Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Irfan Qamruddin, Mohammad Khursheed Alam, Verda Mahroof, Mubassar Fida, Mohd Fadhli Khamis, Adam Husein
IntroductionThe aim of this study was to evaluate the effect of low-level laser irradiation applied at 3-week intervals on orthodontic tooth movement and pain associated with orthodontic tooth movement using self-ligating brackets.MethodsTwenty-two patients (11 male, 11 female; mean age, 19.8 ± 3.1 years) with Angle Class II Division 1 malocclusion were recruited for this split-mouth clinical trial; they required extraction of maxillary first premolars bilaterally. After leveling and alignment with self-ligating brackets (SmartClip SL3; 3M Unitek, St Paul, Minn), a 150-g force was applied to retract the canines bilaterally using 6-mm nickel-titanium closed-coil springs on 0.019 x 0.025-in stainless steel archwires. A gallium-aluminum-arsenic diode laser (iLas; Biolase, Irvine, Calif) with a wavelength of 940 nm in a continuous mode (energy density, 7.5 J/cm2/point; diameter of optical fiber tip, 0.04 cm2) was applied at 5 points buccally and palatally around the canine roots on the experimental side; the other side was designated as the placebo. Laser irradiation was applied at baseline and then repeated after 3 weeks for 2 more consecutive follow-up visits. Questionnaires based on the numeric rating scale were given to the patients to record their pain intensity for 1 week. Impressions were made at each visit before the application of irradiation at baseline and the 3 visits. Models were scanned with a CAD/CAM scanner (Planmeca, Helsinki, Finland).ResultsCanine retraction was significantly greater (1.60 ± 0.38 mm) on the experimental side compared with the placebo side (0.79 ± 0.35 mm) (P <0.05). Pain was significantly less on the experimental side only on the first day after application of LLLI and at the second visit (1.4 ± 0.82 and 1.4 ± 0.64) compared with the placebo sides (2.2 ± 0.41 and 2.4 ± 1.53).ConclusionsLow-level laser irradiation applied at 3-week intervals can accelerate orthodontic tooth movement and reduce the pain associated with it.
http://ift.tt/2zvGxS7
Παρασκευή 3 Νοεμβρίου 2017
Effects of low-level laser irradiation on the rate of orthodontic tooth movement and associated pain with self-ligating brackets
Directory: AAO Officers and Organizations
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
http://ift.tt/2zhaO61
ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders
Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Kay Chung, Tabitha Richards, Romain Nicot, Alexandre R. Vieira, Christiane V. Cruz, Gwénaël Raoul, Joel Ferri, James J. Sciote
IntroductionWe investigated whether ACTN3, ENPP1, ESR1, PITX1, and PITX2 genes which contribute to sagittal and vertical malocclusions also contribute to facial asymmetries and temporomandibular disorders (TMD) before and after orthodontic and orthognathic surgery treatment.MethodsOne hundred seventy-four patients with a dentofacial deformity were diagnosed as symmetric or subdivided into 4 asymmetric groups according to posteroanterior cephalometric measurements. TMD examination diagnosis and jaw pain and function (JPF) questionnaires assessed the presence and severity of TMD.ResultsFifty-two percent of the patients were symmetric, and 48% were asymmetric. The asymmetry classification demonstrated significant cephalometric differences between the symmetric and asymmetric groups, and across the 4 asymmetric subtypes: group 1, mandibular body asymmetry; group 2, ramus asymmetry; group 3, atypical asymmetry; and group 4, C-shaped asymmetry. ENPP1 SNP-rs6569759 was associated with group 1 (P = 0.004), and rs858339 was associated with group 3 (P = 0.002). ESR1 SNP-rs164321 was associated with group 4 (P = 0.019). These results were confirmed by principal component analysis that showed 3 principal components explaining almost 80% of the variations in the studied groups. Principal components 1 and 2 were associated with ESR1 SNP-rs3020318 (P <0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia, and arthralgia were highly prevalent in the asymmetry groups, and all had strong statistical associations with ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF, 7) were significantly higher than for symmetric subjects (JPF, 2). Patients in group 3 had the highest preoperative JPF scores, and groups 2 and 3 were most likely to be cured of TMD 1 year after treatment.ConclusionsPosteroanterior cephalometrics can classify asymmetry into distinct groups and identify the probability of TMD and genotype associations. Orthodontic and orthognathic treatments of facial asymmetry are effective at eliminating TMD in most patients.
http://ift.tt/2zuHuKv
Clinical recognition of mouth breathers by orthodontists: A preliminary study
Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Julia Garcia Costa, Genilza Silva Costa, Carolina Costa, Oswaldo de Vasconcellos Vilella, Claudia Trindade Mattos, Adriana de Alcantara Cury-Saramago
IntroductionA routine diagnosis of a patient's breathing status performed by an orthodontist normally includes visual assessment, medical history, clinical examination of habitual lip posture, size and shape of the nostrils, reflex control of the alar muscle and respiratory tests, and the dental mirror test. The objective of this study was to test the recognition of mouth breathers in young persons by an orthodontist and agreement with an otolaryngologist's reference diagnosis when routine assessments were carried out.MethodsThree independent and blind evaluations were conducted on the same day by 2 orthodontists independently (anamnesis and breathing tests, respectively) and an otolaryngologist (rhinoscopy, nasal endoscopy, and visual assessment). The weighted kappa coefficient was used to test intraexaminer and interexaminer agreement. The frequencies of answers and findings were reported for each breathing status.ResultsFifty-five volunteers composed the sample of this study; 20 participants were nasal breathers, and 35 participants were classified as mouth breathers (and subdivided into mouth breathers with airway obstruction and mouth breathers by habit) by the otolaryngologist. The weighted kappa coefficient showed poor interrater agreement for most comparisons.ConclusionsRecognition of mouth breathing in young persons by orthodontists is poor.
http://ift.tt/2zhbpVv
Protein and mRNA expressions of IL-6 and its key signaling factors under orthodontic forces in mice: An in-vivo study
Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Yi Liu, Fang Song, Shu Wu, Shushu He, Mingmei Meng, Chunxiao Lv, Qingqing Yang, Song Chen
IntroductionThe purpose of this study was to investigate the mechanical loading-induced changes in protein and mRNA expressions of interleukin-6 (IL-6) and its key signaling factors glycoprotein 130 (gp130), signal transducer and activator of transcription 3 (STAT3), and the Src homology phosphotyrosine phosphatase (SHP2) at the tension and compression sides of the teeth in mouse models.MethodsA total of 55 C57B/6 mice (10 weeks old) were divided into 3 groups. Orthodontic force was applied in group A (experimental group, n = 30); the tooth movement device was placed without activation in group B (sham control group, n = 15), and group C (blank control group, n = 10). Tooth movement was induced by a nickel-titanium coil spring inserted between the maxillary left incisor and the first molar with a force of approximately 4 g. The animals were killed 12 days after the interventions; protein and mRNA expressions of IL-6, gp130, STAT3, and SHP2 in the periodontal tissues were observed with immunohistochemistry and in-situ hybridization, respectively.ResultsIn contrast with the control groups, we observed enhanced expressions of IL-6, gp130, STAT3, and SHP2 protein and mRNA at the mesial and distal sides of the teeth with application of orthodontic forces in the experimental group. In contrast with the distal side, we observed enhanced expression of gp130 protein and mRNA at the mesial side in the experimental group.ConclusionsWe observed enhanced expression of IL-6 and its key signaling factors gp130, STAT3, and SHP2 protein and mRNA at the tension and compression sides of the teeth with application of orthodontic forces. The mechanical loading applied for orthodontic tooth movement might induce changes in protein localization and mRNA expression patterns of IL-6 and its key signaling factors gp130, STAT3, and SHP2 at the tension and compression sides of the periodontal ligaments of the teeth in mouse models. The result might demonstrate the special role of IL-6 and its key signaling factors in the alveolar bone-modeling process.
http://ift.tt/2zvzatE
Long-term stability of Class II treatment with the Jasper jumper appliance
Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Camilla Fiedler Foncatti, José Fernando Castanha Henriques, Guilherme Janson, Waleska Caldas, Daniela Gamba Garib
IntroductionTreatment of Class II Division 1 malocclusion with orthopedic devices combined with fixed orthodontic appliances has shown excellent results when used in growing patients. We aimed to evaluate the long-term stability of the cephalometric changes obtained during Class II malocclusion correction with the Jasper jumper associated with fixed appliances.MethodsThe treatment group comprised 24 patients who were evaluated at 3 stages: pretreatment, posttreatment, and long-term posttreatment. The control group comprised 15 subjects with normal occlusion. Intratreatment group comparisons among the 3 stages were performed with repeated measures analysis of variance, followed by Tukey tests. Intergroup comparisons of posttreatment changes and normal growth changes of the treatment group were performed with t tests.ResultsApical base relationship, maxillary incisor anteroposterior position, and overjet demonstrated significant relapses in relation to the control group.ConclusionsMost dentoalveolar changes obtained with the Jasper jumper followed by fixed appliances during treatment remained stable in the long term. However, apical base relationship, maxillary incisor anteroposterior position, and overjet demonstrated significant relapses in relation to the control group. Therefore, active retention time should be increased in the posttreatment period.
http://ift.tt/2zhbokp
Children's orthodontic utilization in the United States: Socioeconomic and surveillance considerations
Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Nadia Laniado, Stephanie Oliva, Gregory J. Matthews
IntroductionThere has been no epidemiologic study of malocclusion prevalence and treatment need in the United States since the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1991. In this descriptive study, the authors sought to estimate orthodontic treatment prevalence by examining a nationally representative survey to assess current pediatric dental and orthodontic utilization.MethodsThe 2009 and 2013 Medical Expenditure Panel Surveys were used to categorize and compare all types of pediatric dental and orthodontic procedures in children and adolescents up to 20 years old. Descriptive variables included dental insurance, poverty level, and racial/ethnic background.ResultsVisits for orthodontic procedures constituted the third largest treatment category (14.5%) and were greatest among the uninsured and higher income populations. Children with public insurance had the fewest orthodontic visits (9.4%). Racial/ethnic disparities were most pronounced among orthodontic visits, with black and Hispanic children receiving the fewest orthodontic procedures (8.89% and 10.56%, respectively).ConclusionsOrthodontic treatment prevalence data suggest that significant disparities exist in orthodontic utilization based on race/ethnicity, poverty level, and insurance status. To establish the burden of malocclusion, describe populations in greatest need of interventions, and craft appropriate programs and policies, an active orthodontic surveillance system is essential.
http://ift.tt/2zvNWk7
Miniscrew-assisted multidisciplinary orthodontic treatment with surgical mandibular advancement and genioplasty in a brachyfacial Class II patient with mandibular asymmetry
Publication date: November 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 5
Author(s): Vanessa Paredes-Gallardo, Verónica García-Sanz, Carlos Bellot-Arcís
This article describes the complex dental treatment of a 43-year-old man with skeletal Class II, mandibular asymmetry, severe brachyfacial pattern, Class II Division 2, canting of the occlusal plane, and an increased curve of Spee. To achieve optimal results, we adopted a multidisciplinary approach to treatment, involving periodontics, oral surgery, orthodontics, maxillofacial surgery, and prosthetics specialists. After periodontal treatment, miniscrews were placed to correct the occlusal plane canting and the excessive curve of Spee with orthodontic treatment. The surgical treatment plan consisted of a bilateral asymmetric sagittal split osteotomy for mandibular advancement and genioplasty. The patient had an infection after the surgery at the site of the right fixation plate, so the plate was removed, and active orthodontic treatment was continued and finished. Mandibular first molar implants and maxillary ceramic crowns using the Digital Smile Design method (Digital Smile Design, Doral, FL) were placed at the end of orthodontic treatment. The patient was satisfied with the treatment results and with his facial and dental appearance, as well as his oral function. The 2-year follow-up pictures show a stable result both esthetically and functionally.
http://ift.tt/2iZH9se
Risk of adverse events with the addition of targeted agents to endocrine therapy in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis
Source:Cancer Treatment Reviews
Author(s): Samuel Martel, Marco Bruzzone, Marcello Ceppi, Christian Maurer, Noam Falbel Ponde, Arlindo R. Ferreira, Giulia Viglietti, Lucia Del Mastro, Catherine Prady, Evandro de Azambuja, Matteo Lambertini
BackgroundCombining targeted agents and endocrine therapy (ET) improves outcomes in hormone receptor-positive metastatic breast cancer patients but increases the risk of adverse events (AEs). This meta-analysis aims to estimate the comparative risk of AEs with ET in addition to targeted agents in this setting.MethodsA systematic literature search of MEDLINE, EMBASE, Cochrane Library and conference proceedings up to July 17th 2017 was conducted to identify randomized controlled trials investigating ET with or without CDK4/6, mTOR, PI3K inhibitors and anti-HER2 agents. We calculated summary risk estimates (odds ratio, OR) and 95% confidence intervals (CI) for each AE within each class of targeted agents for each trial, and pooled analysis using the random and fixed effect models.ResultsSixteen studies (n=8529 patients) were included. The addition of targeted agents to ET was associated with a significant higher risk of grade 3–4 AEs: OR 2.86 (95% CI 2.49–3.27) for CDK4/6 inhibitors, 1.88 (95% CI 1.39–2.53) for mTOR inhibitors, 2.05 (95% CI 1.63–2.58) for PI3K inhibitors, and 2.48 (95% CI 1.09–5.66) for anti-HER2 agents. The highest class-specific risks were neutropenia grade 3–4 for CDK4/6 inhibitors (OR 40.77; 95% CI 19.52–85.19), stomatitis grade 3–4 for mTOR inhibitors (OR 11.92; 95% CI 3.68–38.57), hyperglycemia grade 3–4 for PI3K inhibitors (OR 40.93; 95% CI 10.08–166.22) and diarrhea for anti-HER2 agents (OR 9.93; 95% CI 4.71–20.95).ConclusionsAdding targeted agents to ET is associated with a significant increased risk of AEs. The risk of developing different AEs varies largely according to the type of agent used.
http://ift.tt/2j1XzAp
The impact of sewage sludge and compost on winter triticale
Abstract
There is an increasing interest in the agricultural application of organic waste such as soil amendment, due to the possibility of recycling valuable components, organic matter, and nutrient elements necessary for plant growth. The present study was carried out to evaluate the effects of sewage sludge, and green waste compost application, on a forage crop, triticale "X Triticosecale Wittmack" compared to unfertilized control. The experimental design was installed in the glasshouse conditions at the Regional Field Crop Research Center in Beja, Tunisia. Sewage sludge and green waste compost were added by four rates (0, 5, 10, and 20 t/ha) in soil, 15 days before triticale sowing. The main results showed that plant response differs depending on the type of adding fertilizer. Indeed, compost inputs decreased shoot length and production of triticale, among all sewage sludge rates, by average values of 26 and 60% respectively at final harvest, as compared to unamended soil. However, amendment with different rates of sewage sludge significantly (p < 0.05) increased different plant growth and yield attributes.
http://ift.tt/2zciqow
Vulture mortality resulting from illegal poisoning in the southern Balkan Peninsula
Abstract
A study was carried out to determine the incidents of illegal poisoning of griffon vulture (Gyps fulvus), Egyptian vulture (Neophron percnopterus), black vulture (Aegypius monachus), and bearded vulture (Gypaetus barbatus) in the southern Balkan Peninsula between 1982 and 2017. A total of 38 poisoning cases affecting 224 vultures were analyzed to identify their causes and the primary target species for poisoning. Nine different compounds were used in these incidents and the most frequently applied were strychnine, carbamate, and organophosphoros compounds. The poison used to kill gray wolf had the most significant collateral damage to the vulture populations in comparison to the other investigated reasons. It was the primary cause of 60% of all registered vulture poisoning events in the southern Balkan Peninsula during the last 36 years. Establishing permanent feeding sites for vultures in areas with wolves appears to be an effective way to minimize the risk of poisoning. There is a pressing need for the development of an appropriate conservation practice taking into consideration relationships among the main and casual target species for poisoning as an essential element in conjunction with the human activities.
http://ift.tt/2xYXUGF
Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Zuzana Tothova, John M. Krill-Burger, Katerina D. Popova, Catherine C. Landers, Quinlan L. Sievers, David Yudovich, Roger Belizaire, Jon C. Aster, Elizabeth A. Morgan, Aviad Tsherniak, Benjamin L. Ebert
Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34+ human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation. Employing these models to investigate therapeutic efficacy, we found that TET2 and cohesin-mutated hematopoietic cells were sensitive to azacitidine treatment. These findings demonstrate the potential for generating genetically defined models of human myeloid diseases, and they are suitable for examining the biological consequences of somatic mutations and the testing of therapeutic agents.
Graphical abstract
Teaser
Testing novel therapies for hematologic malignancies requires human cell models that reflect the combinatorial complexity of genetic mutations observed in patients. Ebert and colleagues use multiplex CRISPR/Cas9-based targeting of human hematopoietic stem and progenitor cells to model the genetics of clonal hematopoiesis and myeloid neoplasms in vivo.http://ift.tt/2y37PgC
Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification from Pluripotent Stem Cells
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Yoji Kojima, Kotaro Sasaki, Shihori Yokobayashi, Yoshitake Sakai, Tomonori Nakamura, Yukihiro Yabuta, Fumio Nakaki, So Nagaoka, Knut Woltjen, Akitsu Hotta, Takuya Yamamoto, Mitinori Saitou
Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs. Germline competence of iMeLCs is dictated by the duration and dosage of WNT signaling, which induces expression of EOMES to activate SOX17, a key driver of hPGCLC specification. Upon hPGCLC induction, BMP signaling activates TFAP2C in a SOX17-independent manner. SOX17 and TFAP2C then cooperatively instate an hPGCLC transcriptional program, including BLIMP1 expression. This specification program diverges from its mouse counterpart regarding key transcription factors and their hierarchies, and it provides a foundation for further study of human germ cell development.
Graphical abstract
Teaser
The mechanisms driving human germ cell specification are largely unknown. Kojima et al. define the signaling and transcriptional programs that drive human germ cell specification in vitro, which show substantial evolutionary divergence from mouse programs. These findings serve as a foundation for further reconstitution of human germ cell development.http://ift.tt/2y3fQlF
Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Jingtao Guo, Edward J. Grow, Chongil Yi, Hana Mlcochova, Geoffrey J. Maher, Cecilia Lindskog, Patrick J. Murphy, Candice L. Wike, Douglas T. Carrell, Anne Goriely, James M. Hotaling, Bradley R. Cairns
Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4+ hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4+ hSSCs and differentiating c-KIT+ spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed. Interestingly, open chromatin in hSSCs was strikingly enriched in binding sites for pioneer factors (NFYA/B, DMRT1, and hormone receptors). Remarkably, single-cell RNA-seq clustering analysis identified four cellular/developmental states during hSSC differentiation, involving major transitions in cell-cycle and transcriptional regulators, splicing and signaling factors, and glucose/mitochondria regulators. Overall, our results outline the dynamic chromatin/transcription landscape operating in hSSCs and identify crucial molecular pathways that accompany the transition from quiescence to proliferation and differentiation.
Graphical abstract
Teaser
Cairns and colleagues show that human spermatogonial stem cells (hSSCs) bear unique DNA methylation and open chromatin landscapes, which may enable proper development, niche responsiveness, and "poised" pluripotency. Interestingly, single-cell transcriptome and immunofluorescence analyses reveal four cellular states, spanning from quiescent hSSCs to proliferating, metabolically active, differentiating spermatogonia.http://ift.tt/2y3fRpJ
The LUNGe to Model Alveolar Lung Diseases in a Dish
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Zheng Wang, Nan Tang
Obtaining alveolar epithelial type 2 cells (AEC2s) from human pluripotent stem cells (hPSCs) offers great scientific and clinical promise. In this issue of Cell Stem Cell, Jacob et al. (2017) report a method for the directed differentiation of hPSCs into mature AEC2s and demonstrate its application in modeling alveolar lung diseases.
Teaser
Obtaining alveolar epithelial type 2 cells (AEC2s) from human pluripotent stem cells (hPSCs) offers great scientific and clinical promise. In this issue of Cell Stem Cell, Jacob et al. (2017) report a method for the directed differentiation of hPSCs into mature AEC2s and demonstrate its application in modeling alveolar lung diseases.http://ift.tt/2fXtSPz
E Pluribus Unum (“Out of Many, One”): CRISPR Modeling of Myeloid Expansion
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Jiyung Shin, Jacob E. Corn
In this issue of Cell Stem Cell, Tothova et al. (2017) demonstrate a promising way to model the complex genetics of clonal hematopoiesis and myeloid disorders using CRISPR-Cas9 genome editing in human hematopoietic stem and progenitor cells. Their approach opens the door to genotype-specific pharmacologic testing.
Teaser
In this issue of Cell Stem Cell, Tothova et al. (2017) demonstrate a promising way to model the complex genetics of clonal hematopoiesis and myeloid disorders using CRISPR-Cas9 genome editing in human hematopoietic stem and progenitor cells. Their approach opens the door to genotype-specific pharmacologic testing.http://ift.tt/2y2Pyjz
Gut with the Program: Direct Reprogramming toward Intestinal Epithelium Realized
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Angela Nakauka-Ddamba, Christopher J. Lengner
Intestinal organoids offer great promise for modeling intestinal diseases; however, harvesting intestinal tissue is invasive and directed hPSC differentiation protocols are laborious and costly. In this issue of Cell Stem Cell, Miura and Suzuki (2017) describe the direct conversion of somatic cells from both mice and humans into robust intestinal epithelial tissue.
Teaser
Intestinal organoids offer great promise for modeling intestinal diseases; however, harvesting intestinal tissue is invasive and directed hPSC differentiation protocols are laborious and costly. In this issue of Cell Stem Cell, Miura and Suzuki (2017) describe the direct conversion of somatic cells from both mice and humans into robust intestinal epithelial tissue.http://ift.tt/2fVRnZn
Policing Tumorigenesis within the Skin: Good Outs Bad
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Ramiro Iglesias-Bartolome, Maria I. Morasso
Recently published in Nature, Brown et al. (2017) shed new light on how the skin handles the activation of oncogenic pathways in the stem cell compartment and how wild-type cells limit the proliferation of mutant cells to maintain proper tissue homeostasis.
Teaser
Recently published in Nature, Brown et al. (2017) shed new light on how the skin handles the activation of oncogenic pathways in the stem cell compartment and how wild-type cells limit the proliferation of mutant cells to maintain proper tissue homeostasis.http://ift.tt/2y32xBW
Mononuclear Diploidy at the Heart of Cardiomyocyte Proliferation
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Paula A. da Costa Martins
Reporting in Nature Genetics, Patterson et al. (2017) show that adult mammalian hearts possess an innate capacity to regenerate, which depends on a small population of mononuclear diploid cardiomyocytes. These cells undergo karyokinesis and cytokinesis, raising the possibility that endogenous cardiac muscle cells can be stimulated to proliferate for myocardial repair.
Teaser
Reporting in Nature Genetics, Patterson et al. (2017) show that adult mammalian hearts possess an innate capacity to regenerate, which depends on a small population of mononuclear diploid cardiomyocytes. These cells undergo karyokinesis and cytokinesis, raising the possibility that endogenous cardiac muscle cells can be stimulated to proliferate for myocardial repair.http://ift.tt/2fVDLNA
Human Embryo Editing: Opportunities and Importance of Transnational Cooperation
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Duanqing Pei, David W. Beier, Ephrat Levy-Lahad, Gary Marchant, Janet Rossant, Juan Carlos Izpisua Belmonte, Robin Lovell-Badge, Rudolf Jaenisch, Alta Charo, David Baltimore
A recent National Academies report articulates a path forward for research, ethics, and governance of clinical applications involving genome editing. In light of recent human embryo editing developments, scientists and stakeholders from all nations should cooperate to take advantage of this historic opportunity for medicine and also basic human biology.
Teaser
A recent National Academies report articulates a path forward for research, ethics, and governance of clinical applications involving genome editing. In light of recent human embryo editing developments, scientists and stakeholders from all nations should cooperate to take advantage of this historic opportunity for medicine and also basic human biology.http://ift.tt/2y2Pxw1
Human Genome Editing in the Clinic: New Challenges in Regulatory Benefit-Risk Assessment
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Mohamed Abou-El-Enein, Toni Cathomen, Zoltán Ivics, Carl H. June, Matthias Renner, Christian K. Schneider, Gerhard Bauer
As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues.
Teaser
As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues.http://ift.tt/2y3Ixz3
CRISPR/Cas9-Based Engineering of the Epigenome
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Julian Pulecio, Nipun Verma, Eva Mejía-Ramírez, Danwei Huangfu, Angel Raya
Determining causal relationships between distinct chromatin features and gene expression, and ultimately cell behavior, remains a major challenge. Recent developments in targetable epigenome-editing tools enable us to assign direct transcriptional and functional consequences to locus-specific chromatin modifications. This Protocol Review discusses the unprecedented opportunity that CRISPR/Cas9 technology offers for investigating and manipulating the epigenome to facilitate further understanding of stem cell biology and engineering of stem cells for therapeutic applications. We also provide technical considerations for standardization and further improvement of the CRISPR/Cas9-based tools to engineer the epigenome.
Teaser
Pulecio et al. discuss opportunities that CRISPR/Cas9 technology offers for investigating and manipulating the stem cell epigenome and also provide technical considerations for CRISPR/Cas9 tool standardization and improvement.http://ift.tt/2fSZyFO
Distinct Cell-Cycle Control in Two Different States of Mouse Pluripotency
Publication date: 5 October 2017
Source:Cell Stem Cell, Volume 21, Issue 4
Author(s): Menno ter Huurne, James Chappell, Stephen Dalton, Hendrik G. Stunnenberg
Mouse embryonic stem cells (ESCs) cultured in serum are characterized by hyper-phosphorylated RB protein, lack of G1 control, and rapid progression through the cell cycle. Here, we show that ESCs grown in the presence of two small-molecule inhibitors (2i ESCs) have a longer G1-phase with hypo-phosphorylated RB, implying that they have a functional G1 checkpoint. Deletion of RB, P107, and P130 in 2i ESCs results in a G1-phase similar to that of serum ESCs. Inhibition of the ERK signaling pathway in serum ESCs results in the appearance of hypo-phosphorylated RB and the reinstatement of a G1 checkpoint. In addition, induction of a dormant state by the inhibition of MYC, resembling diapause, requires the presence of the RB family proteins. Collectively, our data show that RB-dependent G1 restriction point signaling is active in mouse ESCs grown in 2i but abrogated in serum by ERK-dependent phosphorylation.
Graphical abstract
Teaser
It is widely thought that embryonic stem cells have an unusual and very rapid cell cycle, lacking normal G1 regulation. Stunnenberg and colleagues show that, in mouse ESCs, G1 regulation is, in fact, intact but abrogated in serum by ERK signaling and RB phosphorylation.http://ift.tt/2y3b3Rm
Oral pregabalin for acute pain relief after cervicofacial surgery: a systematic review
Abstract
Objective
The objectives of this systematic review were to unify criteria on the effectiveness of oral pregabalin to treat acute post-operative pain after cervicofacial surgery, to establish the most effective dose regimens, and to determine its effect on rescue medicine consumption and its association with adverse effects.
Materials and methods
PubMed/Medline (National Library of Medicine, Washington, DC), Scopus, Web of Science, and Cochrane databases were searched for studies in any language published between January 2000 and September 2016. The following question was posed, in accordance with PRISMA guidelines: Is oral pregabalin effective and safe for the relief of acute pain after cervicofacial surgery? The critical reading of the literature utilized a list of questions prepared by the CASPe Network, applying the Jadad scale for evaluation of the methodological quality of trials.
Results
Eleven randomized controlled clinical trials were selected. The 11 trials obtained a score ≥ 3, considered as Ib evidence level and high quality. A single oral dose of 75-mg pregabalin before or after cervicofacial surgery alleviates pain and lessens the need for rescue analgesia consumption, while the statistical significance of these effects is higher with a single dose of 150-mg pregabalin, either before or after the surgery.
Conclusion
Oral pregabalin appears to significantly alleviate post-operative pain and reduce rescue analgesia consumption, with no severe adverse effects. However, the ideal dose and most effective administration regimen remain controversial issues that need to be addressed in further high-quality clinical trials.
Clinical relevance
These findings suggest that pregabalin may be useful for acute pain relief after cervicofacial surgery.
http://ift.tt/2lNhLXp
Collaborative efforts, collective impact
Source:American Journal of Infection Control
Author(s): Linda R. Greene, Sara Cosgrove
http://ift.tt/2AhT0FZ
Analysis of chromium status in the revegetated flora of a tannery waste site and microcosm studies using earthworm E. fetida
Abstract
Chromium from tannery waste dump site causes significant environmental pollution affecting surrounding flora and fauna. The primary aims of this study were to survey vegetation, investigate the degree of soil pollution occurring near tannery waste dump site and make a systematic evaluation of soil contamination based on the chromium levels found in plants and earthworms from the impacted areas. This paper presents the pollution load of toxic heavy metals, and especially chromium, in 10 soil samples and 12 species of plants. Soil samples were analysed for heavy metals by using ICP-MS/ICP-OES method. Results indicated that Cr in soils exceeded soil quality guideline limits (SQGL). The total chromium present in the above ground parts of plants ranged from 1.7 mg kg−1 in Casuarina sp. to 1007 mg kg−1 in Sonchus asper. The Cr bioaccumulation in Eisenia fetida from tannery waste soil ranged from 5 to 194 mg kg−1. The high enrichment factor of Cr in S. asper and bioaccumulation factor in earthworms indicate that there is a steady increase of toxic chromium risk in this area, which could be correlated with the past dumping activity. Emphasis needs to be put on control measures of pollution and remediation techniques in such areas to achieve an ecologically sustainable industrialisation.
http://ift.tt/2iZkgFk
Towards a better understanding of the therapeutic applications and corresponding mechanisms of action of honey
Abstract
Honey is a bee-derived supersaturated solution composed of complex contents mainly glucose, fructose, amino acids, vitamins, and minerals. Composition of honey may vary due to the difference in nectar, season, geography, and storage condition. Honey has been used since times immemorial in folk medicine and has recently been rediscovered as an excellent therapeutic agent. In the past, honey was used for a variety of ailments without knowing the scientific background and active ingredients of honey. Today, honey has been scientifically proven for its antioxidant, regulation of glycemic response, antitumor, antimicrobial, anti-inflammatory, and cardiovascular potentiating agent. It can be used as a wound dressing and healing substance. Honey is different in color, flavor, sensory perception, and medical response. Apart from highlighting the nutritional facts of honey, we collected the finding of the published literature to know the mechanism of action of honey in different diseases. This review covers the composition, physiochemical characteristics, and some medical uses.
http://ift.tt/2AjzYiG
A national assessment of the effect of intensive agro-land use practices on nonpoint source pollution using emission scenarios and geo-spatial data
Abstract
China's intensive agriculture has led to a broad range of adverse impacts upon ecosystems and thereby caused environmental quality degradation. One of the fundamental problems that face land managers when dealing with agricultural nonpoint source (NPS) pollution is to quantitatively assess the NPS pollution loads from different sources at a national scale. In this study, export scenarios and geo-spatial data were used to calculate the agricultural NPS pollution loads of nutrient, pesticide, plastic film residue, and crop straw burning in China. The results provided the comprehensive and baseline knowledge of agricultural NPS pollution from China's arable farming system in 2014. First, the nitrogen (N) and phosphorus (P) emission loads to water environment were estimated to be 1.44 Tg N and 0.06 Tg P, respectively. East and south China showed the highest load intensities of nutrient release to aquatic system. Second, the amount of pesticide loss to water of seven pesticides that are widely used in China was estimated to be 30.04 tons (active ingredient (ai)). Acetochlor was the major source of pesticide loss to water, contributing 77.65% to the total loss. The environmental impacts of pesticide usage in east and south China were higher than other parts. Third, 19.75% of the plastic film application resided in arable soils. It contributed a lot to soil phthalate ester (PAE) contamination. Fourth, 14.11% of straw produce were burnt in situ, most occurring in May to July (post-winter wheat harvest) in North China Plain and October to November (post-rice harvest days) in southeast China. All the above agricultural NPS pollution loadings were unevenly distributed across China. The spatial correlations between pollution loads at land unit scale were also estimated. Rising labor cost in rural China might be a possible explanation for the general positive correlations of the NPS pollution loads. It also indicated a co-occurred higher NPS pollution loads and a higher human exposure risk in eastern regions. Results from this research might provide full-scale information on the status and spatial variation of various agricultural NPS pollution loads for policy makers to control the NPS pollution in China.
http://ift.tt/2j0XZGR
Seasonal impact of regional outdoor biomass burning on air pollution in three Indian cities: Delhi, Bengaluru, and Pune
Publication date: January 2018
Source:Atmospheric Environment, Volume 172
Author(s): Tianjia Liu, Miriam E. Marlier, Ruth S. DeFries, Daniel M. Westervelt, Karen R. Xia, Arlene M. Fiore, Loretta J. Mickley, Daniel H. Cusworth, George Milly
Air pollution in many of India's cities exceeds national and international standards, and effective pollution control strategies require knowledge of the sources that contribute to air pollution and their spatiotemporal variability. In this study, we examine the influence of a single pollution source, outdoor biomass burning, on particulate matter (PM) concentrations, surface visibility, and aerosol optical depth (AOD) from 2007 to 2013 in three of the most populous Indian cities. We define the upwind regions, or "airsheds," for the cities by using atmospheric back trajectories from the HYSPLIT model. Using satellite fire radiative power (FRP) observations as a measure of fire activity, we target pre-monsoon and post-monsoon fires upwind of the Delhi National Capital Region and pre-monsoon fires surrounding Bengaluru and Pune. We find varying contributions of outdoor fires to different air quality metrics. For the post-monsoon burning season, we find that a subset of local meteorological variables (air temperature, humidity, sea level pressure, wind speed and direction) and FRP as the only pollution source explained 39% of variance in Delhi station PM10 anomalies, 77% in visibility, and 30% in satellite AOD; additionally, per unit increase in FRP within the daily airshed (1000 MW), PM10 increases by 16.34 μg m−3, visibility decreases by 0.097 km, and satellite AOD increases by 0.07. In contrast, for the pre-monsoon burning season, we find less significant contributions from FRP to air quality in all three cities. Further, we attribute 99% of FRP from post-monsoon outdoor fires within Delhi's average airshed to agricultural burning. Our work suggests that although outdoor fires are not the dominant air pollution source in India throughout the year, post-monsoon fires contribute substantially to regional air pollution and high levels of population exposure around Delhi. During 3-day blocks of extreme PM2.5 in the 2013 post-monsoon burning season, which coincided with statistically significant high fire activity, concentrations in Delhi averaged 304 μg m−3, or more than 1000% above the 24-h PM2.5 guideline (25 μg m−3) of the World Health Organization. These results suggest that providing viable alternatives to agricultural residue burning could help improve post-monsoon air quality for a growing population of 63 million (39% in urban areas) within Delhi's airshed.
Graphical abstract
http://ift.tt/2zc5RcA
Investigations of VOCs in and around buildings close to service stations
Source:Atmospheric Environment, Volume 172
Author(s): William Hicklin, Pierre S. Farrugia, Emmanuel Sinagra
Gas service stations are one of the major sources of volatile organic compounds in urban environments. Their emissions are expected not only to affect the ambient air quality but also that in any nearby buildings. This is particularly the case in Malta where most service stations have been built within residential zones. For this reason, it is important to understand the dispersion of volatile organic compounds (VOCs) from service stations and their infiltration into nearby residences. Two models were considered; one to predict the dispersion of VOCs in the outdoor environment in the vicinity of the service station and another one to predict the filtration of the compounds indoors. The two models can be used in tandem to predict the concentration of indoor VOCs that originate from a service station in the vicinity. Outdoor and indoor concentrations of VOCs around a service station located in a street canyon were measured, and the results used to validate the models. Predictions made using the models were found to be in general agreement with the measured concentrations of the pollutants.
http://ift.tt/2zbhsbY
Cervical vestibular evoked myogenic potential tuning properties of patients with recurrent peripheral vestibulopathy: Is it Meniere’s disease without hearing loss?
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): Toshihisa Murofushi, Masahito Tsubota, Ryota Suizu, Eriko Yoshimura
http://ift.tt/2A3B6pu
Title: Congenital Cytomegalovirus Infection and the Occurrence of Cystic Periventricular Leukomalacia
Source:Pediatric Neurology
Author(s): Philip N.D. Elders, Josine in 't Veld, Jacqueline Termote, Linda S. de Vries, Marieke A.C. Hemels, Irma L.M. van Straaten, Jacqueline van der Sluijs, René F. Kornelisse, Katja C. Wolthers, Moniek van de Loo, Dasja Pajkrt
http://ift.tt/2xYr6xm
Preface: Engineering of pharmaceutical cocrystals, salts and polymorphs: Advances and Challenges
Publication date: 1 August 2017
Source:Advanced Drug Delivery Reviews, Volume 117
Author(s): Dennis Douroumis, Ali Nokhodchi
http://ift.tt/2xSle8K
Editorial Board
Publication date: 1 August 2017
Source:Advanced Drug Delivery Reviews, Volume 117
http://ift.tt/2AdCMO3
17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle
Publication date: Available online 2 November 2017
Source:Cell Metabolism
Author(s): Maria J. Torres, Kim A. Kew, Terence E. Ryan, Edward Ross Pennington, Chien-Te Lin, Katherine A. Buddo, Amy M. Fix, Cheryl A. Smith, Laura A. Gilliam, Sira Karvinen, Dawn A. Lowe, Espen E. Spangenburg, Tonya N. Zeczycki, Saame Raza Shaikh, P. Darrell Neufer
Menopause results in a progressive decline in 17β-estradiol (E2) levels, increased adiposity, decreased insulin sensitivity, and a higher risk for type 2 diabetes. Estrogen therapies can help reverse these effects, but the mechanism(s) by which E2 modulates susceptibility to metabolic disease is not well understood. In young C57BL/6N mice, short-term ovariectomy decreased—whereas E2 therapy restored—mitochondrial respiratory function, cellular redox state (GSH/GSSG), and insulin sensitivity in skeletal muscle. E2 was detected by liquid chromatography-mass spectrometry in mitochondrial membranes and varied according to whole-body E2 status independently of ERα. Loss of E2 increased mitochondrial membrane microviscosity and H2O2 emitting potential, whereas E2 administration in vivo and in vitro restored membrane E2 content, microviscosity, complex I and I + III activities, H2O2 emitting potential, and submaximal OXPHOS responsiveness. These findings demonstrate that E2 directly modulates membrane biophysical properties and bioenergetic function in mitochondria, offering a direct mechanism by which E2 status broadly influences energy homeostasis.
Graphical abstract
Teaser
Loss of estrogen from menopause increases the risk of developing metabolic diseases. Torres et al. show that 17β-estradiol (E2) localizes to mitochondrial membranes consistent with whole-body E2 status. The presence of E2 decreases microviscosity, which improves bioenergetic function, thus offering a biophysical mechanism by which E2 influences energy homeostasis.http://ift.tt/2lLLZu3
Artemether Does Not Turn α Cells into β Cells
Publication date: Available online 2 November 2017
Source:Cell Metabolism
Author(s): Talitha van der Meulen, Sharon Lee, Els Noordeloos, Cynthia J. Donaldson, Michael W. Adams, Glyn M. Noguchi, Alex M. Mawla, Mark O. Huising
Pancreatic α cells retain considerable plasticity and can, under the right circumstances, transdifferentiate into functionally mature β cells. In search of a targetable mechanistic basis, a recent paper suggested that the widely used anti-malaria drug artemether suppresses the α cell transcription factor Arx to promote transdifferentiation into β cells. However, key initial experiments in this paper were carried out in islet cell lines, and most subsequent validation experiments implied transdifferentiation without direct demonstration of α to β cell conversion. Indeed, we find no evidence that artemether promotes transdifferentiation of primary α cells into β cells. Moreover, artemether reduces Ins2 expression in primary β cells >100-fold, suppresses glucose uptake, and abrogates β cell calcium responses and insulin secretion in response to glucose. Our observations suggest that artemether induces general islet endocrine cell dedifferentiation and call into question the utility of artemisinins to promote α to β cell transdifferentiation in treating diabetes.
Graphical abstract
Teaser
The anti-malaria drug artemether has been recently shown to promote transdifferentiation of α cells into β cells. Instead, van der Meulen et al. now report loss of β cell gene expression, glucose uptake, calcium responses, and insulin secretion following stimulation in intact islets treated with the same high dose of artemether.http://ift.tt/2lLMkNl
Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy
Abstract
Purpose
The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT).
Methods
The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V15Gy, V30Gy, V45Gy and Dmean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated.
Results
Both IMPT and MRI-based target tailoring resulted in significant reductions in V15Gy, V30Gy, V45Gy and Dmean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V45Gy for bowel bag was >275 cm3 and >200 cm3, respectively, during standard IGART alone.
Conclusions
In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity.
http://ift.tt/2zfIYY0
Inviting eating disorder patients to discuss the academic literature: a model program for psychoeducation
Abstract
Background
Psychoeducation initiatives in which patients read primary scientific literature have not yet been studied as a treatment intervention for eating disorders. In this paper, we discuss and evaluate the acceptability of a novel psychoeducational journal club for individuals with anorexia and bulimia nervosa in inpatient and partial hospitalization program settings. Primary literature about eating disorders is presented and discussed with patients. By presenting scientifically-supported information, our "Psychoeducational Research Group" is designed to help patients restructure disordered thoughts and encourage adherence to evidence-based treatment.
Methods
Using a Likert scale questionnaire (0 = not at all; 5 = very much), participants provided ratings for how much they liked the group and felt that it helped them across several domains.
Results
Average scores from 33 participants (26 inpatient, 7 partial hospital patients) indicated they would recommend this group to others receiving eating disorder treatment (4.8 ± 0.6). Scores also suggested patients' likeability (4.6 ± 0.8), benefit regarding challenging eating disorder thoughts (4.1 ± 1.1), improved motivation for eating behavior change (4.0 ± 1.0) and completion of prescribed nutritional plan (3.6 ± 1.0), and usefulness in working towards treatment goals (4.2 ± 0.9) associated with group participation.
Conclusions
Preliminary findings support the acceptability of this psychoeducational group and that it may serve as a useful adjunct to larger evidence-based programming across eating disorder treatment settings.
http://ift.tt/2zhDI6k
Les directives anticipées et le désir de maîtrise de sa fin de vie
Source:Médecine & Droit
Author(s): Augustin Boulanger
Les directives anticipées sont un moyen efficace, pour les personnes majeures, d'exprimer par anticipation, pour le jour où elles ne pourront plus s'exprimer, leurs volontés concernant la poursuite, la limitation, l'arrêt ou le refus de traitement. Conformément aux dispositions de la loi Claeys–Leonetti, les médecins doivent désormais respecter les volontés qui y sont exprimées. En outre, cette loi a supprimé la durée de validité des directives anticipées qui était précédemment fixée à trois ans. Dans ces conditions, l'on peut penser que les personnes ont ainsi l'opportunité de satisfaire leur désir de maîtrise de leur fin de vie. Cependant, les directives anticipées présentent nombre de fragilités. L'on peut, par exemple, souligner leur manque de fiabilité, mais encore la possibilité pour les médecins, dans certains cas, de refuser de les appliquer. Partant, la rédaction de directives anticipées ne paraît pas de nature à permettre la satisfaction du désir de maîtrise de sa fin de vie.Advance directives are an effective mean of transmitting adult's wishes regarding the continuation, limitation, discontinuation or refusal of treatment. According to the terms of the Claeys–Leonetti law, doctors have to follow the express wishes contained in advance care directives. Moreover, this law removed any specific duration of validity for living wills. Thus, we could assume that people have a way to master their end of life. However, the advance directives have weaknesses. For instance, there is a lack of reliability and, in some cases, doctors can refuse to apply this document. To put it in a nutshell, the fact that people want to master their end of life in writing living wills appears to be a delusion.
http://ift.tt/2habgN2
Low-density microcellular carbon foams from sucrose by NaCl particle templating using glycerol as a plasticizing additive
Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): Praveen Wilson, Sujith Vijayan, K. Prabhakaran
Carbon-NaCl composites with high NaCl loading (83.3 to 92.2wt%) were prepared by setting molten sucrose-NaCl-glycerol pastes in a stainless steel mold at 160°C. The carbonization of the composites followed by NaCl removal by washing with water produced low-density microcellular carbon foams. The setting of the paste was due to the caramelization of molten sucrose as well as the slow evaporation of glycerol. The carbon-NaCl composites had the adequate compressive strength (6.9 to 17.8MPa) and ductility for machining using conventional machine tools. Machining of the carbon-NaCl composites followed by NaCl removal was used as a strategy to produce low-density carbon foams with desired contours. The glycerol not only decreased the density of carbon foams produced from the sucrose-NaCl system but also produced a remarkable change in the foam microstructure from a combination of macropores and microcells to only microcells of sizes predominantly in the range of 3 to 6μm. Carbon foams prepared at NaCl to sucrose weight ratios in the range of 1.5 to 3 show density, compressive strength, thermal conductivity and EMI shielding effectiveness in the ranges of 0.096 to 0.214g/cm3, 0.60 to 4.83MPa, 0.087 to 0.235Wm−1K−1 and 24.7 to 41.7dB, respectively.
Graphical abstract
http://ift.tt/2zgpfrb
Editorial Board
Publication date: 15 December 2017
Source:Materials & Design, Volume 136
http://ift.tt/2zhdSPU
Harnessing the native type I-B CRISPR-Cas for genome editing in a polyploid archaeon
Source:Journal of Genetics and Genomics
Author(s): Feiyue Cheng, Luyao Gong, Dahe Zhao, Haibo Yang, Jian Zhou, Ming Li, Hua Xiang
Research on CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated protein) systems has led to the revolutionary CRISPR/Cas9 genome editing technique. However, for most archaea and half of bacteria, exploitation of their native CRISPR-Cas machineries may be more straightforward and convenient. In this study, we harnessed the native type I-B CRISPR-Cas system for precise genome editing in the polyploid haloarchaeon Haloarcula hispanica. After testing different designs, the editing tool was optimized to be a single plasmid that carries both the self-targeting mini-CRISPR and a 600–800 bp donor. Significantly, chromosomal modifications, such as gene deletion, gene tagging or single nucleotide substitution, were precisely introduced into the vast majority of the transformants. Moreover, we showed that simultaneous editing of two genomic loci could also be readily achieved by one step. In summary, our data demonstrate that the haloarchaeal CRISPR-Cas system can be harnessed for genome editing in this polyploid archaeon, and highlight the convenience and efficiency of the native CRISPR-based genome editing strategy.
http://ift.tt/2h1X9Wr
Human Fc receptor-like 5 distinguishes IgG2 disulfide isoforms and deamidated charge variants
Source:Molecular Immunology, Volume 92
Author(s): Oyeleye Alabi, Jessica Dement-Brown, Mate Tolnay
Human Fc receptor-like 5 (FCRL5) is a novel IgG receptor. We reported that IgG2 samples display a thousand-fold range affinity for FCRL5, indicating that attributes beyond the isotype affect binding. We hypothesized that the complex interaction could be exploited to identify distinct changes in the IgG2 molecule. We investigated using surface plasmon resonance two factors that might affect the interaction between IgG2 and FCRL5; heterogeneity related to disulfide isoforms and charge variants. We found that panitumumab and denosumab samples enriched for the more flexible A disulfide isoform bound FCRL5 with two-fold and 82-fold higher apparent affinity, respectively, than the B isoform. We next assessed whether FCRL5 binding can distinguish panitumumab charge variants which increase during storage, using two approaches. First, samples were stored at 40°C to promote acidic variants. Heat stressed panitumumab had up to four-fold higher apparent affinity for FCRL5. Next, we used conditions that promoted deamidation, a common cause of acidic variants. We found that deamidated panitumumab had up to 14-fold higher apparent affinity for FCRL5, indicating that deamidation promotes the interaction. Statistical analyses of kinetic parameters and similarity scores obtained from sensogram comparisons indicated that IgG2 disulfide isoforms, heat stressed and deamidated samples each bind FCRL5 differently. We conclude that based on FCRL5 binding, we can discern distinct changes in the IgG2 molecule, including the disulfide isoform structure and charge variants related to deamidation. Since both IgG2 deamidation and conversion of disulfide isoforms occur in vivo, these findings elucidate the biological FCRL5 ligand.
http://ift.tt/2yrsInF
Molecular characterization of the bovine IER3 gene: Down-regulation of IL-8 by blocking NF-κB activity mediated by IER3 overexpression in MDBK cells infected with bovine viral diarrhea virus-1
Source:Molecular Immunology, Volume 92
Author(s): Melina Villalba, Fernanda Fredericksen, Carola Otth, Víctor H. Olavarría
The immediate early response 3 (IER3) is a key regulatory factor in the immune response, particularly as related to homeostasis immunomodulation via the nuclear factor kappa B (NF-κB) signaling pathway. The IER3 gene has been identified in mammals and, more recently, in other higher vertebrates. Nevertheless, relatively little is known about this regulator in bovines. Therefore, this study explored, characterized, and compared the genetic context of bovine IER3 to homologous genes in the human, mouse, and canine chromosomes. In silico analysis identified several regions of interest preserved in phylogenetically distant species. Similar analyses were also conducted for interleukin-8, a cytokine in which several putative cis elements were identified for the inducible transcription factor NF-κB. Subsequent challenge assays against the bovine viral diarrhea virus-1 revealed NF-κB signaling pathway activation just 15min post-infection, a process blocked by the BAY-117085 inhibitor. Similarly, infection strongly increased IER3 expression. Interestingly, IER3 down-regulated interleukin-8 expression, as confirmed by IER3 gene inhibition using small interfering RNA, RT-qPCR, and luciferase assays. In conclusion, this is the first report to present data indicating that bovine IER3 is a strong regulator of immune-marker expression, specifically modulating bovine interleukin-8 activation through the NF-κB/IER3 pathway in response to the bovine viral diarrhea virus.
http://ift.tt/2lJWptY
MicroRNA-146a promotes IgE class switch in B cells via upregulating 14-3-3σ expression
Source:Molecular Immunology, Volume 92
Author(s): Fei Li, Yi Huang, You-Ying Huang, Yan-Song Kuang, Yong-Jian Wei, Li Xiang, Xing-Ju Zhang, Zheng-Cai Jia, Shan Jiang, Jing-Yi Li, Ying Wan
B cells play a critical role in immune responses both in physiological and pathological conditions, and microRNAs have been shown to play important roles in regulating B cell proliferation and function. MiR-146a has been shown to modulate T cell immunity, but its function in regulating B cell response remains partially understood. Our previous studies indicated that germinal center (GC) B cells are significantly expanded in miR-146a-overexpressing (TG) mice. In this study, we further characterized the roles of miR-146a in regulating humoral immune responses to specific antigens. We found that the production of IgE antibody were significantly elevated in TG mice, while the antibody affinity maturation of IgM and IgG were similar between TG mice and the normal controls. We further found higher IgE antibody levels in TG B cell culture supernatant than that in normal controls. A global protein expression comparison of B cells from TG mice and the normal controls through TMT proteomic assay showed that 14-3-3σ, a key factor of immunoglobulin class switch DNA recombination (CSR) in B cells, was highly up-regulated in B cells with overexpression of miR-146a, while Smad4, the target of miR-146a, was decreased. Using an asthma model induced by OVA immunization, we further confirmed the increased level of OVA specific IgE antibodies in TG mice. These results demonstrate that miR-146a enhances class switch and secretion of IgE in B cells by upregulating 14-3-3σ expression, and suggest that miR-146a may be a potential target for asthma therapy.
http://ift.tt/2yrRqV2
Corrigendum to “Respiratory Syncytial virus infection compromises asthma tolerance by recruiting interleukin-17A-producing cells via CCR6-CCL20 signaling” [Mol. Immunol. 88 (2017) 45–57]
Source:Molecular Immunology
Author(s): Tianyun Shi, Yanchao He, Wei Sun, Yi Wu, Ling Li, Zhijun Jie, Xiao Su
http://ift.tt/2lM7qv5
Gamma Knife Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Ocular Malignancies
Stereotact Funct Neurosurg 2017;95:363-368
http://ift.tt/2yrAbD8
Significant Hemorrhage Rate Reduction after Gamma Knife Radiosurgery in Symptomatic Cavernous Malformations: Long-Term Outcome in 95 Case Series and Literature Review
Stereotact Funct Neurosurg 2017;95:369-378
http://ift.tt/2lLCavZ
Sunscreen formulations do not interfere with sweat cooling during exercise
Abstract
Objective
Sweating plays a critical role in maintaining thermal balance and keeping skin cool during exercise. People often wear sunscreens on hot summer days for sun protection. Most recreational sunscreens are designed to be water and sweat resistant, so that sweating will not remove or compromise the protection. The objective of this study was to determine whether wearing sweat-resistant sunscreen might impede natural sweating, potentially interfering with thermal regulation and resulting in the elevation of skin temperature.
Methods
We conducted a controlled, randomized, split-face, and split-arm clinical study with 24 female subjects wearing an SPF 70 lotion sunscreen on half of the face and an SPF 70 spray sunscreen on one of the forearms at a dosage of 2 mg/cm2. Following sunscreen application, subjects participated in two sessions of indoor exercise to induce clearly visible sweating.
Results
We found that both skin temperatures and sweat evaporation rates were significantly elevated after each session, yet there were no significant differences in either skin temperatures or sweat rates between the treated and untreated control sites at any time point for any of the skin sites measured.
Conclusion
We conclude that the application of tested sweat resistant sunscreen lotions and sprays does not have any measurable effects on skin cooling by natural sweating process. People should continue to use these sunscreens during recreational activities.
This article is protected by copyright. All rights reserved.
http://ift.tt/2irilWa
Laser-induced autofluorescence-based objective evaluation of burn tissue repair in mice
Abstract
Management of burn injuries are a growing concern, especially in determining the progression of healing. Several techniques are being practiced in clinics and have been considered all-time standard approaches to determine pre- and post-treatment outcomes of a healthy healing. However, these kinds of methods involve repeated biopsies and thereby hindering tissue repair. In view of this, our perspective was to develop a non-invasive tool in an attempt to provide a solution to determine the progression of healing, in vivo. Hence, the present study was designed to investigate the ability of laser-induced fluorescence (LIF) to monitor the variations in collagen intensity at various time points (0, 2, 6, 12, 18, 24, and 30 days) during burn tissue repair in mice, post low-power laser therapy (LPLT). The spectral findings demonstrated a significant change in collagen intensity as observed on day 24 (p < 0.05) and 30 (p < 0.01), when treated with LPLT (830 nm 3 J/cm2) as compared to untreated control. From the observation, it was evident that the LIF could objectively monitor the progression of burn tissue repair in vivo.
http://ift.tt/2hA9GRl
Finer parcellation reveals detailed correlational structure of resting-state fMRI signals
Publication date: 15 January 2018
Source:Journal of Neuroscience Methods, Volume 294
Author(s): João V. Dornas, Jochen Braun
BackgroundEven in resting state, the human brain generates functional signals (fMRI) with complex correlational structure. To simplify this structure, it is common to parcellate a standard brain into coarse chunks. Finer parcellations are considered less reproducible and informative, due to anatomical and functional variability of individual brains.New methodsGrouping signals with similar local correlation profiles, restricted to each anatomical region (Tzourio-Mazoyer et al., 2002), we divide a standard brain into 758 'functional clusters' averaging 1.7cm3 gray matter volume ('MD758' parcellation). We compare 758 'spatial clusters' of similar size ('S758').Results'Functional clusters' are spatially contiguous and cluster quality (integration and segregation of temporal variance) is far superior to 'spatial clusters', comparable to multi-modal parcellations of half the resolution (Craddock et al., 2012; Glasser et al., 2016). Moreover, 'functional clusters' capture many long-range functional correlations, with O(105) reproducibly correlated cluster pairs in different anatomical regions. The pattern of functional correlations closely mirrors long-range anatomical connectivity established by fibre tracking.Comparison to existing methodsMD758 is comparable to coarser parcellations (Craddock et al., 2012; Glasser et al., 2016) in terms of cluster quality, correlational structure (54% relative mutual entropy vs 60% and 61%), and sparseness (35% significant pairwise correlations vs 36% and 44%).ConclusionWe describe and evaluate a simple path to finer functional parcellations of the human brain. Detailed correlational structure is surprisingly consistent between individuals, opening new possibilities for comparing functional correlations between cognitive conditions, states of health, or pharmacological interventions.
http://ift.tt/2ha68Z3
Ensemble based on static classifier selection for automated diagnosis of Mild Cognitive Impairment
Source:Journal of Neuroscience Methods
Author(s): Loris Nanni, Alessandra Lumini, Nicolò Zaffonato
BackgroundAlzheimer's disease (AD) is the most common cause of neurodegenerative dementia in the elderly population. Scientific research is very active in the challenge of designing automated approaches to achieve an early and certain diagnosis. Recently an international competition among AD predictors has been organized: "A Machine learning neuroimaging challenge for automated diagnosis of Mild Cognitive Impairment" (MLNeCh). This competition is based on pre-processed sets of T1-weighted Magnetic Resonance Images (MRI) to be classified in four categories: stable AD, individuals with MCI who converted to AD, individuals with MCI who did not convert to AD and healthy controls.New methodIn this work, we propose a method to perform early diagnosis of AD, which is evaluated on MLNeCh dataset. Since the automatic classification of AD is based on the use of feature vectors of high dimensionality, different techniques of feature selection/reduction are compared in order to avoid the curse-of-dimensionality problem, then the classification method is obtained as the combination of Support Vector Machines trained using different clusters of data extracted from the whole training set.ResultsThe multi-classifier approach proposed in this work outperforms all the stand-alone method tested in our experiments. The final ensemble is based on a set of classifiers, each trained on a different cluster of the training data. The proposed ensemble has the great advantage of performing well using a very reduced version of the data (the reduction factor is more than 90%).The MATLAB code for the ensemble of classifiers will be publicly available11 http://ift.tt/2halInP to other researchers for future comparisons.
http://ift.tt/2xXx1m4
Development and Evaluation of Lipid Nanoparticles Containing Natural Botanical Oil for Sun Protection: Characterization and in vitro and in vivo Human Skin Permeation and Toxicity
The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use.
Skin Pharmacol Physiol 2018;31:1-9
http://ift.tt/2Ahseh5
Transversal changes, space closure, and efficiency of conventional and self-ligating appliances
Abstract
Objective
Self-ligating brackets (SLBs) were compared to conventional brackets (CBs) regarding their effectiveness on transversal changes and space closure, as well as the efficiency of alignment and treatment time.
Methods
All previously published randomized controlled clinical trials (RCTs) dealing with SLBs and CBs were searched via electronic databases, e.g., MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, relevant journals were searched manually. Data extraction was performed independently by two reviewers and assessment of the risk of bias was executed using Cochrane Collaboration's tool. Discrepancies were resolved by discussion with a third reviewer. Meta-analyses were conducted using Review Manager (version 5.3).
Results
A total of 976 patients in 17 RCTs were included in the study, of which 11 could be produced quantitatively and 2 showed a low risk of bias. Meta-analyses were found to favor CB for mandibular intercanine width expansion, while passive SLBs were more effective in posterior expansion. Moreover, CBs had an apparent advantage during short treatment periods. However, SLBs and CBs did not differ in closing spaces.
Conclusions
Based on current clinical evidence obtained from RCTs, SLBs do not show clinical superiority compared to CBs in expanding transversal dimensions, space closure, or orthodontic efficiency. Further high-level studies involving randomized, controlled, clinical trials are warranted to confirm these results.
http://ift.tt/2yq3WnP
Ecotoxicological efficiency of advanced ozonation processes with TiO 2 and black light used in the degradation of carbamazepine
Abstract
The aim of the present study was to evaluate the ecotoxicological efficiency of two advanced ozonation processes (AOzPs), the catalytic ozonation (O3/TiO2) and the photocatalytic ozonation (O3/TiO2/black light), in the remotion of carbamazepine. The ecotoxicological efficiency was assessed through the use of lethal and sublethal assays with species Vibrio fischeri and Daphnia magna. Results demonstrated that the AOzPs presented an efficiency of carbamazepine removal higher than 99% (carbamazepine < 2 μg/L) after 12 min of treatment. Relatively to ecotoxicological evaluation, application of acute assay to V. fischeri and chronic assay to D. magna allowed us to highlight that these technologies may form some transformation products that induce toxicity in the bacteria and the crustacean, once these organisms exposed to the undiluted solutions (100%) showed a decrease in the bioluminescence (vibrio) and end up dying before and during the first reproduction (daphnia). Despite that, when the chronic results obtained with the diluted solutions (50 and 25%; important to assess a more realistic scenario considering the dilution factor at the environment) were analyzed, no mortality at the mothers was observed. Compared to a carbamazepine solution (200 μg/L), diluted solutions improved of the reproduction parameters, and no toxic effects in the juvenoid system and in the embryonic development were observed. Relatively to the ecdysteroid effect of a carbamazepine solution (200 μg/L), only the photocatalytic ozonation treatment was able to remove the action of the drug. These results highlight the importance of complementing chemical analysis with ecotoxicological bioassays to assess the best technology to improve the surface water and effluent quality.
http://ift.tt/2lPUFjd
Transversal changes, space closure, and efficiency of conventional and self-ligating appliances
Abstract
Objective
Self-ligating brackets (SLBs) were compared to conventional brackets (CBs) regarding their effectiveness on transversal changes and space closure, as well as the efficiency of alignment and treatment time.
Methods
All previously published randomized controlled clinical trials (RCTs) dealing with SLBs and CBs were searched via electronic databases, e.g., MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, relevant journals were searched manually. Data extraction was performed independently by two reviewers and assessment of the risk of bias was executed using Cochrane Collaboration's tool. Discrepancies were resolved by discussion with a third reviewer. Meta-analyses were conducted using Review Manager (version 5.3).
Results
A total of 976 patients in 17 RCTs were included in the study, of which 11 could be produced quantitatively and 2 showed a low risk of bias. Meta-analyses were found to favor CB for mandibular intercanine width expansion, while passive SLBs were more effective in posterior expansion. Moreover, CBs had an apparent advantage during short treatment periods. However, SLBs and CBs did not differ in closing spaces.
Conclusions
Based on current clinical evidence obtained from RCTs, SLBs do not show clinical superiority compared to CBs in expanding transversal dimensions, space closure, or orthodontic efficiency. Further high-level studies involving randomized, controlled, clinical trials are warranted to confirm these results.
http://ift.tt/2yq3WnP
Scholar : These new articles for Levant are available online
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Editorial board
Source:Revue des Maladies Respiratoires, Volume 34, Issue 8
http://ift.tt/2yrxlOE
Recommandations pratiques sur la fibrose pulmonaire idiopathique : un document actualisé à l’usage des cliniciens
Source:Revue des Maladies Respiratoires, Volume 34, Issue 8
Author(s): V. Cottin
http://ift.tt/2lLKjR6
Stratégies thérapeutiques les 2 premières années après un diagnostic de cancer du poumon. ESCAP-2011-CPHG, étude en situation réelle réalisée dans les hôpitaux généraux français
Source:Revue des Maladies Respiratoires
Author(s): M. Grivaux, F. Goupil, B. Asselain, F. Blanchon, T. Collon, D. Coëtmeur, C. Dayen, C. Locher, O. Molinier, F. Martin, D. Debieuvre
IntroductionESCAP-2011-CPHG est une étude de cohorte ayant pour objectif d'analyser en situation réelle les stratégies thérapeutiques mises en œuvre les 2 premières années après un diagnostic de cancer bronchique primitif. Cet article présente l'étude et ses premiers résultats pour les cancers bronchiques non à petites cellules (CBNPC).MéthodesLes pneumologues exerçant dans le service de pneumologie de 53 hôpitaux généraux ont inclus consécutivement tous les patients adultes avec un cancer du poumon nouvellement diagnostiqué en 2010.RésultatsSur les 3943 patients inclus, 3418 (âge moyen : 65,4 ans ; hommes : 76 % ; non-fumeurs : 12 %) avaient un CBNPC (adénocarcinome : 53 % ; stade 0-II, IIIA, IIIB, et IV : 18, 14, 9, et 59 %). La durée moyenne de suivi était de 13,2 (ET=10,1) mois, le nombre moyen de stratégies de 2 (ET=1,3). En stratégie 1, 62 % des patients recevaient une chimiothérapie (74 % en stratégie 2) ; le taux de chimiothérapie seule augmentait de 6 à 56 % avec le stade du cancer.ConclusionsESCAP-2011-CPHG ouvre la voie à de nombreuses analyses sur les thérapeutiques réellement mises en œuvre dans les centres hospitaliers généraux français basées sur les stratégies ou les caractéristiques des patients et leur survie.IntroductionThe objective of the ESCAP-2011-CPHG cohort study was to perform a real-life analysis of therapeutic strategies used during the first 2years of follow-up after a diagnosis of primary lung cancer. This paper presents the study and its first results in non-small-cell lung cancer (NSCLC).MethodsPulmonologists in the respiratory disease departments of 53 general hospitals consecutively included all patients aged 18years and over with lung cancer newly diagnosed in 2010.ResultsOf the 3943 patients included, 3418 (mean age: 65.4 years; male: 76%; never smokers: 12%) had NSCLC (adenocarcinoma: 53%; stages 0-II, IIIA, IIIB and IV: 18, 14, 9 and 59%, respectively). Mean follow-up was 13.2 (SD: 10.1) months; mean number of strategies implemented was 2 (SD: 1.3). Overall, 62% of patients had chemotherapy in the first strategy (74% in the second strategy); the rate of chemotherapy alone increased from 6 to 56% with cancer stage.ConclusionsESCAP-2011-CPHG opens the way to many possible analyses of the therapeutic strategies currently implemented in French hospitals, comparing strategies, survival or patient characteristics.
http://ift.tt/2yrr6tS
Scholar : These new articles for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad are available online
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Cystic Fibrosis.
Cystic fibrosis is a multi-system genetic disorder affecting the lungs, pancreas, liver and intestine. It can have a significant impact on life expectancy and quality of life. The current median age of those who have died is 28 years and the median predicted survival is 45.1 years.
http://ift.tt/2yqXgpF
Glaucoma.
The scope of this NICE guideline on diagnosing and managing chronic open-angle glaucoma has been extended to cover referral. This includes the most effective service models for referral-filtering schemes (repeat measures, enhanced case finding and referral refinement), the tests to be used for finding people with chronic open-angle glaucoma (COAG), suspected chronic open-angle glaucoma and ocular hypertension (OHT), and thresholds for onward referral. We have also updated the guidance on tests for diagnosis and reassessment, pharmacological treatments for lowering intraocular pressure and preserving visual field and reassessment intervals, which depend on prognosis.
http://ift.tt/2lKR5qx
Cataracts in adults: management.
A cataract is defined as any opacity in the crystalline lens of the eye. It can affect one or both eyes. The changes to the transparency and refractive index of the lens result in various levels of visual impairment. This impairment is associated with decreased quality of life because it may restrict the person's ability to carry out daily activities and function independently, while increasing the risk of accidents and falls.
http://ift.tt/2yqWOrt
Vitamin C – a new player in regulation of the cancer epigenome
Source:Seminars in Cancer Biology
Author(s): Linn Gillberg, Andreas D. Ørskov, Minmin Liu, Laurine B.S. Harsløf, Peter A. Jones, Kirsten Grønbæk
Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care. Recent in vitro studies suggest that vitamin C at physiological concentrations, combined with hypomethylating agents may act synergistically to cause DNA demethylation through active and passive mechanisms, respectively. Additionally, several recent studies have renewed interest in the use of pharmacological doses of vitamin C injected intravenously to selectively kill tumour cells. This review will focus on the potential of vitamin C to optimize the outcome of epigenetic therapy in cancer patients and alternatively to act as a therapeutic at high doses.
http://ift.tt/2A3SElJ
Current insights into functions of phospholipase A2 receptor in normal and cancer cells: More questions than answers
Source:Seminars in Cancer Biology
Author(s): Olga Sukocheva, Mario Menschikowski, Albert Hagelgans, Nagendra Sastry Yarla, Gabriele Siegert, Pallu Reddanna, Anupam Bishayee
Lipid signaling network was proposed as a potential target for cancer prevention and treatment. Several recent studies revealed that phospholipid metabolising enzyme, phospholipase A2 (PLA2), is a critical regulator of cancer accelerating pathologies and apoptosis in several types of cancers. In addition to functioning as an enzyme, PLA2 can activate a phospholipase A2 receptor (PLA2R1) in plasma membrane. While the list of PLA2 targets extends to glucose homeostasis, intracellular energy balance, adipocyte development, and hepatic lipogenesis, the PLA2R1 downstream effectors are few and scarcely investigated. Among the most addressed PLA2R1 effects are regulation of pro-inflammatory signaling, autoimmunity, apoptosis, and senescence. Localized in glomeruli podocytes, the receptor can be identified by circulating anti-PLA2R1 autoantibodies leading to development of membranous nephropathy, a strong autoimmune inflammatory cascade. PLA2R1 was shown to induce activation of Janus-kinase 2 (JAK2) and estrogen-related receptor α (ERRα)-controlled mitochondrial proteins, as well as increasing the accumulation of reactive oxygen species, thus leading to apoptosis and senescence. These findings indicate the potential role of PLA2R1 as tumor suppressor. Epigenetic investigations addressed the role of DNA methylation, histone modifications, and specific microRNAs in the regulation of PLA2R1 expression. However, involvement of PLA2R1 in suppression of malignant growth and metastasis remains controversial. In this review, we summarize the recent findings that highlight the role of PLA2R1 in the regulation of carcinogenesis-related intracellular signaling.
http://ift.tt/2zatNxd
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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...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
