Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
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Τετάρτη 5 Απριλίου 2017
Table of Contents
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
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Authors' response
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Peter Miles, Liz Fisher
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Long-term follow-up of a patient with achondroplasia treated with an orthodontic approach
Publication date: April 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Hiroyo Mori, Kazuma Matsumoto, Nobuhiko Kawai, Takashi Izawa, Shinya Horiuchi, Eiji Tanaka
We successfully treated a patient with achondroplasia with conventional orthodontic techniques. It was followed by long-term retention. The patient, a 12-year-old boy, had chief complaints of occlusal disturbance and mandibular protrusion. He had been diagnosed with achondroplasia and had growth hormone treatment in his early teenage years. His facial profile was concave with a bulging forehead and a retrognathic maxilla. It was characterized by a skeletal Class III jaw-base relationship with a retropositioned maxilla. At the age of 12 years 9 months, maxillary protraction was initiated with a reverse headgear; for 2 years 6 months, the maxillomandibular growth was controlled. After the growth spurt, at the age of 15 years 6 months, leveling and alignment of both dental arches were started with preadjusted edgewise appliances. After 83 months of multibracket treatment, an acceptable occlusion with a Class I molar relationship and an adequate interincisal relationship was achieved, despite the simultaneous marked vertical growth of the mandible. The resultant occlusion was stable during a 6-year retention period, although considerable forward-downward mandibular growth was observed. Conclusively, our results indicated the necessity of long-term observation in this patient with achondroplasia, especially because of the persistent mandibular growth.
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Necessities of documentation in canine-lateral transposition
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Swati Acharya, Pritam Mohanty
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Do web-site postings qualify as learned treatises?
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Laurance Jerrold
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Authors' response
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Yu Lin Hsu, Chris H. Chang, W. Eugene Roberts
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Robert L. Vanarsdall Jr, 1940-2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Peter M. Greco
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Good science, bad science, and junk science
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Florián Benicio Chauca
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Residents’ journal review
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Dan Grauer
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Who benefits?
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Peter M. Greco, Dennis D. Sommers
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Does orthodontic treatment before the age of 18 years improve oral health-related quality of life? A systematic review and meta-analysis
Publication date: April 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Hanieh Javidi, Mario Vettore, Philip E. Benson
IntroductionOrthodontics aims to improve oral health-related quality of life (OHRQoL). In this systematic review, we examined the evidence for changes in OHRQoL after orthodontic treatment for patients treated before they were 18 years old.MethodsThe participants were patients aged less than 18 years. The interventions were nonorthognathic and cleft orthodontic treatment. The comparisons were before and after orthodontic treatment, or nonorthodontic control. The outcomes were validated measures of OHRQoL. The study designs were randomized controlled trials, controlled clinical trials, prospective cohort studies, and cross-sectional or case-control studies. Multiple electronic databases were searched, with no language restrictions; authors were contacted, and reference lists screened. The Newcastle-Ottawa scale was used for quality assessments. Screening, data extraction, and quality assessments were performed by 2 investigators independently.ResultsWe found 1590 articles and included 13 studies (9 cohort, 3 cross sectional, and 1 case control), with 6 in the meta-analyses. All were judged of low or moderate quality. A moderate improvement in OHRQoL was observed before and after orthodontic treatment (n = 243 participants; standardized mean difference, −0.75; 95% CI, −1.15 to −0.36) particularly in the dimensions of emotional well-being (n = 213 participants; standardized mean difference, −0.61; 95% CI, −0.80 to −0.41) and social well-being (n = 213 participants; standardized mean difference, −0.62; 95% CI, −0.82 to −0.43).ConclusionsOrthodontic treatment during childhood or adolescence leads to moderate improvements in the emotional and social well-being dimensions of OHRQoL, although the evidence is of low and moderate quality. More high quality, longitudinal, prospective studies are needed.
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Leveling the curve of Spee with continuous archwire appliances in different vertical skeletal patterns: A retrospective study
Publication date: April 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 4
Author(s): Matteo Rozzi, Manuela Mucedero, Chiara Pezzuto, Paola Cozza
IntroductionThe aim of this study was to determine the effects of the leveling of the curve of Spee in subjects treated with preadjusted appliances in different skeletal vertical patterns.MethodsThe study sample consisted of 90 white patients (39 male, 51 female; age, 19 years 4 months ± 1 year 9 months), with a curve of Spee of 2 mm or greater before treatment. They were categorized into 3 groups: low-angle group (30 subjects; 12 male, 18 female; age, 19 years 1 month ± 1 year 4 months), normal-angle group (30 subjects; 14 male, 16 female; age, 19 years 6 months ± 2 years 1 month), and high-angle group (30 subjects; 13 male, 17 female; age, 19 years 7 months ± 1 year 5 months) by their vertical facial types. Cephalometric parameters were used to evaluate the different dental movements after treatment. The curve of Spee was measured on digital dental casts. Analysis of variance was used to determine any differences between the changes in the groups with time.ResultsFor the skeletal variables, no significant modifications were found in the 3 groups. For the dentoalveolar variables, the low-angle group showed significant buccal movements and intrusion of the mandibular incisors. The high-angle group had greater extrusion of the posterior teeth associated with uprighting of the first and second molars.ConclusionsIn low-angle subjects, leveling of the curve of Spee occurs through buccal movement and intrusion of the mandibular incisors; in high-angle subjects, it occurs through extrusion and uprighting of the posterior teeth.
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Presynaptic morphogenesis, active zone organization and structural plasticity in Drosophila
Publication date: April 2017
Source:Current Opinion in Neurobiology, Volume 43
Author(s): David Van Vactor, Stephan J Sigrist
Effective adaptation of neural circuit function to a changing environment requires many forms of plasticity. Among these, structural plasticity is one of the most durable, and is also an intrinsic part of the developmental logic for the formation and refinement of synaptic connectivity. Structural plasticity of presynaptic sites can involve the addition, remodeling, or removal of pre- and post-synaptic elements. However, this requires coordination of morphogenesis and assembly of the subcellular machinery for neurotransmitter release within the presynaptic neuron, as well as coordination of these events with the postsynaptic cell. While much progress has been made in revealing the cell biological mechanisms of postsynaptic structural plasticity, our understanding of presynaptic mechanisms is less complete.
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The bulbospinal network controlling the phrenic motor system: laterality and course of descending projections
Source:Neuroscience Research
Author(s): Michael George Zaki Ghali
The respiratory rhythm is generated by the parafacial respiratory group, Bötzinger complex, and pre-Bötzinger complex and relayed to pre-motor neurons, which in turn project to and control respiratory motor outputs in the brainstem and spinal cord. The phrenic nucleus is one such target, containing phrenic motoneurons (PhMNs), which supply the diaphragm, the primary inspiratory muscle in mammals. While some investigators have demonstrated both ipsi- and contralateral bulbophrenic projections, there exists controversy regarding the relative physiological contribution of each to phasic and tonic drive to PhMNs and at which levels decussations occur. Following C1- or C2 spinal cord hemisection-induced silencing of the ipsilateral phrenic/diaphragm activity, respiratory stressor-induced, as well as spontaneous, recovery of crossed phrenic activity is observed, suggesting an important contribution of pathways crossing below the level of injury in driving phrenic motor output. The precise mechanisms underlying this recovery are debated. In this review, we seek to present a comprehensive discussion of the organization of the bulbospinal network controlling PhMNs, a thorough appreciation of which is necessary for understanding neural respiratory control, accurate interpretation of studies investigating respiratory recovery following spinal cord injury, and targeted development of therapies for respiratory neurorehabilitation in patients sustaining high cervical cord injury.
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Simultaneous object perception deficits are related to reduced visual processing speed in amnestic mild cognitive impairment
Publication date: Available online 4 April 2017
Source:Neurobiology of Aging
Author(s): Adriana L. Ruiz-Rizzo, Peter Bublak, Petra Redel, Timo Grimmer, Hermann J. Müller, Christian Sorg, Kathrin Finke
Simultanagnosia, an impairment in simultaneous object perception, has been attributed to deficits in visual attention and, specifically, to processing speed. Increasing visual attention deficits manifest over the course of Alzheimer's disease (AD), where the first changes are present already in its symptomatic pre-dementia phase: amnestic mild cognitive impairment (aMCI). In this study, we examined whether patients with aMCI due to AD show simultaneous object perception deficits and whether and how these deficits relate to visual attention. Sixteen AD patients with aMCI and 16 age-, gender-, and education-matched healthy controls were assessed with a simultaneous perception task, with shapes presented in an adjacent, embedded, or overlapping manner, under free viewing without temporal constraints. We used a parametric assessment of visual attention based on the Theory of Visual Attention. Results show that patients make significantly more errors than controls when identifying overlapping shapes, which correlate with reduced processing speed. Our findings suggest simultaneous object perception deficits in very early AD, and a visual processing speed reduction underlying these deficits.
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Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment
Publication date: Available online 5 April 2017
Source:Neurobiology of Aging
Author(s): Thomas Jacquemont, Fabrizio De Vico Fallani, Anne Bertrand, Stéphane Epelbaum, Alexandre Routier, Bruno Dubois, Harald Hampel, Stanley Durrleman, Olivier Colliot
Alzheimer's disease (AD) is increasingly considered as a disconnection syndrome. Previous studies of the structural connectome in early AD stages have focused on mild cognitive impaired subjects (MCI), considering them as a homogeneous group. We studied 168 subjects from the Alzheimer's Disease Neuroimaging Initiative database (116 MCI and 52 cognitively normal subjects). Biomarker-based stratification using amyloid biomarkers (AV45 PET) and neurodegeneration biomarkers (MRI and FDG PET) led to four subgroups based on amyloid positivity (A+/-) and neurodegeneration positivity (N+/-): A-N-, A+N-, A-N+, and A+N+. Using diffusion MRI, we showed that both MCI A-N+ and MCI A+N+ subjects displayed an alteration of the white matter in the fornix and a significant bi-hemispheric network of decreased connections. These network alterations in MCI A+N+ are stronger and more focal than those of MCI A-N+. Only MCI A+N+ subjects exhibited specific changes in hippocampal connectivity and an AD-like alteration pattern. Our results indicate that the connectome disintegration pattern of MCI subgroups differ with respect to brain amyloid and neurodegeneration. Each of these two AD biomarkers induces a connectome alteration that is maximal when they co-exist.
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Scholar : These new articles for Annals of the American Association of Geographers are available online
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Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online
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Scholar : These new articles for The American Journal of Drug and Alcohol Abuse are available online
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Neck pain in Iranian school teachers: Prevalence and risk factors
Publication date: Available online 5 April 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Fatemeh Ehsani, Mohammad Ali Mohseni-Bandpei, César Fernández-de-las-Peñas, Khodabakhsh Javanshir
Neck pain (NP) is a common occupational health problem associated with a number of professions. Many studies indicate that NP is common among teachers, yet no published study was found to address the prevalence and risk factors of NP in Iranian school teachers. The purpose of the current study was to assess the prevalence and risk factors for NP among school teachers in Iran. A cross-sectional study was conducted on 586 randomly selected primary and high schools teachers from 22 schools in Tehran, Iran. Point, last month, last 6 months, annual, and lifetime prevalence rates of NP were 24%, 29%, 33%, 37%, and 43%, respectively. There was a significant association and increased prevalence of NP with a number of risk factors such as; being female, age, general health, length of employment, regular exercise and job satisfaction (P < 0.05 in all instances). Therefore, some individual and occupational factors may make conditions relevant for the development of NP among teachers.
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Scholar : These new articles for Acta Orthopaedica are available online
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Scholar : These new articles for Acta Oncologica are available online
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Scholar : These new articles for Acta Odontologica Scandinavica are available online
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Scholar : These new articles for American Journal of Sexuality Education are available online
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Current significant challenges in the decommissioning and environmental remediation of radioactive facilities: A perspective from outside the nuclear industry
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): V. Gil-Cerezo, E. Domínguez-Vilches, A.J. González-Barrios
This paper presents the results of implementing an extrajudicial environmental mediation procedure in the socioenvironmental conflict associated with routine operation of the El Cabril Disposal Facility for low- and medium- activity radioactive waste (Spain). We analyse the socio-ethical perspective of this facility's operation with regard to its nearby residents, detailing the structure and development of the environmental mediation procedure through the participation of society and interested parties who are or may become involved in such a conflict. The research, action, and participation method was used to apply the environmental mediation procedure. This experience provides lessons that could help improve decision-making processes in nuclear or radioactive facility decommissioning projects or in environmental remediation projects dealing with ageing facilities or with those in which nuclear or radioactive accidents/incidents may have occurred.
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Arabidopsis plants exposed to gamma radiation in two successive generations show a different oxidative stress response
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): S.M.J. Mortazavi, S.A.R. Mortazavi, Maryam Paknahad
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Atmospheric dispersion of radon around uranium mill tailings of the former Pridneprovsky Chemical Plant in Ukraine
Source:Journal of Environmental Radioactivity, Volume 172
Author(s): Ivan V. Kovalets, Christian Asker, Alexander V. Khalchenkov, Christer Persson, Tatyana V. Lavrova
Simulations of atmospheric dispersion of radon around the uranium mill tailings of the former Pridneprovsky Chemical Plant (PChP) in Ukraine were carried out with the aid of two atmospheric dispersion models: the Airviro Grid Model and the CALMET/CALPUFF model chain. The available measurement data of radon emission rates taken in the territories and the close vicinity of tailings were used in simulations. The results of simulations were compared to the yearly averaged measurements of concentration data. Both models were able to reasonably reproduce average radon concentration at the Sukhachivske site using averaged measured emission rates as input together with the measured meteorological data. At the same time, both models significantly underestimated concentrations as compared to measurements collected at the PChP industrial site. According to the results of both dispersion models, it was shown that only addition of significant radon emission rate from the whole territory of PChP in addition to emission rates from the tailings could explain the observed concentration measurements. With the aid of the uncertainty analysis, the radon emission rate from the whole territory of PChP was estimated to be between 1.5 and 3.5 Bq·m−2s−1.
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Editorial board
Source:Journal of Environmental Radioactivity, Volume 171
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Reply to Letter to the Editor
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): Jorden van de Walle
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The novel double-hit, t(8;22)(q24;q11)/MYC-IGL and t(14;15)(q32;q24)/IGH-BCL2A1, in diffuse large B-cell lymphoma
Source:Cancer Genetics
Author(s): Takashi Akasaka, Chiyuki Kishimori, Katsuhiro Fukutsuka, Miho Nakagawa, Kayo Takeoka, Masahiko Hayashida, Gen Honjo, Hitoshi Ohno
An 82-year-old woman presented with generalized lymphadenopathy and skin involvement. Lymph node biopsy revealed diffuse large B-cell lymphoma with a high proliferation index. G-banding and fluorescence in situ hybridization showed a hypertetraploid karyotype with two copies of t(8;22)(q24;q11), generating the fusion of MYC and the immunoglobulin λ chain gene (IGL), and two copies of the novel immunoglobulin heavy chain gene (IGH) translocation, t(14;15)(q32;q24). A long-distance inverse polymerase chain reaction (PCR) using nested primer combinations designed for each constant gene of IGH showed that Cγ4 was juxtaposed to the downstream sequence of the BCL2A1 (BCL2-related protein A1) gene through the Sγ4 switch region. As a result of t(14;15)(q32;q24), BCL2A1 and IGH Sγ4-Cγ4 were aligned in the same transcriptional orientation at a distance of 64 kb. Reverse transcriptase-mediated PCR showed high BCL2A1 mRNA levels in a lymphoma specimen. Since BCL2A1, mapped at 15q24.3 or 15q25.1, encodes a protein that is an anti-apoptotic member of the BCL2 protein family, we herein described the novel double-hit, t(8;22)(q24;q11)/MYC-IGL and t(14;15)(q32;q24)/IGH-BCL2A1, in which BCL2A1 is considered to play a role equivalent to that of BCL2 in the most frequent double-hit, MYC/BCL2.
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Variation in Staphylococcus aureus Colonization in Relation to Disease Severity in Adults with Atopic Dermatitis during av Five-month Follow-up.
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Variation in Staphylococcus aureus Colonization in Relation to Disease Severity in Adults with Atopic Dermatitis during av Five-month Follow-up.
Acta Derm Venereol. 2017 Apr 04;:
Authors: Alsterholm M, Strömbeck L, Ljung A, Karami N, Widjestam J, Gillstedt M, Åhren C, Faergemann J
Abstract
The aim of this study was to monitor Staphylococcus aureus colonization and disease severity in adults with atopic dermatitis (AD) during 5 months. Twenty-one patients attended 3 visits each for severity SCORing of Atopic Dermatitis (SCORAD) assessment, quantitative cultures from the skin and conventional cultures from the anterior nares, tonsils and perineum. S. aureus isolates were typed for strain identity with pulsed-field gel electrophoresis (PFGE). Seventy-one percent of patients were colonized with S. aureus on lesional skin at least once. Density (colony-forming units (CFU)/cm2) was higher on lesional skin than on non-lesional skin (p < 0.05). Density on lesional skin and number of colonized body sites were positively correlated with SCORAD (p = 0.0003 and p = 0.007, respectively). Persistent carriers of the same strain on lesional skin had higher mean SCORAD index than intermittent/non-carriers (36.3 and 17.1, respectively, p = 0.002). The results show a temporal correlation between several aspects of S. aureus colonization and disease severity in AD raising the question of the importance of this in pathogenesis and treatment.
PMID: 28374043 [PubMed - as supplied by publisher]
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Presence of multidrug-resistant organisms in the residents and environments of long-term care facilities in Taiwan.
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Presence of multidrug-resistant organisms in the residents and environments of long-term care facilities in Taiwan.
J Microbiol Immunol Infect. 2017 Feb 20;:
Authors: Lee CM, Lai CC, Chiang HT, Lu MC, Wang LF, Tsai TL, Kang MY, Jan YN, Lo YT, Ko WC, Tseng SH, Hsueh PR
Abstract
OBJECTIVES: This study investigated the prevalence of multidrug-resistant organisms (MDROs) in the residents and environments of long-term care facilities (LTCFs) in Taiwan.
METHODS: We prospectively investigated the distribution of MDROs in residents of six LTCFs and their environments from January 2015 to December 2015 (intervention period). Active surveillance of colonization of MDROs was performed by culturing rectal and nasal swab samples every 3 months for the residents: 63, 79, and 73 in the first, second, and third surveillance investigations, respectively. If MDROs, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa, and MDR Acinetobacter baumannii were identified, then swab specimens from environmental sources were also collected and cultured. During the study period, several infection control measures were also implemented.
RESULTS: The overall infection density decreased significantly from 2.69 per 1000 patient-days in the preintervention (January 2014 to December 2014) to 2.39 per 1000 patient-days during the intervention period (p < 0.001). A total of 154 samples from residents and environmental sources were positive for MDROs. Methicillin-resistant S. aureus (n = 83, 53.9%) was the predominant organism, followed by carbapenem-resistant Enterobacteriaceae (n = 35, 22.7%), MDR A. baumannii (n = 30, 19.5%), and carbapenem-resistant P. aeruginosa (n = 6, 3.9%). The rates of detection of MDROs were 27.9% (60/215) in nasal swabs, 15.8% (34/215) in rectal swabs, and 11.1% (60/542) in the environmental sources.
CONCLUSIONS: The distribution and persistence of MDROs varied among the different LTCFs and time periods.
PMID: 28373038 [PubMed - as supplied by publisher]
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Scholar : Applied Neuropsychology: Child, Volume 6, Issue 2, April-June 2017 is now available online on Taylor & Francis Online
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Large Bowel Obstruction in the Emergency Department: Imaging Spectrum of Common and Uncommon Causes
Subramaniyan Ramanathan, Vijayanadh Ojili, Ravi Vassa, Arpit Nagar
Journal of Clinical Imaging Science 2017 7(1):15-15
Although large bowel obstruction (LBO) is less common than small bowel obstruction, it is associated with high morbidity and mortality due to delayed diagnosis and/or treatment. Plain radiographs are sufficient to diagnose LBO in a majority of patients. However, further evaluation with multidetector computed tomography (MDCT) has become the standard of care to identify the site, severity, and etiology of obstruction. In this comprehensive review, we illustrate the various causes of LBO emphasizing the role of MDCT in the initial diagnosis and detection of complications along with the tips to differentiate from disease which can mimic LBO.
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Journal of Clinical Imaging Science 2017 7(1):15-15
Although large bowel obstruction (LBO) is less common than small bowel obstruction, it is associated with high morbidity and mortality due to delayed diagnosis and/or treatment. Plain radiographs are sufficient to diagnose LBO in a majority of patients. However, further evaluation with multidetector computed tomography (MDCT) has become the standard of care to identify the site, severity, and etiology of obstruction. In this comprehensive review, we illustrate the various causes of LBO emphasizing the role of MDCT in the initial diagnosis and detection of complications along with the tips to differentiate from disease which can mimic LBO.
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News and Announcements
Source:Journal of Dairy Science, Volume 100, Issue 4
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Interpretive Summaries, April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
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The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles
Publication date: Available online 5 April 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Afra Torge, Philipp Grützmacher, Frank Mücklich, Marc Schneider
Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles.In this context we investigated the influence of mannitol on the morphology, aerodynamic properties and disintegration behavior of nano-embedded microparticles.PLGA nanoparticles and mannitol were spray dried each as sole component and in combination in three different ratios. An influence of the mannitol content on the morphology was observed. Pure mannitol microparticles were solid and spherical, while the addition of nanoparticles resulted in raisin-shaped hollow particles. The different morphologies can be explained by diffusion processes of the compounds described by the Péclet-number. All powders showed suitable aerodynamic properties. By dispersion of the powders in simulated lung fluid, initial nanoparticle sizes could be recovered for samples containing mannitol. The fraction of redispersed nanoparticles was increased with increasing mannitol content. To evaluate the disintegration under conditions with higher comparability to the in vivo situation, spray-dried powders were exposed to >90% relative humidity. The disintegration behavior was monitored by analyzing roughness values by white light interferometry and supporting SEM imaging. The exposure to high relative humidity was shown to be sufficient for disintegration of the microparticles containing mannitol, releasing morphologically unchanged nanoparticles. With increasing mannitol content, the disintegration occurred faster and to a higher degree. Under these conditions, microparticles only composed of nanoparticles did not disintegrate.By enabling the release of nanoparticles from nano-embedded microparticles, mannitol was shown to be an ideal excipient to convert nanoparticles by spray drying into an inhalable dry power formulation.
Graphical abstract
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Targetability of hyaluronic acid nanogel to cancer cells: In vitro and in vivo studies
Publication date: Available online 4 April 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): S.S. Pedrosa, P. Pereira, A. Correia, F.M. Gama
We have, in previous work developed, characterized and evaluated the biocompatibility of an engineered hyaluronic acid nanogel. Here we assess the targetability of a hyaluronic acid nanogel towards CD44 overexpressing cells, in vitro and in vivo. Results obtained by flow cytometry and confocal fluorescence microscopy shows that nanogel is greatly internalized by non-small cancer lung cells (A549 cells), that overexpress CD44 receptors. The biodistribution and tumor targetability of the nanogel labelled with a near-infrared (NIR) probe were performed, in mice, through a non-invasive imaging system. Results revealed nanogel high targetability towards an induced subcutaneous A549 tumor. Nanogels pharmacokinetics was evaluated also in healthy animals, and Alexa Fluor 680 labelled nanogel exhibited higher accumulation in liver, kidneys and skin. Also, a comparative biodistribution study was performed, using two NIR imaging probes, Cy5.5 and Alexa Fluor 680.
Graphical abstract
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Significance of breath-hold time in dry powder aerosol drug therapy of COPD patients
Publication date: Available online 4 April 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Alpár Horváth, Imre Balásházy, Gábor Tomisa, Árpád Farkas
Aerosol drugs are effectively used to treat chronic respiratory diseases. The efficiency of the therapy depends also on the amount and distribution of drug deposited within the airways. The objective of this study is to apply numerical techniques to analyse the effect of the duration of breath-hold after the inhalation of six different commercialized dry powder drugs on their lung deposition. For this purpose a computational airway deposition model has been adapted and validated to the special case of therapeutic aerosols. Our results show that lung dose of the studied drugs can be enhanced by 11.3%–26.5% with a 5s breath-hold and by 20.7%–53% with a 25s breath-hold compared to the no-breath-hold case. Although this later duration may not be achieved by COPD patients, present results clearly show the importance of holding the breath as long as possible. Current computations also revealed that there is a strong positive correlation between the enhancement of lung dose as a result of breath-hold and the amount of fine particles in the drugs. Present tendencies aiming at producing drug particles of smaller and smaller sizes will lead to the further enhancement of the importance of producing a sufficiently long breath-hold time after the drug inhalation. In addition, higher lung deposition will be possible by the more correct use of inhalation devices, more precise and detailed patient information materials and personalized drug choice and therapy.
Graphical abstract
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Hypothesis: Exosomal microRNAs as potential biomarkers for schizophrenia
Source:Medical Hypotheses
Author(s): Vijaya Raghavan, Manish Bhomia, Isabel Torres, Sanjeev Jain, Kevin K. Wang
Schizophrenia is a serious mental disorder with lifelong morbidity and increased mortality. Currently, the diagnosis of the disorder is based on patient history and clinical examination, but it has a low inter-rater reliability and validity. Various biological variables, such as event related potentials, hormonal levels, brain ventricular volume and hippocampal size, have been put forth as objective markers to diagnose schizophrenia, but none with the desired sensitivity and specificity. It has been shown that microRNAs play a vital role in gene regulation in schizophrenia and have been proposed as possible biomarkers for the disease. When compared to the free microRNAs in the body fluids, exosomal microRNAs are more resistant to degradation and are easier to isolate. There are no studies reporting exosomal microRNAs as biomarkers for schizophrenia, but we hypothesize that exosomal microRNAs will be found to be potential biomarkers for diagnosis, prognosis assessment and medication response to patients with this disease.
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Scholar : These new articles for Australian Journal of Linguistics are available online
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Interrelations between EOS parameters and cohesive energy of transition metals: Thermostatistical approach, ab initio calculations and analysis of “universality” features
Publication date: August 2017
Source:Journal of Physics and Chemistry of Solids, Volume 107
Author(s): Dalía S. Bertoldi, Susana B. Ramos, Armando Fernández Guillermet
We present a theoretical analysis of the equation of state (EOS) of metals using a quasi-harmonic Einstein model with a dimensionless cohesive energy versus distance function (F(z)) involving the Wigner-Seitz radius and a material-dependent scaling length, as suggested in classical works by Rose, Ferrante, Smith and collaborators. Using this model, and "universal" values for the function and its first and second derivatives at the equilibrium distance (z=0), three general interrelations between EOS parameters and the cohesive energy are obtained. The first correlation involves the bulk modulus, and the second, the thermal expansion coefficient. In order to test these results an extensive database is developed, which involves available experimental data, and results of current ab initio density-functional-theory calculations using the VASP code. In particular, the 0K values for volume, bulk modulus, its pressure derivative, and the cohesive energy of 27 elements belonging to the first (Sc, Ti, V, Cr, Fe, Co, Ni, Cu, Zn), second (Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd) and third (Hf, Ta, W, Re, Os, Ir, Pt, Au) transition row of the Periodic Table are calculated ab initio and used to test the present results. The third correlation obtained, allows an evaluation of the third derivative of F(z) at z=0 for the current elements. With this new information, a discussion is presented of the possibility of finding a "universal" F(z) versus z function able to account accurately for the pressure derivative of the bulk modulus of the transition elements.
http://ift.tt/2oZAV9w
Autophagic flux control in neurodegeneration: Progress and precision targeting—Where do we stand?
Publication date: Available online 3 April 2017
Source:Progress in Neurobiology
Author(s): Dumisile Lumkwana, Andre du Toit, Craig Kinnear, Ben Loos
Neurodegenerative diseases are characterised by the presence of cytoplasmic and nuclear protein aggregates that result in toxicity and neuronal cell death. Autophagy is a physiological cellular process that engulfs primarily long-lived proteins as well as protein aggregates with subsequent cargo delivery for lysosomal degradation. The rate at which the material is degraded through autophagy is referred to as autophagic flux. Although we have progressed substantially in unravelling the role and regulation of the autophagy machinery, its dysfunction in pathology as well as its dynamic changes in the disease progression remains largely unclear. Furthermore, the magnitude of autophagic flux in neuronal subtypes is largely unknown and it is unclear to what extent the flux may be affected in distinct neurodegenerative disease states. In this review, we provide an introduction to autophagy in neuronal homeostasis and indicate how autophagy is currently measured and modulated for therapeutic purposes. We highlight the need not only to develop enhanced methodologies that target and assess autophagic flux precisely, but also to discern the dynamics of autophagy in different neuronal types and brain regions associated with the disease-specific pathology. Finally, we describe how existing and novel techniques for assessing autophagic flux could be implemented in order to distinguish between molecular defects associated with autophagic cargo and the machinery. In doing so, this review may provide novel insights in the assessment and control of autophagic flux that is aligned with the protein clearance dysfunction in neurodegenerative disorders.
Graphical abstract
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Pro(moting) the Turnover of Gluconeogenic Enzymes by a New Branch of the N-end Rule Pathway
Publication date: Available online 4 April 2017
Source:Trends in Biochemical Sciences
Author(s): David A. Dougan
The N-end rule pathway is a set of protein degradation systems that link the in vivo stability of a protein to its N-terminal residue. A recent paper from Alexander Varshavsky's laboratory [1] identifies a new branch of the N-end rule pathway that specifically recognizes the N-terminal Pro residue of key gluconeogenesis enzymes.
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Synthesis and Biological Evaluation of Largazole Zinc-Binding Group Analogs
Publication date: Available online 4 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Bumki Kim, Ranjala Ratnayake, Hyunji Lee, Guqin Shi, Sabrina L. Zeller, Chenglong Li, Hendrik Luesch, Jiyong Hong
Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs and consequent hypoacetylation of histones have been observed in a variety of different diseases, leading to a recent focus of HDACs as attractive drug targets. The natural product largazole is one of the most potent natural HDAC inhibitors discovered so far and a number of largazole analogs have been prepared to define structural requirements for its HDAC inhibitory activity. However, previous structure–activity relationship studies have heavily investigated the macrocycle region of largazole, while there have been only limited efforts to probe the effect of various zinc-binding groups (ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with various ZBGs and evaluated their HDAC inhibition and cytotoxicity. While none of the analogs tested were as potent or selective as largazole, the Zn2+-binding affinity of each ZBG correlated with HDAC inhibition and cytotoxicity. We expect that our findings will aid in building a deeper understanding of the role of ZBGs in HDAC inhibition as well as provide an important basis for the future development of new largazole analogs with non-thiol ZBGs as novel therapeutics for cancer.
Graphical abstract
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Concise Synthesis of Artemisinin from a Farnesyl Diphosphate Analogue
Publication date: Available online 4 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Xiaoping Tang, Melodi Demiray, Thomas Wirth, Rudolf K. Allemann
Artemisinin is one of the most potent anti-malaria drugs and many often-lengthy routes have been developed for its synthesis. Amorphadiene synthase, a key enzyme in the biosynthetic pathway of artemisinin, is able to convert an oxygenated farnesyl diphosphate analogue directly to dihydroartemisinic aldehyde, which can be converted to artemisinin in only four chemical steps, resulting in an efficient synthetic route to the anti-malaria drug.
Graphical abstract
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Binding of thyroglobulin (Tg) to the low-density lipoprotein receptor-associated protein (RAP) during the biosynthetic pathway prevents premature Tg interactions with sortilin
Abstract
Objective
Sortilin, a Vps10p family member, is expressed by thyroid epithelial cells (TEC), where it binds to internalized thyroglobulin (Tg) molecules. Premature binding of Tg to sortilin during biosynthesis may cause intracellular retention of Tg. Such a premature interaction may be prevented by one or more inhibitor/s. Because both sortilin and Tg bind to the low-density lipoprotein receptor-associated protein (RAP), we investigated whether RAP serves such a function.
Methods
Immunofluorescence staining for sortilin, Tg, and RAP was performed in FRTL-5 cells. Co-immunoprecipitation experiments were performed in extracts from FRTL-5 or COS-7 cells, the former co-transfected with Tg and/or RAP and/or sortilin, or in thyroid extracts from RAP KO mice.
Results
Tg and sortilin did not co-localize in FRTL-5 cells following inhibition of protein synthesis, suggesting that newly synthesized, endogenous sortilin and Tg do not interact, in confirmation of which an anti-sortilin antibody did not co-precipitate Tg in FRTL-5 cells. In contrast, Tg co-localized with RAP in FRTL-5 cells. Co-immunoprecipitation of Tg with an anti-sortilin antibody in COS-7 cells transfected with sortilin and Tg was abolished when cells were co-transfected with RAP, indicating that RAP prevents binding of Tg to sortilin during biosynthesis, in confirmation of which an anti-sortilin antibody co-precipitated Tg in thyroid extracts from RAP KO mice to a greater extent than in thyroid extracts from WT mice.
Conclusions
Tg does not bind prematurely to sortilin because of its interaction with RAP during protein biosynthesis. These findings add new information to the knowledge of thyroid physiology.
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Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog
Publication date: Available online 4 April 2017
Source:Clinical Immunology
Author(s): Mark R. Tanner, Rajeev B. Tajhya, Redwan Huq, Elizabeth J. Gehrmann, Kathia E. Rodarte, Mustafa A. Atik, Raymond S. Norton, Michael W. Pennington, Christine Beeton
Effector memory T lymphocytes (TEM cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The Kv1.3 potassium channel is a key regulator of CCR7− TEM cell activation. Blocking Kv1.3 inhibits TEM cell activation and attenuates inflammation in autoimmunity, and as such, Kv1.3 has emerged as a promising target for the treatment of TEM cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent Kv1.3 blockers and HsTX1[R14A] is selective for Kv1.3 over closely-related Kv1 channels. PEGylation of HsTX1[R14A] to create a Kv1.3 blocker with a long circulating half-life reduced its affinity but not its selectivity for Kv1.3, dramatically reduced its adsorption to inert surfaces, and enhanced its circulating half-life in rats. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7− TEM cell proliferation, leaving CCR7+ naïve and central memory T cells able to proliferate. It reduced inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduced inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases. PEG-HsTX1[R14A] has the additional advantages of reduced non-specific adsorption to inert surfaces and enhanced circulating half-life.
http://ift.tt/2nIRqpX
Effects of acute dopaminergic and serotonergic manipulations in the ACI paradigm depend on the basal valence of cognitive judgement bias in rats
Source:Behavioural Brain Research SreeTestContent1, Volume 327
Author(s): Joanna Golebiowska, Rafal Rygula
Recent findings have revealed that pharmacological enhancement of dopaminergic (DA) function by the administration of a DA precursor (dihydroxy-l-phenylalanine; L-DOPA), but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increases an optimism bias in humans. To test whether dopamine might play a similar role in non-human animals, in the present study, we evaluated the effects of acute injections of L-DOPA, the D2 receptor antagonist haloperidol, and the SSRI escitalopram on cognitive judgement bias of rats in the ambiguous-cue interpretation (ACI) paradigm. Three different doses of each drug were administered in a fully randomised Latin-square design, along with saline treatment as a control, 30min before the ACI tests. Initial analysis revealed that only animals treated with L-DOPA were more 'pessimistic' than the saline-treated controls. Neither haloperidol nor escitalopram significantly affected the cognitive judgement bias of rats. However, further analysis revealed that the effects of the tested compounds might depend on the basal cognitive judgement bias of the tested animals. When we divided the rats into 'optimistic' and 'pessimistic' groups based on their cognitive judgement bias in the drug-free state, it turned out that acute administration of L-DOPA caused a 'pessimistic' shift in 'optimistic' animals while showing no significant effects on 'pessimists'. Acute administration of haloperidol caused a 'pessimistic' shift in 'optimistic' animals and an 'optimistic' shift in 'pessimists'. Acute administration of escitalopram caused a 'pessimistic' shift in 'optimistic' animals and had no significant effects on 'pessimists', except that the middle tested dose rendered the rats more 'optimistic'.
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High-sucrose diets in male rats disrupt aspects of decision making tasks, motivation and spatial memory, but not impulsivity measured by operant delay-discounting
Source:Behavioural Brain Research SreeTestContent1, Volume 327
Author(s): Alanna Wong, Vimi R. Dogra, Amy C. Reichelt
Excessive consumption of sugar sweetened drinks is proposed to produce functional changes in the hippocampus and prefrontal cortex, leading to perturbations in behavioural control. Impairments in behavioural control have been observed in obese people on tasks that involve making choices, including delay-discounting, indicative of increased impulsivity. In this study we examined the impact of 2h daily access to 10% sucrose (or no sucrose in controls) in young male rats on behavioural tasks reliant on hippocampal function including delay-discounting, T-maze forced choice alternation and place recognition memory, as well as progressive ratio to measure motivation. We observed deficits in place recognition memory and T-maze forced choice alternation, indicative of hippocampal deficits in rats with a history of sucrose consumption. Moreover, rats with a history of sucrose consumption were less motivated to lever press for rewards on a progressive ratio schedule. However, rats with a history of sucrose consumption performed equally to control animals during the delay-discounting task, suggesting that they discounted for reward size over a delay in a manner comparable to control animals. These findings indicate that high-sucrose diets impact on spatial and working memory processes, but do not induce impulsive-like choice behaviours in rats, suggesting that unhealthy diet choices may not influence this aspect of decision-making behaviour.
http://ift.tt/2nID4WM
Vertical Head Thrusting in Acquired Supranuclear Vertical Ophthalmoplegia.
Patients with congenital ocular motor apraxia (OMA) typically show head thrusts while attempting to shift gaze. In congenital OMA, this compensatory head motion mostly occurs in the horizontal plane. Two patients with acquired palsy of voluntary vertical gaze and continuous upward gaze deviation, one from aortic surgery and the other from multiple infarctions involving the mesodiencephalic junction, showed intermittent downward head thrusting to redirect the eyes straight ahead or downward. The head thrusting behavior improved markedly after surgical correction of the upward gaze deviation in one patient. Vertical head thrusting may be a characteristic sign of acquired vertical gaze palsy when combined with vertical gaze deviation. (C) 2017 by North American Neuro-Ophthalmology Society
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
