Development of the GREEN (Garden Resources, Education, and Environment Nexus) Tool: An Evidence-Based Model for School Garden Integration

Publication date: Available online 4 April 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Kate Gardner Burt, Pamela Koch, Isobel Contento
BackgroundResearchers have established the benefits of school gardens on students' academic achievement, dietary outcomes, physical activity, and psychosocial skills, yet limited research has been conducted about how school gardens become institutionalized and sustained.ObjectiveOur aim was to develop a tool that captures how gardens are effectively established, integrated, and sustained in schools.DesignWe conducted a sequential, exploratory, mixed-methods study. Participants were identified with the help of Grow To Learn, the organization coordinating the New York City school garden initiative, and recruited via e-mail.Participants/settingA stratified, purposeful sample of 21 New York City elementary and middle schools participated in this study throughout the 2013/2014 school year. The sample was stratified in their garden budgets and purposeful in that each of the schools' gardens were determined to be well integrated and sustained.Main outcome measuresThe processes and strategies used by school gardeners to establish well-integrated school gardens were assessed via data collected from surveys, interviews, observations, and concept mapping.Statistical analyses performedDescriptive statistics as well as multidimensional scaling and hierarchical cluster analysis were used to examine the survey and concept mapping data. Qualitative data analysis consisted of thematic coding, pattern matching, explanation building and cross-case synthesis.ResultsNineteen components within four domains of school garden integration were found through the mixed-methods concept mapping analysis. When the analyses of other data were combined, relationships between domains and components emerged. These data resulted in the development of the GREEN (Garden Resources, Education, and Environment Nexus) Tool.ConclusionsWhen schools with integrated and sustained gardens were studied, patterns emerged about how gardeners achieve institutionalization through different combinations of critical components. These patterns are best described by the GREEN Tool, the first framework to identify how to operationalize school gardening components and describe an evidence-based strategy of successful school garden integration.



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Simplifying the Forehead Flap for Nasal Reconstruction: A review of 420 consecutive cases.

Background: The forehead flap is an important tool in nasal reconstruction. We present objective data and recommendations based on over a decade of consecutive forehead flap nasal reconstructions performed by the senior author (J.F.T.). Additionally, we separate the technique into its individual steps and provide details of his approach to each. Methods: We performed a retrospective analysis of patients who underwent nasal reconstruction with forehead flap over a ten-year period by the senior author (J.F.T.). Each case was evaluated for defect location, pedicle design, time of division, number of stages, use of cartilage grafts, lining reconstruction, donor site closure, and complications. Results: 420 patients underwent forehead flap nasal reconstruction. Average time to pedicle division was 32 days. Three-fourths of patients completed reconstruction in two stages. Defects most commonly involved nasal ala and tip. Approximately half of patients received cartilage grafts and half underwent lining reconstruction. There were 16 complications, ranging from partial flap loss to one post-operative death. Conclusion: Confidently grasping the nuances of forehead flap nasal reconstruction arms the reconstructive surgeon with a reliable tool that can effectively treat a variety of defects. It is safe to use in an outpatient setting even in elderly patients. Recommendations include ipsilateral flap design and turn-in component as first choice for lining replacement. (C)2017American Society of Plastic Surgeons

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Components of the Hanging Columella: Strategies for Refinement.

The columella is a significant factor in the aesthetic balance of the nose and particularly the lower one-third of the nose. Its position is dependent upon the anatomic constituents of the columella, as well neighboring anatomic structures. Six components of the hanging columella have been identified: the caudal septum, medial crura, columellar skin, membranous septum, anterior nasal spine, and the depressor nasi septi muscle. Columellar refinement begins with a careful analysis and diagnosis of the contributing components, followed by surgical techniques to address these components individually. The cumulative effect of correction of individual components appropriately positions the columella and contributes significantly to the enhancement of nasal aesthetics. Refinement of the columella can be achieved through appropriate trimming of the caudal septum, repositioning and reshaping the medial crura, excising redundant columellar skin, membranous septum and nasal mucosa, appropriately contouring the anterior nasal spine, and dividing the depressor nasi septi. (C)2017American Society of Plastic Surgeons

http://ift.tt/2nIwsYm

A National Study of the Impact of Delayed Flap Timing for Treatment of Patients with Deep Sternal Wound Infection.

Background: This study aims to evaluate the impact of delayed flap closure on mortality and resource utilization for treatment of deep sternal wound infection (DSWI). Methods: We analyzed the Truven MarketScan Databases from 2009 - 2013 to identify adult patients who developed DSWI after open cardiac surgery and who received flap closure for treatment. A multivariable logistic regression model was created to evaluate the relationship between mortality and flap timing. Multivariable Poisson regressions were utilized to investigate the relationship between flap timing and number of procedures, number of hospitalizations, and length of stay (LOS) outcomes. A multivariable log-linear regression model was created for cost analysis. All analyses were adjusted for patient risk factors and treatment characteristics. Results: We identified 612 patients with DSWI who underwent flap closure. The timing of flap closure was delayed >7 days after diagnosis in 39% of patients. Delayed time to flap closure >3 days after diagnosis of DSWI was associated with higher mortality odds (4-7 days OR 2.94; >7 days OR 2.75, P7 days IRR 1.93, P

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Comments on "Seroma in Prosthetic Breast Reconstruction".

No abstract available

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Reply to Comments on "Seroma in Prosthetic Breast Reconstruction".

No abstract available

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New cranium of the endemic Caribbean platyrrhine, Antillothrix bernensis, from La Altagracia Province, Dominican Republic

Publication date: May 2017
Source:Journal of Human Evolution, Volume 106
Author(s): Lauren B. Halenar, Siobhán B. Cooke, Alfred L. Rosenberger, Renato Rímoli
Recent paleontological collection in submerged caves in the eastern Dominican Republic has yielded new specimens of Antillothrix bernensis. Here we describe a complete cranium of an adult individual (MHD 20) and provide phenetic comparisons to other endemic Caribbean taxa and extant mainland platyrrhines using three-dimensional geometric morphometric methods (3DGM). Qualitative and quantitative comparisons support conclusions based on other recently described fossil material: Antillothrix has a dentition lacking clear dietary specialization, an elongated brain case with strong temporal lines, and a vertically oriented nuchal plane. MHD 20 shares a combination of traits with a previously published subadult specimen (MHD 01) including a deep depression at glabella, dorsoventrally elongated orbits, and a relatively large face. This shared morphology reinforces the taxonomic affinity of the two specimens, with differences between the two likely reflecting the younger ontogenetic age of MHD 01.Comparisons to the extant platyrrhines paint a complicated picture as the results of between-group principal components analyses (bgPCA) indicate that Antillothrix does not share a suite of morphological features exclusively with any one genus. Depending on which bgPC axes are visualized, and which subset of landmarks is included (i.e., only those describing the shape of the face/palate for inclusion of Xenothrix), MHD 20 is most similar in shape to the atelids, Alouatta, Lagothrix, and Brachyteles, or an otherwise "empty" region of shape space. It groups neither with Cebus nor Callicebus, two taxa that Antillothrix has been associated with in previous studies based on much less complete material. The Antillothrix cranium does not exhibit any of the derived characters classically used to diagnose or define any single clade; rather its morphology shares features with multiple platyrrhine groups. This is consistent with the interpretation that Antillothrix preserves a primitive morphology, which accords with the hypothesis positing an early arrival of platyrrhines in the Caribbean.



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Seeds in the liver

Publication date: Available online 4 April 2017
Source:Acta Histochemica
Author(s): Hongjie Ji, Yanrong Lu, Yujun Shi
The liver is a crucial organ for homeostasis and has a tremendous self-renewal and regenerative capacity. It has long been believed that the self-renewal and repair of the liver within a given physiological condition or its repopulation in chronic liver diseases, when hepatocyte proliferation is impaired, will primarily be conducted by the proliferating duct cells, termed "oval cells" or hepatic progenitor cells (HPCs). In addition, numerous studies have revealed that HPCs are the initial tumor cells of liver cancer under certain micro-environments. However, benefit from the extensive application of lineage tracing strategies using the Cre/LoxP system, researchers have redefined the fate of these bipotential cells, raising obvious controversies regarding the capacity of liver cells to control their own biology and differentiation. Here, we review the relevant articles, focusing on cell-lineage tracing to better understanding seed cells and their distinct fate in the liver.



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Elongated Dorsal Nasal Flap to Reconstruct Large Defects of the Nose.

BACKGROUND: The typical reconstructive option for closing large-sized defects of the distal half of the nose is the paramedian forehead flap. Other alternatives are a melolabial interpolation flap and bilobed or trilobed flaps. The dorsal nasal (Rieger) flap is suitable for closing small-sized defects at this location, especially when they are medially located. OBJECTIVE: The authors describe a modified dorsal nasal flap reconstruction for large nasal defects. The novelty of this study lies in lengthening the leading edge of flap rotation, which may provide tissue either from the adjacent nasal skin, the nasofacial groove, or the cheek. METHODS AND MATERIALS: The authors performed a retrospective chart review of all patients with large defects (>20 mm) of the nose who underwent modified dorsal nasal flap repair between January 2004 and March 2015 at a single academic center. RESULTS: Twenty-seven patients (16 male, 11 female; ages 44-88, mean age 62 years) had defects (the smallest 15 x 21 mm, and the largest 32 x 37 mm) on the lower portion of the nasal pyramid. Follow-up ranged from 12 months to 11 years with good or excellent results in all cases. CONCLUSION: Elongated dorsal nasal flap is a reproducible one-stage flap for large defects of the nose, with minimal risk of aesthetic or functional complications. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Large Elliptical Specimens and the Single Section Method.

No abstract available

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Corrective Hyaluronic Acid Fillers and Combination Cosmetic Treatments for Facial Cutaneous Defects Due to Autoimmune Connective Tissue Diseases: A Retrospective Review.

No abstract available

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Striae Distensae: Preventative and Therapeutic Modalities to Improve Aesthetic Appearance.

BACKGROUND: Striae distensae (SD) are aesthetically troublesome to patients and therapeutically challenging. OBJECTIVE: Herein, the authors comprehensively review the literature pertaining to the history, pathogenesis, clinical presentation, clinical rating scales, and laboratory, imaging, and histologic features of SD. METHODS AND MATERIALS: A review of PubMed, MEDLINE, Scopus, Embase, and Google scholar was conducted, including literature published from 1773 to August 6, 2016. RESULTS: The authors identified 68 articles that met inclusion and exclusion criteria. CONCLUSION: There are few randomized controlled trials evaluating the long-term efficacy and safety of various topical and energy-based devices. Based on clinical and anecdotal experience, both nonablative and ablative fractionated lasers have shown modest SD improvement compared with other treatment modalities (including Excimer laser, CuBr laser, pulsed dye laser, and 1,064-nm Nd:YAG laser). In the authors' experience, 1,540-nm nonablative fractionated laser is a worthy first-line modality for the treatment of SD. Future researchers may consider greater focus on enhanced study design, including larger, long-term split-body, or split-SD head-to-head randomized comparative trials with objective outcome measures and end points, such as biopsy and molecular studies demonstrating increased collagen and elastic fibers that correlate to clinical improvement. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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IncobotulinumtoxinA for Aesthetic Indications: A Systematic Review of Prospective Comparative Trials.

BACKGROUND: IncobotulinumtoxinA is a botulinum toxin type A (BoNTA) indicated for temporary improvement in the appearance of upper facial lines with well-established efficacy and safety profiles. Whether incobotulinumtoxinA and other BoNTAs are equipotent is subject of debate. OBJECTIVE: To compare the efficacy of incobotulinumtoxinA and other BoNTAs for aesthetic applications. MATERIALS AND METHODS: PubMed and Embase were systematically searched for prospective clinical trials comparing incobotulinumtoxinA with onabotulinumtoxinA, abobotulinumtoxinA, or placebo for aesthetic applications. RESULTS: Fifteen articles met the selection criteria. Two studies found that incobotulinumtoxinA was noninferior or equivalent to onabotulinumtoxinA for the treatment of glabellar frown lines (GFLs). Eight studies found no difference in efficacy between incobotulinumtoxinA and other BoNTAs. One study suggested differences in response rates at certain time points between incobotulinumtoxinA and onabotulinumtoxinA for GFLs, and one suggested differences for dynamic horizontal forehead lines but not for GFLs or lateral periorbital lines, but both had study design issues limiting the ability to draw conclusions. Finally, 3 placebo-controlled studies demonstrated the efficacy of incobotulinumtoxinA for treating GFLs and upper facial lines. CONCLUSION: The weight of the evidence from comparative clinical trials indicates that incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA have similar efficacy for aesthetic applications. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Creation and Validation of a Photonumeric Scale to Assess Volume Deficiency in the Infraorbital Region.

BACKGROUND: The eyes are particularly important aesthetic features of the face and revitalization of the infraorbital region has become a focus of aesthetic treatments. Published infraorbital scales to date have limitations in that they have been descriptive, subjective, or have used computer-generated images. Thus, there is an unmet need for a validated scale based on actual images. OBJECTIVE: To develop a practical photonumeric scale that respects the complex anatomy and age-related changes occurring in the orbital area. METHODS AND MATERIALS: The Allergan Infra-oRbital Scale (AIRS) was developed through a multistep process in collaboration with 16 physicians (plastic surgeons, dermatologists, and aesthetic physicians). Scale development involved both online photographs and live assessments of subjects. Interrater and intrarater reliability was assessed using intraclass correlation coefficients (ICCs). RESULTS: The final AIRS showed intrarater and interrater ICCs of 0.78 to 0.86 and 0.91 to 0.98 for live validation and 0.76 to 0.82 and 0.86 to 0.91 for online validation, respectively, demonstrating robust validity. CONCLUSION: The AIRS can be considered a photonumeric scale that accurately describes volume loss in the infraorbital region. It has been validated and is appropriate for use in research or for everyday clinical use for both live and photographic assessment. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Autologous Pure Platelet-Rich Plasma Dermal Injections for Facial Skin Rejuvenation: Clinical, Instrumental, and Flow Cytometry Assessment.

BACKGROUND: Platelet-rich plasma (PRP) is an emerging treatment in dermatology recently proposed for skin rejuvenation. OBJECTIVE: To evaluate the efficacy and safety of autologous pure PRP dermal injections on facial skin rejuvenation, investigating the cellularity of PRP samples. MATERIALS AND METHODS: Twelve patients underwent 3 sessions of PRP injection at 1-month intervals. The clinical and instrumental outcomes were evaluated before (T0) and 1 month (T1) after the end of treatment by means of transepidermal water loss, corneometry, Cutometer, Visioscan, and Visioface. A flow cytometry characterization on PRP and peripheral blood (PB) samples was performed. RESULTS: Clinical and patient evaluation showed improvement of skin texture. Skin gross elasticity, skin smoothness parameters, skin barrier function, and capacitance were significantly improved. No difference between PRP and PB lymphocyte immunological asset was observed. A leukocyte population (mainly CD3+) and neutrophils depletion were documented in all the PRP samples. CONCLUSION: This instrumental study demonstrated that PRP poor in leukocytes can provide objective improvements in skin biostimulation. Flow cytometry showed no variability among the PRP samples using a reproducible separation system and a low content in proinflammatory cells. Although a pilot study, it may be helpful for future investigations on PRP cellularity. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Advancing Keloid Treatment: A Novel Multimodal Approach to Ear Keloids.

BACKGROUND/OBJECTIVE: Management of keloids of the pinna, in particular, those located in the helix and antihelix and lobule that occur as complications of ear piercing. MATERIALS AND METHODS: Retrospective analysis of 49 patients treated with extralesional surgical excision of keloids localized to the ear followed by the application of autologous platelet-rich plasma (PRP) to wound site and postoperative in-office superficial radiation therapy (SRT). Radiation protocol consisted of 1 to 3 fractions, with cumulative dosage ranging from 1,300 to 1,800 cGy. Average follow-up was 24 months to assess for evidence of recurrence and adverse side effects. RESULTS: Fifty ear keloids were treated with this method, age from 15 to 66 (mean = 32, SD = 16) of which 14 were male and 35 female. Almost 30% (n = 14) of patients acknowledged the source of injury that led to the development of the keloid was ear piercing. Treatment protocol achieved a 94% success rate with 3 patients who reported recurrence. CONCLUSION: Surgical excision combined with intraoperative PRP, adjuvant postoperative in-office SRT achieved a 94% nonrecurrence rate on follow-up over a 2-year period. Outcomes provide preliminary, albeit, strong evidence to support this multimodal method as a viable alternative in the management of keloids localized to the ear. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Platelet-Rich Plasma for the Treatment of Female Pattern Hair Loss: A Patient Survey.

No abstract available

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A 56-Year-Old Woman With Multiple Subcutaneous Painful Nodules in the Absence of Renal Disease.

No abstract available

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A 56-Year-Old Woman With Multiple Subcutaneous Painful Nodules in the Absence of Renal Disease.

No abstract available

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Primary Cutaneous Follicular Helper T-Cell Lymphoma: A Case Series and Review of the Literature.

Primary cutaneous follicular helper T-cell (Tfh) lymphoma is a recently described variant of peripheral T-cell lymphoma-not otherwise specified. This particular variant, usually presenting as a sudden onset of multiple plaques and nodules, is characterized by tumoral atypical T cells that express an array of Tfh markers, such as inducible T-cell costimulator, Bcl-6, CXCL13, PD-1, and CD10. The authors now present 3 patients whose known clinical skin findings are consistent with PTCL of Tfh origin (PTCL-Tfh). The typically protracted pattern of skin disease manifesting as scaly patches and plaques encountered in mycosis fungoides was not seen in our 3 cases, and there were distinguishing light microscopic and phenotypic features. These cases are similar to the few previous reported cases of PTCL-Tfh, although systemic involvement was not seen. The categorization of additional patients into this PTCL subtype in the medical literature would be needed to further characterize this new entity and may lead to better targeted treatments based on specific T-cell subtypes. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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A 32-Year-Old Woman With Tender Nodules That Ulcerate.

No abstract available

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Winkelmann Granuloma.

No abstract available

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Erythematous Bullous Patch in a Patient With Myelodysplastic Syndrome.

No abstract available

http://ift.tt/2n9GLIP

Commentary on Some Recent Theses Relevant to Combating Aging: April 2017

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2nI2Ydg

Multiple cutaneous reticulohistiocytosis with T-cell large granular lymphocyte clonopathy

Abstract

A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68⁺ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3⁺, CD8⁺ CD57⁺ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.

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Unusual clinical umbilical hernia: pitfall

Description

A 75-year-old alcoholic male patient with severe malnutrition was admitted to the hospital with the diagnosis of pneumonia. The finding of a symptomatic umbilical hernia on patient examination mandated a surgical consultation with the question of an operative hernia repair.

Clinically, the abdomen was distended with spider angiomas. Palpation of the umbilical hernia was painless. The hernia content was not reducible. A suspicious murmur (Cruveilhier-Baumgarten murmur) was identified on auscultation of the umbilicus (figure 1). The abdominal CT scan showed signs of portal hypertension. A large recanalised paraumbilical vein coursing from the left side of the portal vein through the falciform ligament and draining into a large umbilical varicose vein was visible. An enlarged right inferior epigastric vein originating from the umbilical varicose vein drained into the right femoral vein. The hernial sac contained only the umbilical varicose (figure 2A,B,C). On further investigation,...

http://ift.tt/2oAmYT9

Multiple cutaneous reticulohistiocytosis with T-cell large granular lymphocyte clonopathy

Abstract

A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68⁺ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3⁺, CD8⁺ CD57⁺ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.

http://ift.tt/2oAjcZW

Biologics,Biologic Response Modifiers,Biopharmaceutical.

http://otorhinolarygology.blogspot.com/2017/04/biologicsbiologic-response.html

Major kinds of biopharmaceuticals include:

Blood factors (Factor VIII and Factor IX)

Thrombolytic agents (tissue plasminogen activator)

Hormones (insulin, glucagon, growth hormone, gonadotrophins)

Haematopoietic growth factors (Erythropoietin, colony stimulating factors)

Interferons (Interferons-α, -β, -γ)

Interleukin-based products (Interleukin-2)

Vaccines (Hepatitis B surface antigen)

Monoclonal antibodies (Various)

Additional products (tumour necrosis factor, therapeutic enzymes)

Research and development investment in new medicines by the biopharmaceutical industry stood at $65.2 billion in 2008.[11] A few examples of biologics made with recombinant DNA technology include:

USAN/INN Trade name Indication Technology Mechanism of action

abatacept Orencia rheumatoid arthritis immunoglobin CTLA-4 fusion protein T-cell deactivation

adalimumab Humira rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Ulcerative Colitis, Crohn's disease monoclonal antibody TNF antagonist

alefacept Amevive chronic plaque psoriasis immunoglobin G1 fusion protein incompletely characterized

erythropoietin Epogen anemia arising from cancer chemotherapy, chronic renal failure, etc. recombinant protein stimulation of red blood cell production

etanercept Enbrel rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis recombinant human TNF-receptor fusion protein TNF antagonist

infliximab Remicade rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Ulcerative Colitus, Crohn's disease monoclonal antibody TNF antagonist

trastuzumab Herceptin breast cancer humanized monoclonal antibody HER2/neu (erbB2) antagonist

ustekinumab Stelara psoriasis humanized monoclonal antibody IL-12 and IL-23 antagonist

denileukin diftitox Ontak cutaneous T-cell lymphoma (CTCL) Diphtheria toxin engineered protein combining Interleukin-2 and Diphtheria toxin Interleukin-2 receptor binder

golimumab Simponi rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Ulcerative colitis monoclonal antibody TNF antagonist

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Biologic Therapies of Immunologic Diseases.

Related Articles

Biologic Therapies of Immunologic Diseases.

Immunol Allergy Clin North Am. 2017 May;37(2):xvii-xviii

Authors: Chipps BE, Peters SP

PMID: 28366489 [PubMed - in process]

http://ift.tt/2oGyqJM

Biopharmaceuticals in Allergic Disease: Finding the Right Patients at the Right Time.

Related Articles

Biopharmaceuticals in Allergic Disease: Finding the Right Patients at the Right Time.

Immunol Allergy Clin North Am. 2017 May;37(2):xv-xvi

Authors: Tilles SA

PMID: 28366488 [PubMed - in process]

http://ift.tt/2oGGp9B

Erratum.

Related Articles

Erratum.

Immunol Allergy Clin North Am. 2017 May;37(2):xiii

Authors:

PMID: 28366487 [PubMed - in process]

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Future Prospects of Biologic Therapies for Immunologic Diseases.

Related Articles

Future Prospects of Biologic Therapies for Immunologic Diseases.

Immunol Allergy Clin North Am. 2017 May;37(2):431-448

Authors: Kumar S, Ward BR, Irani AM

Abstract
This article presents an overview of future uses for biologic therapies in the treatment of immunologic and allergic conditions. Discussion is centered on the use of existing therapies outside of their current indication or on new therapies that are close to approval. This information may help familiarize practicing allergists and immunologists with therapies they may soon encounter in their practice as well as help identify conditions and treatments that will require further study in the near future.

PMID: 28366486 [PubMed - in process]

http://ift.tt/2oGJuGU

Pharmacoeconomics of Biologic Therapy.

Related Articles

Pharmacoeconomics of Biologic Therapy.

Immunol Allergy Clin North Am. 2017 May;37(2):413-430

Authors: Bukstein DA, Luskin AT

Abstract
Novel biologic agents have allowed clinicians to achieve improved patient outcomes. Appropriate pharmacoceconomic analyses demand evaluation of all relevant costs, including the treatments, the disease and comorbidities, and costs of alternative treatments, including their short- and long-term side effects. Only with complete data can the value of therapies be correctly estimated. By assessing costs, pharmacoeconomic studies complement studies of efficacy and safety, helping to determine the relationships of treatment and outcome. This article provides a broad framework for understanding and evaluating published economic analyses and identifying the key costs and benefits caring for patients with asthma and other immune diseases.

PMID: 28366485 [PubMed - in process]

http://ift.tt/2oGQ5RJ

Adverse Reactions to Biologic Therapy.

Related Articles

Adverse Reactions to Biologic Therapy.

Immunol Allergy Clin North Am. 2017 May;37(2):397-412

Authors: Patel SV, Khan DA

Abstract
Biologic therapies are emerging as a significant therapeutic option for many with debilitating inflammatory and autoimmune conditions. As expansion in the number of FDA-approved agents continue to be seen, more unanticipated adverse reactions are likely to occur. Currently, the diagnostic tools, including skin testing and in vitro testing, to evaluate for immediate hypersensitivity reactions are insufficient. In this review, management strategies for common acute infusion reactions, injection site reactions, and immediate reactions suggestive of IgE-mediated mechanisms are discussed. Desensitization can be considered for reactions suggestive of IgE-mediated mechanisms, but allergists/immunologists should be involved in managing these patients.

PMID: 28366484 [PubMed - in process]

http://ift.tt/2oGoznb

Biologic Therapies for Immunoglobulin E-mediated Food Allergy and Eosinophilic Esophagitis.

Related Articles

Biologic Therapies for Immunoglobulin E-mediated Food Allergy and Eosinophilic Esophagitis.

Immunol Allergy Clin North Am. 2017 May;37(2):369-396

Authors: Otani IM, Nadeau KC

Abstract
Immunoglobulin (Ig) E-mediated food allergy and eosinophilic esophagitis (EoE) are chronic, allergen-mediated disorders characterized by an aberrant TH2 immune response. The development and investigation of biologics for the treatment of IgE-mediated food allergy and eosinophilic esophagitis have provided further insight into the pathophysiology and management of these disorders. This article provides an overview of biologic therapies that are being investigated or have potential as treatments for IgE-mediated food allergy and eosinophilic esophagitis. Identification of EoE phenotypes that are responsive to biologics and investigation of biologics combined with other therapies may help elucidate a role for biologics in EoE.

PMID: 28366483 [PubMed - in process]

http://ift.tt/2oGDaPr

Monoclonal Antibodies for the Treatment of Nasal Polyps.

Related Articles

Monoclonal Antibodies for the Treatment of Nasal Polyps.

Immunol Allergy Clin North Am. 2017 May;37(2):357-367

Authors: Willson TJ, Naclerio RM, Lee SE

Abstract
Biologics are novel therapeutic medications developed for the targeted therapy for a variety of inflammatory conditions. The biologics currently investigated for the treatment of chronic rhinosinusitis (CRS) with nasal polyps modulate specific inflammatory pathways involved in the pathogenesis of disease. Investigations have focused on the most severe form of the disease, namely, CRS with nasal polyps. It is hoped that specific targeted therapies using these biologics can significantly modulate the immune system, offering both disease control and symptomatic relief. This review summarizes those therapies that have been used to treat nasal polyps.

PMID: 28366482 [PubMed - in process]

http://ift.tt/2oGXfFh

Biologic Therapy in Chronic Obstructive Pulmonary Disease.

Related Articles

Biologic Therapy in Chronic Obstructive Pulmonary Disease.

Immunol Allergy Clin North Am. 2017 May;37(2):345-355

Authors: Tripple JW, McCracken JL, Calhoun WJ

Abstract
Chronic obstructive pulmonary disease (COPD) is common worldwide. The predominant cause in most COPD is environmental exposure to toxicants. The inflammatory processes in COPD are multifactorial, complex, and interacting, leading to many potential therapeutic targets. Although most typically associated with neutrophilic/macrophagic inflammation (type 1), it is now known that COPD can also be associated with eosinophilic inflammation (type 2), particularly in exacerbations. Accordingly, there is an active program of investigation of highly selective biologic therapeutic agents in the management of COPD. This review summarizes clinical trials of the use of these novel agents in the management of COPD.

PMID: 28366481 [PubMed - in process]

http://ift.tt/2oGDcqx

Biologic and New Therapies in Asthma.

Related Articles

Biologic and New Therapies in Asthma.

Immunol Allergy Clin North Am. 2017 May;37(2):329-343

Authors: Tabatabaian F, Ledford DK, Casale TB

Abstract
Several biologics are currently FDA approved for asthma that target Th2 high patients. Unfortunately, 50% of patients with severe asthma do not fit this phenotype of disease and have fewer effective therapeutic options. In the clinical setting, total IgE, FeNO and peripheral blood eosinophils are important tools in defining Th2 high patients with asthma. However, precise biomarkers to predict better response to one specific Th2 high asthma therapy versus another is lacking. It is important to recognize that none of the current medications targeting the Th2 pathway induces persistent immunomodulation or remission.

PMID: 28366480 [PubMed - in process]

http://ift.tt/2oGxGEe

Biologic Therapy in the Treatment of Chronic Skin Disorders.

Related Articles

Biologic Therapy in the Treatment of Chronic Skin Disorders.

Immunol Allergy Clin North Am. 2017 May;37(2):315-327

Authors: Fernandez JM, Fernandez AP, Lang DM

Abstract
Understanding of the immunologic pathways involved in the pathogenesis of skin-related diseases is constantly advancing. Several biologic agents play important therapeutic roles for management of patients with chronic urticaria, atopic dermatitis, and psoriasis, particularly omalizumab for antihistamine-resistant chronic urticaria, interleukin (IL)-1 inhibitors for cryopyrin-associated periodic syndrome and Schnitzler syndrome, dupilumab for recalcitrant atopic dermatitis, and IL-17 inhibitors for psoriasis. The therapeutic utility of biologic agents for patients with immune-related dermatologic disorders is likely to expand in the future. This article reviews the data regarding biologic agents and their utility in the management of specific skin-related disorders.

PMID: 28366479 [PubMed - in process]

http://ift.tt/2oGMrHn

Immune Mechanisms and Novel Targets in Rheumatoid Arthritis.

Related Articles

Immune Mechanisms and Novel Targets in Rheumatoid Arthritis.

Immunol Allergy Clin North Am. 2017 May;37(2):301-313

Authors: Venuturupalli S

Abstract
Significant progress has been made in understanding the pathophysiology of rheumatoid arthritis. It is widely recognized that early institution of treatment is one of the best predictive factors for response to therapy. Several novel approaches are currently being investigated and several novel biologics are in various stages of development. With advances in the fields of proteomics, genomics, and metabolomics, specific phenotypes of the disease can be better identified and specific therapies for particular phases of the disease and specific patients will allow for improved control of this condition.

PMID: 28366478 [PubMed - in process]

http://ift.tt/2oGtxQO

Biologic Therapies for Autoimmune and Connective Tissue Diseases.

Related Articles

Biologic Therapies for Autoimmune and Connective Tissue Diseases.

Immunol Allergy Clin North Am. 2017 May;37(2):283-299

Authors: Wolfe RM, Ang DC

Abstract
Biologic therapy continues to revolutionize the treatment of autoimmune disease, especially in rheumatology as the pathophysiology of both inflammation and autoimmune disease becomes better understood. These therapies are designed to dampen the response of the inflammatory cascades. Although the first biologic therapies were approved many years ago, expanding indications and new agents continue to challenge the traditional treatment strategies for rheumatic diseases. This article reviews the data supporting the current use of biologic therapies, including off-label indications, in a subset of rheumatic diseases including rheumatoid arthritis, lupus, inflammatory myositis, ankylosing spondylitis, psoriatic arthritis, vasculitis, and gout.

PMID: 28366477 [PubMed - in process]

http://ift.tt/2oGDRsh

Patient Characteristics and Individualization of Biologic Therapy.

Related Articles

Patient Characteristics and Individualization of Biologic Therapy.

Immunol Allergy Clin North Am. 2017 May;37(2):261-281

Authors: Draikiwicz S, Oppenheimer J

Abstract
Progress in the understanding of disease processes has provided additional therapeutic targets, best exemplified by the increasing role of biologics in the clinical armamentarium. This article provides a focused review of current treatment paradigms and pathophysiology for asthma, atopic dermatitis, urticaria, as well as C1 inhibitor deficiency. It elucidates the populations in which biologics were studied for the aforementioned disease states, emphasizing characteristics to consider when selecting therapy. It is important to correctly estimate patient outcome before starting therapy based on cost analysis. Treatment decisions need to be guided by appropriate patient stratification based on each individual's underlying phenotype.

PMID: 28366476 [PubMed - in process]

http://ift.tt/2oGypWe

Biological Therapies of Immunologic Diseases: Strategies for Immunologic Interventions.

Related Articles

Biological Therapies of Immunologic Diseases: Strategies for Immunologic Interventions.

Immunol Allergy Clin North Am. 2017 May;37(2):247-259

Authors: Polk BI, Rosenwasser LJ

Abstract
The immune system possesses a vast number of potential targets for therapeutic intervention. Although therapies for many pathways have been pursued, only few have yielded significant success. Hindrances in altering biologic pathways include the potential for unwanted downstream effects, ineffectiveness owing to biological redundancy, recognition of a therapeutic molecule as foreign by the body's innate immune system, and the risks of subsequent malignancy and/or autoimmunity. This article covers currently available biotherapeutic agent classes as well as potential direction for future therapy.

PMID: 28366475 [PubMed - in process]

http://ift.tt/2oGNVS2

Inflammatory Disorders Associated with Allergy: Overview of Immunopathogenesis and Implications for Treatment.

Related Articles

Inflammatory Disorders Associated with Allergy: Overview of Immunopathogenesis and Implications for Treatment.

Immunol Allergy Clin North Am. 2017 May;37(2):233-246

Authors: Corren J

Abstract
A number of chronic inflammatory diseases are associated with IgE-mediated immunologic hypersensitivity, including atopic dermatitis, chronic rhinosinusitis, and asthma. Pathogenetic studies of well-characterized patient groups has allowed investigators to more precisely define the molecular pathways involved in these diseases. Specific cytokines and chemokines, as well as other unique proteins, have now been identified in each of these common disorders and a number of medications are currently in development for inhibiting their actions. Continual refinement of our understanding of the pathogenesis of these diseases will undoubtedly yield increasingly precise, and potentially more effective, treatments.

PMID: 28366474 [PubMed - in process]

http://ift.tt/2oGBFRg

Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness

Publication date: July 2017
Source:Biomaterials, Volume 131
Author(s): Soah Lee, Vahid Serpooshan, Xinming Tong, Sneha Venkatraman, Meelim Lee, Jaecheol Lee, Orlando Chirikian, Joseph C. Wu, Sean M. Wu, Fan Yang
Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1.25 × 10⁸/mL) with tunable stiffness and degradation. In comparison to the cells in high stiffness (16 kPa)/slow degrading hydrogels, hiPSC-CMs in low stiffness (2 kPa)/fast degrading and intermediate stiffness (9 kPa)/intermediate degrading hydrogels exhibit increased intercellular network formation, α-actinin and connexin-43 expression, and contraction velocity. Only the 9 kPa microtissues exhibit organized sarcomeric structure and significantly increased contractile stress. This demonstrates that muscle-mimicking stiffness together with robust cellular interconnection contributes to enhancement in sarcomeric organization and contractile function of the engineered cardiac tissue. This study highlights the importance of intercellular connectivity, physiologically-relevant cell density, and matrix stiffness to best support 3D cardiac tissue engineering.



http://ift.tt/2nA2epI

Microfluidic-enhanced 3D bioprinting of aligned myoblast-laden hydrogels leads to functionally organized myofibers in vitro and in vivo

Publication date: July 2017
Source:Biomaterials, Volume 131
Author(s): Marco Costantini, Stefano Testa, Pamela Mozetic, Andrea Barbetta, Claudia Fuoco, Ersilia Fornetti, Francesco Tamiro, Sergio Bernardini, Jakub Jaroszewicz, Wojciech Święszkowski, Marcella Trombetta, Luisa Castagnoli, Dror Seliktar, Piotr Garstecki, Gianni Cesareni, Stefano Cannata, Alberto Rainer, Cesare Gargioli
We present a new strategy for the fabrication of artificial skeletal muscle tissue with functional morphologies based on an innovative 3D bioprinting approach. The methodology is based on a microfluidic printing head coupled to a co-axial needle extruder for high-resolution 3D bioprinting of hydrogel fibers laden with muscle precursor cells (C2C12). To promote myogenic differentiation, we formulated a tailored bioink with a photocurable semi-synthetic biopolymer (PEG-Fibrinogen) encapsulating cells into 3D constructs composed of aligned hydrogel fibers. After 3–5 days of culture, the encapsulated myoblasts started migrating and fusing, forming multinucleated myotubes within the 3D bioprinted fibers. The obtained myotubes showed high degree of alignment along the direction of hydrogel fiber deposition, further revealing maturation, sarcomerogenesis, and functionality. Following subcutaneous implantation in the back of immunocompromised mice, bioprinted constructs generated organized artificial muscle tissue in vivo. Finally, we demonstrate that our microfluidic printing head allows to design three dimensional multi-cellular assemblies with an exquisite compartmentalization of the encapsulated cells. Our results demonstrate an enhanced myogenic differentiation with the formation of parallel aligned long-range myotubes. The approach that we report here represents a robust and valid candidate for the fabrication of macroscopic artificial muscle to scale up skeletal muscle tissue engineering for human clinical application.



http://ift.tt/2o5Etto

Raman spectroscopy for the detection of organ distribution and clearance of PEGylated reduced graphene oxide and biological consequences

Publication date: July 2017
Source:Biomaterials, Volume 131
Author(s): Santhakumar Syama, Willi Paul, Arumugam Sabareeswaran, Parayanthala Valappil Mohanan
Graphene, a 2D carbon material has found vast application in biomedical field because of its exciting physico-chemical properties. The large planar sheet like structure helps graphene to act as an effective carrier of drug or biomolecules in enormous amount. However, limited data available on the biocompatibility of graphene upon interaction with the biological system prompts us to evaluate their toxicity in animal model. In this study organ distribution, clearance and toxicity of PEGylated reduced nanographene (PrGO) on Swiss Albino mice was investigated after intraperitoneal and intravenous administration. Biodistribution and blood clearance was monitored using confocal Raman mapping and indicated that PrGO was distributed on major organs such as brain, liver, kidney, spleen and bone marrow. Presence of PrGO in brain tissue suggests that it has the potential to cross blood brain barrier. Small amount of injected PrGO was found to excrete via urine. Repeated administration of PrGO induced acute liver injury, congestion in kidney and increased splenocytes proliferation in days following exposure. Hence the result of the study recommended that PrGO should undergo intensive safety assessment before clinical application or validated to be safe for medical use.

Graphical abstract

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Can We Improve the Laser Etching with the Digitally Controlled Laser Handpiece—Xrunner?

Photomedicine and Laser Surgery , Vol. 0, No. 0.


http://ift.tt/2nCvUCt

Minimally Invasive Excision of Epulides with a CO2 Laser: A Retrospective Study of 90 Patients

Photomedicine and Laser Surgery , Vol. 0, No. 0.


http://ift.tt/2o7ZPq0

Future Meetings

Thyroid Apr 2017, Vol. 27, No. 4: 593-594.


http://ift.tt/2nCqzeo

Magnetic and thermal transport properties of SrFe12O19 permanent magnets with anisotropic grain structure

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): A.D. Volodchenkov, S. Ramirez, R. Samnakay, R. Salgado, Y. Kodera, A.A. Balandin, J.E. Garay
Permanent magnets are gaining increasing interest and importance for applications such as generators and motors. Thermal management is a key concern since performance of magnets decreases with temperature. We investigate the magnetic and thermal transport properties of rare earth-free, fine-grained SrFe12O19 magnets produced by the current activated pressure assisted densification. We propose a cooling scheme based on an anisotropic grain structure that can help retain magnetic performance under high temperature conditions. The synthesized magnets have aligned grains such that their magnetic easy axis is perpendicular to their largest surface area to maximize their magnetic performance. The SrFe12O19 magnets have fine grain sizes in the cross-plane direction and substantially larger grain sizes in the in-plane direction. This microstructure results in approximately a factor of two higher thermal conductivity in the in-plane direction, providing an opportunity for effective cooling. The phonons are the dominant heat carriers near room temperature. Temperature and direction dependent thermal conductivity measurements indicate that both Umklapp and grain boundary scattering are important in the in-plane direction, while grain boundary scattering dominates the cross-plane thermal transport. The proposed design strategy should translate well to other material systems and has important implications for thermal management of nanostructured permanent magnets.

Graphical abstract

http://ift.tt/2n9iNNS

Functionally graded shape memory alloys: Design, fabrication and experimental evaluation

Publication date: 15 June 2017
Source:Materials & Design, Volume 124
Author(s): Bashir S. Shariat, Qinglin Meng, Abdus S. Mahmud, Zhigang Wu, Reza Bakhtiari, Junsong Zhang, Fakhrodin Motazedian, Hong Yang, Gerard Rio, Tae-hyun Nam, Yinong Liu
Functionally graded shape memory alloys have the advantage of combining the functionalities of the shape memory effect and those of functionally graded structures. By proper design, they can exhibit new and complex deformation behaviour that is unmatched in uniform shape memory alloys. One obvious advantage of functionally graded shape memory alloys is their widened transformation stress and temperature windows that provide improved controllability in actuating applications. This paper reports on the concept, fabrication, experimentation and thermomechanical behaviour of several designs of functionally graded NiTi alloys, including compositionally graded, microstructurally graded and geometrically graded NiTi alloys, and the various techniques that may be used to create these functionally graded materials. It is found that the property gradients created along the loading direction or perpendicular to the loading direction produce distinct thermomechanical behaviours. The property gradient along the loading direction provides stress gradient over stress-induced transformation, which can be adjusted by the property gradient profile. The property gradient through the thickness direction of plate specimens and perpendicular to the loading direction provides four-way shape memory behaviour during stress-free thermal cycling after tensile deformation.

Graphical abstract

http://ift.tt/2n9i5jr

Future Meetings

Thyroid Apr 2017, Vol. 27, No. 4: 593-594.


http://ift.tt/2nCqzeo

Controlling Human Papilloma Virus: A Public Health Perspective of Treatment of Anogenital Warts

http://ift.tt/2oGMP8D

Complete Metabolic Response on Interim 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Long-Term Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy

Background.

This study aims to investigate the prognostic role of complete metabolic response (CMR) on interim ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with breast cancer (BC) receiving neoadjuvant chemotherapy (NAC) according to tumor subtypes and PET timing.

Patients and Methods.

Eighty-six consecutive patients with stage II/III BC who received PET/CT during or following NAC were included. Time-dependent receiver operating characteristic analysis and Kaplan-Meier analysis were used to determine correlation between metabolic parameters and survival outcomes.

Results.

The median follow-up duration was 71 months. Maximum standardized uptake value (SUV_max) on an interim PET/CT independently correlated with survival by multivariate analysis (overall survival [OS]: hazard ratio: 1.139, 95% confidence interval: 1.058–1.226, p = .001). By taking PET timing into account, best association of SUV_max with survival was obtained on PET after two to three cycles of NAC (area under the curve [AUC]: 0.941 at 1 year after initiation of NAC) and PET after four to five (AUC: 0.871 at 4 years), while PET after six to eight cycles of NAC had less prognostic value. CMR was obtained in 62% of patients (23/37) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2–) BC, in 48% (12/25) triple-negative BC (TNBC), and in 75% (18/24) HER2-positive (HER2+) tumors. Patients with CMR on an early-mid PET had 5-year OS rates of 92% for ER+/HER2– tumors and 80% for TNBC, respectively. Among HER2+ subtype, 89% patients (16/18) with CMR had no relapse.

Conclusion.

CMR indicated a significantly better outcome in BC and may serve as a favorable imaging prognosticator. The Oncologist 2017;22:1–9

Implications for Practice: This study shows a significantly better outcome for breast cancer (BC) patients who achieved complete metabolic response (CMR) on ¹⁸F-fluorodeoxyglucose emission tomography/computed tomography (PET/CT) during neoadjuvant chemotherapy, especially for hormone receptor-positive tumors and triple negative BC. Moreover, PET/CT performed during an early- or mid-course neoadjuvant therapy is more predictive for long-term survival outcome than a late PET/CT. These findings support that CMR may serve as a favorable imaging prognosticator for BC and has potential for application to daily clinical practice.

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Silk I and Silk II Studied by Fast Scanning Calorimetry

Publication date: Available online 5 April 2017
Source:Acta Biomaterialia
Author(s): Peggy Cebe, Benjamin P. Partlow, David L. Kaplan, Andreas Wurm, Evgeny Zhuravlev, Christoph Schick
Using fast scanning calorimetry (FSC), we investigated the glass transition and crystal melting of samples of B. mori silk fibroin containing Silk I and/or Silk II crystals. Due to the very short residence times at high temperatures during such measurements, thermal decomposition of silk protein can be significantly suppressed. FSC was performed at 2000 K/s using the Mettler Flash DSC1 on fibroin films with masses around 130-270 ng. Films were prepared with different crystalline fractions (ranging from 0.26 to 0.50) and with different crystal structures (Silk I, Silk II, or mixed) by varying the processing conditions. These included water annealing at different temperatures, exposure to 50% MeOH in water, or autoclaving. The resulting crystal structure was examined using wide angle X-ray scattering. Degree of crystallinity was evaluated from Fourier transform infrared (FTIR) spectroscopy and from analysis of the heat capacity increment at the glass transition temperature. Silk fibroin films prepared by water annealing at 25 °C were the least crystalline and had Silk I structure. FTIR and FSC studies showed that films prepared by autoclaving or 50% MeOH exposure were the most crystalline and had Silk II structure. Intermediate crystalline fraction and mixed Silk I/Silk II structures were found in films prepared by water annealing at 37 °C. FSC results indicate that Silk II crystals exhibit endotherms of narrower width and have higher mean melting temperature Tm(II) = 351 ± 2.6 °C, compared to Silk I crystals which melt at Tm(I) = 292 ± 3.8 °C. Films containing mixed Silk I/Silk II structure showed two clearly separated endothermic peaks. Evidence suggests that the two types of crystals melt separately and do not thermally interconvert on the extremely short time scale (0.065 s between onset and end of melting) of the FSC experiment.Statement of significanceSilkworm silk is a naturally occurring biomaterial. The fibroin component of silk forms two types of crystals. Silk properties depend upon the amount and type of crystals, and their stability. One measure of stability is crystal melting temperature. Crystals which are more stable have a higher melting temperature. Until now, it has been challenging to study thermal behavior of silk crystals because they degrade at high temperature. To avoid degradation, and study the melting properties of silk biomaterial, we heated silk at a very fast rate of 2000 K/s using a special calorimeter. We have shown that the two crystal types have very different melting temperatures, indicating that one crystal type is much more stable than the other.

Graphical abstract

http://ift.tt/2o7QU8a

Cancer chemopreventive activity of compounds isolated from Waltheria indica

Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Aymeric Monteillier, Sylvian Cretton, Olivier Ciclet, Laurence Marcourt, Samad Nejad Ebrahimi, Philippe Christen, Muriel Cuendet
Ethnopharmacological relevanceWaltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts.Aim of the studyThe transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations.Materials and methodsCompounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells.ResultsTwenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds.ConclusionThe presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention.

Graphical abstract

http://ift.tt/2nIaPr3

IFC (Journal of Ethnopharmacology)

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202





http://ift.tt/2oA2bzb

Predictors of hearing recovery in patients with severe sudden sensorineural hearing loss

Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient's social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not pre...

http://ift.tt/2oB68TF

The T4/T3 quotient as a risk factor for differentiated thyroid cancer: a case control study

The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid di...

http://ift.tt/2nI7J6v

Systemic therapy in the curative treatment of head and neck squamous cell cancer: a systematic review

To review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in...

http://ift.tt/2nI90dV

Predictors of hearing recovery in patients with severe sudden sensorineural hearing loss

Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient's social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not pre...

http://ift.tt/2oB68TF

The T4/T3 quotient as a risk factor for differentiated thyroid cancer: a case control study

The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid di...

http://ift.tt/2nI7J6v

Systemic therapy in the curative treatment of head and neck squamous cell cancer: a systematic review

To review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in...

http://ift.tt/2nI90dV

Recovery of Abnormal ABR in Neonates and Infants at Risk of Hearing Loss

The purpose of this retrospective study is to present the clinical experience of a single institution on the recovery of ABR thresholds in a large population of neonates and infants at risk of hearing loss. Potential prognostic factors associated with this phenomenon were also investigated. Out of 2248 high risk infants, 384 had abnormal ABR at initial hearing evaluation and 168 of them had absent ABR or a threshold ≥80 dBnHL. From this subgroup, a significant percentage showed complete or partial recovery on reexamination (32.7% and 9.3%, resp.), performed 4–6 months later. The presence of normal otoacoustic emissions was associated with the ABR restoration on reexamination. Moreover, the very young age at the initial hearing screening seems to be related to higher probabilities of false positive ABR. The potential recovery of hearing in HR infants raises concerns about the very early cochlear implantation in HR infants less than one year. Such a treatment modality should be decided cautiously and only after obtaining valid and stable objective and subjective hearing thresholds. This holds especially true for infants showing an auditory neuropathy profile, as they presented a much greater probability of ABR recovery.

http://ift.tt/2oxq5L4

Recovery of Abnormal ABR in Neonates and Infants at Risk of Hearing Loss

The purpose of this retrospective study is to present the clinical experience of a single institution on the recovery of ABR thresholds in a large population of neonates and infants at risk of hearing loss. Potential prognostic factors associated with this phenomenon were also investigated. Out of 2248 high risk infants, 384 had abnormal ABR at initial hearing evaluation and 168 of them had absent ABR or a threshold ≥80 dBnHL. From this subgroup, a significant percentage showed complete or partial recovery on reexamination (32.7% and 9.3%, resp.), performed 4–6 months later. The presence of normal otoacoustic emissions was associated with the ABR restoration on reexamination. Moreover, the very young age at the initial hearing screening seems to be related to higher probabilities of false positive ABR. The potential recovery of hearing in HR infants raises concerns about the very early cochlear implantation in HR infants less than one year. Such a treatment modality should be decided cautiously and only after obtaining valid and stable objective and subjective hearing thresholds. This holds especially true for infants showing an auditory neuropathy profile, as they presented a much greater probability of ABR recovery.

http://ift.tt/2oxq5L4

Prolactin receptors in Rip-cre cells, but not in AgRP neurons, are involved in energy homeostasis

Abstract

Among its many functions, prolactin has been implicated in energy homeostasis, particularly during pregnancy and lactation. The arcuate nucleus is a key site in the regulation of energy balance. The aim of this study was to examine whether arcuate nucleus neuronal populations involved in energy homeostasis are prolactin responsive and if they can mediate the effects of prolactin on energy homeostasis. To determine if Agrp neurons or Rip-Cre neurons are prolactin responsive, transgenic mice expressing the reporter td-tomato in Agrp neurons (td-tomato/AgRP-Cre) or Rip-Cre neurons (td-tomato/Rip-Cre) were treated with prolactin and perfused 45 minutes later. Brains were processed for double-labeled immunohistochemistry for pSTAT5, a marker of prolactin-induced intracellular signaling, and td-tomato. In addition, Agrp-Cre mice and Rip-Cre mice were crossed with mice in which the prolactin receptor gene (Prlr) was flanked with LoxP sites (Prlr^lox/lox mice). The Prlr^lox/lox construct was designed such that Cre-mediated recombination resulted in deletion of the Prlr and expression of GFP in its place. In td-tomato/Rip-Cre mice, prolactin-induced pSTAT5 was co-localized with td-tomato, indicating that there is a subpopulation of Rip-Cre neurons in the arcuate nucleus that respond to prolactin. Furthermore, mice with a specific deletion of Prlr in Rip-Cre neurons had lower body weights, increased oxygen consumption, increased running wheel activity, and numerous cells in the arcuate nucleus had positive GFP staining indicating deletion of Prlr from Rip-Cre neurons. In contrast, no co-localization of td-tomato and pSTAT5 was observed in td-tomato/Agrp-Cre mice following prolactin treatment. Moreover, Prlr^lox/lox/Agrp-Cre mice had no positive GFP staining in the arcuate nucleus and did not differ in body weight compared to litter mate controls. Overall these results indicate that Rip-Cre neurons in the arcuate nucleus are responsive to prolactin and may play a role in the orexigenic effects of prolactin, while prolactin does not directly affect Agrp neurons.

This article is protected by copyright. All rights reserved.

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"J BUON"[jour]; +44 new citations

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PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2ozWJMq

Idiopathic atrophoderma of Pasini and Pierini: A case study of collagen and elastin texture by multiphoton microscopy

The diagnosis of idiopathic atrophoderma of Pasini and Pierini (IAPP) relies on typical clinical features, particularly distinctive pigmented ovular/round depressed plaques. Histologic examination often reveals no obvious changes, but patterns of collagen distribution, using multiphoton imaging and second harmonic generation can help track hidden details of tissue organization contributing to atrophy.

http://ift.tt/2oAUgkK

Topical Drug Therapies for Chronic Rhinosinusitis

Chronic rhinosinusitis is recognized as an inflammatory syndrome involving the nose and paranasal sinuses of multifactorial etiology. Research has demonstrated a complex interplay between host factors, microbiota, environmental exposures, and epigenetics resulting in chronic mucosal inflammation. The mainstay of medical therapy addresses this inflammation. In previously operated sinuses this includes topical saline and corticosteroids, reserving antibiotics for culture-directed acute exacerbations. Topical antiinflammatory therapies allow increased local concentration of drugs while minimizing side effects. Topical therapies have advanced the surgical field by improving and maintaining postoperative outcomes. The topical therapies include saline, corticosteroids, antibiotics, and antifungals.

http://ift.tt/2nC0PyO

Evolution in Visualization for Sinus and Skull Base Surgery

Rhinoscopy became a formal field of study in the mid-nineteenth century as improvements in nasal specula were made and the potent vasoconstrictive effects of cocaine on the intranasal tissues were discovered. Since then, a multitude of advances in visualization and illumination have been made. The advent of the Storz-Hopkins endoscope in the mid-twentieth century represents a culmination of efforts spanning nearly 2 centuries, and illumination has evolved concomitantly. The future of endoscopic sinus surgery may integrate developing technologies, such as 3-dimensional endoscopy, augmented reality navigation systems, and robotic endoscope holders.

http://ift.tt/2o7wAUx

Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats

Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, while only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level; whereas, AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities.

http://ift.tt/2nVsgpc

Topical Drug Therapies for Chronic Rhinosinusitis

Chronic rhinosinusitis is recognized as an inflammatory syndrome involving the nose and paranasal sinuses of multifactorial etiology. Research has demonstrated a complex interplay between host factors, microbiota, environmental exposures, and epigenetics resulting in chronic mucosal inflammation. The mainstay of medical therapy addresses this inflammation. In previously operated sinuses this includes topical saline and corticosteroids, reserving antibiotics for culture-directed acute exacerbations. Topical antiinflammatory therapies allow increased local concentration of drugs while minimizing side effects. Topical therapies have advanced the surgical field by improving and maintaining postoperative outcomes. The topical therapies include saline, corticosteroids, antibiotics, and antifungals.

http://ift.tt/2nC0PyO

Evolution in Visualization for Sinus and Skull Base Surgery

Rhinoscopy became a formal field of study in the mid-nineteenth century as improvements in nasal specula were made and the potent vasoconstrictive effects of cocaine on the intranasal tissues were discovered. Since then, a multitude of advances in visualization and illumination have been made. The advent of the Storz-Hopkins endoscope in the mid-twentieth century represents a culmination of efforts spanning nearly 2 centuries, and illumination has evolved concomitantly. The future of endoscopic sinus surgery may integrate developing technologies, such as 3-dimensional endoscopy, augmented reality navigation systems, and robotic endoscope holders.

http://ift.tt/2o7wAUx

A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System

Publication date: Available online 4 April 2017
Source:Immunity
Author(s): Alon Oyler-Yaniv, Jennifer Oyler-Yaniv, Benjamin M. Whitlock, Zhiduo Liu, Ronald N. Germain, Morgan Huse, Grégoire Altan-Bonnet, Oleg Krichevsky
Immune cells communicate by exchanging cytokines to achieve a context-appropriate response, but the distances over which such communication happens are not known. Here, we used theoretical considerations and experimental models of immune responses in vitro and in vivo to quantify the spatial extent of cytokine communications in dense tissues. We established that competition between cytokine diffusion and consumption generated spatial niches of high cytokine concentrations with sharp boundaries. The size of these self-assembled niches scaled with the density of cytokine-consuming cells, a parameter that gets tuned during immune responses. In vivo, we measured interactions on length scales of 80–120 μm, which resulted in a high degree of cell-to-cell variance in cytokine exposure. Such heterogeneous distributions of cytokines were a source of non-genetic cell-to-cell variability that is often overlooked in single-cell studies. Our findings thus provide a basis for understanding variability in the patterning of immune responses by diffusible factors.

Graphical abstract

Teaser

Cytokine-mediated communication allows immune cells to achieve a context-appropriate response, but the distance over which this communication happens is unclear. Oyler-Yaniv et al. (2017) show that a simple diffusion-consumption mechanism quantitatively describes the spatial spread of cytokines in vivo and results in localized niches of high cytokine concentrations that contribute to cell-to-cell variability.


http://ift.tt/2oAWxMB

Iodide Handling Disorders (NIS, TPO, TG, IYD)

Publication date: Available online 4 April 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Héctor M. Targovnik, Cintia E. Citterio, Carina M. Rivolta
Iodide Handling Disorders lead to defects of the biosynthesis of thyroid hormones (thyroid dyshormonogenesis, TD) and thereafter congenital hypothyroidism (CH), the most common endocrine disease characterized by low levels of circulating thyroid hormones. The prevalence of CH is 1 in 2000 – 3000 live births. Prevention of CH is based on prenatal diagnosis, carrier identification, and genetic counseling. In neonates a complete diagnosis of TD should include clinical examination, biochemical thyroid tests, thyroid ultrasound, radioiodine or technetium scintigraphy and perchlorate discharge test (PDT).Biosynthesis of thyroid hormones requires the presence of iodide, thyroid peroxidase (TPO), a supply of hydrogen peroxide (DUOX system), an iodine acceptor protein, thyroglobulin (TG), and the rescue and recycling of iodide by the action of iodotyrosine deiodinase or dehalogenase 1 (IYD or DEHAL1). The iodide transport is a two-step process involving transporters located either in the basolateral or apical membranes, sodium iodide symporter (NIS) and pendrin (PDS), respectively. TD has been linked to mutations in the solute carrier family 5, member 5 transporter (SLC5A5, encoding NIS), solute carrier family 26, member 4 transporter (SLC26A4, encoding PDS), TPO, DUOX2, DUOXA2, TG and IYD genes. These mutations produce a heterogeneous spectrum of CH, with an autosomal recessive inheritance. Thereafter, the patients are usually homozygous or compound heterozygous for the gene mutations and the parents, carriers of one mutation. In the last two decades, considerable progress has been made in identifying the genetic and molecular causes of TD. Recent advances in DNA sequencing technology allow the massive screening and facilitate the studies of phenotype variability. In this article we included the most recent data related to disorders caused by mutations in NIS, TPO, TG and IYD.



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Features of sinonasal hemangioma: A retrospective study of 31 cases

Although hemangiomas are common lesions of the head and neck, sinonasal hemangiomas are rare. The purpose of this study was to analyze the clinical features (sex, age, symptoms, and size and anatomical location of the lesion) and the histological findings of sinonasal hemangioma cases, to assess preoperative transarterial embolization, and to evaluate the outcome (recurrence or no recurrence) of endoscopic sinus surgery.

http://ift.tt/2oAEoP3

A case of extensive pharyngeal vascular malformation successfully treated with Kampo medicine

To present the efficacy of Japanese-traditional medicine (Kampo) for a case with vascular malformation.

http://ift.tt/2nHCAjO

Features of sinonasal hemangioma: A retrospective study of 31 cases

Although hemangiomas are common lesions of the head and neck, sinonasal hemangiomas are rare. The purpose of this study was to analyze the clinical features (sex, age, symptoms, and size and anatomical location of the lesion) and the histological findings of sinonasal hemangioma cases, to assess preoperative transarterial embolization, and to evaluate the outcome (recurrence or no recurrence) of endoscopic sinus surgery.

http://ift.tt/2oAEoP3

A case of extensive pharyngeal vascular malformation successfully treated with Kampo medicine

To present the efficacy of Japanese-traditional medicine (Kampo) for a case with vascular malformation.

http://ift.tt/2nHCAjO

Reading Comprehension Deficits in Adolescents: Addressing Underlying Language Abilities

Purpose

The purpose of this article is to discuss reading comprehension deficits in adolescents in relation to their word reading skills and lexical and syntactic development. Although reading comprehension strategies (e.g., "Find the main idea") are often recommended, it is argued that before these can be effective, students' underlying language deficits should be addressed.

Method

Data from a longitudinal study are analyzed to determine the relationship between reading comprehension, word reading, and lexical and syntactic development in adolescents.

Results

The findings indicate that poor reading comprehension in adolescents is predicted by concurrent deficits in word reading ability, lexical development, and syntactic development.

Conclusion

When poor comprehension is accompanied by deficits in word reading ability and/or lexical and syntactic development, intervention should target the underlying areas of deficiency. Studies designed to improve reading comprehension in adolescents are needed.

http://ift.tt/2oY5Pib

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration

Summary

Background

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod", which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators.

Objective

Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin.

Methods

Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed.

Results

After 10 min in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 min, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase, previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin.

Conclusions and Clinical Relevance

Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate on periostin-rich extracellular matrix in the asthmatic airway in an ADAM8-dependent manner, making ADAM8 a possible therapeutic target.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oXVi6V

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration

Summary

Background

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod", which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators.

Objective

Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin.

Methods

Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed.

Results

After 10 min in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 min, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase, previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin.

Conclusions and Clinical Relevance

Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate on periostin-rich extracellular matrix in the asthmatic airway in an ADAM8-dependent manner, making ADAM8 a possible therapeutic target.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oXVi6V

A randomized controlled phase II clinical trial comparing ONO-4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis

Abstract

Background

Prostaglandin D₂ (PGD₂) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.

Objective

This study aimed to evaluate the efficacy and safety of a novel PGD₂ receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR).

Methods

This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.

Results

Both ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study.

Conclusions

We demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).

This article is protected by copyright. All rights reserved.

http://ift.tt/2o0NZxm

RNase 7 downregulates TH2 cytokine production by activated human T-cells

Abstract

Background

The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T-cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity immunoregulatory functions have been published for several AMPs. In this study we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T-cells.

Methods

Isolated human CD3+ T-cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T-cells and in polarised TH2 cells using skin derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.

Results

Treatment of activated human CD4+ T-cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T-cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T-cells with RNase7.

Conclusion

Our data indicate that RNase 7 has immunomodulatory functions on TH2-cells and decreases the production of TH2 cytokines in the skin

This article is protected by copyright. All rights reserved.

http://ift.tt/2nCfLNl

A randomized controlled phase II clinical trial comparing ONO-4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis

Abstract

Background

Prostaglandin D₂ (PGD₂) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.

Objective

This study aimed to evaluate the efficacy and safety of a novel PGD₂ receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR).

Methods

This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.

Results

Both ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study.

Conclusions

We demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).

This article is protected by copyright. All rights reserved.

http://ift.tt/2o0NZxm

RNase 7 downregulates TH2 cytokine production by activated human T-cells

Abstract

Background

The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T-cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity immunoregulatory functions have been published for several AMPs. In this study we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T-cells.

Methods

Isolated human CD3+ T-cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T-cells and in polarised TH2 cells using skin derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.

Results

Treatment of activated human CD4+ T-cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T-cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T-cells with RNase7.

Conclusion

Our data indicate that RNase 7 has immunomodulatory functions on TH2-cells and decreases the production of TH2 cytokines in the skin

This article is protected by copyright. All rights reserved.

http://ift.tt/2nCfLNl

Attention Mediates the Flexible Allocation of Visual Working Memory Resources.

Author: Emrich, Stephen M.; Lockhart, Holly A.; Al-Aidroos, Naseem

DOI: 10.1037/xhp0000398

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2nVlqji

Conceptual Biases Explain Distortion Differences Between Hand and Objects in Localization Tasks.

Author: Saulton, Aurelie; Bulthoff, Heinrich H.; de la Rosa, Stephan

DOI: 10.1037/xhp0000396

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2ozLmnR

The Motor-Cognitive Model of Motor Imagery: Evidence From Timing Errors in Simulated Reaching and Grasping.

Author: Glover, Scott; Baran, Marek

DOI: 10.1037/xhp0000389

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2nVvCbB

The Magical Number One-on-Square-Root-Two: The Double-Target Detection Deficit in Brief Visual Displays.

Author: Corbett, Elaine A.; Smith, Philip L.

DOI: 10.1037/xhp0000386

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2ozTfto

Avoiding the Conflict: Metacognitive Awareness Drives the Selection of Low-Demand Contexts.

Author: Desender, Kobe; Buc Calderon, Cristian; Van Opstal, Filip; Van den Bussche, Eva

DOI: 10.1037/xhp0000391

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2nVA7mI

The Role of Allograph Representations in Font-Invariant Letter Identification.

Author: Rothlein, David; Rapp, Brenda

DOI: 10.1037/xhp0000384

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2ozPkg7

Domain-General Biases in Spatial Localization: Evidence Against a Distorted Body Model Hypothesis.

Author: Medina, Jared; Duckett, Caitlin

DOI: 10.1037/xhp0000397

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2nVgJGb

Co-Representation of Others' Task Constraints in Joint Action.

Author: Schmitz, Laura; Vesper, Cordula; Sebanz, Natalie; Knoblich, Gunther

DOI: 10.1037/xhp0000403

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2nVtdxH

Dual-Target Cost in Visual Search for Multiple Unfamiliar Faces.

Author: Mestry, Natalie; Menneer, Tamaryn; Cave, Kyle R.; Godwin, Hayward J.; Donnelly, Nick

DOI: 10.1037/xhp0000388

Publication Date: POST AUTHOR CORRECTIONS, 3 April 2017

http://ift.tt/2ozOwbi

Cognitive-Behavioral High Parental Involvement Treatments for Pediatric Obsessive-Compulsive Disorder: A Meta-analysis

Publication date: Available online 4 April 2017
Source:Journal of Anxiety Disorders
Author(s): Marina Iniesta-Sepúlveda, Ana I. Rosa-Alcázar, Julio Sánchez-Meca, Ángel Rosa-Alcázar, José L. Parada-Navas




http://ift.tt/2ozMw2L

Clinical laser treatment of toenail onychomycoses

Abstract

Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.

http://ift.tt/2nGqO9n

Training spatial-simultaneous working memory in individuals with Down syndrome

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Silvia Lanfranchi, Francesca Pulina, Barbara Carretti, Irene C. Mammarella
Recent studies have suggested that the spatial-simultaneous component of working memory (WM), which is involved when stimuli are presented simultaneously, is selectively impaired in individuals with Down syndrome (DS).The main objective of the present study was to examine whether WM performance can be enhanced in individuals with DS by analyzing the immediate and maintenance effects of a training program. For this purpose, 61 individuals with DS were randomly assigned to three groups: one trained on simultaneous components of visuospatial WM; one serving as an active control group, that completed activities on vocabulary; and one serving as a passive control group, that only attended the pre- and post-test and follow-up assessments. The efficacy of the training was analyzed in terms of specific (spatial-simultaneous WM tasks), near transfer (spatial-sequential and verbal WM tasks), far transfer (spatial abilities, everyday competences), and maintenance effects (with a follow-up at 1 month). The results showed an overall significant effect on the WM on the group receiving the training. The benefit was generally specific, however, with some transfer to other WM tasks, but only in the immediate (post-test) assessment.



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