost and high-impact skin bank provides a model to expand this system to other hospitals both within Nepal and beyond.

http://ift.tt/2CvviYm

Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis

Background: Hypertrophic scar formation is unpredictable and poorly understood, afflicting both the pediatric and adult populations. Treatment methods with conservative and invasive approaches have low rates of compliance and high rates of morbidity. The purpose of this study was to test a reproducible scar model and investigate a new technique of scar modification through the use of adipose- derived progenitor stromal cells (ASCs). Methods: Twenty thermal deep-partial thickness contact burns were created on the dorsum of three 8-week-old domestic swine and allowed to mature for 10 weeks. Scars were then injected with 2 cc saline, expanded autologous ASCs, or 2 cc fresh lipoaspirate and sampled at 2 week intervals up to 10 weeks postinjection. Volumetric analysis with a 3-D scanner, mechanical elasticity testing through negative pressure transduction, and standardized photography evaluation with Image J was performed. RNA sequencing was performed on scar tissue samples, cultured cells, and fresh lipoaspirate to determine relevant gene transcription regulation. Immunohistochemistry was used to verify expression level changes within the scars. Results: Volumetric analysis demonstrates a reduction in average scar thickness at 6 weeks when injected with ASCs (−1.6 cc3) and autologous fat (−1.95 cc3) relative to controls (−0.121 cc3; P

http://ift.tt/2Cvv7wa

REM-associated sleep disordered breathing: prevalence and clinical significance in the hypnolaus cohort

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): P. Acosta-Castro, P. Marques-Vidal, P. Vollenweider, N. Tobback, J. Haba-Rubio, R. Heinzer




http://ift.tt/2ElOWXn

Obstructive sleep apnea is highly undetected in non-obese patients with atrial fibrillation

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): A.M. Abumuamar, P. Sandor, P. Dorian, D. Newman, C. Shapiro




http://ift.tt/2q3HwoL

Use of occlusal splint or mandibular advancement appliance by sleep bruxism patients do not normalize arousal related heart rate variability

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): S. Abe, P.H. Rompré, N.T. Huynh, A. Landry-Schönbeck, M.-L. Landry, P. de Grandmont, F. Kawano, G.J. Lavigne




http://ift.tt/2EnafIh

Irregular sleep-wake rhythm disorder in a young woman with Townes-Brocks-syndrome

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): J. Acker, L. Gerber, M. Wüst, C. Niederberger, A. Nirkko




http://ift.tt/2q3HoFN

World Association of Sleep Medicine (WASM) historical summary

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): Allan O'Bryan, Luigi Ferini Strambi, Thomas Penzel




http://ift.tt/2EnwHAL

Treatment of obstructive sleep apnea decreases the recurrence of atrial and ventricular ectopy in patients with atrial fibrillation

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): A.M. Abumuamar, P. Dorian, D. Newman, P. Sandor, C. Shapiro




http://ift.tt/2q68Gez

Clinical and polysomnographic differences in elderly patients with obstructive sleep apnea (OSA)

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): M. Erdemir Isık, B. Gulbay, T. Acican, F. Çiftçi, Z.P. Önen, A. Azeez, K. Turkel




http://ift.tt/2EqDwBx

Handheld mobile biofeedback of heart rate variability in patients with chronic insomnia disorder – a pilot study

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): J. Acker, A. Nirkko, M. Wüst, K. Richter




http://ift.tt/2q3H2yX

Effect of sleep apnea and insomnia on the association of depression with quantitative electroencephalogram measures (QEEG) in adult men during sleep – the MAILES study

Publication date: December 2017
Source:Sleep Medicine, Volume 40, Supplement 1
Author(s): R. Adams, S. Appleton, A. Vakulin, A. D'Rozario, R.D. McEvoy, P. Catcheside, S. Martin, C. Lang, A. Vincent, G. Wittert




http://ift.tt/2EobpTU

Surface EMG patterns for quantification of thigh muscle co-contraction in school-age children: Normative data during walking

Publication date: March 2018
Source:Gait & Posture, Volume 61
Author(s): Francesco Di Nardo, Annachiara Strazza, Alessandro Mengarelli, Serena Ercolani, Nicole Morgoni, Laura Burattini, Valentina Agostini, Marco Knaflitz, Sandro Fioretti
Muscle co-contractions are particularly relevant in analyzing children pathologies. To interpret surface electromyography (sEMG) in pathological conditions, reliable normative data in non-pathological children are required for direct comparison. Aim of the study was the quantification of co-contraction activity between quadriceps femoris (QF) and hamstring muscles during walking in healthy children. To this aim, Statistical gait analysis was performed on sEMG signals from rectus femoris (RF), vastus medialis (VM), and lateral hamstrings (LH), in 16401 strides walked by 100 healthy school-age children. Co-contractions were assessed as overlapping period between activation intervals of considered muscles. Results showed full superimpositions of LH with both RF and VL activity from terminal swing, 80–100% of gait cycle, to successive loading response (0–15% of gait cycle), in around 90% of strides, as reported in adults. This indicates that children regularly use a cocontraction activity between QF and hamstring muscles in weight acceptance during walking, supporting the hypothesis of a regulatory role of co-contraction in providing knee joint stability. Concomitant activity of QF and hamstring muscles was detected also during push-off phase (30–50% of gait cycle), showing a large variability intra and inter subjects and a lower occurrence frequency (around 25% of strides). This could be intended for controlling rapid knee flexion and/or stabilizing pelvis during body progression. Present findings represent the first attempt to provide normative sEMG dataset on variability of QF and hamstring muscles co-contractions during child walking, useful for discriminating physiological and pathological behavior and for designing future studies on maturation of gait.



http://ift.tt/2lz3yKt

Surface EMG patterns for quantification of thigh muscle co-contraction in school-age children: Normative data during walking

Publication date: March 2018
Source:Gait & Posture, Volume 61
Author(s): Francesco Di Nardo, Annachiara Strazza, Alessandro Mengarelli, Serena Ercolani, Nicole Morgoni, Laura Burattini, Valentina Agostini, Marco Knaflitz, Sandro Fioretti
Muscle co-contractions are particularly relevant in analyzing children pathologies. To interpret surface electromyography (sEMG) in pathological conditions, reliable normative data in non-pathological children are required for direct comparison. Aim of the study was the quantification of co-contraction activity between quadriceps femoris (QF) and hamstring muscles during walking in healthy children. To this aim, Statistical gait analysis was performed on sEMG signals from rectus femoris (RF), vastus medialis (VM), and lateral hamstrings (LH), in 16401 strides walked by 100 healthy school-age children. Co-contractions were assessed as overlapping period between activation intervals of considered muscles. Results showed full superimpositions of LH with both RF and VL activity from terminal swing, 80–100% of gait cycle, to successive loading response (0–15% of gait cycle), in around 90% of strides, as reported in adults. This indicates that children regularly use a cocontraction activity between QF and hamstring muscles in weight acceptance during walking, supporting the hypothesis of a regulatory role of co-contraction in providing knee joint stability. Concomitant activity of QF and hamstring muscles was detected also during push-off phase (30–50% of gait cycle), showing a large variability intra and inter subjects and a lower occurrence frequency (around 25% of strides). This could be intended for controlling rapid knee flexion and/or stabilizing pelvis during body progression. Present findings represent the first attempt to provide normative sEMG dataset on variability of QF and hamstring muscles co-contractions during child walking, useful for discriminating physiological and pathological behavior and for designing future studies on maturation of gait.



http://ift.tt/2lz3yKt

Near infrared hyperspectral dataset of healthy and infected apple tree leaves images for the early detection of apple scab disease

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Maroua Nouri, Nathalie Gorretta, Pierre Vaysse, Michel Giraud, Christian Germain, Barna Keresztes, Jean-Michel Roger
This dataset presents two series of hyperspectral images of healthy and infected apple tree leaves acquired daily, from two days after inoculation until an advanced stage of infection (11 days after inoculation). The hyperspectral images were calibrated by reflection correction and registered to match the geometry of one reference image. On the last experiment day, scab positions are provided.



http://ift.tt/2CrQyRa

Fibroblast and keratinocyte gene expression following exposure to extracts of neem plant (Azadirachta indica)

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Takao Someya, Katsura Sano, Kotaro Hara, Yoshimasa Sagane, Toshihiro Watanabe, R.G.S. Wijesekara
This data article provides gene expression profiles, determined by using real-time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts of neem plant (Azadirachta indica), local name "Kohomba" in Sri Lanka, harvested in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes encoding hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2), hyaluronidase-1 (HYAL1), hyaluronidase-2 (HYAL2), versican, aggrecan, CD44, collagen, type I, alpha 1 (COL1A1), collagen, type III, alpha 1 (COL3A1), collagen, type VII, alpha 1 (COL7A1), matrix metalloproteinase 1 (MMP1), acid ceramidase, basic fibroblast growth factor (bFGF), fibroblast growth factor-7 (FGF7), vascular endothelial growth factor (VEGF), interleukin-1 alpha (IL-1α), cyclooxygenase-2 (cox2), transforming growth factor beta (TGF-β), and aquaporin 3 (AQP3). For keratinocytes, the expression profiles are for genes encoding HAS1, HAS2, HYAL1, HYAL2, versican, CD44, IL-1α, cox2, TGF-β, AQP3, Laminin5, collagen, type XVII, alpha 1 (COL17A1), integrin alpha-6 (ITGA6), ceramide synthase 3 (CERS3), elongation of very long chain fatty acids protein 1 (ELOVL1), elongation of very long chain fatty acids protein 4 (ELOVL4), filaggrin (FLG), transglutaminase 1 (TGM1), and keratin 1 (KRT1). The expression profiles are provided as bar graphs.



http://ift.tt/2BZVTMm

Data on a single oral dose of camu camu (Myrciaria dubia) pericarp extract on flow-mediated vasodilation and blood pressure in young adult humans

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Tadayoshi Miyashita, Ryosuke Koizumi, Takao Myoda, Yoshimasa Sagane, Koichi Niwa, Toshihiro Watanabe, Kazuhiro Minami
This data article describes the flow-mediated vasodilation (FMD) responses, represented by changes in arterial diameter, and blood pressure changes in young adults after a single oral dose of camu camu (Myrciaria dubia) pericarp extract or placebo (cross-over design). Ten healthy men and 10 healthy women participated in this study. Ultrasonic diagnostic equipment was used to monitor arterial diameter changes, indicative of FMD, for 110s after the administration of the camu camu extract or placebo. In addition, the systolic and diastolic blood pressure values were recorded.



http://ift.tt/2CqydEf

Data on a delivery of biomolecules into Nicothiana benthamiana leaves using different nanoparticles

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Antonida V. Makhotenko, Ekaterina A. Snigir, Natalia O. Kalinina, Valentin V. Makarov, Michael E. Taliansky
Nanoparticles (NPs) have a number of unique properties associated with their ultrasmall size and exhibit many advantages compared with existing plant biotechnology platforms for delivery of proteins, RNA and DNA of various sizes into the plant cells (Arruda et al., 2015; Silva et al., 2010; Martin-Ortigosa et al., 2014; Mitter et al., 2017) [1–4]. The data presented in this article demonstrate a delivery of biomolecules into Nicotiana benthamiana plant leaves using various types of NPs including gold, iron oxide and chitosan NPs and methods of biolistic bombardment and infiltration. The data demonstrate physical characteristics of NPs coated with fluorescently labeled protein and small RNA (size and zeta-potential) and visualization of nanocomplexes delivery into cells of N. benthamiana leaves by fluorescence microscopy.



http://ift.tt/2C0bcEC

A novel pathogenic variant c.975G>A (p.Trp325*) in the POU3F4 gene in Yakut family (Eastern Siberia, Russia) with the X-linked deafness-2 (DFNX2).

Related Articles

A novel pathogenic variant c.975G>A (p.Trp325*) in the POU3F4 gene in Yakut family (Eastern Siberia, Russia) with the X-linked deafness-2 (DFNX2).

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:94-97

Authors: Barashkov NA, Klarov LA, Teryutin FM, Solovyev AV, Pshennikova VG, Konnikova EE, Romanov GP, Tobokhov AV, Morozov IV, Bondar AA, Posukh OL, Dzhemileva LU, Tomsky MI, Khusnutdinova EK, Fedorova SA

Abstract
Here, we report a novel hemizygous transition c.975G>A (p.Trp325*) in POU3F4 gene (Xq21) found in two deaf half-brothers from one Yakut family (Eastern Siberia, Russia) with identical inner ear abnormalities ("corkscrew" cochlea with an absence of modiolus) specific to X-linked deafness-2 (DFNX2). Comprehensive clinical evaluation (CT and MR-imaging, audiological and stabilometric examinations) of available members of this family revealed both already known (mixed progressive hearing loss) and additional (enlargement of semicircular canals and postural disorders) clinical DFNX2 features in affected males with c.975G>A (p.Trp325*). Moreover, mild enlargement of semicircular canals, postural abnormalities and different types of hearing thresholds were found in female carrier of this POU3F4-variant.

PMID: 29287890 [PubMed - in process]

http://ift.tt/2CkHdeb

A novel mutation of the EYA4 gene associated with post-lingual hearing loss in a proband is co-segregating with a novel PAX3 mutation in two congenitally deaf family members.

Related Articles

A novel mutation of the EYA4 gene associated with post-lingual hearing loss in a proband is co-segregating with a novel PAX3 mutation in two congenitally deaf family members.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:88-93

Authors: Cesca F, Bettella E, Polli R, Cama E, Scimemi P, Santarelli R, Murgia A

Abstract
OBJECTIVES: This work was aimed at establishing the molecular etiology of hearing loss in a 9-year old girl with post-lingual non-syndromic mild sensorineural hearing loss with a complex family history of clinically heterogeneous deafness.
METHODS: The proband's DNA was subjected to NGS analysis of a 59-targeted gene panel, with the use of the Ion Torrent PGM platform. Conventional Sanger sequencing was used for segregation analysis in all the affected relatives. The proband and all the other hearing impaired members of the family underwent a thorough clinical and audiological evaluation.
RESULTS: A new likely pathogenic mutation in the EYA4 gene (c.1154C > T; p.Ser385Leu) was identified in the proband and in her 42-year-old father with post-lingual non-syndromic profound sensorineural hearing loss. The EYA4 mutation was also found in the proband's grandfather and uncle, both showing clinical features of Waardenburg syndrome type 1. A novel pathogenic splice-site mutation (c.321+1G > A) of the PAX3 gene was found to co-segregate with the EYA4 mutation in these two subjects.
CONCLUSION: The identified novel EYA4 mutation can be considered responsible of the hearing loss observed in the proband and her father, while a dual molecular diagnosis was reached in the relatives co-segregating the EYA4 and the PAX3 mutations. In these two subjects the DFNA10 phenotype was masked by Waardenburg syndrome. The use of NGS targeted gene-panel, in combination with an extensive clinical and audiological examination led us to identify the genetic cause of the hearing loss in members of a family in which different forms of autosomal dominant deafness segregate. These results provide precise and especially important prognostic and follow-up information for the future audiologic management in the youngest affected member.

PMID: 29287889 [PubMed - in process]

http://ift.tt/2Cr3kQd

A novel splicing mutation in SMPX is linked to nonsyndromic progressive hearing loss.

Related Articles

A novel splicing mutation in SMPX is linked to nonsyndromic progressive hearing loss.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:47-50

Authors: Niu Z, Yan D, Bressler S, Mei L, Feng Y, Liu X

Abstract
OBJECTIVE: X-linked nonsyndromic hearing impairment is the rarest form of genetic hearing loss and represents only a minor fraction of all cases. The aim of this study was to investigate the cause of X-linked nonsyndromic sensorineural hearing loss in a three-generation American family.
METHODS: Whole-exome sequencing and co-segregation analysis were used to identify disease-causing genes.
RESULTS: In this study, we described in detail the clinical characteristics of the family and identified a novel frameshift mutation creating a premature stop codon (c.133-1 G > A, p.(Gly45fs*36)) of SMPX. The loss-of-function mutation was co-segregated with the progressive hearing loss phenotype and was absent in 200 normal controls.
CONCLUSIONS: We report the first SMPX (DFNX4) mutation in a North American family. Our findings contribute to the existing genotypic and phenotypic spectrum of SMPX associated hearing loss. Furthermore, our data suggest that exome sequencing is promising in the genetic diagnosis of hearing loss.

PMID: 29287879 [PubMed - in process]

http://ift.tt/2CrDbAs

Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I.

Related Articles

Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:200-204

Authors: Chen K, Zhan Y, Wu X, Zong L, Jiang H

Abstract
OBJECTIVES: Waardenburg syndrome mutations are most often recurrent or de novo. The rate of familial recurrence is low and families with several affected children are extremely rare. In this study, we aimed to clarify the underlying hereditary cause of Waardenburg syndrome type I in two siblings in a Chinese family, with a mother affected by prelingual mild hearing loss and a father who was negative for clinical symptoms of Waardenburg syndrome and had a normal hearing threshold.
METHODS: Complete characteristic features of the family members were recorded and genetic sequencing and parent-child relationship analyses were performed.
RESULTS: The two probands were found to share double mutations in the PAX3/GJB2 genes that caused concurrent hearing loss in Waardenburg syndrome type I. Their mother carried the GJB2 c.109G > A homozygous mutation; however, neither the novel PAX3 c.592delG mutation, nor the Waardenburg syndrome phenotype, was observed in either parent.
CONCLUSION: These previously unreported digenic mutations in PAX3/GJB2 resulted in deafness associated with Waardenburg syndrome type I in this family. To our knowledge, this is the first report describing germinal mosaicism in Waardenburg syndrome. This concept is important because it complicates genetic counseling of this family regarding the risk of recurrence of the mutations in subsequent pregnancies.

PMID: 29287868 [PubMed - in process]

http://ift.tt/2CpPHkc

SLC52A2 mutations cause SCABD2 phenotype: A second report.

Related Articles

SLC52A2 mutations cause SCABD2 phenotype: A second report.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:195-199

Authors: Babanejad M, Adeli OA, Nikzat N, Beheshtian M, Azarafra H, Sadeghnia F, Mohseni M, Najmabadi H, Kahrizi K

Abstract
INTRODUCTION: Autosomal recessive cerebellar ataxias (ARCAs) are a large group of neurodegenerative disorders that manifest mainly in children and young adults. Most ARCAs are heterogeneous with respect to age at onset, severity of disease progression, and frequency of extracerebellar and systemic signs.
METHODS: The phenotype of a consanguineous Iranian family was characterized using clinical testing and pedigree analysis. Whole-exome sequencing was used to identify the disease-causing gene in this family.
RESULTS AND CONCLUSION: Using whole exome sequencing (WES), a novel missense mutation in SLC52A2 gene is reported in a consanguineous Iranian family with progressive severe hearing loss, optic atrophy and ataxia. This is the second report of the genotype-phenotype correlation between this syndrome named spinocerebellar ataxia with blindness and deafness type 2 (SCABD2) and SLC52A2 gene.

PMID: 29287867 [PubMed - in process]

http://ift.tt/2Cqj8SW

A novel variant in the CDH23 gene is associated with non-syndromic hearing loss in a Chinese family.

Related Articles

A novel variant in the CDH23 gene is associated with non-syndromic hearing loss in a Chinese family.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:108-112

Authors: Liang Y, Wang K, Peng Q, Zhu P, Wu C, Rao C, Chang J, Li S, Lu X

Abstract
OBJECTIVES: To explore the pathogenic causes of a proband who was diagnosed with non-syndromic hearing loss.
METHODS: We performed targeted capture of 159 known deafness-related genes and next-generation sequencing in the proband who was tested negative for the twenty hotspot variants in four common deafness-related genes(GJB2, GJB3, SLC26A4 and MTRNR1); Clinical reassessments, including detailed audiological and ocular examinations were performed in the proband and his normal parents.
RESULTS: We identified a novel heterozygous variant of CDH23:c.4567A > G (p.Asn1523Asp) in exon 37 (NM_022124), in conjunction with a reported mutation of CDH23:c.5101G > A (p.Glu1701Lys) in exon 40, to be a potentially pathogenic compound heterozygosity in the proband. The unaffected father has a heterozygous variant of CDH23:c.4567A > G, and the normal mother has another heterozygous variant, CDH23:c.5101G > A. The novel variant was absent in the 1000 Genomes Project. The clinical reassessments revealed binaural profound sensorineural hearing loss (DFNB12) without retinitis pigmentosa in the proband.
CONCLUSIONS: This study demonstrates that the novel variant c.4567A > G (p.Asn1523Asp) in compound heterozygosity with c.5101G > A (p. Glu1701Lys) in the CDH23 gene is the main cause of DFNB12 in the proband. Simultaneously, this study provides a foundation to further elucidate the CDH23-related mechanisms of DFNB12.

PMID: 29287849 [PubMed - in process]

http://ift.tt/2Co6i7S

A novel pathogenic variant c.975G>A (p.Trp325*) in the POU3F4 gene in Yakut family (Eastern Siberia, Russia) with the X-linked deafness-2 (DFNX2).

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A novel pathogenic variant c.975G>A (p.Trp325*) in the POU3F4 gene in Yakut family (Eastern Siberia, Russia) with the X-linked deafness-2 (DFNX2).

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:94-97

Authors: Barashkov NA, Klarov LA, Teryutin FM, Solovyev AV, Pshennikova VG, Konnikova EE, Romanov GP, Tobokhov AV, Morozov IV, Bondar AA, Posukh OL, Dzhemileva LU, Tomsky MI, Khusnutdinova EK, Fedorova SA

Abstract
Here, we report a novel hemizygous transition c.975G>A (p.Trp325*) in POU3F4 gene (Xq21) found in two deaf half-brothers from one Yakut family (Eastern Siberia, Russia) with identical inner ear abnormalities ("corkscrew" cochlea with an absence of modiolus) specific to X-linked deafness-2 (DFNX2). Comprehensive clinical evaluation (CT and MR-imaging, audiological and stabilometric examinations) of available members of this family revealed both already known (mixed progressive hearing loss) and additional (enlargement of semicircular canals and postural disorders) clinical DFNX2 features in affected males with c.975G>A (p.Trp325*). Moreover, mild enlargement of semicircular canals, postural abnormalities and different types of hearing thresholds were found in female carrier of this POU3F4-variant.

PMID: 29287890 [PubMed - in process]

http://ift.tt/2CkHdeb

A novel mutation of the EYA4 gene associated with post-lingual hearing loss in a proband is co-segregating with a novel PAX3 mutation in two congenitally deaf family members.

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A novel mutation of the EYA4 gene associated with post-lingual hearing loss in a proband is co-segregating with a novel PAX3 mutation in two congenitally deaf family members.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:88-93

Authors: Cesca F, Bettella E, Polli R, Cama E, Scimemi P, Santarelli R, Murgia A

Abstract
OBJECTIVES: This work was aimed at establishing the molecular etiology of hearing loss in a 9-year old girl with post-lingual non-syndromic mild sensorineural hearing loss with a complex family history of clinically heterogeneous deafness.
METHODS: The proband's DNA was subjected to NGS analysis of a 59-targeted gene panel, with the use of the Ion Torrent PGM platform. Conventional Sanger sequencing was used for segregation analysis in all the affected relatives. The proband and all the other hearing impaired members of the family underwent a thorough clinical and audiological evaluation.
RESULTS: A new likely pathogenic mutation in the EYA4 gene (c.1154C > T; p.Ser385Leu) was identified in the proband and in her 42-year-old father with post-lingual non-syndromic profound sensorineural hearing loss. The EYA4 mutation was also found in the proband's grandfather and uncle, both showing clinical features of Waardenburg syndrome type 1. A novel pathogenic splice-site mutation (c.321+1G > A) of the PAX3 gene was found to co-segregate with the EYA4 mutation in these two subjects.
CONCLUSION: The identified novel EYA4 mutation can be considered responsible of the hearing loss observed in the proband and her father, while a dual molecular diagnosis was reached in the relatives co-segregating the EYA4 and the PAX3 mutations. In these two subjects the DFNA10 phenotype was masked by Waardenburg syndrome. The use of NGS targeted gene-panel, in combination with an extensive clinical and audiological examination led us to identify the genetic cause of the hearing loss in members of a family in which different forms of autosomal dominant deafness segregate. These results provide precise and especially important prognostic and follow-up information for the future audiologic management in the youngest affected member.

PMID: 29287889 [PubMed - in process]

http://ift.tt/2Cr3kQd

A novel splicing mutation in SMPX is linked to nonsyndromic progressive hearing loss.

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A novel splicing mutation in SMPX is linked to nonsyndromic progressive hearing loss.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:47-50

Authors: Niu Z, Yan D, Bressler S, Mei L, Feng Y, Liu X

Abstract
OBJECTIVE: X-linked nonsyndromic hearing impairment is the rarest form of genetic hearing loss and represents only a minor fraction of all cases. The aim of this study was to investigate the cause of X-linked nonsyndromic sensorineural hearing loss in a three-generation American family.
METHODS: Whole-exome sequencing and co-segregation analysis were used to identify disease-causing genes.
RESULTS: In this study, we described in detail the clinical characteristics of the family and identified a novel frameshift mutation creating a premature stop codon (c.133-1 G > A, p.(Gly45fs*36)) of SMPX. The loss-of-function mutation was co-segregated with the progressive hearing loss phenotype and was absent in 200 normal controls.
CONCLUSIONS: We report the first SMPX (DFNX4) mutation in a North American family. Our findings contribute to the existing genotypic and phenotypic spectrum of SMPX associated hearing loss. Furthermore, our data suggest that exome sequencing is promising in the genetic diagnosis of hearing loss.

PMID: 29287879 [PubMed - in process]

http://ift.tt/2CrDbAs

Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I.

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Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:200-204

Authors: Chen K, Zhan Y, Wu X, Zong L, Jiang H

Abstract
OBJECTIVES: Waardenburg syndrome mutations are most often recurrent or de novo. The rate of familial recurrence is low and families with several affected children are extremely rare. In this study, we aimed to clarify the underlying hereditary cause of Waardenburg syndrome type I in two siblings in a Chinese family, with a mother affected by prelingual mild hearing loss and a father who was negative for clinical symptoms of Waardenburg syndrome and had a normal hearing threshold.
METHODS: Complete characteristic features of the family members were recorded and genetic sequencing and parent-child relationship analyses were performed.
RESULTS: The two probands were found to share double mutations in the PAX3/GJB2 genes that caused concurrent hearing loss in Waardenburg syndrome type I. Their mother carried the GJB2 c.109G > A homozygous mutation; however, neither the novel PAX3 c.592delG mutation, nor the Waardenburg syndrome phenotype, was observed in either parent.
CONCLUSION: These previously unreported digenic mutations in PAX3/GJB2 resulted in deafness associated with Waardenburg syndrome type I in this family. To our knowledge, this is the first report describing germinal mosaicism in Waardenburg syndrome. This concept is important because it complicates genetic counseling of this family regarding the risk of recurrence of the mutations in subsequent pregnancies.

PMID: 29287868 [PubMed - in process]

http://ift.tt/2CpPHkc

SLC52A2 mutations cause SCABD2 phenotype: A second report.

Related Articles

SLC52A2 mutations cause SCABD2 phenotype: A second report.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:195-199

Authors: Babanejad M, Adeli OA, Nikzat N, Beheshtian M, Azarafra H, Sadeghnia F, Mohseni M, Najmabadi H, Kahrizi K

Abstract
INTRODUCTION: Autosomal recessive cerebellar ataxias (ARCAs) are a large group of neurodegenerative disorders that manifest mainly in children and young adults. Most ARCAs are heterogeneous with respect to age at onset, severity of disease progression, and frequency of extracerebellar and systemic signs.
METHODS: The phenotype of a consanguineous Iranian family was characterized using clinical testing and pedigree analysis. Whole-exome sequencing was used to identify the disease-causing gene in this family.
RESULTS AND CONCLUSION: Using whole exome sequencing (WES), a novel missense mutation in SLC52A2 gene is reported in a consanguineous Iranian family with progressive severe hearing loss, optic atrophy and ataxia. This is the second report of the genotype-phenotype correlation between this syndrome named spinocerebellar ataxia with blindness and deafness type 2 (SCABD2) and SLC52A2 gene.

PMID: 29287867 [PubMed - in process]

http://ift.tt/2Cqj8SW

A novel variant in the CDH23 gene is associated with non-syndromic hearing loss in a Chinese family.

Related Articles

A novel variant in the CDH23 gene is associated with non-syndromic hearing loss in a Chinese family.

Int J Pediatr Otorhinolaryngol. 2018 Jan;104:108-112

Authors: Liang Y, Wang K, Peng Q, Zhu P, Wu C, Rao C, Chang J, Li S, Lu X

Abstract
OBJECTIVES: To explore the pathogenic causes of a proband who was diagnosed with non-syndromic hearing loss.
METHODS: We performed targeted capture of 159 known deafness-related genes and next-generation sequencing in the proband who was tested negative for the twenty hotspot variants in four common deafness-related genes(GJB2, GJB3, SLC26A4 and MTRNR1); Clinical reassessments, including detailed audiological and ocular examinations were performed in the proband and his normal parents.
RESULTS: We identified a novel heterozygous variant of CDH23:c.4567A > G (p.Asn1523Asp) in exon 37 (NM_022124), in conjunction with a reported mutation of CDH23:c.5101G > A (p.Glu1701Lys) in exon 40, to be a potentially pathogenic compound heterozygosity in the proband. The unaffected father has a heterozygous variant of CDH23:c.4567A > G, and the normal mother has another heterozygous variant, CDH23:c.5101G > A. The novel variant was absent in the 1000 Genomes Project. The clinical reassessments revealed binaural profound sensorineural hearing loss (DFNB12) without retinitis pigmentosa in the proband.
CONCLUSIONS: This study demonstrates that the novel variant c.4567A > G (p.Asn1523Asp) in compound heterozygosity with c.5101G > A (p. Glu1701Lys) in the CDH23 gene is the main cause of DFNB12 in the proband. Simultaneously, this study provides a foundation to further elucidate the CDH23-related mechanisms of DFNB12.

PMID: 29287849 [PubMed - in process]

http://ift.tt/2Co6i7S

Molecular imaging of tumor photoimmunotherapy: Evidence of photosensitized tumor necrosis and hemodynamic changes

Publication date: 20 February 2018
Source:Free Radical Biology and Medicine, Volume 116
Author(s): Shun Kishimoto, Nobu Oshima, Kazutoshi Yamamoto, Jeeva Munasinghe, Jan Henrik Ardenkjaer-Larsen, James B. Mitchell, Peter L. Choyke, Murali C. Krishna
Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode of cytotoxicity based mainly on in vitro studies. To better understand the acute effects of NIR PIT, molecular imaging studies were performed to assess its cellular and vascular effects.In addition to in vitro studies for cytotoxicity of NIR PIT, the in vivo tumoricidal effects and hemodynamic changes induced by NIR PIT were evaluated by ¹³C MRI using hyperpolarized [1,4-¹³C2] fumarate, R2* mapping from T2*-weighted MRI, and photoacoustic imaging. In vitro studies confirmed that NIR PIT resulted in rapid cell death via membrane damage, with evidence for rapid cell expansion followed by membrane rupture. Following NIR PIT, metabolic MRI using hyperpolarized fumarate showed the production of malate in EGFR-expressing A431 tumor xenografts, providing direct evidence for photosensitized tumor necrosis induced by NIR PIT. R2* mapping studies showed temporal changes in oxygenation, with an accompanying increase of deoxyhemoglobin at the start of light exposure followed by a sustained decrease after cessation of light exposure. This result suggests a rapid decrease of blood flow in EGFR-expressing A431 tumor xenografts, which is supported by the results of the photoacoustic imaging experiments. Our findings suggest NIR PIT mediates necrosis and hemodynamic changes in tumors by photosensitized oxidation pathways and that these imaging modalities, once translated, may be useful in monitoring clinical treatment response.

Graphical abstract

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Sulfur dioxide exposure enhances Th2 inflammatory responses via activating STAT6 pathway in asthmatic mice.

Sulfur dioxide exposure enhances Th2 inflammatory responses via activating STAT6 pathway in asthmatic mice.

Toxicol Lett. 2017 Dec 27;:

Authors: Li X, Huang L, Wang N, Yi H, Wang H

Abstract
Sulfur dioxide (SO2) is one of potential risk factors for induction and/or exacerbation of asthma, but the underlying mechanisms are not well understood. In this study, we investigate the role of SO2 in asthma using a classical asthmatic model with allergic airway inflammation by treating C57BL/6 mice with ovalbumin (OVA) and/or 10 mg/m3 SO2. Our results showed that SO2 exposure alone induced slight pathological changes but did not significantly increase inflammatory cell counts, pro-inflammatory cytokine expression, and mucus production in the airway of mice, whereas SO2 exposure in OVA-induced asthmatic mice caused marked pulmonary pathological changes and significantly increased the counts of eosinophil-rich leukocytes compared with OVA alone asthmatic mice. The expression of MUC5AC, TNF-α, Th2 cytokines (IL-4, IL-5, and IL-13) and STAT6 was further up-regulated in OVA plus SO2 treated mice compared with OVA alone treated mice. In addition, exposure to SO2 alone markedly elevated STAT6 mRNA levels and hydrogen peroxide (H2O2) content in the lung. These findings suggest that SO2 amplifies Th2 inflammatory responses in OVA-induced asthmatic mice by activating STAT6, which can further induce Th2 cytokine expression. Induction of STAT6 expression might be an important mechanism underlying the increased risk for asthma after environmental exposure.

PMID: 29288730 [PubMed - as supplied by publisher]

http://ift.tt/2CqSiKN

Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Zhi-Hui Wang, Dong-Dong Li, Wei-Lin Chen, Qi-Dong You, Xiao-Ke Guo
The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed.

Graphical abstract

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Current knowledge on the nucleotide agonists for the P2Y2 receptor

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Pengfei Xu, Xi Feng, Hongyu Luan, Jubo Wang, Raoling Ge, Zhiyu Li, Jinlei Bian
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. There are eight mammalian P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14). P2Y2 receptors are widely expressed and play important roles in multiple functionalities. Diquafosol tetrasodium, known as INS365, which was the first P2Y2 receptor agonists that had been approved in April 2010 and launched in Japan by Santen Pharmaceuticals. Besides, a series of similar agonists for the P2Y2 receptor are undergoing development to cure different diseases related to the P2Y2 receptor. This article illustrated the structure and functions of the P2Y2 receptor and focused on several kinds of agonists about their molecular structures, research progress and chemical synthesis methods. Last but not the least, we summarized the structures-activity relationship (SAR) of agonists for the P2Y2 receptor and expected more efficient agonists for the P2Y2 receptor.

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Editorial Board

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2





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Selective inhibition of β-N-acetylhexosaminidases by thioglycosyl–naphthalimide hybrid molecules

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Wei Chen, Shengqiang Shen, Lili Dong, Jianjun Zhang, Qing Yang
To develop selective inhibitors for β-N-acetylhexosaminidases which are involved in a myriad of physiological processes, a series of novel thioglycosyl–naphthalimide hybrid inhibitors were designed, synthesized and evaluated for inhibition activity against glycosyl hydrolase family 20 and 84 (GH20 and GH84) β-N-acetylhexosaminidases. These compounds which incorporate groups with varied sizes and lengths at the linker region between thioglycosyl moiety and naphthalimide moiety are designed to improve the selectivity and stacking interactions. The GH84 human O-GlcNAcase (hOGA) was sensitive to the subtle changes in the linker region and the optimal choice is a small size linker with six atoms length. And the GH20 insect β-N-acetylhexosaminidase OfHex1 could tolerate compounds with a hydrophobic bulky linker. Especially, the compound 5c (hOGA, Ki = 3.46 μM; OfHex1, Ki > 200 μM) and the compound 6f (hOGA, Ki > 200 μM; OfHex1, Ki = 21.81 μM) displayed high selectivity. The molecular docking results indicated that the inhibition mechanism was different between the two families due to their different structural characteristics beyond the active sites. These results provide some promising clues to improve selectivity of potent molecules against β-N-acetylhexosaminidases.

Graphical abstract

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Immunoproteasome inhibition and bioactivity of thiasyrbactins

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Nicole A. Bakas, Chad R. Schultz, Lisette P. Yco, Christopher C. Roberts, Chia-en A. Chang, André S. Bachmann, Michael C. Pirrung
A family of macrodilactam natural products, the syrbactins, are known proteasome inhibitors. A small group of syrbactin analogs was prepared with a sulfur-for-carbon substitution to enhance synthetic accessibility and facilitate modulation of their solubility. Two of these compounds surprisingly proved to be inhibitors of the trypsin-like catalytic site, including of the immunoproteasome. Their bound and free conformations suggest special properties of the thiasyrbactin ring are responsible for this unusual preference, which may be exploited to develop drug-like immunoproteasome inhibitors. These compounds show greater selectivity than earlier compounds used to infer phenotypes of immunoproteasome inhibition, like ONX-0914.

Graphical abstract

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Monoterpene indole alkaloid azine derivatives as MDR reversal agents

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Angela Paterna, Ruttiros Khonkarn, Silva Mulhovo, Alexis Moreno, Patricia Madeira Girio, Hélène Baubichon-Cortay, Pierre Falson, Maria-José U. Ferreira
Aiming at generating a library of bioactive indole alkaloid derivatives as multidrug resistance (MDR) reversers, two epimeric indole alkaloids (1 and 2) were submitted to chemical transformations, giving rise to twenty-four derivatives (5-28), bearing new aromatic or aliphatic azine moieties. The structure of the compounds was established by 1D and 2D NMR (COSY, HMBC, HMQC and NOESY) experiments. Two different strategies were employed for assessing their anti-MDR potential, namely through the evaluation of their activity as inhibitors of typical MDR ABC transporters overexpressed by cell transfection, such as ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP), or by evaluating their ability as collateral sensitivity (CS) agents in cells overexpressing MRP1. A considerable MDR reversing activity was observed for compounds bearing the aromatic azine moiety. The strongest and most selective P-gp inhibition was found for the epimeric azines 5 and 6, bearing a para-methylbenzylidene moiety. Instead, compounds 17 and 18 that possess a di-substituted benzylidene portion with methoxy and hydroxyl groups, selectively inhibited MRP1 drug-efflux. None of these compounds inhibited BCRP. Compounds 5, 6 and 18 were further investigated in drug combination experiments, which corroborated their anti-MDR potential. Moreover, it was observed that compound 12, with an aromatic azine moiety, and compounds 23-26, sharing a new aliphatic substituent, displayed a CS activity, selectively killing MRP1-overexpressing cells. Among these last compounds, it could be established that addition of 19, 23 and 25 to MRP1-overexpressing cells led to glutathione depletion triggering cell death through apoptosis.

Graphical abstract

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Design, synthesis and pharmacological evaluation of new acyl sulfonamides as potent and selective Bcl-2 inhibitors

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Xiaohua Liu, Yu Zhang, Wenjing Huang, Wenfu Tan, Ao Zhang
The antiapoptotic protein Bcl-2, overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, we report a different structural modification approach on ABT-263 by merging the piperazinyl-phenyl fragment into a bicyclic framework leading to a series of novel analogues, among which tetrahydroisoquinoline 13 was nearly equally potent against Bcl-2 as ABT-263. Further SAR in the P4-interaction pocket affored the difluoroazetidine substituted analogue 55, which retained good Bcl-2 activity with improved Bcl-2/Bcl-xL selectivity.

Graphical abstract

http://ift.tt/2Csa5ib

Evaluation of 18F-labeled exendin(9-39) derivatives targeting glucagon-like peptide-1 receptor for pancreatic β-cell imaging

Publication date: 15 January 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2
Author(s): Hiroyuki Kimura, Yu Ogawa, Hiroyuki Fujimoto, Eri Mukai, Hidekazu Kawashima, Kenji Arimitsu, Kentaro Toyoda, Naotaka Fujita, Yusuke Yagi, Keita Hamamatsu, Takaaki Murakami, Atsushi Murakami, Masahiro Ono, Yuji Nakamoto, Kaori Togashi, Nobuya Inagaki, Hideo Saji
β-cell mass (BCM) is known to be decreased in subjects with type-2 diabetes (T2D). Quantitative analysis for BCM would be useful for understanding how T2D progresses and how BCM affects treatment efficacy and for earlier diagnosis of T2D and development of new therapeutic strategies. However, a noninvasive method to measure BCM has not yet been developed.We developed four ¹⁸F-labeled exendin(9-39) derivatives for β-cell imaging by PET: [¹⁸F]FB9-Ex(9-39), [¹⁸F]FB12-Ex(9-39), [¹⁸F]FB27-Ex(9-39), and [¹⁸F]FB40-Ex(9-39). Affinity to the glucagon-like peptide-1 receptor (GLP-1R) was evaluated with dispersed islet cells of ddY mice. Uptake of exendin(9-39) derivatives in the pancreas as well as in other organs was evaluated by a biodistribution study. Small-animal PET study was performed after injecting [¹⁸F]FB40-Ex(9-39).FB40-Ex(9-39) showed moderate affinity to the GLP-1R. Among all of the derivatives, [¹⁸F]FB40-Ex(9-39) resulted in the highest uptake of radioactivity in the pancreas 30 min after injection. Moreover, it showed significantly less radioactivity accumulated in the liver and kidney, resulting in an overall increase in the pancreas-to-organ ratio. In the PET imaging study, pancreas was visualized at 30 min after injection of [¹⁸F]FB40-Ex(9-39).[¹⁸F]FB40-Ex(9-39) met the basic requirements for an imaging probe for GLP-1R in pancreatic β-cells. Further enhancement of pancreatic uptake and specific binding to GLP-1R will lead to a clear visualization of pancreatic β-cells.

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Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2





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Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2





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Graphical abstract TOC

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Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 2





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Thalassemia

Publication date: Available online 30 December 2017
Source:Hematology/Oncology Clinics of North America
Author(s): Ali T. Taher




http://ift.tt/2zSEwer

Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC

Publication date: Available online 30 December 2017
Source:Radiotherapy and Oncology
Author(s): Annett Linge, Ulrike Schötz, Steffen Löck, Fabian Lohaus, Cläre von Neubeck, Volker Gudziol, Alexander Nowak, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Hatice Bunea, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Kirsten Lauber, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Gustavo B. Baretton, Frank Buchholz, Mechthild Krause, Claus Belka, Michael Baumann
ObjectiveTo compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy.Materials and methodsHPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression.ResultsCorrelation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method.ConclusionsThe most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies.



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Precision medicine in ALK rearranged NSCLC: A rapidly evolving scenario

Publication date: Available online 30 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Addeo Alfredo, Tabbò Fabrizio, Robinson Tim, Buffoni Lucio, Novello Silvia




http://ift.tt/2CtAk7P

Loco-regional treatment for castration-resistant prostate cancer: is there any rationale?A critical review from the AFU-GETUG

Publication date: Available online 30 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Jean-Baptiste Beauval, Yohann Loriot, Christophe Hennequin, François Rozet, Philippe Barthelemy, Delphine Borchiellini, Friederike Schlürmann Constans, Emmanuel Gross, Denis Maillet, Gilles Pasticier, Géraldine Pignot, Marc-Olivier Timsit, Sébastien Vincendeau, Guillaume Ploussard, Paul Sargos
Emerging evidence from population-based and retrospective series suggests a potential improvement of clinical outcomes in metastatic prostate cancer. Moreover, metastasis-directed treatment has shown encouraging results in this setting. There is an increasing interest in exploring the potential of local therapies in advanced prostate cancer, but this has rarely been specifically addressed in the castration-resistant state, whether non-metastatic or metastatic. A review of relevant articles was performed on the oncologic benefit of local treatment of the primary tumor or metastasis-targeted treatment in castration-resistant prostate cancer patients. The main goal of this strategy is to delay introduction of a new systemic agent to maintain quality of life and potentially to limit resistance. Further investigation is required to provide high-level evidence for the oncologic benefit of this treatment modality.



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Hold your horses: A comparison of human laryngomalacia with analogous equine airway pathology

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Rachael J. Lawrence, Matthew J. Butterell, James D. Constable, Matija Daniel
ObjectivesLaryngomalacia is the most common cause of stridor in infants. Dynamic airway collapse is also a well-recognised entity in horses and an important cause of surgical veterinary intervention. We compare the aetiology, clinical features and management of human laryngomalacia with equine dynamic airway collapse.MethodsA structured review of the PubMed, the Ovid Medline and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews).ResultsThere are numerous equine conditions that cause dynamic airway collapse defined specifically by the anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF) is the condition most clinically analogous to laryngomalacia in humans, and is likewise most prevalent in the immature equine airway. Both conditions are managed either conservatively, or if symptoms require it, with surgical intervention. The operative procedures performed for ADAF and laryngomalacia are technically comparable.ConclusionDynamic collapse of the equine larynx, especially ADAF, is clinically similar to human laryngomalacia, and both are treated in a similar fashion.



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Hold your horses: A comparison of human laryngomalacia with analogous equine airway pathology

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Rachael J. Lawrence, Matthew J. Butterell, James D. Constable, Matija Daniel
ObjectivesLaryngomalacia is the most common cause of stridor in infants. Dynamic airway collapse is also a well-recognised entity in horses and an important cause of surgical veterinary intervention. We compare the aetiology, clinical features and management of human laryngomalacia with equine dynamic airway collapse.MethodsA structured review of the PubMed, the Ovid Medline and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews).ResultsThere are numerous equine conditions that cause dynamic airway collapse defined specifically by the anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF) is the condition most clinically analogous to laryngomalacia in humans, and is likewise most prevalent in the immature equine airway. Both conditions are managed either conservatively, or if symptoms require it, with surgical intervention. The operative procedures performed for ADAF and laryngomalacia are technically comparable.ConclusionDynamic collapse of the equine larynx, especially ADAF, is clinically similar to human laryngomalacia, and both are treated in a similar fashion.



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Priorities for future research into asthma diagnostic tools: A PAN-EU Consensus exercise from the European asthma research innovation partnership (EARIP)

Abstract

The diagnosis of asthma is currently based on clinical history, physical examination and lung function; and to date there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state-of-the-art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients.

Using a two-stage e-Delphi process and a summarising workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face to face workshop.

The three most important diagnostic/predictive tools ranked were: “New biological markers of asthma (e.g. genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring”, “Prediction of future asthma in preschool children with reasonable accuracy” and “Tools to measure volatile organic compounds (VOCs) in exhaled breath”.

This article is protected by copyright. All rights reserved.

http://ift.tt/2lvviQ4

Priorities for future research into asthma diagnostic tools: A PAN-EU Consensus exercise from the European asthma research innovation partnership (EARIP)

Abstract

The diagnosis of asthma is currently based on clinical history, physical examination and lung function; and to date there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state-of-the-art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients.

Using a two-stage e-Delphi process and a summarising workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face to face workshop.

The three most important diagnostic/predictive tools ranked were: "New biological markers of asthma (e.g. genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring", "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath".

This article is protected by copyright. All rights reserved.

http://ift.tt/2lvviQ4

Lipid-lowering and antiatherogenic effects of Vitex megapotamica (Spreng.) Moldenke in a mice experimental model

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Vanessa Aranega Pires, Euclides Lara Cardozo-Junior, Caroline Flach Ortmann, Jhonatan Christian Maraschin, Wagner Alex Jann Favreto, Carmen Maria Donaduzzi, Flávio Henrique Reginatto, Jamil Assreuy
Ethnopharmacological relevanceVitex megapotamica (Spreng.) Moldenke is a deciduous tree, native of South America. Its leaves are traditionally used to treat cardiovascular diseases. This activity is related to the presence of flavonoids, the major compounds of the crude extract.Aim of the studyThis study investigated the effects of the oral administration of crude extract and standardized fractions from V. megapotamica leaves on lipid profile and on the formation of atherosclerotic plaque in C57BL/6 LDLr-KO mice treated with high-fat diet (HFD).Materials and methodsMale C57BL/6 LDLr-KO mice were fed with HFD (cholesterol, 1.25%) for 30 days. They were treated with hydroethanolic extract (500 or 1000mg/kg/day) or fractions (125 or 250mg/kg/day). After 30 days of treatment, it was evaluated the serum lipid profile, atherogenic index, and atherosclerotic plaque.ResultsAll doses of the hydroethanolic extract reduced significantly the levels of total cholesterol, triglycerides, LDL-c and the atherogenic index. The n-butanolic fraction also reduced significantly the levels of total cholesterol, triglycerides, LDL-c and the atherogenic index, at all doses, with exception for the triglycerides, which only the lower dose was effective. The residual fraction reduced significantly the levels of total cholesterol, LDL-c and the atherogenic index, at all doses, with exception for the atherogenic index, which only the higher dose was effective. The atherosclerotic plaque formation was impaired only by the lower dose of the hydroethanolic extract.ConclusionsOverall, our data suggest that V. megapotamica has potential for the treatment of dyslipidemias.

Graphical abstract

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Baccharis trimera protects against ethanol induced hepatotoxicity in vitro and in vivo

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Ana Carolina Silveira Rabelo, Karine de Pádua Lúcio, Carolina Morais Araújo, Glaucy Rodrigues de Araújo, Pedro Henrique de Amorim Miranda, Ana Claudia Alvarenga Carneiro, Érica Milena de Castro Ribeiro, Breno de Melo Silva, Wanderson Geraldo de Lima, Daniela Caldeira Costa
Ethnopharmacological relevanceBaccharis trimera has been traditionally used in Brazil to treat liver diseases.Aim of the studyTo evaluate the protective effect of Baccharis trimera in an ethanol induced hepatotoxicity model.Materials and methodsThe antioxidant capacity was evaluated in vitro by the ability to scavenged the DPPH radical, by the quantification of ROS, NO and the transcription factor Nrf2. Hepatotoxicity was induced in animals by administration of absolute ethanol for 2 days (acute) or with ethanol diluted for 28 days (chronic). The biochemical parameters of hepatic function (ALT and AST), renal function (urea and creatinine) and lipid profile (total cholesterol, triglycerides and HDL) were evaluated. In addition to antioxidant defense (SOD, catalase, glutathione), oxidative damage markers (TBARS and carbonylated protein), MMP-2 activity and liver histology.ResultsBaccharis trimera promoted a decrease in ROS and NO, and at low concentrations promoted increased transcription of Nrf2. In the acute experiment it promoted increase of HDL, in the activity of SOD and GPx, besides diminishing TBARS and microesteatosis. Already in the chronic experiment B. trimera improved the hepatic and renal profile, decreased triglycerides and MMP-2 activity, in addition to diminishing microesteatosis.ConclusionWe believe that B. trimera action is possibly more associated with direct neutralizing effects or inhibition of reactive species production pathways rather than the modulation of the antioxidant enzymes activity. Thus it is possible to infer that the biological effects triggered by adaptive responses are complex and multifactorial depending on the dose, the time and the compounds used.

Graphical abstract

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High-expressed CKS2 is associated with hepatocellular carcinoma cell proliferation though down-regulating PTEN

Publication date: Available online 30 December 2017
Source:Pathology - Research and Practice
Author(s): Xiaonan Ji, Yayu Xue, Yu Wu, Fang Feng, Xiangdong Gao
BackgroundHepatocellular carcinoma (HCC) is a product of cumulative genetic, epigenetic, somatic, and endocrine aberrations. Identifying the differentially expressed genes (DEGs) in HCC is of critical importance for diagnosis and treatment. The purpose of the present study was to screen the key genes associated with hepatocellular carcinoma and to investigate the functions underlying hepatocellular carcinoma progression.Materials and MethodsThe gene expression profile of GSE64041, GSE40367 and GSE60502, including 100 specimens from HCC patients and 92 specimens from normal liver controls, was downloaded from the GEO database. DEGs were screened using the online analysis tool from the GCBI website and validated by Q-PCR and Kaplan-Meier survival analysis. After knockdown by siRNA in HepG2/C3A and Bel7402 HCC cells, the CCK-8 assay and colony formation assay were used to measure the clonogenic capacity of the tumor cells. Western blotting assay was used to measure the expression of PTEN.ResultsFive up-regulated genes were identified as overlapping genes associated with tumor cell activation. Upon validation by Q-PCR and Kaplan-Meier survival analysis, CKS2 was selected for further study. Although the results of CCK-8 did not show a significant difference, the colony formation assay results indicated that the silencing of CKS2 significantly inhibited cancer cell proliferation. Further study found that CKS2 knockdown induced PTEN up-regulation and may associate with P53 pathway activation.ConclusionThese findings indicated that CKS2 play a role in tumor activation and serve as a useful potential target for the treatment of HCC.



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The effects of insomnia symptoms and objective short sleep duration on memory performance in adolescents and young adults

Introduction: Insufficient sleep and sleep disruption, especially insomnia symptoms, are common problems among adolescents and young adults. While the association between insufficient sleep and poor memory performance is well established, there has been limited research on how insomnia may affect memory performance, especially in adolescents. Recent evidence suggests that insomnia with objective short sleep duration, a more severe insomnia phenotype, is associated with an elevated risk for medical morbidity as well as neurocognitive impairments.

http://ift.tt/2CnjREA

Effects of chronic sleep restriction on decision making in youth

Introduction: Adolescence is often linked to sleep deprivation and increased impulsivity and risk behaviours. Whilst previous research has found that sleep deprivation is associated with increased impulsivity and risk-taking, most of previous studies adopted an experimentally induced sleep deprivation paradigm for a certain period of time. There has been limited research on the effects of habitual chronic sleep restriction on behavioural consequences. The current study aimed to examine the influence of habitual chronic sleep restriction on decision making among youth.

http://ift.tt/2BZHCPI

On the effects of two versions of slow wave sleep deprivation in the relation to REM sleep

Introduction: Although a number of interesting articles have been published about rapid eye movement (REM)-sleep regulation considering the results of total sleep deprivation or REM-sleep deprivation, the idea that REM-sleep propensity accumulates during waking or non-rapid eye movement sleep, slow wave sleep (SWS), in particular, is still debatable. This study was aimed to analyze the changes in sleep-wake architecture occurred during SWS deprivation and recovery periods.

http://ift.tt/2Cp6Wls

A path towards brain rejuvenation: the effect of chronic physical activity on EEG slow-wave activity in mice

Introduction: Physical activity is beneficial for health. It has been shown to improve brain functioning and cognition, reduce severity of mood disorders as well as promote healthy sleep and healthy aging. We recently found that aged mice have increased absolute electroencephalogram (EEG) slow-wave activity (SWA, EEG power density between 0.75-4.0 Hz) during non-rapid eye movement (NREM) sleep compared to young controls, suggesting changes in brain connectivity in the course of aging.

http://ift.tt/2BX2nvj

Use of occlusal splint or mandibular advancement appliance by sleep bruxism patients do not normalize arousal related heart rate variability

Introduction: Oral appliance is among first-line therapy for sleep bruxism (SB). However, mechanism of action for SB remains unknown. The aim of study is to assess if changes in heart rate variability (HRV) related to SB arousal could explain their action.

http://ift.tt/2CnjPfW

Graph theory-based analysis of EEG during nREM sleep reveals changes in functional connectivity in sleep-related hypermotor epilepsy (SHE)

Introduction: Dynamic key points of sleep microstrucure have been shown to be associated with epileptic activation in Sleep-Related Hypermotor Epilepsy (SHE), identified within the system of the cyclic alternating pattern (CAP), that correlate with reactive slow wave events [1].

http://ift.tt/2BZUnK0

Treatment of obstructive sleep apnea decreases the recurrence of atrial and ventricular ectopy in patients with atrial fibrillation

Introduction: Obstructive Sleep Apnea (OSA) has been recognized as an independent risk factor for the development and progression of atrial fibrillation (AF). OSA decreases patients' response to anti-arrhythmic medication, and decreases the success rate of surgical ablation of AF. OSA remains undiagnosed in many patients with AF. There is evidence that continuous positive airway pressure (CPAP) treatment decreases the activity of the sympathetic nervous system and oxidative stress, which play a crucial role in the development of AF.

http://ift.tt/2CpeSDy

The effect of zonisamide on abnormal muscle tone during REM sleep in a mouse model of REM sleep behavior disorder

Introduction: Zonisamide, first launched as an anti-epileptic drug (Excegran® or Zonegran®), has been approved as a drug for Parkinson's disease (PD) in Japan (Trerief®). Zonisamide ameliorates motor symptoms and improves activities of daily living in patients with advanced PD. In addition, it has been recently reported that zonisamide also improves the symptom of REM sleep behavior disorder (RBD) in some PD patients. In this study, we examined the effectiveness of zonisamide for RBD, by using a novel RBD model, Glra1flox/flox; Chat-Cre mice.

http://ift.tt/2BYckbR

Obstructive sleep apnea is highly undetected in non-obese patients with atrial fibrillation

Introduction: Obstructive sleep apnea (OSA) is a sleep disorder associated with several cardiovascular morbidity. OSA is an independent risk factor for the development and progression of atrial fibrillation (AF). We aimed to estimate the prevalence of OSA in patients with AF, and to investigate the relation between obesity and OSA in these patients.

http://ift.tt/2CjN8QH

Sleep disturbance mediates the relationship between injury severity and executive function difficulties in children 18 months following traumatic brain injury

Introduction: Sleep is a neurorestorative process and provides a plausible candidate mechanism to explain variability in children's functional outcomes after Traumatic Brain Injury (TBI). A common consequence of TBI is difficulty with self-regulation and the mental processes required for planning, working memory and focussed attention. The aim of this study was to examine whether sleep disturbance mediates the relationship between TBI severity and executive functioning difficulties.

http://ift.tt/2C05se6

Clinical and polysomnographic differences in elderly patients with obstructive sleep apnea (OSA)

Introduction: Although sleep related complaints are common in the community, there is little information on the clinical and polysomnographic differences elderly patients with obstructive sleep apnea (OSA).

http://ift.tt/2Cp3EyQ

Pain drawing characteristics and risk for sleep breathing disorders in an orofacial pain service

Introduction: Subjects living with chronic pain are at risk for developing sleep breathing disorders (SBD). Altered sleep modifies the perception and reported intensity of pain. Many tools exist to evaluate pain, including validated scales and pain drawings. Pain drawings are associated to psychological profiles and prognostic variables in published studies on nociceptive lower back or peripheral pain. The utility of pain drawings in the orofacial pain area may be associated to disability, pain intensity, and risk for altered sleep.

http://ift.tt/2BZkaC0

Irregular sleep-wake rhythm disorder in a young woman with Townes-Brocks-syndrome

Introduction: Referral of female 22-year-old former psychology-student from oncology unit.

http://ift.tt/2Cl0jAN

Preliminary data of a prospective study on the effectiveness and compliance of a mandibular advancement device alone versus a mandibular advancement device combined with a sleep positioning pillow in the treatment of mild to moderate sleep apnea

Introduction: Although continuous positive airway pressure treatment (CPAP) remains the primary intervention for moderate to severe obstructive sleep apnea (OSA), a wide array of therapeutic interventions exist for treating the milder sleep-related breathing disorders (SRBD). Oral appliances (in particular mandibular advancement devices–MAD) and positional therapy (PT) are the most frequently used in day-to-day practice as a result of their affordable pricing as well as their relative ease of use.

http://ift.tt/2BZUkxO

Handheld mobile biofeedback of heart rate variability in patients with chronic insomnia disorder – a pilot study

Introduction: The hyperarousal concept in patients with insomnia has been tested by measuring autonomous variables, including electrocardiogram (ECG)-derived heart rate and heart rate variability. In stress-related insomnia an elevated nocturnal sympathetic activity was found, while parasympathetic activity was reduced. In this Pilot-study we tested the usefulness of a mobile heart-rate-variability (HRV) biofeedback device in outpatients of a specialized sleep clinic.

http://ift.tt/2CpsFda

Comparison of actigraphy scoring protocols to define the rest interval and optimally derive pediatric sleep dimensions

Introduction: While polysomnography is the established gold standard, technological advances have enabled more resource efficient (cost, time, user-ease) assessment of select sleep dimensions and patterns. Wrist actigraphy is an ambulatory wearable increasingly used in research and clinical settings as it permits unobtrusive measurement of sleep in one's home environment. Previous research analyzed accelerometry data to yield validated algorithms (e.g., Sadeh, Cole) to distinguish sleep/wake epochs.

http://ift.tt/2BZHz6u

REM-associated sleep disordered breathing: prevalence and clinical significance in the hypnolaus cohort

Introduction: Nocturnal respiratory events are usually more frequent and of longer duration in rapid eyes movement sleep (REM) compared with non-REM sleep (NREM), probably due to greater pharyngeal muscle relaxation and a reduction in the hypoxic and hypercapnic ventilatory response throughout . However, the prevalence and clinical impact of REM-related sleep-disordered breathing (REM-SDB) are still debated. The aim of this study was to determined the prevalence of REM-related sleep-disordered breathing (REM-SDB) in the general population and to investigate the associations between REM-SDB and hypertension, metabolic syndrome, diabetes and depression.

http://ift.tt/2ClMfXI

Association between SaO2 levels and brain connectivity using PDC (partial directed coherence) in a Brazilian populational based sample (EPISONO)

Introduction: Desaturation during sleep is initially associated with poor quality of sleep in short term. However, in long term, due to chronically intermittent hypoxia, some degree of brain structural impairment can be detected using interconnectivity dependence measurements like PDC (partial Directed Coherence) in PSG data during sleep. Our aim is to assess the association between Desaturation among sleep stages and EEG bands with PDC levels in a Brazilian populational Based sample (EPISONO).

http://ift.tt/2BZzIWA

Effect of sleep apnea and insomnia on the association of depression with quantitative electroencephalogram measures (QEEG) in adult men during sleep – the MAILES study

Introduction: Quantitative EEG (qEEG) abnormalities are present in 80% of patients with psychiatric disorders. Small studies of resting, awake qEEG in patients with depression show variation in findings. Both increase and decrease in slow wave activity has been reported in depressed patients in addition to increased alpha and beta activity. We have previously shown co-morbid sleep apnea and insomnia have additive effects on depression prevalence and severity. We aimed to determine the effect of sleep apnea and insomnia symptoms on the relation between sleep qEEG parameters and depression in a large sample of community dwelling men.

http://ift.tt/2CpvRp9

PSQI largely ignores sleep on work-free days both in the general population and in clinical sleep medicine samples

Introduction: The Pittsburgh Sleep Quality Index (PSQI) is currently the most common measure of sleep quality. Its questions refer to "usual" sleep habits over the past month. However, for long it is known that sleep timing and sleep duration varies significantly between workdays and work-free days. A recently submitted study in the general population used the original and two adapted versions of the PSQI that replaced "usual" by explicitly referring to sleep on work- or work-free days. This study showed, that also sleep quality differs significantly between work- and work-free days.

http://ift.tt/2BZzn6g

Novel metal modified diatomite, zeolite and carbon xerogel catalysts for mild conditions wet air oxidation of phenol: Characterization, efficiency and reaction pathway

Publication date: 31 May 2018
Source:Separation and Purification Technology, Volume 197
Author(s): Raluca Pleşa Chicinaş, Emese Gál, Horea Bedelean, Mircea Darabantu, Andrada Măicăneanu
Metal (Co, Ce, Ni, Fe, Zn, Mn and Cu) containing Diatomite (D), Zeolite (Z) and Carbon Xerogel (CX) catalysts were prepared, characterized (SEM-EDX, TEM, FTIR and XRD) and tested as new catalysts in Catalytic Wet Air Oxidation (CWAO) of phenol in aqueous solution. Maximum values of Chemical Oxygen Demand (COD) or Total Organic Carbon (TOC) efficiencies were obtained in the case of Fe-D, Cu-Z, and Co-CX catalysts. Reaction pathway and kinetics for CWAO of phenol revealed a pseudo first-order catalytic process and a kcat between 0.0473 × 10⁻³ and 1.4183 × 10⁻³ L/min g. (Di)carboxylic acids, acetic and oxalic were identified as oxidation organic products.



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Synthesis of core cross-linked star polymers carrying helical poly(phenyl isocyanide) arms via “core-first” strategy and their surface chiral recognition ability

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Qian Wang, Jian Huang, Zhi-Qiang Jiang, Li Zhou, Na Liu, Zong-Quan Wu
A norbornene functionalized alkyne-Pd(II) complex was designed and synthesized, which copolymerized with a bisnorbornene cross linker via ring-opening metathesis polymerization (ROMP) afforded a cross-linked Pd(II) macroinitiator. Living polymerization of phenyl isocyanides with the Pd(II) macroinitiator lead to the formation of well-defined core cross-linked star polymer carrying helical poly(phenyl isocyanide)s arms. Because of the living nature of Pd(II)-initiated phenyl isocyanide polymerization, a series of star polymers with controlled structure and tunable compositions was readily prepared. Optically active star polymers with excess of one handed helical arms were obtained by using enantiopure phenyl isocyanide monomers. Such star polymer exhibited excellent chiral recognition ability. The contact angle of the star polymer is strongly dependent on the chirality of the D/L-phenylglycinol droplets. The enantioselective surface recognition can be further applied to the chiral resolution of racemic D/L-phenylglycinol. The enantiomeric excess (ee) of the isolated enantiomer is up to 75%. The chiral star polymers can also be used to induce enantioselectively crystallization of racemic Boc-alanine. The ee value of the induced enantiomer can be up to 91%.

Graphical abstract

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Effects of livestock exclusion on density, survival and biomass of the perennial sagebrush grass Hymenachne pernambucense (Poaceae) from a temperate fluvial wetland

Publication date: January 2018
Source:Acta Oecologica, Volume 86
Author(s): Andrea L. Magnano, Analía S. Nanni, Pamela Krug, Elizabeth Astrada, Ricardo Vicari, Rubén D. Quintana
In Argentina, the intensification of soybean production has displaced a substantial proportion of cattle ranching to fluvial wetlands such as those in the Delta of the Paraná River. Cattle grazing affects structure and dynamics of native forage plants but there is little information on this impact in populations from fluvial wetlands. This study addresses the effect of cattle ranching on density, survival, mean life-span and aerial biomass of Hymenachne pernambucense (Poaceae), an important forage species in the region. The study was carried out monthly for one year in permanents plots subject to continuous grazing and plots excluded from grazing in the Middle Delta of the Paraná River. In plots excluded from grazing, tillers showed significantly higher population density and survival, and a two-fold increase in mean life-span, while continuous grazing decreased survival of cohorts. The largest contribution to tiller density in ungrazed and grazed populations was made by spring and summer cohorts, respectively. Total and green biomass were significantly higher in the ungrazed population, with highest differences in late spring-early summer. Cattle grazing affected the relationship between tiller density and green biomass suggesting that cattle prefer sprouts because they are more palatable and nutritious than older tissue.



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Hydrocephalus in pyridoxine-dependent epilepsy: New case and literature review

Publication date: Available online 30 December 2017
Source:Brain and Development
Author(s): Virginia Navarro-Abia, María Soriano-Ramos, Noemí Núñez-Enamorado, Ana Camacho-Salas, Ana Martinez-de Aragón, Elena Martín-Hernández, Rogelio Simón-de las Heras
IntroductionPyridoxine-dependent epilepsy (PDE) is a rare disorder of the lysine metabolism, characterized by a pharmacoresistant epileptic encephalopathy that usually begins in the neonatal period. However, its phenotypic spectrum is wide and not limited to seizures. We report a new case of PDE who developed hydrocephalus, along with an exhaustive review of the literature.Case reportOur patient presented with seizures at 13 h of life. Antiepileptic drugs, vitamins and cofactors were required to achieve seizure control. Laboratory tests were congruent with PDE. She remained seizure-free until age five months, when seizures reappeared in the context of increasing head size and irritability. A cranial ultrasound showed hydrocephalus, for which she underwent ventriculoperitoneal shunting.DiscussionSeven other patients with same features have been previously reported. Seizure onset occurred within the first 7 days in all patients. Most of the children developed hydrocephalus at 6–7 months of age. In 4 out of 7 a genetic mutation was identified, despite the accurate etiology of hydrocephalus was unknown in most of them. The case we report behaved similarly to the others previously described. We postulate that the pathogenesis of this complication could be related to the high expression of antiquitin in choroid plexus epithelium, where the cerebrospinal fluid is produced.Conclusionspatients with PDE should be closely monitored, since they may present severe complications. We highlight the development of hydrocephalus, an uncommon but potentially life-threatening problem reported in 8 patients up to present time.



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Differential effects on sodium current impairments by distinct SCN1A mutations in GABAergic neurons derived from Dravet syndrome patients

Publication date: Available online 30 December 2017
Source:Brain and Development
Author(s): Hyun Woo Kim, Zhejiu Quan, Young-Beom Kim, Eunji Cheong, Heung Dong Kim, Minjung Cho, Jiho Jang, Young Rang You, Joon Soo Lee, Ji Hun Kim, Yang In Kim, Dae-Sung Kim, Hoon-Chul Kang
BackgroundWe investigated how two distinct mutations in SCN1A differentially affect electrophysiological properties of the patient-derived GABAergic neurons and clinical severities in two Dravet syndrome (DS) patients.Materials and MethodsWe established induced pluripotent stem cells from two DS patients with different mutations in SCN1A and subsequently differentiated them into forebrain GABAergic neurons. Functionality of differentiated GABAergic neurons was examined by electrophysiological recordings.ResultsDS-1 patient had a missense mutation, c.4261G > T [GenBank: NM_006920.4] and DS-2 patient had a nonsense frameshift mutation, c.3576_3580 del TCAAA [GenBank: NM_006920.4]. Clinically, contrary to our expectations, DS-1 patient had more severe symptoms including frequency of seizure episodes and the extent of intellectual ability penetration than DS-2 patient. Electrophysiologic recordings showed significantly lower sodium current density and reduced action potential frequency at strong current injection (>60 pA) in GABAergic neurons derived from both. Intriguingly, unique genetic alterations of SCN1A differentially impacted electrophysiological impairment of the neurons, and the impairment's extent corresponded with the symptomatic severity of the donor from which the iPSCs were derived.ConclusionOur results suggest the possibility that patient-derived iPSCs may provide a reliable in vitro system that reflects clinical severities in individuals with DS.



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Prevalence of idiopathic epilepsy among school children in Gharbia Governorate, Egypt

Publication date: Available online 30 December 2017
Source:Brain and Development
Author(s): Azza Kamal Alshahawy, Amira Hamed Darwish, Safynaz Elsaid Shalaby, Wegdan Mawlana
BackgroundEpilepsy is one of the most common neurological disorders among children. Data about its prevalence in Egypt is limited. Our aim was to study the prevalence of idiopathic epilepsy among school children in Gharbia governorate, Egypt.Subjects and MethodsA Cross-sectional school-based survey study was conducted; a validated screening questionnaire was distributed among urban and rural primary and preparatory school children. Students with suspected epilepsy were subjected to clinical evaluation, Electroencephalogram (EEG), and neuroimaging.Results9545 students completed the questionnaire, of whom 69 children proved to have idiopathic epilepsy. The lifetime prevalence of idiopathic epilepsy among school students aged 6–14 years was 7.2/1000. Higher prevalence was reported in males (7.7/1000) and in children from urban areas (8.25/1000). Generalized seizures were observed in 56.5% of the children with epilepsy, whereas focal seizures were present in 43.5%. Thirty-four (49.27%) children were diagnosed with specific childhood epileptic syndrome: 25 children had benign childhood epilepsy with centrotemporal spikes and nine children had typical childhood absence epilepsy. Treatment gap is around 12.5% in the studied children. Family history of epilepsy and parental consanguinity were evident in 73.9% and 21.7% of the epileptic children, respectively. The odds ratio for idiopathic epilepsy in children with family history of epilepsy was 23.9.ConclusionThe prevalence of idiopathic epilepsy among school students aged 6–14 years in Gharbia Governorate was 7.2/1000. The reported prevalence is similar to the prevalence of epilepsy in other Arab countries, but lower than the prevalence in Upper Egypt and in most developing countries.



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Cortical inhibition assessed using paired-pulse TMS-EEG is increased in older adults

Publication date: Available online 30 December 2017
Source:Brain Stimulation
Author(s): George M. Opie, Simranjit K. Sidhu, Nigel C. Rogasch, Michael C. Ridding, John G. Semmler
BackgroundAlterations in inhibitory processes mediated by gamma-aminobutyric acid type B (GABAB) receptors may contribute to age-related functional impairments. However, investigation of these circuits using conventional paired-pulse transcranial magnetic stimulation (TMS) at long interstimulus intervals (∼100-200ms) have produced conflicting results in older adults, possibly due to the indirect nature of the TMS motor evoked potential (MEP).ObjectiveTo utilise electroencephalography and TMS coregistration (TMS-EEG) to more directly assess age-related changes in GABAB-mediated long-interval intracortical inhibition (LICI).MethodsIn 17 young (24.2 ± 1.1 years) and 17 older (71.4 ± 1.4 years) subjects, the TMS-evoked potential (TEP) was used to assess the global scalp response to single-pulse TMS and LICI applied at two interstimulus intervals of 100 ms (LICI100) and 150 ms (LICI150).ResultsFor single-pulse stimulation, P30 amplitude was unaffected by age. Despite this, N45 amplitude was increased in older adults and both N100 and P180 showed altered spatial distributions. Furthermore, the latency of P30 was shorter, while the latency of P180 was longer, in the elderly. In addition, inhibition of the N100 and P180 was increased in older adults following both LICI100 and LICI150.ConclusionsThese findings with TMS-EEG suggest that the ageing process is associated with a potentiation of GABAergic inhibition, particularly for the GABAB-receptor subtype.



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