High service temperature, self-mendable thermosets networked by isocyanurate rings

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Lisha Zhang, Florian Julé, Henry A. Sodano
A new mending chemistry exhibiting stability at extreme temperatures and holding mechanical properties as well as mechanical stability comparable to widely used engineering plastics is reported here. This mendable thermoset polymer is synthesized using commodity reactants through the formation of an isocyanurate-oxazolidone network which exhibit a high service temperature as shown by their Tg of 270 °C and Td of 365 °C. We demonstrate that this network polymer is repeatedly self-mendable in the presence of a macroscopic crack, yielding considerable recovery of the polymer's strength after thermal annealing. This self-mending behavior is derived from a high density of mechano-responsive isocyanurate rings which are introduced as cross-links in the network. After mechanically initiated cycloreversion, the recovery of isocyanurate rings in a solid state is thermally initiated. This research is the first demonstration of an isocyanurate ring as a repairing moiety. We developed a new class of intrinsic self-mendable polymers withstanding high temperatures, which will greatly impact the application of thermoset polymers in the field of structural laminates and electronics packaging.

Graphical abstract

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Segmented imidazolium ionenes: Solution rheology, thermomechanical properties, and electrospinning

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Christian Schreiner, Alexander T. Bridge, Matthew T. Hunley, Timothy E. Long, Matthew D. Green
Segmented imidazolium ionenes with poly (tetramethylene oxide) (PTMO) soft segments and ionic, bis-imidazolium hard segments formed nonwoven fibrous mats upon electrospinning. The segmented imidazolium ionenes exhibited high thermal stability, excellent mechanical properties, and two glass transition temperatures indicative of microphase separation. Tensile analysis revealed strain-induced crystallization for ionenes with a 2 kg/mol PTMO soft segment and increased stress at break with increasing soft segment molecular weight. Solution rheology enabled the determination of solvent quality, overlap and entanglement concentrations, and the influence of ion content on solution properties. Fiber diameters for polymeric fibers electrospun from acetonitrile suggested solution polyelectrolyte behavior that was independent of the PTMO molecular weight. This work reports the successful electrospinning of segmented imidazolium-containing ionenes and an in-depth analysis of their thermomechanical and solution properties.

Graphical abstract

http://ift.tt/2n8SUg7

Cost-effective Alternative for Negative-pressure Wound Therapy

Background: Current predominantly used equipments for negative-pressure wound therapy (NPWT) are expensive. In current healthcare climate continually emphasizing cost containment, importance in developing more cost-effective alternatives cannot be understated. Previously, therapeutically equivalent methods of providing NPWT was demonstrated using just low-cost, universally available supplies, coined Gauze-SUCtion (GSUC). Here, we examine long-term potential financial savings of utilizing GSUC over commercialized products. Methods: A retrospective cost analysis was performed at the University of Chicago Medical Center between 1999 and 2014. All NPWT was provided via either GSUC or commercialized vacuum-assisted closure (VAC, KCI) device. Sum of all material component costs were reviewed to determine theoretical average daily cost. For the VAC group, recorded institutional spend to KCI was also reviewed to determine actual daily cost. In the GSUC group, this figure was extrapolated using similar ratios. Labor costs for each method were determined using analysis from prior study. Patient demographics, etiology, wound location, and treatment length were also reviewed. Results: Total of 35,871 days of NPWT was provided during the 15-year span. Theoretical average cost of VAC was $94.01/d versus $3.61/d for GSUC, whereas actual average was $111.18/d versus $4.26/d. Average labor cost was $20.11/dressing change versus $12.32. Combined, total cost of VAC therapy was estimated at $119,224 per every 1,000 days of therapy versus $9,188 for the GSUC. Conclusions: There is clear and significant cost savings from utilization of GSUC method of NPWT. Furthermore, the added advantage of being able to provide NPWT from universally accessible materials cannot be overstated.

http://ift.tt/2mraybC

Asian Facial Rejuvenation by Extended SMAS Facelift Technique

No abstract available

http://ift.tt/2m09eLv

Pulsed CO2 Laser Ablation of Superficial Basal Cell of Limbs and Trunk: A Comparative Randomized Clinical Trial With Cryotherapy and Surgical Ablation.

BACKGROUND: Pulsed CO2 laser is a treatment of superficial basal cell carcinoma (sBCC) although robust clinical evidence has not been reported so far. OBJECTIVE: The authors investigated efficacy, safety, time to wound healing, cosmetic outcome, patient satisfaction, and cost-effectiveness ratio of pulsed CO2 laser in comparison to cryotherapy and surgery. MATERIALS AND METHODS: BCCs of the trunk and extremities were randomized to one of the treatments. After 90 days, efficacy and cosmetic outcome were assessed. Patients recorded the time to complete healing of the wound and scored their overall satisfaction. RESULTS: Two hundred forty patients were randomized. After 3 months, complete remission (CR) rate with pulsed CO2 laser was 78.8%. This was significantly lower than surgery, whereas the CR rate with cryotherapy was not significantly different. Cosmetic result was better with surgery. High satisfaction was reported by 65.0% of patients treated with CO2 ablation. Time of wound healing was significantly shorter with CO2 laser. CONCLUSION: In comparison to cryotherapy, pulsed CO2 laser showed no statistically significant difference in efficacy, cosmetic outcome, and patient satisfaction. Time to healing was shorter; the cost and cost-effectiveness ratio were similar. Surgery had the greatest efficacy rate. The main limitation of this study was the short duration of follow-up (3 months). (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nrhGpe

Mohs Micrographic Surgery as a Digit-Sparing Treatment for Aggressive Digital Papillary Adenocarcinoma.

No abstract available

http://ift.tt/2mYhdNC

Scrotal Melanoma: A Systematic Review of Presentation, Treatment, and Outcomes.

BACKGROUND: Primary male genital melanomas are rare. Of these, scrotal melanoma is the least common, and is unfortunately often detected late in the disease course. OBJECTIVE: To assess the clinical presentation, treatment modalities, and outcome of scrotal melanoma to aid clinician management. METHODS: Systematic literature review of PubMed, yielding 23 cases, of which 20 met the inclusion criteria. RESULTS: Although previously thought to have the best outcome of genitourinary melanomas, scrotal melanomas are associated with high mortality and late presentation. Scrotal melanoma presented as Stage I/II disease 18.75% of the time, Stage III 56.3% of the time, and Stage IV 25% of the time, whereas typical cutaneous melanoma presents as Stage I/II disease 84% of the time, Stage III 8% of the time, and Stage IV 4% of the time. Half of patients experienced recurrence of their disease. All patients who presented with metastases to distant organs died. LIMITATIONS: Small sample size. Few cases described a Breslow's depth making it difficult to draw conclusions on tumor thickness and survival outcome. CONCLUSION: Scrotal melanoma is rare, aggressive, and is often caught late in the disease course. The authors encourage dermatologists to educate patients and destigmatize genital lesions to increase the likelihood of earlier detection and better patient outcomes. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nrnrDd

Antimicrobial Prophylaxis for Full-Face Laser Resurfacing in Transplant Recipients.

No abstract available

http://ift.tt/2mYoNaW

Transplantation of In Vivo-Harvested Epidermal Cell Suspension for Acute Cutaneous Lupus Erythematosus-Induced Depigmentation.

No abstract available

http://ift.tt/2mYfFTF

Quality of Life With Ingrown Toenails: A Cross-Sectional Study.

No abstract available

http://ift.tt/2nr9Mwc

Reconstruction of a Combined Nose and Cheek Defect.

No abstract available

http://ift.tt/2nqVOKB

Submental Alopecia at Deoxycholic Acid Injection Site.

No abstract available

http://ift.tt/2mr4zU4

Down syndrome: Age-dependence of PiB binding in postmortem frontal cortex across the lifespan

Publication date: Available online 14 March 2017
Source:Neurobiology of Aging
Author(s): Harry LeVine, H. Peter Spielmann, Sergey Matveev, Francesca Macchiavello Cauvi, M. Paul Murphy, Tina L. Beckett, Katie McCarty, Ira T. Lott, Eric Doran, Frederick Schmitt, Elizabeth Head
Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh Compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro ³H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (N=25) and DS (N=39). In DS, ³H-PiB binding was significantly associated with age. After age 40 years in DS, ³H-PiB binding rose dramatically along with increasing individual variability. ³H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy (CAA) showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and CAA in DS brain.



http://ift.tt/2nm8ntS

Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans

Publication date: Available online 14 March 2017
Source:Neurobiology of Aging
Author(s): Matthias Thienel, Ines Wilhelm, Christian Benedict, Jan Born, Manfred Hallschmid
Aging is associated with increases in hypothalamic-pituitary-adrenal (HPA) axis activity that can predispose to metabolic and cognitive impairments. We investigated in elderly and young subjects whether intranasal insulin administration to the human brain reduces early-sleep nadir concentrations of adrenocorticotropin (ACTH) and cortisol, i.e., indicators of baseline HPA axis activity. In within-subject comparisons, intranasal insulin (160 IU) or placebo was administered to 14 elderly (mean age 70.0 years) and 30 young (23.6 years) healthy subjects before bedtime. Sleep was polysomnographically assessed and blood samples were repeatedly collected. Elderly compared to young participants displayed increased early-sleep cortisol concentrations (P < 0.04) and reductions in slow wave and REM sleep (P < 0.001). Insulin administration reduced cortisol levels between 2300 h and 0020 h in the elderly (P = 0.03) but not young participants (P = 0.56; P = 0.003 for interaction). Findings indicate that central nervous insulin acts as an inhibitory signal in basal HPA axis activity regulation and suggest that intranasal insulin may normalize sleep-associated stress axis activity in older age.



http://ift.tt/2mqFRCE

Subcutaneous Histiocytoid Sweet Syndrome in a Patient With Relapsed Acute Myeloblastic Leukemia.

No abstract available

http://ift.tt/2mMfFWp

A Rapidly Growing Facial Mass: Answer.

No abstract available

http://ift.tt/2mr73ln

A Rapidly Growing Facial Mass: Challenge.

No abstract available

http://ift.tt/2mM2CEq

Depletion of Epidermal Langerhans Cells in the Skin Lesions of Pellagra Patients.

Pellagra is a nutrient deficiency disease caused by insufficient niacin levels. Recent studies have shown that numbers of epidermal Langerhans cells decreased in other diseases caused by nutritional deficiencies, including necrolytic migratory erythema and acrodermatitis enteropathica. Epidermal Langerhans cells are capable of modulating or even halting the inflammatory reaction. The aim of this study was to examine changes in the number of Langerhans cells and other dendritic cells, and maturation of epidermal Langerhans cells in the lesional and adjacent non-lesional skin in pellagra patients. Seven pellagra patients and 10 healthy individuals who served as controls were included. The number and distribution of dendritic cells and other cutaneous cells were examined by immunohistochemistry. Epidermal Langerhans cells decreased considerably in the skin lesions of pellagra patients, whereas other dendritic cells did not change. The decrease in the number of Langerhans cells was positively correlated with the histological severity of skin lesions. As the number of Langerhans cells was not reduced in the undisturbed neighboring skin, the depletion of epidermal Langerhans cells did not precede skin damage but was a cause of prolonged severe inflammation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2mrcKQb

Bilateral and Symmetrical Linear Plaques on the Hands.

No abstract available

http://ift.tt/2mM5xwE

On Allusive Names for the Syphilitic Patient From the 16th to the 19th Century: The Role of Dermatopathology.

No abstract available

http://ift.tt/2mqSj5Y

Study of Selected BRCA1, BRCA2, and PIK3CA Mutations in Benign and Malignant Lesions of Anogenital Mammary-Like Glands.

Anogenital mammary-like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selected BRCA1, BRCA2, and PIK3CA mutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. No BRCA mutation was detected, whereas 3 neoplasms yielded PIK3CA mutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the whole BRCA1 and BRCA2 genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2mMjzi5

Nonhealing Ulcerations of the Breast.

No abstract available

http://ift.tt/2mr3Y4F

Nonhealing Ulcerations of the Breast: Challenge.

No abstract available

http://ift.tt/2mMjAm9

Melanoma Manifesting as Tumoral Melanosis; Now You See It, Now You Don't.

No abstract available

http://ift.tt/2mqGBZi

Comparative study of autologous fat vs hyaluronic acid in correction of the nasolabial folds

Summary

Objective

In the article, comparison of the hyaluronic acid (HA) and autologous fat is conducted to evaluate the effectiveness and safety in correction of the nasolabial folds (NLFs).

Methods

From November 2012 to December 2015, a single-blinded, randomized study was conducted. Sixty-two patients were included in the study, and 57 of them completed the whole procedure. The patients were randomly allocated to receive the treatments of HA or fat in both NLFs. The Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale (GAIS) were used for assessment. Efficacy was assessed using two parameters: evaluation of final improvement by blinded evaluator and patient-self using photographs. The effectiveness endpoint was improvement of scores at 1, 3, 6, 9, and 12 months from baseline. The adverse events (AEs) were recorded.

Results

In the blinded evaluator scores for NLF in accordance with WSRS, there were no significant differences between the two methods within 9 months. A statistically significant difference between the lipoinjection and HA groups was found at 12-month follow-up period. Subjects' self-assessment was similar to the results seen for the evaluator scores. The difference of AEs between the HA and fat group was obvious in the early stage of recovery. In the later stage, the AEs of the HA and fat group were similar.

Conclusions

Both HA gel and autologous fat provide augmentation of NLFs. The magnitude and duration of NLF correction appear to be similarly effective and safe within a period.

http://ift.tt/2mqwaE7

GreenLight laser photoselective vaporization of the prostate for treatment of benign prostate hyperplasia/lower urinary tract symptoms in patients with different post-void residual urine

Abstract

The purpose of this study is to assess the safety and efficacy of GreenLight laser photoselective vaporization of the prostate (PVP) for the treatment of benign prostate hyperplasia/lower urinary tract symptoms (BPH/LUTS) in patients with different post-void residual urine (PVR). BPH/LUTS patients treated with PVP from January 2014 to January 2016 were enrolled in the present study. All patients were divided into PVR > 50, 50 ≤ PVR < 400, and PVR ≥ 400 ml groups, and standard general and urological methods for BPH/LUTS were carried out. PVP surgery was performed, and the follow-up outcome was investigated 6 months after surgery. A total of 429 patients were included, and there were no significant differences in comorbid diseases or habits among the three groups. The maximum urinary flow rate (Qmax) differed significantly among the groups (P < 0.001), while patients in the PVR < 50 ml group had higher maximum detrusor pressure (Pdet.max) level than the other two groups (P < 0.001). Patients in 50 ≤ PVR < 400 (P < 0.001) and PVR ≥ 400 (P < 0.001) ml groups were more likely to develop detrusor underactivity than those in the PVR < 50 ml group. All patients were treated with PVP, and there were no severe complications requiring rehospitalization or reoperation except nine designed re-treatments. Follow-up data of 387 patients were available. Significant improvement in outcome parameters (International Prostate Symptom Score [IPSS], Qmax, and PVR) was observed in comparison with baseline measurements for the three groups. PVP significantly improved the IPSS, Qmax, and PVR in patients with different PVR; PVP is a safe and effective procedure for BPH/LUTS patients.

http://ift.tt/2n63k0e

Effect of high laser output on the central bronchi and pulmonary artery

Abstract

A diode-pump Nd:YAG high-power laser (wavelength 1320 nm, power 100 W) is routinely used to surgically remove lung metastases. Even pulmonary lesions in central locations are resectable via this method, yet it also carries a potential risk of damaging the larger bronchi and vessels in the vicinity. Studies investigating the safety of using high-power lasers are lacking. We therefore aimed to examine the direct effects of a 100-watt laser on the bronchi and pulmonary artery at a standard working velocity. From freshly slaughtered pigs, we isolated cylindrical specimens of the trachea, the main and lobar bronchi, and the central pulmonary artery from the both lungs. These specimens were fixed consecutively in rows behind each other on a Styrofoam surface in the laboratory. The laser's handle was clamped into a hydraulic feed unit so that the laser was focused at constant distance perpendicular to the tissue and would move at 10 mm/s over the specimens. The Nd:YAG Laser LIMAX® 120 functioned at a consistent power of 100 W during all the experiments. The lasered specimens were examined macroscopically and histologically for tissue damage. None of the trachea or bronchial walls were perforated. Compared to the pulmonary parenchyma, we observed no vaporization effects—only minor superficial coagulation (with a mean depth of 2.1 ± 0.8 mm). This finding was histologically confirmed in each specimen, which revealed mild superficial coagulation and no damage to the cartilage. In the presence of a residual peribronchial fatty tissue, the laser effect was even attenuated. The pulmonary arteries presented no lumen openings whatsoever, merely a discrete trace of coagulation. The vessel wall revealed increased vacuolization without alteration of the remaining vessel wall. In conclusion, laser resection at 100 W of the central lung areas is safe with respect to airways and blood vessels and the laser output does not need to be reduced when treating these areas.

http://ift.tt/2moawAf

The association between Nd:YAG laser and desensitizing dentifrices for the treatment of dentin hypersensitivity

Abstract

This study aims to evaluate the association between Nd:YAG laser (with and without a photoabsorber) and two desensitizing dentifrices containing 15% NovaMin or 8% arginine, as potential treatments for dentin hypersensitivity (DH). DH was simulated by EDTA application for 2 min. Specimens were then analyzed with an environmental scanning electron microscope (ESEM) to ensure open dentin tubules (ODT), counted by using ImageJ software. Specimens were randomized into eight groups (n = 10): Laser (L), Laser+Photoabsorber (LP), Arginine (A), Arginine+Laser (AL), Arginine+Laser+Photoabsorber (ALP), NovaMin (N), NovaMin+Laser (NL), and NovaMin+Laser+Photoabsorber (NLP). Laser irradiation was performed with 1 W, 100 mJ, 10 Hz, ≅85 J/cm²; 4 irradiations of 10 s each, with 10 s intervals between them. After treatment, specimens were again analyzed by ESEM and submitted to erosive/abrasive cycling for 5 days. A final ESEM analysis was performed. Data were analyzed with two-way repeated measure ANOVA and Tukey tests (α = 0.05). After treatment, groups N, NL, and NLP presented the lower number of ODT, but they did not different from LP, ALP, and AL. Group A presented the highest number of ODT and it did not differ from group L. Groups L, AL, ALP, and LP presented intermediate results, without differing from each other. After cycling, group A presented the highest number of ODT and did not differ significantly from the other groups, except NLP. None of the associations tested presented better tubule occlusion than NovaMin by itself. Arginine was the only treatment that presented improved tubule occlusion when associated with Nd:YAG laser.

http://ift.tt/2n5V93U

Familiarity Speeds Up Visual Short-Term Memory Consolidation.

Author: Xie, Weizhen; Zhang, Weiwei

DOI: 10.1037/xhp0000355

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2lYIJuX

Abstract Feature Codes: The Building Blocks of the Implicit Learning System.

Author: Eberhardt, Katharina; Esser, Sarah; Haider, Hilde

DOI: 10.1037/xhp0000380

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mHgTjY

Cerebral Hemodynamics During Scene Viewing: Hemispheric Lateralization Predicts Temporal Gaze Behavior Associated With Distinct Modes of Visual Processing.

Author: Mills, Mark; Alwatban, Mohammed; Hage, Benjamin; Barney, Erin; Truemper, Edward J.; Bashford, Gregory R.; Dodd, Michael D.

DOI: 10.1037/xhp0000357

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2lYr5Hz

Beyond Scene Gist: Objects Guide Search More Than Scene Background.

Author: Koehler, Kathryn; Eckstein, Miguel P.

DOI: 10.1037/xhp0000363

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mHgsWN

Pushing Typists Back on the Learning Curve: Memory Chunking Improves Retrieval of Prior Typing Episodes.

Author: Yamaguchi, Motonori; Randle, James M.; Wilson, Thomas L.; Logan, Gordon D.

DOI: 10.1037/xlm0000385

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mLvJaE

Eye Movements in Implicit Artificial Grammar Learning.

Author: Silva, Susana; Inacio, Filomena; Folia, Vasiliki; Petersson, Karl Magnus

DOI: 10.1037/xlm0000350

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mqCLz6

Comparing Theories of Reference-Dependent Choice.

Author: Bhatia, Sudeep

DOI: 10.1037/xlm0000384

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mLC7ig

Predictors of Verb-Mediated Anticipatory Eye Movements in the Visual World.

Author: Hintz, Florian; Meyer, Antje S.; Huettig, Falk

DOI: 10.1037/xlm0000388

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mqnoqC

Distinguishing Discrete and Gradient Category Structure in Language: Insights From Verb-Particle Constructions.

Author: Brehm, Laurel; Goldrick, Matthew

DOI: 10.1037/xlm0000390

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mLATDX

How Performance-Contingent Reward Prospect Modulates Cognitive Control: Increased Cue Maintenance at the Cost of Decreased Flexibility.

Author: Hefer, Carmen; Dreisbach, Gesine

DOI: 10.1037/xlm0000397

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mqw2VV

Disentangling the Effects of Advisor Consensus and Advice Proximity.

Author: Wanzel, Stella K.; Schultze, Thomas; Schulz-Hardt, Stefan

DOI: 10.1037/xlm0000396

Publication Date: POST AUTHOR CORRECTIONS, 13 March 2017

http://ift.tt/2mLCJo7

Tumor cells interact with red blood cells via galectin-4 - a short report

Abstract

Background

The ability of tumor cells to invade and metastasize is relevant to the process of cancer progression and, as such, it represents an obstacle to cancer cure. So far, limited information is available on interactions between circulating tumor cells and blood cells. It is well-documented that galectin-4 is upregulated in many types of tumor cells and is involved in metastasis. Here, we address the hypothesis that tumor cells may interact with red blood cells (RBCs) via galectin-4.

Methods

High galectin-4 expressing colon, normal pancreatic and pancreatic cancer-derived cell lines (n = 5) were incubated with peripheral blood cells from different donors. Their interactions and associated proteins were examined by immunostaining and live cell imaging.

Results

We found that (endogenous or exogenous) galectin-4 expressing tumor cells interact directly with RBCs. We also observed an accumulation of galectin-4 and human blood group antigens at the contact sites between these cells. By comparing the number of RBCs attaching to each tumor cell, we found that cells with high pre-incubation expression levels of galectin-4 attached significantly more RBCs than those with low expression levels (p < 1 × 10⁻⁷). Conversely, we found that RBC attachment induces galectin-4 expression in tumor cells.

Conclusions

From our data we conclude that tumor cells directly interact with red blood cells via galectin-4.

http://ift.tt/2mpRUjs

Increasing Calcium Level Limits Schwann Cell Numbers In Vitro following Peripheral Nerve Injury

J reconstr Microsurg
DOI: 10.1055/s-0037-1599836

Background After peripheral nerve injury, there is an increase in calcium concentration in the injured nerves. Our previous publications have shown that increase in calcium concentration correlated well with degree of nerve injury and that local infusion of calcitonin has a beneficial effect on nerve recovery. Schwann cells play a pivotal role in regeneration and recovery. We aim to examine cultured Schwann cell survivals in various concentrations of calcium-containing growth media and the effect of calcitonin in such media. Methods To establish baseline in postinjury state, crush injury was induced in male Sprague-Dawley rats' sciatic nerves. Extra- and intraneural calcium concentrations were measured. To study Schwann cell survival, uninjured sciatic nerve segment was harvested and cultured in media containing various amounts of calcium. To study the effect of calcitonin, nerve harvest and culture were done in four additional media: (1) normal control, (2) normal control with calcitonin, (3) high calcium medium, and (4) high calcium medium with calcitonin. Schwann cells were studied and analyzed under fluorescent conditions. Results With increasing calcium concentration, there was a significant decrease in the number of Schwann cells. For the experimental groups, in which calcitonin had been added to the growth medium, there were similar amounts of Schwann cells present in both high and low calcium-containing medium. Conclusion Schwann cells are sensitive to increasing calcium concentration. Calcitonin counteracts the detrimental effects of high calcium on Schwann cell survival. This can have significant future clinical implications for patients with peripheral nerve injuries.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2n882KV

The effect of caudal extension graft on nostril in rhinoplasty

Abstract

Background

Caudal extension graft technique is a versatile technique in rhinoplasty providing good tip support and maintaining tip projection. In this study, we evaluated the clinical outcomes of this technique and performed anthropometric analysis of nostril shape from the basal view.

Methods

Thirty-two patients undergoing caudal extension graft technique were identified from December 2011 to July 2016. Patients with a minimum of 12 month follow-up were included. Quantitative analysis was performed on standard pre- and postoperative photos.

Results

Nasal tip protrusion and columellar width were increased significantly (p value < 0.001), while apex angle was decreased significantly (p value <0.001). Caudal extension graft placement resulted in a non-significant decrease in nostril size on the side of graft placement. There was no significant change in columellar length or nostril width.

Conclusions

Caudal extension graft technique is a versatile and reliable technique for addressing poor tip support and setting tip projection. Disadvantages of caudal extension graft include asymmetric nostrils and over projection in cases where projection reduction is needed. We showed that while there is a significant increase in columellar width, there is no significant increase in nostril asymmetry.

Level of Evidence: Level IV, risk/prognostic study.

http://ift.tt/2mH3Lex

A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma

Abstract

Purpose

To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC).

Methods

Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m², day 1), nab-paclitaxel (mg/m², day 1), and S-1 (mg/day, days 1–7) were 800/100/60–100 at level 1, and 1000/125/60–100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630).

Results

We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients.

Conclusion

In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m², gemcitabine: 1000 mg/m² on day 1, S-1: <1.25 m², 60 mg; 1.25–1.5 m², 80 mg; >1.5 m², 100 mg twice a day on days 1–7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.

http://ift.tt/2nlg0AJ

Static Solid-state 2H NMR Methods in Studies of Protein Side-chain Dynamics

Publication date: Available online 14 March 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Liliya Vugmeyster, Dmitry Ostrovsky
In this review, we discuss the experimental static deuteron NMR techniques and computational approaches most useful for the investigation of side-chain dynamics in protein systems. Focus is placed on the interpretation of line shape and relaxation data within the framework of motional modeling. We consider both jump and diffusion models and apply them to uncover glassy behaviors, conformational exchange and dynamical transitions in proteins. Applications are chosen from globular and membrane proteins, amyloid fibrils, peptide adsorbed on surfaces and proteins specific to connective tissues.

Graphical abstract

http://ift.tt/2mKjRWs

Association of psoriasis and psoriatic arthritis with osteoporosis and pathological fractures

Publication date: Available online 14 March 2017
Source:Journal of the American Academy of Dermatology
Author(s): Parul Kathuria, Kenneth B. Gordon, Jonathan I. Silverberg
BackgroundPrevious studies examining the relationship between psoriasis (Pso), osteoporosis, and pathological fractures found conflicting results.ObjectiveTo determine whether Pso and psoriatic arthritis (PsA) are associated with osteoporosis and fractures in US adults.MethodsCross-sectional study of 198,102,435 children and adults, including 183,725 with Pso and 28,765 with PsA from the 2006-2012 National Emergency Department Sample, including 20% of the emergency care visits throughout the United States.ResultsIn a pooled analysis across all 7 years, patients with Pso had significantly higher odds (multivariate logistic regression; odds ratio, 95% confidence intervals) of diagnosis with osteopenia (2.86, 2.70-3.02), osteoporosis (2.97, 2.89-3.06), osteomalacia (4.40, 2.50-7.74), ankylosing spondylitis (13.34, 12.02-14.81), and pathological fractures (2.35, 2.19-2.53). Similar associations were observed for PsA. Pso was also associated with vertebral (1.17, 1.09-1.25), pelvic (1.18, 1.06-1.31), femoral (1.68, 1.60-1.78), and tibial/fibular fractures (1.28, 1.16-1.41). Whereas, PsA was associated with stress (2.87, 1.08-7.64) and vertebral (1.45, 1.24-1.70), pelvic (1.75, 1.41-2.18), femoral (2.07, 1.85-2.32), and tibial/fibular (1.60, 1.28-2.01) fractures.LimitationsData on severity and treatments of Pso were not available.ConclusionPso and PsA were associated with osteopenia, osteoporosis, ankylosing spondylitis, and pathologic fractures.



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Reporting of harm and safety results in randomized controlled trials published in 5 dermatology journals

Publication date: Available online 14 March 2017
Source:Journal of the American Academy of Dermatology
Author(s): Cynthia Haddad, Odette Berline Sigha, Bénédicte Lebrun-Vignes, Olivier Chosidow, Laurence Fardet
BackgroundRandomized controlled trials (RCTs) are considered the gold standard for assessing efficacy and short-term harm of medicines. However, several studies have come to the conclusion that harm is less well reported than efficacy outcomes.ObjectiveTo describe harm reporting in publications on dermatological RCTs and assess parameters that could influence the quality of harm reporting.MethodsMethodologic systematic review of dermatologic RCTs published from 2010 to 2014 in 5 dermatological journals.ResultsAmong 110 assessed publications on RCTs, 80 (73%) adequately reported harm and 52% adequately reported its severity. Overall, 40% of the assessed manuscripts perfectly reported and discussed harm. The adequate reporting of harm was significantly associated with the type of trial (odds ratio [OR] 4.41, 95% confidence interval [CI] 1.60-12.35 for multicenter compared with monocentric trials) and having a predefined method for collecting harm data (OR 5.93, 95% CI 2.26-15.56). Reporting of harm severity was better in pharmacologic trials (OR 6.48, 95% CI 2.00-21.0) compared with nonpharmacologic trials and in trials for which a method for collecting harm (OR 5.65, 95% CI 2.00-16.4) and its severity (OR 3.60, 95% CI 1.00-12.8) was defined before the study onset.LimitationsAssessment was restricted to RCTs and 5 dermatological journals.ConclusionHarm is quite well reported in dermatologic journals. Efforts should be made on reporting severity of harm.



http://ift.tt/2mGzaOk

Hereditary leiomyomatosis and renal cell cancer syndrome: An update and review

Publication date: Available online 14 March 2017
Source:Journal of the American Academy of Dermatology
Author(s): Viral M. Patel, Marc Z. Handler, Robert A. Schwartz, W. Clark Lambert
Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a rare genetic disorder that predisposes individuals to multiple cutaneous leiomyomas, renal cell carcinomas, and in women, uterine leiomyomas. Also known as Reed syndrome, it is caused by a germline heterozygous mutation of the fumarate hydratase tumor suppressor gene. HLRCC is associated with significant morbidity because of pain from cutaneous and uterine leiomyomas, the cutaneous pain often of unique character. Although genetic testing is currently considered the criterion standard to diagnose HLRCC, newer immunohistochemistry markers may provide rapid and cost effective alternatives to genetic testing. Because of the potentially aggressive nature of renal cell carcinomas that develop as early as in childhood, close annual cancer surveillance is desirable in individuals with HLRCC. In this review, we offer an update and an approach to the diagnosis, management, and renal cancer surveillance in HLRCC.



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The adverse prognostic effect of tumor budding on the evolution of cutaneous head and neck squamous cell carcinoma

Publication date: Available online 14 March 2017
Source:Journal of the American Academy of Dermatology
Author(s): Miriam Gonzalez-Guerrero, Pablo Martínez-Camblor, Blanca Vivanco, Ivan Fernández-Vega, Pablo Munguía-Calzada, Maria Paz Gonzalez-Gutierrez, Juan Pablo Rodrigo, Cristina Galache, Jorge Santos-Juanes
BackgroundTumor budding is a readily detectable histopathologic feature that has been recognized as an adverse prognostic factor in several human cancers.ObjectiveWe sought to assess the correlation of tumor budding with the clinicopathologic features and the prognostic value of tumor budding in cutaneous squamous cell carcinoma (cSCC).MethodsForty-nine primary nonmetastatic and 49 primary metastatic cSCCs to regional lymph nodes were retrospectively studied. Statistical analyses were carried out to assess the relationship between tumor budding, clinicopathologic parameters, and patient survival.ResultsTumor budding was observed in 45 cases of 98 (46%). High-intensity budding (≥5 tumor buds) was observed in 20 tumors. Presence of tumor buds was a significant risk factor for nodal metastasis with crude and adjusted hazard ratios (HRs) of 8.92 (95% CI, 4.39-18.1) and 6.93 (95% CI, 3.30-14.5), respectively, and for reduced overall survival time (crude and adjusted HRs of 2.03 [95% CI, 1.26-3.28] and 1.72 [95% CI, 1.05-2.83], respectively).LimitationsThis was a retrospective study limited to cSCCs of the head and neck. Examined tumors were >2 mm thick, and all were from a primary excision.ConclusionThese results indicate an increased frequency of nodal metastasis and risk of death in patients with tumor buds.



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Seasonal alterations in the daily rhythms in hypothalamic expression of genes involved in the photoperiodic transduction and neurosteroid-dependent processes in migratory blackheaded buntings

Abstract

This study investigated seasonal alterations in the daily rhythms of hypothalamic expression of genes involved in the photoperiodic regulation of annual cycles in birds. We measured 4-hourly mRNA expression of genes involved in the photoperiodic transduction (OPN5, EYA3, CGA, TSHβ, DIO2, DIO3) and neurosteroid-dependent processes (AR, CYP19, ERα, ERβ) in the hypothalamus of migratory blackheaded buntings photoinduced with photosensitive, photostimulated (early and late stimulated) and photorefractory seasonal states. There were significant differences in daily mRNA profiles between the photoperiodic states. Particularly, increased CGA, TSHβ and DIO2, and decreased DIO3 mRNA levels in the early photostimulated state, as compared to photosensitive state, suggests that there is a role of thyroid hormones in photostimulation in buntings. Similar differences in the expression of genes coding for the aromatase enzyme (CYP19) and receptors for estrogen (ERα, ERβ), but not androgen (AR), indicates that there is seasonal alteration in the neuroestrogen-mediated functions. Further, peak expression times of CGA, TSHβ and DIO2 genes at hour 14-15 of the day in early stimulated state evidenced molecular regulation of the daily rhythm of photoinducibility in buntings. Most significantly, however, we found an attenuated daily rhythm in thyroid hormone modulatory genes and switch of peak expression time from day to night in CYP19 mRNA rhythm in the subsequent late photostimulated state, although testicular maturation still persisted. Perhaps, these alterations in daily rhythms signalled the initiation of processes underlying other seasonal phenologies in parallel with gonadal response, such as the manifestation of the nighttime flight in buntings. These results show alterations in daily rhythms underlying the transcriptional regulation of the photoperiod-induced seasonal states in migratory blackheaded buntings.

This article is protected by copyright. All rights reserved.

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Green Light Inhibits GnRH-I Expression by Stimulating the Melatonin-GnIH Pathway in the Chick Brain

Abstract

To study the mechanism by which monochromatic light affects gonadotropin-releasing hormone (GnRH) expression in chicken hypothalamus, a total of 192 newly hatched chicks were divided into intact, sham-operated and pinealectomy groups and exposed to white (WL), red (RL), green (GL) and blue (BL) lights using a light-emitting diode (LED) system for 2 wk. In the GL intact group, the mRNA and protein levels of GnRH-I in the hypothalamus, the mean cell area and mean cell optical density (OD) of the GnRH-I-ir cells of the nucleus commissurae pallii (nCPa) were decreased by 13.2-34.5%, 5.7-39.1% and 9.9-17.3% compared to those in the chicks exposed to the WL, RL and BL, respectively. GL decreased these factors related to GnRH-I expression and the effect of GL was not observed in pinealectomized (PINX) birds. However, the mRNA and protein levels of hypothalamic gonadotropin-inhibitory hormone (GnIH) and GnIH receptor (GnIHR), the mean cell area and mean cell OD of the GnIH-ir cells of the paraventricularis magnocellularis (PVN), and the plasma melatonin concentration in the chicks exposed to GL were increased by 18.6-49.2%, 21.1-60.0%, and 8.6-30.6% compared to the WL, RL and BL intact groups, respectively. The plasma melatonin concentration showed a negative correlation with GnRH-I protein and a positive correlation with GnIH and GnIHR proteins. Both protein expressions of GnRH-I and GnIHR showed a negative correlation in the hypothalamus. After pinealectomy, GnRH-I expression increased, whereas plasma melatonin concentration, GnIH and GnIHR expressions decreased, and there were no significant differences among the WL, RL, GL and BL groups. Double-labeled immunofluorescence showed that GnIH axon terminals were near GnRH-I neurons, some GnRH-I neurons coexpressed with GnIHR, and GnIH neurons coexpressed with melatonin receptor subtype QR2. These results demonstrated that green light inhibits GnRH-I expression by increasing melatonin secretion and stimulating melatonin receptor-GnIH-GnIH receptor pathway in the chick brain.

This article is protected by copyright. All rights reserved.

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Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps

Abstract

Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action. We found that GH treatment of human melanoma cells upregulates expression of multiple ABC transporters and increases the EC50 of melanoma drug vemurafenib. Also, vemurafenib-resistant melanoma cells had upregulated levels of GH receptor (GHR) expression as well as ABC efflux pumps. GHR knockdown (KD) using siRNA in human melanoma cells treated with sub-EC50 doses of anti-tumor compounds resulted in significantly increased drug retention, decreased cell proliferation and increased drug efficacy, compared to mock-transfected controls. Our set of findings identify an unknown mechanism of GH regulation in mediating melanoma drug resistance and validates GHR as a unique therapeutic target for sensitizing highly therapy-resistant human melanoma cells to lower doses of anti-cancer drugs.

http://ift.tt/2npxEQF

Effect of cilostazol in treating diabetes-associated microvascular complications

Abstract

Purpose

Cilostazol (Pletal), a phosphodiesterase-3 inhibitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phosphodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular complications. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating microvascular complications associated with diabetes mellitus.

Methods

A review of literature was conducted using PubMed and Embase databases focusing on cilostazol use in diabetes mellitus.

Results

Cilostazol demonstrated renoprotective effects in patients with diabetic nephropathy by reducing serum soluble adhesion molecule-1 and monocyte chemoattractant protein-1. Cilostazol's anti-inflammatory actions predictably attenuate glomerular damage from increased leukocyte adherence. Additionally, cilostazol delayed renal dysfunction secondary to type 2 diabetes mellitus as albuminuria was reduced most likely resulting from inhibition of nuclear factor kappa-induced inflammatory and endothelial markers. Cilostazol's anti-inflammatory actions in addition to its vasodilatory actions relieved retinal hypoxia and decreased excessive production of retinal blood vessels suggesting benefit in diabetic retinopathy. Cilostazol did not improve neuropathy symptom scores signifying that it may not be as beneficial in patients with diabetic peripheral neuropathy without diabetic nephropathy or diabetic retinopathy.

Conclusions

Cilostazol's pleiotropic effects may be beneficial in patients with type 2 diabetes mellitus and diabetic nephropathy. Additional, larger studies need to be conducted to assess the benefits and risks of using cilostazol as an alternative agent in treating patients with diabetic microvascular complications.

http://ift.tt/2mJonVd

Imaging of diabetic bone

Abstract

Diabetes is an important concern in terms of medical and socioeconomic costs; a high risk for low-trauma fractures has been reported in patients with both type 1 and type 2 diabetes. The mechanism involved in the increased fracture risk from diabetes is highly complex and still not entirely understood; obesity could play an important role: recent evidence suggests that the influence of fat on bone is mainly dependent on the pattern of regional fat deposition and that an increased amount of visceral adipose tissue negatively affects skeletal health.

Correct and timely individuation of people with high fracture risk is critical for both prevention and treatment: Dual-energy X-ray Absorptiometry (currently the "gold standard" for diagnosis of osteoporosis) underestimates fracture risk in diabetic patients and therefore is not sufficient by itself to investigate bone status. This paper is focused on imaging, covering different modalities involved in the evaluation of skeletal deterioration in diabetes, discussing the limitations of conventional methods and exploring the potential of new tools and recent high-resolution techniques, with the intent to provide interesting insight into pathophysiology and fracture risk.

http://ift.tt/2mG5IrE

Effect of cilostazol in treating diabetes-associated microvascular complications

Abstract

Purpose

Cilostazol (Pletal), a phosphodiesterase-3 inhibitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phosphodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular complications. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating microvascular complications associated with diabetes mellitus.

Methods

A review of literature was conducted using PubMed and Embase databases focusing on cilostazol use in diabetes mellitus.

Results

Cilostazol demonstrated renoprotective effects in patients with diabetic nephropathy by reducing serum soluble adhesion molecule-1 and monocyte chemoattractant protein-1. Cilostazol's anti-inflammatory actions predictably attenuate glomerular damage from increased leukocyte adherence. Additionally, cilostazol delayed renal dysfunction secondary to type 2 diabetes mellitus as albuminuria was reduced most likely resulting from inhibition of nuclear factor kappa-induced inflammatory and endothelial markers. Cilostazol's anti-inflammatory actions in addition to its vasodilatory actions relieved retinal hypoxia and decreased excessive production of retinal blood vessels suggesting benefit in diabetic retinopathy. Cilostazol did not improve neuropathy symptom scores signifying that it may not be as beneficial in patients with diabetic peripheral neuropathy without diabetic nephropathy or diabetic retinopathy.

Conclusions

Cilostazol's pleiotropic effects may be beneficial in patients with type 2 diabetes mellitus and diabetic nephropathy. Additional, larger studies need to be conducted to assess the benefits and risks of using cilostazol as an alternative agent in treating patients with diabetic microvascular complications.

http://ift.tt/2mJonVd

Imaging of diabetic bone

Abstract

Diabetes is an important concern in terms of medical and socioeconomic costs; a high risk for low-trauma fractures has been reported in patients with both type 1 and type 2 diabetes. The mechanism involved in the increased fracture risk from diabetes is highly complex and still not entirely understood; obesity could play an important role: recent evidence suggests that the influence of fat on bone is mainly dependent on the pattern of regional fat deposition and that an increased amount of visceral adipose tissue negatively affects skeletal health.

Correct and timely individuation of people with high fracture risk is critical for both prevention and treatment: Dual-energy X-ray Absorptiometry (currently the "gold standard" for diagnosis of osteoporosis) underestimates fracture risk in diabetic patients and therefore is not sufficient by itself to investigate bone status. This paper is focused on imaging, covering different modalities involved in the evaluation of skeletal deterioration in diabetes, discussing the limitations of conventional methods and exploring the potential of new tools and recent high-resolution techniques, with the intent to provide interesting insight into pathophysiology and fracture risk.

http://ift.tt/2mG5IrE

Age-Related Changes in the Morphology of Tanycytes in the Human Female Infundibular Nucleus/Median Eminence

Abstract

Tanycytes have been emerging as key players in the neuroendocrine control of gonadotropin-releasing hormone (GnRH) release. Rodent studies have demonstrated that the structural relationship between tanycytes and GnRH terminals in the median eminence is highly dynamic, regulated by gonadal steroids and undergoes age-related changes. Our objective was to determine whether the number and organization of tanycytes changes throughout life in the female infundibular nucleus/median eminence (INF/ME) region. Post-mortem hypothalamic tissues were collected at the Netherlands Brain Bank and were stained for vimentin by immunohistochemistry. Hypothalami of 22 control female subjects were categorized into 3 periods: infant/prepubertal, adult and elderly periods. We measured the fractional area covered by vimentin immunoreactivity in the INF. Qualitative analysis demonstrated a remarkable parallel organization of vimentin-immunoreactive processes at the infant/prepubertal and adult periods. At the elderly period, this organization was largely lost. Semi-quantitatively, the fractional area covered in vimentin immunoreactivity was significantly higher at the infant/prepubertal compared to the adult period and almost reached statistical significance compared to the elderly period. By contrast, the number of tanycyte cell bodies did not seem to change throughout life. Our results thus demonstrate that the number and structure of tanycytic processes are altered during aging, and suggest that tanycytes might be involved in the age-related changes observed in GnRH release.

This article is protected by copyright. All rights reserved.

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Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: A meta-analysis

Publication date: April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 168
Author(s): Cedric F. Garland, Edward D. Gorham
Fifteen nested case-control or cohort studies in 14 countries have examined the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of colorectal cancer. A meta-analysis of these studies would provide a useful dose-response gradient curve based on pooling of the results of known studies to date. An up-to-date dose-response curve that combines the findings of these studies has not been reported, to our knowledge. This curve would help in designing interventions for future studies. A new meta-analysis would be more precise than any previous analysis due to its larger sample size. Therefore a search of PubMed and other resources was performed in May 2016 for all cohort or nested case-control observational studies that reported risk of colon or colorectal cancer by quantiles of 25(OH)D. All but two of the 15 studies found a trend toward lower risk of colorectal cancer associated with higher serum 25(OH)D. There was a linear reduction in the odds ratio (OR) with each 10ng/ml-increment in 25(OH)D concentration. The lowest quantile of the serum 25(OH)D concentration was generally<20ng/ml. The downward trend in ORs associated with higher serum 25(OH)D concentrations was statistically significant in 3 studies. The pooled OR from all studies comparing highest with lowest quantile of 25(OH)D was 0.67 (95% confidence interval [CI], 0.59–0.76), meaning there was a 33% lower risk associated with the highest compared with the lowest quantile of serum 25(OH)D. A dose-response analysis revealed that a serum 25(OH)D of 50ng/ml was associated with an OR of 0.4 (95% CI, 0.2–1.0) compared with a concentration of 5ng/ml. The formula for the linear relationship was OR=0.008x. For example, individuals with a 25(OH)D concentration of 50ng/ml had an approximately 60% lower risk of colorectal cancer than those with a concentration of 5ng/ml. Those with a 25(OH)D concentration of 30ng/ml had a 33% lower risk than those with a concentration of 5ng/ml. The inverse association between serum 25(OH)D and risk of colorectal cancer overall was strong and statistically significant. There also was a mostly linear dose response relationship between serum 25(OH)D and risk of colorectal cancer when all studies were combined. No study reported significant adverse effects, and there was no evidence of publication bias. Misclassification in some studies could have influenced the association, causing it to appear weaker than the true association.



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Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology

Publication date: April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 168
Author(s): Fernand Labrie, Céline Martel, Alain Bélanger, Georges Pelletier
The objective is to review how the cell-specific amounts of intracellular androgens are all made in women from circulating dehydroepiandrosterone (DHEA) in each peripheral tissue, independently from the rest of the body. Following 500 million years of evolution, approximately three dozen cell-specific intracrine enzymes have been engineered in human peripheral tissues whereby the inactive sex steroid precursor DHEA mainly of adrenal origin is transformed into the appropriate minute intracellular amounts of androgens. These intracellular androgens are inactivated in the same cells, with no biologically significant release of active androgens in the circulation. The best estimate is that approximately 50% as much androgens are synthesized in women, compared to men of the same age. The problem with DHEA, however, the exclusive source of androgens in women of all ages, is that DHEA secretion has already decreased by an average of 60% at time of menopause and continues to decrease thereafter. The human-specific and highly sophisticated mechanisms of intracrinology permit each cell to control androgen availability according to its own needs independently from the remaining of the body. Such a mechanism is completely different from classical endocrinology well understood in men where testosterone of testicular origin is transported through the blood and has indiscriminate access to the androgen receptor (AR) in all AR-containing cells of the body. In men, both the endocrine and intracrine mechanisms are in operation while, in women, only the intracrine mechanisms responsible for intracellular formation from DHEA provide androgens.



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Editorial board

Publication date: April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 168





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Novel recursive partitioning analysis classification for newly diagnosed glioblastoma: A multi-institutional study highlighting the MGMT promoter methylation and IDH1 gene mutation status

Publication date: Available online 13 March 2017
Source:Radiotherapy and Oncology
Author(s): Chan Woo Wee, Eunji Kim, Nalee Kim, In Ah Kim, Tae Min Kim, Yu Jung Kim, Chul-Kee Park, Jin Wook Kim, Chae-Yong Kim, Seung Hong Choi, Jae Hyoung Kim, Sung-Hye Park, Gheeyoung Choe, Soon-Tae Lee, Jong Hee Chang, Se Hoon Kim, Chang-Ok Suh, Il Han Kim
Background and purposeTo refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status.Methods and MaterialsThree-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42.4% and 6.2% of the patients, respectively.ResultsThe median follow-up for survivors and all patients was 33.2 and 20.5months, respectively. The median survival (MS) was 23.6months. RPA was performed on behalf of the results of the Cox proportional hazards model. MGMT methylation generated the initial partition (MGMTmeth vs. MGMTunmeth) in the RPA. Three final RPA classes were identified; class I=MGMTmeth/IDH1mut or MGMTmeth/IDH1wt/GTR/KPS≥90 (MS, 67.2months); class II=MGMTmeth/IDH1wt/GTR/KPS<90, MGMTmeth/IDH1wt/residual disease, MGMTunmeth/age<50, or MGMTunmeth/age≥50/GTR (MS, 24.0months); class III=MGMTunmeth/age≥50/residual disease (MS, 15.2months).ConclusionsA novel RPA classification for glioblastoma was formulated highlighting the impact of MGMTmeth and IDH1mut in the temozolomide era. This model integrating pertinent molecular information can be used effectively for the patient stratification in future clinical trials. An external validation is ongoing.



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Constraints for symptomatic radiation pneumonitis of helical tomotherapy hypofractionated simultaneous multitarget radiotherapy for pulmonary metastasis from hepatocellular carcinoma

Publication date: Available online 14 March 2017
Source:Radiotherapy and Oncology
Author(s): Genlai Lin, Han Xiao, Zhaochong Zeng, Zhiyong Xu, Jian He, Taiwei Sun, Jin Liu, Genwu Guo, Weixing Ji, Yong Hu
Background and purposeThis study was aimed to identify the clinical and dosimetric parameters that predict symptomatic radiation pneumonitis (SRP, radiation pneumonitis≥2 grade) in patients with pulmonary metastasis from hepatocellular carcinoma (HCC) after helical tomotherapy (HT) hypofractionated simultaneous multitarget radiotherapy.Materials and Methods62 patients with 407 pulmonary metastases from HCC were consecutively treated with HT. The median radiation dose was a 49.7Gy in 4.0Gy/fraction to 95% of the planning target volume (PTV). The associations between the clinical and dosimetric data and incidences of SRP were analyzed. The dose–pneumonitis relationship was analyzed based on Biologically Effective Dose (BED).ResultsUnivariate analysis showed that the gross tumor volume (GTV), PTV, median lung dose (MLD), the number of pulmonary metastatic lesions (NPML), and the percentage of non-target normal lung (NTNL) volume receiving more than a BED of 3–50Gy (VBED3-50) were associated with SRP. Multivariate logistic regression analysis showed that VBED20 and NPML were significant parameters (both P<0.001)ConclusionsOur findings indicated that SRP can be predicted with NPML>5 and VBED20≥30.4% with the α/β ratio of 3Gy.



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Role of the unfolded protein response in topography-induced osteogenic differentiation in rat bone marrow mesenchymal stem cells

Publication date: Available online 14 March 2017
Source:Acta Biomaterialia
Author(s): Mengqi Shi, Wen Song, Tianxiao Han, Bei Chang, Guangwen Li, Jianfeng Jin, Yumei Zhang
The topography of biomaterials can significantly influence the osteogenic differentiation of cells. Understanding topographical signal transduction is critical for developing biofunctional surfaces, but the current knowledge is insufficient. Recently, numerous reports have suggested that the unfolded protein response (UPR) and osteogenic differentiation are inter-linked. Therefore, we hypothesize that the UPR pathway may be involved in the topography-induced osteogenesis. In the present study, different surface topographies were fabricated on pure titanium foils and the endoplasmic reticulum (ER) stress and UPR pathway were systematically investigated. We found that ER stress and the PERK-eIF2α-ATF4 pathway were activated in a time- and topography-dependent manner. Additionally, the activation of the PERK-eIF2α-ATF4 pathway by different topographies was in line with their osteogenic induction capability. More specifically, the osteogenic differentiation could be enhanced or weakened when the PERK-eIF2α-ATF4 pathway was promoted or inhibited, respectively. Furthermore, tuning of the degree of ER stress with different concentrations of thapsigargin revealed that mild ER stress promotes osteogenic differentiation, whereas excessive ER stress inhibits osteogenic differentiation and causes apoptosis. Taken together, our findings suggest that the UPR may play a critical role in topography-induced osteogenic differentiation, which may help to provide new insights into topographical signal transduction.Statement of SignificanceSuitable implant surface topography can effectively improve bioactivity and eventual bone affinity. However, the mechanism of topographical signaling transduction is unclear and criteria for designation of an appropriate implant surface topography is lacking. This study shows that the ER stress and PERK-eIF2α-ATF4 pathway were activated by micro- and micro/nano-topographies, which is corresponding to the osteogenic induction abilities of these topographies. Furthermore, we have found that mild ER stress improves osteogenic differentiation, whereas excessive ER stress inhibits osteogenic differentiation and causes apoptosis. Our findings demonstrate that the UPR plays a critical role in the topography induced osteogenic differentiation, which may help to provide new insights into the topographical signaling transduction.

Graphical abstract

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An osteogenesis/angiogenesis-stimulation artificial ligament for anterior cruciate ligament reconstruction

Publication date: Available online 14 March 2017
Source:Acta Biomaterialia
Author(s): Hong Li, Jinyan Li, Jia Jiang, Fang Lv, Jiang Chang, Shiyi Chen, Chengtie Wu
To solve the poor healing of polyethylene terephthalate (PET) artificial ligament in bone tunnel, copper-containing bioactive glass (Cu-BG) nanocoatings on PET artificial ligaments were successfully prepared by pulsed laser deposition (PLD). It was hypothesized that Cu-BG coated PET (Cu-BG/PET) grafts could enhance the in vitro osteogenic and angiogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo graft-bone healing after anterior cruciate ligament (ACL) reconstruction in a goat model. Scanning electron microscope and EDS mapping analysis revealed that the prepared nanocoatings had uniform element distribution (Cu, Ca, Si and P) and nanostructure. The surface hydrophilicity of PET grafts was significantly improved after depositing Cu-BG nanocoatings. The in vitro study displayed that the Cu-BG/PET grafts supported the attachment and proliferation of rBMSCs, and significantly promoted the expression of HIF-1α gene, which up-regulated the osteogenesis-related genes (S100A10, BMP2, OCN) and angiogenesis-related genes (VEGF) in comparison with PET or BG coated PET (BG/PET) grafts which do not contain Cu element. Meanwhile, Cu-BG/PET grafts promoted the bone regeneration at the graft-host bone interface and decreased graft-bone interface width, thus enhancing the bonding strength as well as angiogenesis (as indicated by CD31 expression) in the goat model as compared with BG/PET and pure PET grafts. The study demonstrates that the Cu-containing biomaterials significantly promote osteogenesis and angiogenesis in the repair of bone defects of large animals and thus offering a promising method for ACL reconstruction by using Cu-containing nanobioglass modified PET grafts.Statement of significanceIt remains a significant challenge to develop an artificial graft with distinct osteogenetic/angiogenetic activity to enhance graft-bone healing for ligament reconstruction. To solve these problems, copper-containing bioactive glass (Cu-BG) nanocoatings on PET artificial ligaments were successfully prepared by pulsed laser deposition (PLD). It was found that the prepared Cu-BG/PET grafts significantly stimulated the proliferation and osteogenic/angiogenic differentiation of bone marrow stromal cells (BMSCs) through activating HIF-1α/S100A10/Ca²⁺ signal pathway. The most important is that the in vivo bone-forming ability of Cu-containing biomaterials was, for the first time, elucidated in a large animal model, revealing the enhanced capacity of osteogenesis and angiogenesis with incorporation of bioactive Cu elements. It is suggested that the copper-containing biomaterials significantly promote osteogenesis and angiogenesis in large animal defects and thus offering a promising method for ACL reconstruction by using Cu-containing nanobioglass modification of PET grafts, paving the way to apply Cu-containing biomaterials for tissue engineering and regenerative medicine.

Graphical abstract

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Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study

Abstract

Objectives

We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma.

Methods

At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography. All enrolled patients were genotyped for ABCB1 (rs2032582; rs1045642) and ABCG2 (rs2231137; rs2231142; rs2622604) by blood genomic DNA extraction and Mass ARRAY genotyping. The clinical response was evaluated after 3months of treatment according to the RECIST criteria.

Key findings

Significant associations between sorafenib exposure and the studied polymorphisms were observed for ABCB1 3435C>T, ABCG2 34G>A, ABCG2 1143C>T and ABCG2 421C>A, but not for ABCB1 2677G>TA SNP. In heterozygous patients for ABCB1 3435 C>T, ABCG2 34 G>A and ABCG2 1143 C>T polymorphisms were significantly associated with the lowest sorafenib plasma levels. Those patients presented a tendency to have the best clinical evolution.

Conclusion

Heterozygous forms of the studied polymorphisms could be associated with a better therapeutic response.

http://ift.tt/2np9PIU

Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia

Abstract

Purpose

The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.

Methods

Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients' characteristics or not.

Results

We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.

Conclusions

The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.

http://ift.tt/2mVOU28

A phase II study of REOLYSIN ® (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma

Abstract

REOLYSIN^® (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN^® on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN^®. Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN^® in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN^®, including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN^® combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN^® with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.

http://ift.tt/2nyfImb

The role of circulating tumor cells in evaluation of prognosis and treatment response in advanced non-small-cell lung cancer

Abstract

Purpose

Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict the prognosis and treatment response. This study investigated whether circulating tumor cells (CTCs) detectable could reminder high risk of distant metastasis, provide prognostic information, and early indicate the response to the conventional therapy in patients with advanced NSCLC.

Patients and methods

In this single-center prospective study, blood samples for CTC analysis were obtained from 59 patients with previously untreated, stage III or IV NSCLC both before and after administration of two cycles of chemotherapy. CTCs took in peripheral blood were measured by Cell Search detect technique.

Results

Carcino-embryonic antigen and count of metastatic sites were positively related to CTC count analyzed by multiple linear regression (P < 0.05). The median overall survival was 11.2 months (95% CI: 10.37–12.03 months) for the baseline CTC ≥ 2 group compared with 8.3 months (95% CI: 7.72–8.88 months) for the CTC < 2 group (log-rank test P < 0.05). Similarly, patients with CTC ≥ 2 at baseline had a significantly shorter median PFS (4.3 months, 95% CI: 3.7–4.9 months) compared with patients with CTC < 2 (6.2 months, 95% CI: 5.59–6.82 months) (log-rank test P < 0.05). For the disease control (stable disease, partial response, or complete response), group CTC value before treatment did not present difference with that after therapy compared by pared-samples T test (t = 1.455, P = 0.154), similar to the result of progressed group (progressive disease) (t = −0.987, P = 0.335). The CTC value of progressed group was higher than that of disease control group either at baseline or post chemotherapy.

Conclusion

These data provide an evidence of positive correlation between CTC counts with CEA, as well as count of metastatic sites. Meanwhile, CTCs could be an effective predictor of distant metastasis and poor prognosis. In this study, CTCs are poorly related to treatment response. Whether CTCs could be a predictor of curative effect in advanced NSCLC should be validated by more researches in the future.

http://ift.tt/2mINSpW

Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients

Abstract

Purpose

A phase I two-period two sequence cross-over study compared the bioavailability of two pimasertib (MSC1936369B/AS703026) formulations (capsule versus tablet) in advanced cancer patients.

Methods

Patients with advanced solid tumors were randomized to one of two treatment sequences utilizing pimasertib tablet (test; 3 × 20 mg, PO QD) and capsule (standard; 2 × 30 mg, PO QD). The trial comprised a screening and baseline period, two time periods or parts A and B, and a trial extension phase.

Results

N = 38 patients were randomized to two treatment sequences S1 and S2. PK parameters t _1/2, CL/f, and V _z/f were within the same range for the two formulations. Tablet had bioavailability comparable to capsule based on the analysis of AUC_0–t, however, tablet administration resulted in an increase of ~25% in C _max versus capsule. Common predicted adverse events of pimasertib included ocular events, diarrhea and creatine phosphokinase elevation. Disease control rate was ~29% with 1 partial response and 4 of 10 patients with stable disease >4 months.

Conclusions

Pimasertib tablet was overall well tolerated, had a similar safety and efficacy profile to standard capsule formulation and had bioavailability comparable to capsule.

http://ift.tt/2mnWHTk

Treatment of contaminated greywater using pelletised mine water sludge

Publication date: 15 July 2017
Source:Journal of Environmental Management, Volume 197
Author(s): Suhail N. Abed, Suhad A. Almuktar, Miklas Scholz
Precipitated sludge (ochre) obtained from a mine water treatment plant was considered as an adsorbent substance for pollutants, since ochre is relatively free from problematic levels of toxic elements, which could impair on the quality of water to be treated. Artificially created ochre pellets from mixing Portland cement with raw ochre sludge were utilised to remediate either high (HC) or low (LC) contaminated synthetic greywater (SGW) in mesocosm–scale stabilisation ponds at 2–day and 7–day contact times under real weather conditions in Salford. After a specific retention time, treated SGW was agitated before sampling to evaluate pollutant removal mechanisms (other than sedimentation) such as adsorption by ochre pellets, before replacing the treated water with new inflow SGW. The results showed that cement–ochre pellets have a high ability to adsorb ortho–phosphate–phosphorous (PO4–P) significantly (p < 0.05) by 70.7% and 56.0% at 7–day contact time for HC–SGW and LC–SGW, respectively. After the experiment, an analysis revealed that elements such as boron (B), cadmium (Cd), magnesium (Mg), manganese (Mn), nickel (Ni) and zinc (Zn) accumulated significantly (p < 0.05) within the ochre pellets. The notable accumulation of Cd within ochre pellets reflects the significant (p < 0.05) remediation of greywater during the first 35 and 20 successive times of treatment for HC–SGW at 2– and 7–day contact times, respectively. Cadmium was still adsorbed significantly (p < 0.05) during the treatment of LC–SGW. However, the calcium (Ca) content decreased significantly (p < 0.05) within ochre pellets treating both types of greywaters due to mobilisation. The corresponding increases of Ca in greywater were significant (p < 0.05).

Graphical abstract

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The impact of sewage sludge treatment on the content of selected heavy metals and their fractions

Publication date: July 2017
Source:Environmental Research, Volume 156
Author(s): Katarzyna Ignatowicz
The aim of the study was to assess the physicochemical properties of compost made of municipal sewage sludge from selected Municipal Sewage Treatment Plant. Content of basic macroelements and heavy metals (Zn, Cu, Cr, Cd, Ni, Pb, Hg, Mg, Ca, N, P, K, Na) and their fractions was determined by means of BCR method. Based on the analyzes, it was found that the content of heavy metals in compost did not exceed the limits set by natural land management of sewage sludge; the compost is very abundant in biogenic elements - nitrogen and phosphorus – and it can be also considered a significant source of calcium and magnesium. The analysis of results obtained from the three-stage chemical extraction revealed that deposits subjected to aerobic stabilization and composting accumulate metals (in descending sequence) in fractions III and II, i.e. fractions virtually inaccessible to the ecosystem in optimal conditions of use.



http://ift.tt/2mnWsaR

Evaluation of auditory perception development in neonates by event-related potential technique

Publication date: Available online 13 March 2017
Source:Brain and Development
Author(s): Qinfen Zhang, Hongxin Li, Aibin Zheng, Xuan Dong, Wenjuan Tu
ObjectiveTo investigate auditory perception development in neonates and correlate it with days after birth, left and right hemisphere development and sex using event-related potential (ERP) technique.MethodsSixty full-term neonates, consisting of 32 males and 28 females, aged 2–28days were included in this study. An auditory oddball paradigm was used to elicit ERPs. N2 wave latencies and areas were recorded at different days after birth, to study on relationship between auditory perception and age, and comparison of left and right hemispheres, and males and females.ResultsAverage wave forms of ERPs in neonates started from relatively irregular flat-bottomed troughs to relatively regular steep-sided ripples. A good linear relationship between ERPs and days after birth in neonates was observed. As days after birth increased, N2 latencies gradually and significantly shortened, and N2 areas gradually and significantly increased (both P<0.01). N2 areas in the central part of the brain were significantly greater, and N2 latencies in the central part were significantly shorter in the left hemisphere compared with the right, indicative of left hemisphere dominance (both P<0.05). N2 areas were greater and N2 latencies shorter in female neonates compared with males.ConclusionThe neonatal period is one of rapid auditory perception development. In the days following birth, the auditory perception ability of neonates gradually increases. This occurs predominantly in the left hemisphere, with auditory perception ability appearing to develop earlier in female neonates than in males. ERP can be used as an objective index used to evaluate auditory perception development in neonates.



http://ift.tt/2mIHleD

The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS)

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Yasuhiro Tsume, Kazuki Matsui, Amanda L. Searls, Susumu Takeuchi, Gregory E. Amidon, Duxin Sun, Gordon L. Amidon
The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and demonstrate supersaturation and precipitation of dipyridamole and ketoconazole. We therefore conclude that the GIS has been shown to be a good biopredictive tool to predict in vivo bioperformance of BCS class IIb drugs that can be used to optimize oral formulations.

Graphical abstract

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Development and characterisation of cellulose based electrospun mats for buccal delivery of non-steroidal anti-inflammatory drug (NSAID)

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Kazem Nazari, Eleni Kontogiannidou, Rita Haj Ahmad, Aggeliki Gratsani, Manoochehr Rasekh, Muhammad Sohail Arshad, Burde Suheyla Sunar, David Armitage, Nikolaos Bouropoulos, Ming-Wei Chang, Xiang Li, Dimitrios G Fatouros, Zeeshan Ahmad
In this study conventional electrospinning (ESp) was used to prepare a series of buccal films containing indomethacin (INDO, a nonsteroidal anti-inflammatory drug), Ethocel (10), hydroxypropylmethylcellulose (HPMC) and Tween^® 80 at various concentrations. The films were characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM), fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Drug release behaviour was assessed in vitro (buffer pH6.8). SEM revealed film morphology and mean fibre diameter was dependent on the process formulation. INDO was encapsulated in the amorphous state once electrospun as evidenced from DSC and XRD studies. The presence of other excipients within fibrous matrices was confirmed using FTIR and Raman spectroscopy. Loading and release of INDO from filamentous structures was influenced by formulation composition; indicating potential to 'fine-tune' dosage forms. Given that ESp is a one-step preparation method and operational at ambient conditions; an attractive route for engineering tailored film type dosage forms is presented. This is a valuable approach for optimizing dosage forms as needed in a single step for various age groups.

Graphical abstract

http://ift.tt/2mVQTU0

Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders: Proceedings of a Workshop [Prepublication Draft].

Compared with other disease areas, central nervous system (CNS) disorders have had the highest failure rate for new compounds in advanced clinical trials. Most CNS drugs fail because of efficacy, and the core issue underlying these problems is a poor understanding of disease biology. Concern about the poor productivity in neuroscience drug development has gained intensity over the past decade, amplified by a retraction in investment from the pharmaceutical industry. This retreat by industry has been fueled by the high failure rate of compounds in advanced clinical trials for nervous system disorders.

http://ift.tt/2mFC5Hj

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

The study found that the use of novel oral anticoagulants has advantages over warfarin in patients with atrial fibrillation, but there was no strong evidence that they should replace warfarin or low-molecular-weight heparin in the primary prevention, treatment or secondary prevention of venous thromboembolic disease.

http://ift.tt/2lX3h72

A randomised controlled trial to compare the safety, effectiveness and cost-effectiveness of doxycycline (200 mg/day) with that of oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) trial.

The study found that a strategy of starting bullous pemphigoid patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and considerably safer in the long term.

http://ift.tt/2mFCDNk

Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention

Background: One of the most important dermatologic side effects of doxycycline is photosensitivity. As doxycycline is important for malaria prophylaxis and malaria is mainly spread in countries with high sun radiation, special attention should be paid to this adverse effect. While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. The objective of this systematic review was to summarize all available reports on clinical manifestations, influencing factors like UV dose or dose of medication, and the possibilities of prevention by sun protection. Methods: This review is based on a systematic search in PubMed for articles in English and German and a manual search between 1990 and 2015. Results: The number of publications is low. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. Also, onycholysis is possible. The triggering UV spectrum seems to consist mainly of UVA1 (340-400 nm), so UV-protective products should be used that cover this range. Travelers to tropical countries taking doxycycline for malaria prophylaxis need thorough medical counseling to avoid possibly severe phototoxic reactions. Conclusion: Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure.
Skin Pharmacol Physiol 2017;30:76-80

http://ift.tt/2nAaLt1

Wash or wipe? A comparative study of skin physiological changes between water washing and wiping after skin cleaning

Background/purpose

Presently, skin-cleaning agents that claim to be removed by water or wiping alone are commercially available and have been used for the purpose of bed baths. However, there is a lack of knowledge on how water washing and wiping differently affect skin physiological functions or ceramide content. The aim of this study was to compare the effects of water washing and wiping on skin physiological functions and ceramide content.

Methods

Three kinds of the cleaning agents with different removal techniques (ie, water washing and wiping) were used in this study. Skin physiological functions (ie, transepidermal water loss, skin hydration, and skin pH) and skin ceramide content were measured before and after seven consecutive days of the application of each cleaning agent.

Results

No significant differences in skin physiological functions or ceramide content were observed between water washing and wiping.

Conclusion

Cleaning agents that claim to be removed by water washing or wiping do not affect skin physiological functions or ceramide content by either removal method.

http://ift.tt/2n5nozR

Relationship between the changes in blood flow and volume in the finger during a Braille character discrimination task

Purpose

We hypothesized that skin blood flow (SBF) of fingers are modulated during concentrated finger perception and that the changes in SBF reflect fluctuations in finger volume (FV). The aim of this study, therefore, was examine the relationship between the changes in SBF and FV during Braille reading.

Methods

We measured SBF of the finger, cutaneous vascular conductance (CVC), FV, and arterial blood pressure during Braille reading performed under blind conditions in thirty healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 15 seconds using their forefinger, and to touch a blank plate as a control for the Braille discrimination procedure.

Results

Arterial blood pressure slightly increased during Braille reading but remained unchanged during the touching of the blank plate. SBF, CVC, and FV were reduced during Braille reading (decreased by −26%, −29%, and −0.3 mL/100 mL respectively). Furthermore, a significant relationship was observed between the changes in SBF and FV (r=.613) during Braille reading.

Conclusion

These results suggested that SBF of fingers is modulated during concentrated finger perception, and that the variability of blood flow reflects the response in FV.

http://ift.tt/2nADg9Q

Cutaneous Crohn disease with superimposed psoriasis: a unique case with overlapping histology

Abstract

Crohn disease is an idiopathic, chronic inflammatory disorder of the gastrointestinal tract. We recently encountered a unique case in which a patient with longstanding Crohn disease presented with skin lesions with histopathologic features of both psoriasis and granulomatous inflammation suggestive of cutaneous Crohn disease. To our knowledge, this has not been described concomitantly in the same patient, in the same lesions. Review of the literature suggests that the intersection of these two histopathological reaction patterns may not be pure coincidence. Clinical-pathologic correlation of this case will be discussed, along with a review of the potential mechanisms of this unique disease presentation.

http://ift.tt/2mFp4NU

Injectable and thermally contractible hydroxypropyl methyl cellulose/Fe3O4 for magnetic hyperthermia ablation of tumors

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Fengjuan Wang, Yang Yang, Yi Ling, Jianxin Liu, Xiaojun Cai, Xiaohan Zhou, Xiuzhen Tang, Bing Liang, Yini Chen, Hangrong Chen, Dengming Chen, Chunhong Li, Zhigang Wang, Bing Hu, Yuanyi Zheng
The development of efficient strategies for the magnetic hyperthermia ablation of tumors remains challenging. To overcome the significant safety limitations, we developed a thermally contractible, injectable and biodegradable material for the minimally invasive and highly efficient magnetic hyperthermia ablation of tumors. This material was composed of hydroxypropyl methyl cellulose (HPMC), polyvinyl alcohol (PVA) and Fe3O4. The thermal contractibility of HPMC/Fe3O4 was designed to avoid damaging the surrounding normal tissue upon heating, which was confirmed by visual inspection, ultrasound imaging and computed tomography (CT). The efficient injectability of HPMC/Fe3O4 was proven using a very small needle. The biosafety of HPMC/Fe3O4 was evaluated by MTT and biochemical assays as well as flow cytometry (FCM). All the aforementioned data demonstrated the safety of HPMC/Fe3O4. The results of in vitro and ex vivo experiments showed that the temperature and necrotic volume of excised bovine liver were positively correlated with the HPMC/Fe3O4 weight, iron content and heating duration. The in vivo experimental results showed that the tumors could be completely ablated using 0.06 ml of HPMC/60%Fe3O4 after 180 s of induction heating. We believe that this novel, safe and biodegradable material will promote the rapid bench-to-bed translation of magnetic hyperthermia technology, and it is also expected to bring a new concept for the biomaterial research field.



http://ift.tt/2n5cQ3v

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Christa L. Pawlowski, Wei Li, Michael Sun, Kavya Ravichandran, DaShawn Hickman, Clarissa Kos, Gurbani Kaur, Anirban Sen Gupta
Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A2. Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment.

Graphical abstract

http://ift.tt/2n54jh5

Bilateral sagittal split osteotomy-parameters and correlations of postoperative pain management

Abstract

Objectives

Postoperative pain management is of utmost interest for patients undergoing orthognathic surgery. Currently, there is a lack of information regarding process and outcome parameters of postoperative pain management after bilateral sagittal split osteotomy.

Materials and methods

In a prospective clinical study, 31 adults were evaluated on the first postoperative day following bilateral sagittal split osteotomy using the standardized questionnaire of the Germany-wide project Quality Improvement in Postoperative Pain Management (QUIPS). It allows a standardized assessment of patients' characteristics, pain parameters, outcome, and pain therapy process parameters.

Results

Pain management consisted mainly of premedication with midazolam, sufentanil, and metamizol intraoperatively; piritramide in the recovery room; and metamizol and tramadol on ward. Twenty patients (64.5%) showed inadequate pain management with pain levels ≥4. Patients receiving tramadol as opioid on ward presented significantly higher maximum pain levels (p = .037). Significantly lower satisfaction with postoperative pain intensity (p > .001) and significantly higher desire for additional pain medication (p = .023) were detected, when duration of surgery was above the median of 107.5 min.

Conclusions

Inadequate pain management on the first postoperative day following bilateral sagittal split osteotomy was widespread on our ward. QUIPS helped us to identify it and thereby gave us the possibility to improve the situation. Prolonged duration of surgery seems to be a predictor of an elevated postoperative pain medication demand.

Clinical relevance

Only the establishment of an ongoing monitoring of postoperative pain management can help to reduce or even avoid inadequate postoperative pain management. In accordance to the existing literature, we found inadequate postoperative pain management more widespread than thought.

http://ift.tt/2mIhP9j

Antimicrobial copper alloys decreased bacteria on stethoscope surfaces

Publication date: Available online 13 March 2017
Source:American Journal of Infection Control
Author(s): Michael G. Schmidt, Rachel E. Tuuri, Arif Dharsee, Hubert H. Attaway, Sarah E. Fairey, Keith T. Borg, Cassandra D. Salgado, Bruce E. Hirsch
BackgroundStethoscopes may serve as vehicles for transmission of bacteria among patients. The aim of this study was to assess the efficacy of antimicrobial copper surfaces to reduce the bacterial concentration associated with stethoscope surfaces.MethodsA structured prospective trial involving 21 health care providers was conducted at a pediatric emergency division (ED) (n = 14) and an adult medical intensive care unit located in tertiary care facilities (n = 7). Four surfaces common to a stethoscope and a facsimile instrument fabricated from U.S. Environmental Protection Agency–registered antimicrobial copper alloys (AMCus) were assessed for total aerobic colony counts (ACCs), methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and vancomycin-resistant enterococci for 90 days.ResultsThe mean ACCs collectively recovered from all stethoscope surfaces fabricated from the AMCus were found to carry significantly lower concentrations of bacteria (pediatric ED, 11.7 vs 127.1 colony forming units [CFU]/cm², P < .00001) than their control equivalents. This observation was independent of health care provider or infection control practices. Absence of recovery of bacteria from the AMCu surfaces (66.3%) was significantly higher (P < .00001) than the control surfaces (22.4%). The urethane rim common to the stethoscopes was the most heavily burdened surface; mean concentrations exceeded the health care–associated infection acquisition concentration (5 CFU/cm²) by at least 25×, supporting that the stethoscope warrants consideration in plans mitigating microbial cross-transmission during patient care.ConclusionsStethoscope surfaces fabricated with AMCus were consistently found to harbor fewer bacteria.

Graphical abstract

http://ift.tt/2njgs2l