The BREASTrial Stage II: ADM Breast Reconstruction Outcomes from Definitive Reconstruction to 3 Months Postoperative

Background: The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a prospective randomized trial comparing outcomes of tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The trial was divided into 3 outcome stages; this study reports stage II outcomes, which are those from the time of definitive reconstruction to 3 months postoperative. Methods: A randomized trial was conducted to compare complication rates between AlloDerm and DermaMatrix groups. The impact of matrix type, age, obesity, radiation therapy, chemotherapy, and reconstruction type on complications was analyzed with regression models. Results: Of the 128 patients (199 breasts) who were randomly assigned into the trial, 111 patients (173 breasts) were available for analysis in stage II. There was no difference in overall rates of complications (15.4% vs 18.3%, P = 0.8) or implant loss (2.2% vs 3.7%, P = 0.5) between the AlloDerm and DermaMatrix groups, respectively. Obesity was the only significant predictor of complications on regression analysis (odds ratio, 4.31, P = 0.007). Matrix type, age, radiation therapy, chemotherapy, or reconstruction type had no impact on the incidence/severity of complications. Conclusions: Acellular dermal matrix (ADM) will likely continue to have a role in breast reconstructive surgery; however, caution should be taken when using ADM because of relatively high complication rates, especially in obese patients. The particular ADM product should be selected based on individual surgeon preference, experience, and success rates. These data and forthcoming long-term outcomes from the Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial will enable surgeons to carefully weigh the risks and benefits of ADM use in breast reconstruction.

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Safety and Effectiveness of Juvéderm Ultra Plus Injectable Gel in Correcting Severe Nasolabial Folds in Chinese Subjects

Background: Hyaluronic acid dermal fillers are effective in correcting severe nasolabial folds (NLFs) in non-Asian populations. We assessed safety and effectiveness of Juvéderm Ultra Plus in a Chinese population. Methods: This double-blind study randomized Chinese subjects with severe NLFs to Juvéderm Ultra Plus (24 mg/mL) in 1 NLF and Restylane injectable gel (20 mg/mL) in the other NLF. NLFs were evaluated using the validated 5-point photonumeric Allergan NLF Severity Scale (0 is "no wrinkle" and 4 is "very deep wrinkle"). Investigator-assessed responder rates (primary outcome at 6 months), NLF mean improvements, and subject-assessed responder rates and preference were assessed. Results: Of 124 subjects randomized, 122 completed the 6-month visit. NLFs treated with Juvéderm Ultra Plus required less volume than those treated with Restylane (median [range]: 0.80 [0.3–2.0] vs 1.00 [0.3–1.9]; P

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Abstract: 15.20 Revisited Fascia Lata In Facial Palsy.

No abstract available

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Abstract: 9.50 The Assessment Of The Protective Effect Of Lactobacillus Plantarum From Methicillin-Resistant Staphylococcus Aureus Infections In An Experimental Burn Model.

No abstract available

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Abstract: 17.40 Assessing Clinical Risk Factors For Early (30 Day) And Late (1 Year) Re-Admission Following Immediate Breast Reconstruction.

No abstract available

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Flap Reconstruction for Pressure Ulcers: An Outcomes Analysis

Background: Historically, complication rates after pressure ulcer reconstruction utilizing flap coverage have been high. Patients undergoing operations for pressure ulcer coverage typically have multiple risk factors for postoperative complications. The purpose of this study was to examine a large patient series in the pressure ulcer population to uncover objective evidence of the linkage between risk factors and outcomes after flap coverage. Methods: This study was a retrospective chart review of patients who underwent flap reconstruction for a pressure ulcer between 1997 and 2015. The characteristics of patients were analyzed to determine those who had complications such as pressure ulcer recurrence, wound dehiscence, and wound infection. Results: All patients (N = 276) underwent flap coverage of their pressure ulcers. The overall complication rate was 58.7% (162 patients). Wound dehiscence was the most common complication (31.2%), and the pressure ulcer recurrence rate was 28.6%. Multivariate regression for pressure ulcer recurrence revealed that body mass index

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Abstract: 11.10 Gluteal Augmentation Techniques: A Comprehensive Literature Review.

No abstract available

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Effect of Relaxing Incisions on the Maxillary Growth after Primary Unilateral Cleft Palate Repair in Mild and Moderate Cases: A Randomized Clinical Trial

Background: The purpose of this study was to evaluate the association between the use of relaxing incisions and maxillary growth disturbance after primary palatoplasty in patients with unilateral cleft lip and palate. Methods: This is a prospective, randomized, double-blind controlled trial study with ethical committee approval between 2 groups of patients with unilateral cleft lip and palate who were operated on using the two-flap and one-flap techniques from 2008 to 2011. Two groups of patients with unilateral cleft lip and palate were operated on using the mentioned techniques by the Outreach Surgical Center Program Lima since 2008. Data collection was accomplished by evaluation of maxillary arch dimensions and dental arch relationships (scored using the 5-year-olds' index). Results: The mean score for the 5-year-olds' index was 2.57 for two-flap technique and 2.80 for one-flap technique without statistical significant differences (P = 0.71). Our comparative study did not find statistically significant differences in maxillary arch dimensions between the studied techniques for unilateral cleft palate repair. Good levels of agreement were observed according to the κ statistics. Conclusions: The results arising from this clinical trial do not provide statistical evidence that one technique let us obtain better maxillary development than the other at 5 years. The use of relaxing incisions was not associated with maxillary growth impairment. A technique with limited relaxing incisions does not has better maxillary growth. Additional longer term study is necessary to confirm this preliminary report.

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Abstract: 17.00 Freestyle Pedicled Perforator And Propellar Flaps: Anatomic Studies And Clinical Application.

No abstract available

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Sandwich Fascial Anterolateral Thigh Flap in Head and Neck Reconstruction: Evolution or Revolution?

Introduction: The anterolateral thigh perforator flap (ALT) represents the workhorse for most reconstructive efforts in the head and neck regions. The main advantages of this flap are its versatility, the length of the pedicle, and the low morbidity of the donor site. The major drawback is the bulkiness of this flap with the frequent need for secondary revisions. To overcome this, we have developed a novel way to harvest and inset the ALT, called the sandwich fascial ALT flap (SALT). Methods: All patients undergoing head and neck reconstruction using the SALT flap from January 2013 to March 2016 were included in this retrospective analysis. The SALT flap was harvested as a composite flap including the superficial fascia, the subscarpal fat, and the deep fascia. At the recipient site, the flap was inset with the deep fascia facing out. A split thickness skin graft (± dermal substitute) was used to cover the deep fascia and the pedicle. Results: Eleven patients were included: 8 cases of orbital exenteration, 1 case of forehead reconstruction, and 2 cases of palatal reconstruction after radical maxillectomy. Flap survival was 100%. One patient required an early take back for venous thrombosis. The reconstruction was effective in all cases, allowing a prosthetic rehabilitation when required. Donor-site morbidity was minimal. Conclusions: The reconstruction of head and neck defects with a bulky fasciocutaneous ALT flap might not be the best option in every case. The SALT flap could represent a valid alternative for selected cases, with encouraging functional and cosmetic outcomes.

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Abstract: 8.20 Circumflex Scapular Artery Vascularized Scapular Chimeric Flaps: A New Experimental Flap Model.

No abstract available

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Refinement of Nasal Reconstruction with a V/Y-alar-perforator Flap

Background: The ala of the nose is vascularized by a dense net of perforators originating from the lateral nasal artery or the angular artery. These vessels reach the ala in a cascade fashion from the alar groove/lateral nasal wall. Based on these vessels, a V/Y flap can be dissected with a wide range of mobility. Materials and Methods: Nineteen patients underwent reconstruction of the nose by means of a V/Y-alar-perforator flap alone or in combination with a myocutaneous rotation flap from the lateral nasal wall and/or from the nasal dorsum for reconstruction of defects at the nasal tip, ala of the nose, and/or lateral nasal wall. All patients were followed up 8 months after surgery in average. Results: There was no prolonged congestion or any tissue loss. All patients presented postoperatively with excellent aesthetic results, and no nasal distortion was observed. Conclusion: The V/Y-alar-perforator flap alone or in combination with a myocutaneous rotation flap proved to be a reliable tool in the armamentarium for reconstruction of nasal tip and alar defects providing good aesthetic results.

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Abstract: 10.30 Intratissular Expansion And Layered Fat Grafting In Autologous Breast Reconstruction.

No abstract available

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Reconstructive Surgery for Bronchopleural Fistula and Empyema: New Application of Free Fascial Patch Graft Combined with Free Flap

Background: Postoperative bronchopleural fistula (BPF) and empyema are not uncommon after lung cancer surgery. Some patients require reconstructive surgery to achieve wound healing. In this report, we describe a novel method of reconstructive surgery for BPF and empyema. Methods: From 1996 through 2014, we performed reconstructive surgery for the treatment of BPF and empyema in 13 cases. BPF or a pulmonary fistula was present in 11 patients at the time of reconstruction. Of these, a free fascial patch graft combined with a free soft tissue flap was used to close the fistula in 6 cases. In the other 5 cases, primary fistula closure or direct coverage of the fistula with a transferred flap was performed. Medical records were retrospectively reviewed, and postoperative results were compared for these methods. Results: All the flaps were transferred successfully except in 1 case. Although postoperative air leakage was observed in 5 cases, most of these healed with conservative management. Of 11 fistulas, 8 were successfully controlled. Although differences were not statistically significant, a higher success rate of fistula closure was obtained in patients with a fascial patch graft (100% vs 40%). As a result, 9 patients could be discharged from the hospital, but 4 died during their hospital stay. Conclusion: Although the incidence of in-hospital mortality was high, fistula closure with a fascial patch graft combined with free flap transfer was effective for the treatment of BPF and empyema, compared with other procedures.

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Abstract: 11.50 An International Comparison Of Reimbursement For Dieap Flap Breast Reconstruction.

No abstract available

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Abstract: 16.40 Exploiting More Superficial Inferior Epigastric Artery (Siea) Flaps: Increasing Numbers With The Wow-Manoeuvre - Size Does Not Matter.

No abstract available

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Lymphaticovenous Anastomosis Releases the Lower Extremity Lymphedema-associated Pain

Background: We investigate the effectiveness of lymphaticovenous anastomosis (LVA) in releasing lymphedema-associated pain. Methods: We performed a retrospective analysis. Subjects of this study included lower extremity lymphedema patients who presented persistent and constant degrees of pain in their lower limbs. LVA was performed under local anesthesia. The preoperative lower extremity pain and postoperative lower extremity pain were surveyed using the visual analog scale on a score from 0 to 10. The circumferences of the limbs were also recorded. Results: A total of 8 patients (16 lower limbs) were included. The subjects included 1 man and 7 women, and their average age was 72 years. The average follow-up period was 17 months. The average preoperative and postoperative visual analog scale scores were 5.3 and 1.8, respectively. Moreover, 7 patients who had records of their lower extremity circumference observed an average changing rate of −4.7% in lower extremity lymphedema index after the surgery. Conclusion: LVA can release the pain in the affected limbs of lymphedema.

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Abstract: 17.20 Ligasure Impact Reduces Blood Loss, Complications And Re-Operation Occurrence In Abdominoplasty: A Comparative Study.

No abstract available

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A Retrospective Look at Integrating a Novel Regenerative Medicine Approach in Plastic Limb Reconstruction

Full-thickness wounds that have rendered patients candidates for amputation may require techniques that may include a combinatorial approach above traditional standard of care. The purpose of this retrospective study was to evaluate the effectiveness of an innovative approach whereby several therapies were combined to avoid amputation. Patients with full-thickness wounds who were previously recommended for amputation and were treated with the combinatorial approach of muscle flap reconstruction and concentrated bone marrow aspirate, platelet-rich plasma, INTEGRA Wound matrix, vacuum-assisted closure, and split-thickness skin grafts were assessed retrospectively. The mean age of the patients identified was 48 years (range, 34–66 years). The average size of the defects was 19.6 cm2. All defects were successfully covered with medial hemisoleus, lateral hemisoleus, or peroneus brevis muscle flaps combined with split-thickness skin grafts, concentrated bone marrow aspirate, and platelet-rich plasma. All flaps healed with an average time to fixator removal of 8.3 weeks; there was 1 above-knee amputation that occurred approximately after successful wound closing and fixator removal. The combinatorial approach described here including several regenerative medicine tools is an effective means of lower limb reconstruction to avoid amputation.

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Abstract: 8.00 Novel Perfusion Diagnostics In Reconstructive Surgery: Towards Prediction Of Free Flap Failure.

No abstract available

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Dataset on absorption spectra and bulb concentration of phenolic compounds that may interfere with onion pyruvate determinations

Publication date: Available online 7 February 2017
Source:Data in Brief
Author(s): Vanesa H. Beretta, Florencia Bannoud, Marina Insani, Claudio R. Galmarini, Pablo F. Cavagnaro
We present data on absorption spectra (400–540nm) and concentration of phenolic compounds quercetin, myricetin, kaempferol, rutin, catechin, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), in yellow, red and white onions. These data are related to the article entitled "Variability in spectrophotometric pyruvate analyses for predicting onion pungency and nutraceutical value" [1]. Given the relevance of pyruvate determinations for estimating onion pungency and functional value, it is important to identify compounds that can interfere with pyruvate determinations when using two previously published analytical procedures, namely Schwimmer and Weston (1961) (SW) [2] and Anthon and Barret (2002) (AB) [3], which are based on spectrophotometry and light-absorbance at 420nm and 515nm, respectively. The data presented in this article are absorption spectra for 7 onion phenolic compounds in the range 400–540nm, which include wavelengths used by the two pyruvate analytical methods [2,3] that were compared in our reference article [1]. Additionally, bulb content data for these 7 phenolic compounds in onion cultivars and F2 progenies with different bulb color were included to allow further analyses.



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Dataset of differentially accumulated proteins in Mucor strains representative of four species grown on synthetic Potato Dextrose Agar medium and a cheese mimicking medium

Publication date: Available online 7 February 2017
Source:Data in Brief
Author(s): Stéphanie Morin-Sardin, Jean-Luc JANY, Sébastien Artigaud, Vianney Pichereau, Benoît Bernay, Emmanuel Coton, Stéphanie Madec
The data presented are associated with the "Proteomic analysis of the adaptative response of Mucor spp. to cheese environment" (S. MORIN-SARDIN, J.L. JANY, S. ARTIGAUD, V. PICHEREAU, B. BERNAY, E. COTON, S. MADEC, 2016) article [1]. Mucor metabolism is poorly documented in the litterature and while morphology and growth behavior suggest potential adaptation to cheese for some strains, no adaptation markers to cheese environment have been identified for this genus. To establish the possible existence of metabolic functions related to cheese adaptation, we used a gel based 2-DE proteomic approach coupled to LC-MS/MS to analyze three strains from species known or proposed to have a positive or negative role in cheese production as well as a strain from a non-related cheese-species.



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Germinotropic Onychocytic Matricoma: A New Histopathologic Subtype of Onychocytic Matricoma in the Light of the Microanatomy of the Normal Nail Unit, With Special Reference to Nail Mesenchyme.

Onychocytic matricoma (OCM) is a benign tumor of adnexal keratinocytes in which there is complete cytodifferentiation toward the germinative cells of the nail matrix, the keratogenous zone cells, and cells of the nail plate. Several microscopic variants of OCM were initially recognized; acanthotic type, acanthotic and papillomatous type, keratogenous type, and melanocytic as slight proliferation of dendritic melanocytes within the basaloid cells. This study reports an additional histopathologic variant of OCM. The case presented as an acquired localized longitudinal pachymelanonychia of the thumb in a 50-year-old man. The excisional biopsy, with partial nail plate avulsion, showed a matrical acanthoma composed of basaloid cells with peripheral palisading. This matrical lesion showed extension into the proximal nail bed. The boundary between the matrix and nail bed was identified by the 2 microanatomical zones of the matrical mesenchyme, and the matrix metaplasia of the proximal nail bed was identified by the coexpression of hair-related keratins and K75. This onychogenic epithelial benign tumor presented a prominent germinative compartment without spheres of prekeratogenous and keratogenous zone cells and exhibited an unusual expression of K35. The melanocyte count was high in the proximal nail bed with matrix metaplasia (22.25 melanocytes per mm). By contrast, the distal nail bed, showed only rare melanocytes. This study describes a previously uncharacterized histopathologic subtype of OCM that can microscopically mimic onychocytic carcinoma, onychomatricoma and basal cell carcinoma. Careful conventional microscopy coupled with knowledge of the fine microanatomy of the normal nail mesenchyme can facilitate a correct diagnosis to be established. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Commentary to the Article "A Rare Collision in Dermatopathology: Basal Cell Carcinoma and Atypical Fibroxanthoma".

No abstract available

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The So-Called Aggressive Digital Papillary Adenocarcinoma Is Epithelial-Myoepithelial Carcinoma.

No abstract available

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Sarcoidosis Presenting as Frontal Fibrosing Alopecia: A Master Mimicker or a Coincidental Finding?.

No abstract available

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Factitious Dermatitis Due to Thermal Burn With Histologic Features Simulating Fixed Drug Eruption.

Factitious dermatitis (FD) (dermatitis artefacta) is rare and often difficult to diagnose because of conflicting history and nonspecific clinical and histologic findings. It can present with varied clinical features including geometric ulcers, erosions, and less commonly bullae secondary to external trauma from chemicals, electric burns, heat, and suction. Herein, we describe a case of bullous FD due to thermal burn with histologic features demonstrating overlap with fixed drug eruption. Histopathology demonstrated a subepidermal blister with epidermal necrosis along with pigment incontinence and dermal eosinophils and neutrophils. Although these features, and the clinician's impression, were suggestive of fixed drug eruption, several morphologic findings allowed accurate diagnosis of FD: sharp demarcation of necrotic keratinocytes from adjacent uninvolved epidermis, elongated keratinocytes reminiscent of thermal or electrical artifact, and multinucleated keratinocytes. Although FD is often considered a diagnosis of exclusion, these clues may help dermatopathologists distinguish this entity from inflammatory dermatoses. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-Control Study.

Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0-9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Borderline Tuberculoid Leprosy Masquerading as Granuloma Annulare: A Clinical and Histological Pitfall.

Introduction: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, an intracellular acid-fast bacillus that tends to infect the skin and peripheral nerves. Because of the wide array of cutaneous manifestation, diagnosis is not always straightforward, especially in nonendemic regions of the world such as the United States. Case Report: The authors report an unusual case of borderline tuberculoid leprosy in an 80-year-old white woman from California. Clinical examination revealed multiple nonscaly annular plaques, with central clearing and absence of lesional anesthesia, distributed over the trunk and extremities initially clinically diagnosed as granuloma annulare (GA). After 2 years of unsuccessful treatment with topical corticosteroid, biopsy revealed a palisaded and interstitial granulomatous infiltrate with necrobiosis, without discrete granulomas, compatible with GA. However, the presence of perineural lymphocytes in the reticular dermis prompted a Fite stain, which revealed acid-fast bacilli within the Schwann cells of a small peripheral nerve, pathognomonic for leprosy. Conclusion: This is the first reported case of leprosy masquerading both clinically and histologically as GA. Dermatopathologists should be aware of the possibility of leprosy given the presence of perineural lymphocytes amidst any pattern of granulomatous infiltrate and obtain a Fite stain. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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"Joining the Spots in Adults and Young Tots": A Clinicopathological Study of Henoch-Schonlein Purpura (IgA Vasculitis).

Introduction: Henoch-Schonlein Purpura (HSP; IgA vasculitis), the most common vasculitis of childhood, has a wide spectrum of clinical manifestations ranging from palpable purpura with abdominal pain and arthritis to the more morbid renal involvement. Aims and Objectives: To study and correlate the clinical presentation, laboratory values, skin and renal histopathology and immunofluoroscence findings in HSP. Material and Methods: A total of 44 cases of HSP from March 2011 to February 2014 were studied for the above features along with their clinical outcomes. Results: The mean age of the patients at presentation was 28.4 years (range 4.5-69 years) with 26.2% being children younger than 15 years. Purpura at presentation was seen in all with 77.1% showing extracutaneous involvement. Skin biopsy showed leukocytoclastic vasculitis in all and dominant IgA deposition in the papillary dermal vessels in 43 cases (97.7%), associated C3 in 10 (23.3%), and full-house positivity in 1 case. One case without skin immunofluorescence had renal mesangial IgA deposits. Nine cases (20.9%) with an average age of 39 years had renal symptoms and showed varied histology from focal mesangioproliferative glomerulonephritis to crescentic. All of them had dominant mesangial IgA deposits, majority falling into International Study of Kidney Disease in Children (ISKDC) class IIIb. Peritubular capillaritis was noted in 3 cases. Two patients (4.5%) progressed to end stage renal disease, 1 of whom had cellular crescents at presentation. Conclusions: HSP was seen both in children and adults. Renal involvement was seen in 20.9% cases, all older than 14 years, and 66.7% with extracutaneous manifestations. The outcome in this series was favorable in 96% cases. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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A Case of Cutaneous Focal Mucinosis With Follicular Induction.

No abstract available

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Generalized Indeterminate Cell Histiocytosis Presenting as Eroded Papules and Crusts.

Indeterminate cell histiocytosis (ICH) is a very rare histiocytic disease. We reported a case of generalized ICH presenting as eroded papules and crusts, accompanied with intermittent fever, pulmonary disorder, lymphadenectasis in the mediastinum, and the retroperitoneum. The histopathology indicated a neoplasm that was composed of small nests of large cells with ample pale cytoplasm. Immunohistochemistry results and the absence of Birbeck granules led us to the diagnosis of ICH. Four months later, the patient died of anemia, ascites, and swelling of the limbs. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The Histopathology of Urticaria Revisited-Clinical Pathological Study.

Background: The classic histopathological findings of urticaria include dermal edema and a sparse perivascular infiltrate of neutrophils, eosinophils, macrophages, and lymphocytes. However, this pattern is inconsistently described. Objective: To describe the histological and immunofluorescence characteristics of urticaria and to identify distinctive patterns. Methods: A retrospective study was performed in which the medical files and biopsy specimens of 58 patients with acute and chronic classical urticaria were reviewed. Pathological parameters were quantified. Results: We recognized 2 distinctive patterns of urticaria: lymphocyte and neutrophil predominant; the former was characterized by a perivascular location, whereas the latter was associated with an interstitial location and a denser infiltrate. Mast cells were relatively sparse, better demonstrated with special stains. Tryptase stain demonstrated more mast cells than Giemsa stain. Extravasated erythrocytes were present in 50% of the cases, but vasculitis was not observed. Conclusions: Histological findings in classical urticaria show a spectrum of findings from a sparse superficial perivascular to a deep perivascular and interstitial infiltrate. Distinctive groups based on the dominant cell type can be identified, accounting for the similarity to neutrophilic urticarial dermatosis. Lesions may have a purpuric appearance, but leukocytoclastic vasculitis is never present. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Microscopy of Common Nail Cosmetics.

Nail clipping specimens are commonly submitted for the microscopic evaluation of nail disease; however, there may be missing clinical history regarding nail polish or other adornments present on the nail at the time of specimen retrieval. For this study, 6 types of nail cosmetics were chosen and applied to the nail plate of a volunteer. After a period of at least 24 hours, the nail plates with adornments and a control nail plate were clipped and placed in formalin. Specimens were processed using a standard nail protocol. All of the specimens, except the sticker applique, survived the fixation process. The glitter nail polish was the only specimen found to be polarizable. None of the specimens that survived fixation were found to be PAS-positive. Cosmetic nail enhancements are easily differentiated from the nail plate microscopically; nail cosmetics appear as a distinct layer of inorganic material lying atop the nail plate. There were 2 main microscopic patterns noted on the specimens: those with 2 layers and those with 3 layers. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Putative Intravascular Myofibroma Mimicking a Vascular Malformation With Phleboliths.

Myofibroma is a rare, benign myofibroblastic tumor that commonly presents at birth or in early infancy, usually as a painless, slow-growing, solitary, nodular mass. We present a case of a 40-year-old woman with a painful, solitary, myofibroma on the right elbow. The unique features of this case include age and gender of the patient, site, pain on presentation, tumor morphology, and putative intravascular nature of the tumor. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Eccrine Syringofibroadenoma in Association With Acquired Epidermodysplasia Verruciformis.

A 75-year-old man with human immunodeficiency virus infection and numerous biopsy-proven warts for 10 years, refractory to cryosurgery, cimetidine, and topical imiquimod, presented with numerous pink to hypopigmented verrucous papules and plaques involving the face, trunk, buttocks, and groin. Laboratory evaluation revealed a CD4 T-cell count of 62 cells per microliter and human immunodeficiency virus viral load of

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Pathological Sampling of Basal Cell Carcinoma Re-excision Specimens: How Much is Enough?.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy, comprising approximately 75%-80% of all skin cancers. Surgical excision is the most common first line treatment modality, with the intent of obtaining clear margins. If the initial excision is incomplete or inadequate, a re-excision will often be performed in an attempt to achieve histological clearance. The pathological examination of these specimens requires a balance between the need for adequate assessment and efficient use of laboratory resources. In this study, we sought to systematically compare different approaches to the pathological sampling of these specimens in the hope of providing an evidential basis for a rational approach. Seventy-four BCC re-excision specimens were entirely sampled and retrospectively examined to determine the rate of detection of residual BCC which would have been achieved using different sampling methodologies. Residual BCC was identified in 37 specimens (50%). Limited transverse sections through the centre of the ellipse resulted in a sensitivity for detection of residual BCC of 78% (or 85% if only "significant" residual tumor is considered). By including the entire scar or the remainder of the specimen except the polar pieces, the sensitivity improved to 95% and 97%, respectively. Only one case showed residual tumor in the apical sections alone, with tumor extending to the new surgical margin in that case. We hope that this data may help laboratories develop sampling protocols appropriate to their own cost-benefit analyses and patient populations. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Cutaneous Apocrine Carcinoma With an In Situ Component and Histiocytoid and Signet-Ring Cells.

We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Low-Grade Neuroendocrine Carcinoma of the Skin (Primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review.

There is scarcity of information on primary cutaneous low-grade neoplasms commonly known as carcinoid tumors, owing to their rarity. The authors present 3 cases that were named "low-grade neuroendocrine carcinoma of the skin" (LGNECS). These occurred in the dermis and subcutis of the anterior chest or the inguinal region in the elderly. Histologically, the tumors showed infiltrating proliferation of nests of various sizes, with low-grade neuroendocrine cytologic features but without mucin production. All cases exhibited varying degrees of intraductal tumor components. On immunohistochemical examination, these tumors expressed estrogen receptor alpha, progesterone receptor, androgen receptor, gross cystic disease fluid protein 15, mammaglobin, and GATA3 as well as neuroendocrine markers. Although a literature review revealed 8 additional possible cases with no evidence of other diseases, it was difficult to determine if these were true cases of LGNECS, because of the limited information available. Based on its characteristic histologic features and immunoprofile, it can be proposed designating LGNECS as a distinct entity among cutaneous neuroendocrine tumors. Otherwise, such tumors could be misdiagnosed as mammary carcinomas (particularly when involving the skin of the breast) or as metastatic visceral neuroendocrine tumors of the skin. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Editorial Board/Aims and Scope

Publication date: 22 February 2017
Source:Vaccine, Volume 35, Issue 8





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Toward understanding the mechanisms underlying the strong adjuvant activity of aluminium salt nanoparticles. Ruwona TB, Xu H, Li X, Taylor AN, Shi Y, Cui Z. Vaccine 2016;34:3059–67

Publication date: 22 February 2017
Source:Vaccine, Volume 35, Issue 8
Author(s): Matthew Mold, Emma Shardlow, Christopher Exley




http://ift.tt/2kRaDaD

Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles. Ruwona TB, Xu H, Li X, Taylor AN, Shi Y, Cui Z. Vaccine 2016;34:3059–67

Publication date: 22 February 2017
Source:Vaccine, Volume 35, Issue 8
Author(s): Haiyue Xu, Xu Li, Zhengrong Cui




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The Advisory Committee on Immunization Practices’ controversial recommendation against the use of live attenuated influenza vaccine is based on a biased study design that ignores secondary protection

Publication date: 22 February 2017
Source:Vaccine, Volume 35, Issue 8
Author(s): Parker A. Small, Brendan J. Cronin




http://ift.tt/2kRbN62

An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers

Publication date: 22 February 2017
Source:Vaccine, Volume 35, Issue 8
Author(s): Limin Wijaya, Christine Y.L. Tham, Yvonne F.Z. Chan, Abigail W.L. Wong, L.T. Li, Lin-Fa Wang, Antonio Bertoletti, Jenny G. Low
BackgroundRabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response.MethodsWe conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses.ResultsBoth the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p=0.411) and 16.7% in control vaccine classic regimen (p=0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42.ConclusionThe investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.



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Maintaining Shoulder Health After Spinal Cord Injury: A Guide to Understanding Treatments for Shoulder Pain

Publication date: Available online 7 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Meegan G. Van Straaten, Beth A. Cloud, Kristin D. Zhao, Emma Fortune, Melissa M.B. Morrow




http://ift.tt/2kLfXwi

Polyanhydride nanovaccine against swine influenza virus in pigs

Publication date: 22 February 2017
Source:Vaccine, Volume 35, Issue 8
Author(s): Santosh Dhakal, Jonathan Goodman, Kathryn Bondra, Yashavanth S. Lakshmanappa, Jagadish Hiremath, Duan-Liang Shyu, Kang Ouyang, Kyung-il Kang, Steven Krakowka, Michael J. Wannemuehler, Chang Won Lee, Balaji Narasimhan, Gourapura J. Renukaradhya
We have recently demonstrated the effectiveness of an influenza A virus (IAV) subunit vaccine based on biodegradable polyanhydride nanoparticles delivery in mice. In the present study, we evaluated the efficacy of ∼200nm polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV) as a vaccine to induce protective immunity against a heterologous IAV challenge in pigs. Nursery pigs were vaccinated intranasally twice with inactivated SwIAV H1N2 (KAg) or polyanhydride nanoparticle-encapsulated KAg (KAg nanovaccine), and efficacy was evaluated against a heterologous zoonotic virulent SwIAV H1N1 challenge. Pigs were monitored for fever daily. Local and systemic antibody responses, antigen-specific proliferation of peripheral blood mononuclear cells, gross and microscopic lung lesions, and virus load in the respiratory tract were compared among the groups of animals. Our pre-challenge results indicated that KAg nanovaccine induced virus-specific lymphocyte proliferation and increased the frequency of CD4⁺CD8αα⁺ T helper and CD8⁺ cytotoxic T cells in peripheral blood mononuclear cells. KAg nanovaccine-immunized pigs were protected from fever following SwIAV challenge. In addition, pigs immunized with the KAg nanovaccine presented with lower viral antigens in lung sections and had 6 to 8-fold reduction in nasal shedding of SwIAV four days post-challenge compared to control animals. Immunologically, increased IFN-γ secreting T lymphocyte populations against both the vaccine and challenge viruses were detected in KAg nanovaccine-immunized pigs compared to the animals immunized with KAg alone. However, in the KAg nanovaccine-immunized pigs, hemagglutination inhibition, IgG and IgA antibody responses, and virus neutralization titers were comparable to that in the animals immunized with KAg alone. Overall, our data indicated that intranasal delivery of polyanhydride-based SwIAV nanovaccine augmented antigen-specific cellular immune response in pigs, with promise to induce cross-protective immunity.



http://ift.tt/2kQXOge

Exoskeleton-Assisted Walking for People With Spinal Cord Injury

Publication date: Available online 7 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Paula Richley Geigle, Marni Kallins




http://ift.tt/2kG0Sty

Coping With Caregiver Burnout When Caring for a Person With Neurodegenerative Disease: A Guide for Caregivers

Publication date: Available online 7 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Shilpa Krishnan, Michele K. York, Deborah Backus, Patricia C. Heyn




http://ift.tt/2kpPwLM

Brief Review of Psychometric Properties and Clinical Utility of the Ages and Stages Questionnaires, Third Edition for Evaluating Pediatric Development

Publication date: Available online 7 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Aliza Rothstein, Ana Miskovic, Kristian Nitsch




http://ift.tt/2kG4HyO

Work limitations four years following mild traumatic brain injury: A Cohort Study

Publication date: Available online 8 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alice Theadom, Suzanne Barker-Collo, Kelly Jones, Michael Kahan, Braden Te Ao, Kathryn McPherson, Nicola Starkey, Valery Feigin
ObjectiveTo explore employment status, work limitations and productivity loss following mild traumatic brain injury (TBI).Study DesignInception cohort study over four years.SettingGeneral community.Participants245 Adults (>16 years at the time of injury), who experienced a mild TBI and who were employed prior to their injury.InterventionsNot applicableMain Outcome MeasuresDetails of the injury, demographic information and pre-injury employment status were collected from medical records and self-report. Symptoms and mood were assessed one-month post-injury using the Rivermead Post-Concussion Symptom Questionnaire and the Hospital Anxiety and Depression Scale. Post-injury employment status and work productivity were assessed four-years post-injury using the Work Limitations Questionnaire.ResultsFour-years following mild TBI, 17.3% of participants had exited the workforce (other than for reasons of retirement or to study) or had reduced their working hours compared to pre-injury. A further 15.5% reported experiencing limitations at work as a result of their injury. Average work productivity loss was 3.6% The symptom of 'taking longer to think' one month post-injury significantly predicted work productivity loss four years later (β = 0.47, t = 3.79, p = <0.001).ConclusionsWhilst changes in employment status and difficulties at work are likely over time, the results indicate increased unemployment rates, work limitations and productivity loss in the longer-term following a mild TBI. Identification of cognitive difficulties one month following TBI in working aged adults and subsequent interventions to address these difficulties are required to facilitate work productivity.



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Chimpanzee and human midfoot motion during bipedal walking and the evolution of the longitudinal arch of the foot

Publication date: March 2017
Source:Journal of Human Evolution, Volume 104
Author(s): Nicholas B. Holowka, Matthew C. O'Neill, Nathan E. Thompson, Brigitte Demes
The longitudinal arch of the human foot is commonly thought to reduce midfoot joint motion to convert the foot into a rigid lever during push off in bipedal walking. In contrast, African apes have been observed to exhibit midfoot dorsiflexion following heel lift during terrestrial locomotion, presumably due to their possession of highly mobile midfoot joints. This assumed dichotomy between human and African ape midfoot mobility has recently been questioned based on indirect assessments of in vivo midfoot motion, such as plantar pressure and cadaver studies; however, direct quantitative analyses of African ape midfoot kinematics during locomotion remain scarce. Here, we used high-speed motion capture to measure three-dimensional foot kinematics in two male chimpanzees and five male humans walking bipedally at similar dimensionless speeds. We analyzed 10 steps per chimpanzee subject and five steps per human subject, and compared ranges of midfoot motion between species over stance phase, as well as within double- and single-limb support periods. Contrary to expectations, humans used a greater average range of midfoot motion than chimpanzees over the full duration of stance. This difference was driven by humans' dramatic plantarflexion and adduction of the midfoot joints during the second double-limb support period, which likely helps the foot generate power during push off. However, chimpanzees did use slightly but significantly more midfoot dorsiflexion than humans in the single limb-support period, during which heel lift begins. These results indicate that both stiffness and mobility are important to longitudinal arch function, and that the human foot evolved to utilize both during push off in bipedal walking. Thus, the presence of human-like midfoot joint morphology in fossil hominins should not be taken as indicating foot rigidity, but may signify the evolution of pedal anatomy conferring enhanced push off mechanics.



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2-D and 3-D Ultrasound for Tumor Volume Analysis: A Prospective Study

Publication date: Available online 7 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Segundo J. González, Blaise Mooney, Hui-Yi Lin, Xiuhua Zhao, John V. Kiluk, Nazanin Khakpour, Christine Laronga, M. Catherine Lee
Ultrasound (US) allows real-time tumor assessment. We evaluated the volumetric limits of 2-D and 3-D US, compared with magnetic resonance imaging (MRI), with a prospective institutional review board–approved clinical evaluation of US-to-MRI volumetric correlation. US images of pre- and post-neoadjuvant breast cancers were obtained. Volume discrepancy was evaluated with the non-parametric Wilcoxon signed-rank test. Expected inter-observer variability <14% was evaluated as relative paired difference (RPD); clinical relevance was gauged with the volumetric standard error of the mean (SEM). For 42 patients, 133 of 170 US examinations were evaluable. For tumors ≤20 cm³, both highly correlated to MRI with RPD within inter-observer variability and Pearson's correlation up to 0.86 (0.80 before and 0.86 after neoadjuvant chemotherapy, respectively). Lesions 20–40 cm³ had US-to-MRI discrepancy within inter-observer variability for 2-D (RPD: 13%), but not 3-D (RPD: 27%) US (SEM: 1.47 cm³ for 2-D, SEM: 2.28 cm³ for 3-D), suggesting clinical utility. Tumors >40 cm³ correlated poorly. Tumor volumes ≤20 cm³ exhibited a good correlation to MRI. Studies of clinical applications are warranted.



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Value of Shear Wave Elastography in the Diagnosis of Gouty and Non-gouty Arthritis

Publication date: Available online 7 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Yuanjiao Tang, Feng Yan, Yujia Yang, Xi Xiang, Liyun Wang, Lingyan Zhang, Li Qiu
Our aim was to analyze the diagnostic performance of shear wave elastography (SWE) in the diagnosis of gouty arthritis (GA) and non-gouty arthritis (non-GA). Thirty-nine patients in the GA group and 55 patients in the non-GA group were included in the study. Based on the echo intensity of the joint lesions, the GA group was subdivided into hypo-echoic GA, slightly hyper-echoic GA and hyper-echoic GA subgroups. Quantitative SWE features were evaluated and receiver operating characteristic analysis was performed. On the basis of the study, the elastic modulus (Emax), mean elastic modulus (Emean), minimum elastic modulus (Emin) and elastic modulus standard deviation (ESD) were significantly higher in the GA group than in the non-GA group and were highest in the hyper-echoic GA subgroup (p < 0.01 for all). Emin, Emean and Emax were significantly higher in the hyper-echoic GA subgroup than in the hypo-echoic GA subgroup and non-GA group (p < 0.001 for all), and ESD was significantly higher in the hyper-echoic GA subgroup than in the non-GA group (p = 0.001). Emin, Emean, Emax and ESD were higher in the hypo-echoic GA subgroup than in the non-GA group, and the differences were significant (p < 0.001 for all). Based on the hypo-echoic GA subgroup and non-GA group, areas under the receiver operating characteristic curves for the prediction of GA were 0.749 for Emin, 0.877 for Emean, 0.896 for Emax and 0.886 for ESD, with optimal cutoff values of 29.40 kPa for Emin, 45.35 kPa for Emean, 67.54 kPa for Emax and 7.85 kPa for ESD. Our results indicate that SWE can differentially diagnose GA and non-GA, especially when the ultrasound manifestations are not typical.



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Biochemical control and toxicity for favorable- and intermediate-risk patients using real-time intraoperative inverse optimization prostate seed implant: Less is more!

Publication date: Available online 7 February 2017
Source:Brachytherapy
Author(s): G. Shukla, A. Sarkar, A. Hanlon, E. Crockett, H.C. Chen, J. Martelli-Raben, A. Glick, B. Benge, M. Lobis, S. Terranova, T. Desperito, D. Cozzolino, E. Kemmerer, F. Mourtada, A. Raben
PurposeTo report the biochemical control rate and clinical outcomes with real-time inverse planning (inverse optimization prostate seed implant [IO-PSI]) for favorable-risk (FR) and intermediate-risk (IR) prostate adenocarcinoma in a community practice setting. This analysis is an extended followup of our initial report, with favorable early biochemical control rate (biochemical nonevidence of disease) of 97% at 4 years.Methods and MaterialsThree hundred fifty-seven evaluable patients with FR and IR prostate cancer underwent real-time IO-PSI (iodine-125/145 Gy or palladium-103/120 Gy) between 2001 and 2013.ResultsWith a median followup of 54 months (range, 24–110 months), the absolute biochemical failure free survival of disease was 96%. The 8-year actuarial probability of prostate-specific antigen failure-free survival for FR and IR cohorts was 92.4% and 87%, respectively. Late genitourinary and gastrointestinal toxicity remained low. Late Grade 2 and Grade 3 genitourinary toxicity was 19% and 1%, respectively. Late Grade 2 and 3 rectal bleeding rates were 1% and 0%, respectively. No difference in biochemical control was observed with preimplant short course androgen deprivation or between Gleason score 3 + 4 vs. 4 + 3 patients. No dosimetric parameter was predictive of biochemical failure. Patients with FR had a significantly decreased risk of failure (hazard ratio = 0.26; 95% confidence interval = 0.09–0.78; p = 0.02) compared with those with IR. Patients with a prostate-specific antigen nadir >0.4 ng/mL had an increased risk of failure (hazard ratio = 1.37; 95% confidence interval = 1.27–1.47; p < 0.0001).ConclusionsOur initial biochemical and clinical outcomes using real-time IO-PSI persisted with extended followup and support our original hypothesis for use of a reduced number of sources, needles, and total activity, suggesting that with IO, less is more.



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Enhanced critical-size calvarial bone healing by ASCs engineered with Cre/loxP-based hybrid baculovirus

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Shih-Chun Lo, Kuei-Chang Li, Yu-Han Chang, Mu-Nung Hsu, Li-Yu Sung, Truong Anh Vu, Yu-Chen Hu
Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell-derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs. We demonstrated that transduction of rat ASCs with the hybrid Cre/loxP-based baculovirus enabled robust and sustained expression of functional BMP-2 and SDF-1. Expression of BMP-2 or SDF-1 alone failed to effectively induce rat ASCs osteogenesis and healing of critical-size calvarial bone defects. Nonetheless, prolonged BMP-2/SDF-1 co-expression in ASCs synergistically activated both Smad and ERK1/2 pathways and hence potentiated the osteogenesis. Consequently, transplantation of the hybrid baculovirus-engineered, BMP-2/SDF-1-expressing ASCs/scaffold constructs potently healed the critical-size (6 mm) calvarial bone defects (filling ≈70% of defect volume), which considerably outperformed the calvarial bone repair using BMP-2/SDF-1 delivered with biomaterial-based scaffolds. These data implicated the potential of Cre/loxP-based hybrid baculovirus vector for ASCs engineering and calvarial bone healing.



http://ift.tt/2jXNzI2

Positioning metal-organic framework nanoparticles within the context of drug delivery – A comparison with mesoporous silica nanoparticles and dendrimers

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Stefan Wuttke, Marjorie Lismont, Alberto Escudero, Bunyarat Rungtaweevoranit, Wolfgang J. Parak
Nanotechnology enables the creation of delivery vehicles able to overcome physiologically imposed barriers, allowing new approaches for reducing the unwanted side effects of systemic delivery of drug, increasing targeting efficiency and so improving therapy efficacy. Owing to the considerable advances in material sciences and pharmaceutics, a broad range of different inorganic or organic drug nanocarriers have been developed. Furthermore, researchers have shown that the combination of inorganic and organic chemistries in one single material, named metal-organic framework (MOF), offers structural designability at the molecular level together with tunable porosity and chemical functionalisability. While the MOF size can be controlled at the nanometer scale, these features are of paramount interest in the development of the next generation of drug delivery systems. After a short state-of-the-art about MOF technology and within the drug delivery context, this paper discusses the benefits of using MOF nanoparticles compared to dendrimers and mesoporous silica nanoparticles in order to understand the challenges that must still be overcome.



http://ift.tt/2khdI0o

Biomechanically primed liver microtumor array as a high-throughput mechanopharmacological screening platform for stroma-reprogrammed combinatorial therapy

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Lu Zhu, Xingliang Fan, Bingjie Wang, Longwei Liu, Xiaojun Yan, Lyu Zhou, Yang Zeng, Mark C. Poznansky, Lili Wang, Huabiao Chen, Yanan Du
Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types. Here, a high-throughput mechanopharmacological drug screening platform for SRCT was established based on biomechanically primed hepatic stromal stellate cells to recapitulate state-specific liver microtumors with barrier effects. Fifteen generic chemotherapy drugs co-administered with VDR ligand were screened to obtain optimal SRCT formulations (e.g. carboplatin + calcipotriol), which efficacy was successfully verified in xenograft tumor models. Overall, this platform provides a powerful tool for discovery and optimization of tissue-specific SRCT and realizes 'mechanopharmacology' to translate insights of stromal mechanobiology to pharmaceutical applications.



http://ift.tt/2khnJLd

The impact of emotion intensity on recognition memory: Valence polarity matters

Publication date: Available online 7 February 2017
Source:International Journal of Psychophysiology
Author(s): Xianxin Meng, Ling Zhang, Wenwen Liu, XinSheng Ding, Hong Li, Jiemin Yang, JiaJin Yuan
Although the effects of emotion of different emotional intensity on memory have been investigated, it remain unclear whether the influence of emotional intensity on memory varies depending on the stimulus valence polarity (i.e., positive or negative). To address this, event-related potentials were recorded when subjects performed a continuous old/new discrimination task, for highly negative (HN), mildly negative (MN) and neutral pictures in the negative block; and for highly positive (HP), mildly positive (MP) and neutral pictures in the positive block. The results showed that relative to neutral stimuli, both HN and MN stimuli showed increased memory discrimination scores, and enhanced old/new effect in early FN400 (Frontal Negativity), but not late positive component (LPC) amplitudes. By contrast, relative to MP stimuli, HP and neutral stimuli showed increased memory discrimination scores and enhanced old/new effect in LPC but not FN400 amplitudes. Additionally, we observed a significant positive correlation between the memory discrimination score and the old/new effect in the amplitudes of the FN400 and LPC, respectively. These results indicate that both HN and MN stimuli were remembered better than neutral stimuli; whereas the recognition was worse for MP stimuli than Neutral and HP stimuli. In conclusion, in the present study, we observed that the effect of emotion intensity on memory depends on the stimulus valence polarity.



http://ift.tt/2liGkdL

Should bariatric surgery be performed in adolescents?

Adolescent obesity has markedly increased worldwide in both its extent and prevalence in recent decades and obesity prevention strategies are failing. As a result, effective treatment strategies are urgently needed. As behavioral and pharmacological treatment approaches have only moderate effects in severe obesity, bariatric surgery has begun to emerge as a treatment option. In this debate article, we offer arguments opposing and supporting bariatric surgery in the treatment of severe obesity in adolescents. Bariatric surgery has superior therapeutic outcomes with respect to weight loss and resolution of comorbid diseases over other existing treatments. However, long-term outcomes after bariatric surgery in adolescents are only just beginning to emerge. Furthermore, the procedures are generally considered irreversible, apart from gastric banding. Most importantly, not all adolescents seem to benefit greatly from bariatric surgery and we are not yet able to reliably identify those who stand to gain the greatest benefit. The authors agree that adolescent bariatric surgery should be offered exclusively within formal adolescent obesity programs, delivered by specialist multidisciplinary child/adolescent obesity teams, and within specialist centers, in order to optimize outcomes and minimize potential detrimental effects. Patients and their family/carers must be educated regarding the benefits and risks, potential side effects, expected changes in eating behavior and the lifelong requirement for regular medical follow-up after surgery. Before embarking upon a surgical treatment pathway in adolescents with severe obesity, it may also be beneficial to ensure compliance to treatment is demonstrated, in order to minimize the risk of nutritional deficiencies and associated potential complications.

http://ift.tt/2loKoGr

A comparison of lobectomy and total thyroidectomy in patients with papillary thyroid microcarcinoma: a retrospective individual risk factor-matched cohort study

Objective

Papillary thyroid microcarcinoma (PTMC) accounts for most of the increase in thyroid cancer in recent decades. We compared clinical outcomes and surgical complications of lobectomy and total thyroidectomy (TT) in PTMC patients.

Design and methods

In this retrospective individual risk factor-matched cohort study, 2031 patients with PTMC were initially included. Patients who underwent lobectomy or TT were one-to-one matched according to individual risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality and cervical lymph node (LN) metastasis.

Results

In total, 688 patients were assigned to each group. During the median 8.5 years of follow-up, 26 patients (3.8%) in the lobectomy group and 11 patients (1.6%) in the TT group had recurrences. The relative risk of recurrence was significantly less in the TT than that in the lobectomy group (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.21–0.81; P = 0.01). Most recurrences (84.6%) in the lobectomy group occurred in the contralateral lobe, and all patients were disease-free after completion of thyroidectomy. There were no significant differences in recurrence-free survival between the two groups after exclusion of contralateral lobe recurrences (HR, 2.75; 95% CI, 0.08–8.79; P = 0.08). There were significantly more patients with transient and permanent hypoparathyroidism in the TT than that in the lobectomy group (P < 0.001).

Conclusions

Lobectomy could be appropriate for most patients with PTMC when there is no evidence of extrathyroidal disease in the preoperative work-up. Preoperative and postoperative imaging studies are important for patients who undergo lobectomy for PTMC, because most recurrences are in the contralateral lobe.

http://ift.tt/2liGXUV

Dynamic GnRH and hCG testing: establishment of new diagnostic reference levels

Objective

Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after GnRH and hCG stimulation in healthy men and assess the impact of six single nucleotide polymorphisms on the responses.

Design

GnRH and hCG stimulation tests were performed on 77 healthy men, 18–40 years (reference group) at a specialized andrology referral center at a university hospital. The potential influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic–pituitary–gonadal axis.

Methods

Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC–MS/MS.

Results

For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. Testosterone increased approximately 110% (range: 18.7–67.6 nmol/L) during hCG testing. None of the polymorphisms had any major impact on the test results. Results from GnRH and hCG tests in patients compared with the reference group showed that the stimulated level and absolute increase in LH showed superior identification of patients compared with the relative increase, and the absolute change in testosterone was superior in identifying men with Leydig cell insufficiency, compared with the relative increase.

Conclusions

We provide novel reference ranges for GnRH and hCG test in healthy men, which allows future diagnostic evaluation of hypothalamic–pituitary–gonadal disorders in men.

http://ift.tt/2lowPqp

A universal aptameric biosensor: Multiplexed detection of small analytes via aggregated perylene-based broad-spectrum quencher

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Rong Hu, Xi Zhang, Qiang Xu, Dan-Qing Lu, Yun-Hui Yang, Quan-Qing Xu, Qiong Ruan, Liu-Ting Mo, Xiao-Bing Zhang
A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets.



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Piezoelectric immunochip coated with thin films of bacterial cellulose nanocrystals for dengue detection

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Cleverton Luiz Pirich, Rilton Alves de Freitas, Roberto Manuel Torresi, Guilherme Fadel Picheth, Maria Rita Sierakowski
Low-cost piezoelectric devices, such as simple frequency monitoring quartz crystal microbalance (QCM) devices, have good clinical utility as fast diagnostic tools for the detection of several diseases. However, unspecific antigen recognition, poor molecular probe adsorption and the need for sample dilution are still common drawbacks that hinder their use in routine diagnosis. In this work, piezoelectric sensors were previously coated with thin films of bacterial cellulose nanocrystals (CN) to provide a more sensitive and adapted interface for the attachment of monoclonal immunoglobulin G (IgGNS1) and to favor specific detection of non-structural protein 1 (NS1) of dengue fever. The assembly of the immunochip surface was analyzed by atomic force microscopy (AFM) and the NS1 detection was followed by quartz crystal microbalance with (QCM-D) and without energy dissipation monitoring (QCM). The CN surface was able to immobilize 2.30±0.5mgm⁻² of IgGNS1, as confirmed by AFM topography and phase images along with QCM-D. The system was able to detect the NS1 protein in serum with only 10-fold dilution in the range of 0.01–10µgmL⁻¹ by both QCM and QCM-D. The limits of detection of the two devices were 0.1μgmL⁻¹ for QCM-D and 0.32μgmL⁻¹ for QCM. As a result, QCM-D and QCM apparatuses can be used to follow NS1 recognition and have good potential for more sensitive, fast and/or less expensive diagnostic assays for dengue.

Graphical abstract

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Development of biohybrid immuno-selective membranes for target antigen recognition

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Francesca Militano, Teresa Poerio, Rosalinda Mazzei, Simona Salerno, Loredana De Bartolo, Lidietta Giorno
Membranes are gaining increasing interest in solid-phase analytical assay and biosensors applications, in particular as functional surface for bioreceptors immobilization and stabilization as well as for the concentration of target molecules in microsystems.In this work, regenerated cellulose immuno-affinity membranes were developed and they were used for the selective capture of interleukin-6 (IL-6) as targeted antigen. Protein G was covalently linked on the membrane surface and it was successfully used for the oriented site-specific antibody immobilization. The antibody binding capacity of the protein G-coupled membrane was evaluated. The specific anti IL-6 antibody was immobilized and a quantitative analysis of the amount of IL-6 captured by the immuno-affinity membrane was performed. The immobilization procedure was optimized to eliminate the non-specific binding of antigen on the membrane surface. Additionally, the interaction between anti IL-6 antibody and protein G was stabilized by chemical cross-linking with glutaraldehyde and the capture ability of immuno-affinity membranes, with and without the cross-linker, was compared. The maximum binding capacity of the protein G-coupled membrane was 43.8µg/cm² and the binding efficiency was 88%. The immuno-affinity membranes showed a high IL-6 capture efficiency at very low antigen concentration, up to a maximum of 91%, the amount of captured IL-6 increased linearly as increasing the initial concentration. The cross-linked surface retained the antigen binding capacity demonstrating its robustness in being reused, without antibody leakage or reduction in antibody binding capacity. The overall results demonstrated the possibility of a reliable application of the immuno-affinity membrane developed for biosensors and bioassays also in multiple use.



http://ift.tt/2kFRnL4

Electrospun template directed molecularly imprinted nanofibers incorporated with BiOI nanoflake arrays as photoactive electrode for photoelectrochemical detection of triphenyl phosphate

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Xiaomin Yang, Xin Li, Lizhi Zhang, Jingming Gong
Triphenyl Phosphate (TPhP), as a typical model of organophosphorus flame retardants (OPFRs), has been regarded as emerging environmental contaminants of health concern. In this study, a rapid and highly sensitive visible-light-response PEC sensor has been developed for the detection of Triphenyl Phosphate (TPhP) using electrospun template directed molecularly imprinted nanofibers modified BiOI nanoflake arrays (BiOINFs) as a photoactive electrode. The molecularly imprinted electrospun nanofibers (labeled as MI-ESNFs) were carefully characterized by scanning electron microscopy (SEM), UV spectra, FTIR spectra measurements and various electrochemical techniques. Under the optimized experimental conditions, the photoelectrochemical response was linearly proportional to the logarithm value of TPhP concentrations in the range of 0.01ngmL⁻¹ to 500ngmL⁻¹. Meanwhile, the sensor exhibited high selectivity and stability.



http://ift.tt/2kpJUkQ

The preparation of dual-functional hybrid nanoflower and its application in the ultrasensitive detection of disease-related biomarker

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yucheng Liu, Jinyang Chen, Mingyuan Du, Xinxin Wang, Xinghu Ji, Zhike He
In this work, dual-functional streptavidin (SA)-horseradish peroxidase (HRP) hybrid nanoflowers, integrating the functions of biological recognition and signal amplification, were prepared through facile one-pot green synthesis method. The prepared SA-HRP-Cu3(PO4)2 hybrid nanoflowers loaded abundant HRP and simultaneously exhibited enhanced catalytic activity, stability, and durability compared with free enzyme, which fits greatly well with the requirement of signal tag for bioassay. Besides, due to the general SA-biotin linking interaction, the SA-HRP-Cu3(PO4)2 hybrid nanoflowers possess universal capture ability to the biotinylated antibody. Hence, combined with enzyme-linked immunosorbent assay (ELISA), the dual-functional hybrid nanoflowers were used to construct a colorimetric sensor for the ultrasensitive detection of alpha-fetoprotein (AFP). The detection limit is 78pg/mL, which is far superior to commercial ELISA kits. This presented approach holds great promise to develop on-demand hybrid system for a variety of applications ranging from biosensor and biomedicine to biocatalytic process.



http://ift.tt/2kFN1U2

A kinetic study of bitter taste receptor sensing using immobilized porcine taste bud tissues

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Lihui Wei, Lixin Qiao, Guangchang Pang, Junbo Xie
At present, developing an efficient assay method for truly reflecting the real feelings of gustatory tissues is of great importance. In this study, a novel biosensor was fabricated to investigate the kinetic characteristics of the receptors in taste bud tissues sensing bitter substances for the first time. Porcine taste bud tissues were used as the sensing elements, and the sandwich-type sensing membrane was fixed onto a glassy carbon electrode for assembling the biosensor. With the developed sensor, the response currents induced by sucrose octaacetate, denatonium benzoate, and quercetin stimulating corresponding receptors were determined. The results demonstrated that the interaction between the analyst with their receptors were fitting to hyperbola (R²=0.9776, 0.9980 and 0.9601), and the activation constants were 8.748×10⁻¹⁵mol/L, 1.429×10^–12mol/L, 6.613×10^–14mol/L, respectively. The average number of receptors per cell was calculated as 1.75, 28.58, and 13.23, while the signal amplification factors were 1.08×10⁴, 2.89×10³ and 9.76×10⁴. These suggest that the sensor can be used to quantitatively describe the interaction characteristics of cells or tissue receptors with their ligands, the role of cellular signaling cascade, the number of receptors, and the signal transmission pathways.



http://ift.tt/2kFOpWF

Editorial Board ((ofc))

Publication date: March 2017
Source:Acta Histochemica, Volume 119, Issue 2





http://ift.tt/2kkvrEk

Biomechanically primed liver microtumor array as a high-throughput mechanopharmacological screening platform for stroma-reprogrammed combinatorial therapy

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Lu Zhu, Xingliang Fan, Bingjie Wang, Longwei Liu, Xiaojun Yan, Lyu Zhou, Yang Zeng, Mark C. Poznansky, Lili Wang, Huabiao Chen, Yanan Du
Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types. Here, a high-throughput mechanopharmacological drug screening platform for SRCT was established based on biomechanically primed hepatic stromal stellate cells to recapitulate state-specific liver microtumors with barrier effects. Fifteen generic chemotherapy drugs co-administered with VDR ligand were screened to obtain optimal SRCT formulations (e.g. carboplatin + calcipotriol), which efficacy was successfully verified in xenograft tumor models. Overall, this platform provides a powerful tool for discovery and optimization of tissue-specific SRCT and realizes 'mechanopharmacology' to translate insights of stromal mechanobiology to pharmaceutical applications.



http://ift.tt/2khnJLd

Enhanced critical-size calvarial bone healing by ASCs engineered with Cre/loxP-based hybrid baculovirus

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Shih-Chun Lo, Kuei-Chang Li, Yu-Han Chang, Mu-Nung Hsu, Li-Yu Sung, Truong Anh Vu, Yu-Chen Hu
Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell-derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs. We demonstrated that transduction of rat ASCs with the hybrid Cre/loxP-based baculovirus enabled robust and sustained expression of functional BMP-2 and SDF-1. Expression of BMP-2 or SDF-1 alone failed to effectively induce rat ASCs osteogenesis and healing of critical-size calvarial bone defects. Nonetheless, prolonged BMP-2/SDF-1 co-expression in ASCs synergistically activated both Smad and ERK1/2 pathways and hence potentiated the osteogenesis. Consequently, transplantation of the hybrid baculovirus-engineered, BMP-2/SDF-1-expressing ASCs/scaffold constructs potently healed the critical-size (6 mm) calvarial bone defects (filling ≈70% of defect volume), which considerably outperformed the calvarial bone repair using BMP-2/SDF-1 delivered with biomaterial-based scaffolds. These data implicated the potential of Cre/loxP-based hybrid baculovirus vector for ASCs engineering and calvarial bone healing.



http://ift.tt/2jXNzI2

Nano-on-micro fibrous extracellular matrices for scalable expansion of human ES/iPS cells

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Li Liu, Ken-ichiro Kamei, Momoko Yoshioka, Minako Nakajima, Junjun Li, Nanae Fujimoto, Shiho Terada, Yumie Tokunaga, Yoshie Koyama, Hideki Sato, Kouichi Hasegawa, Norio Nakatsuji, Yong Chen
Human pluripotent stem cells (hPSCs) hold great potential for industrial and clinical applications. Clinical-grade scaffolds and high-quality hPSCs are required for cell expansion as well as easy handling and manipulation of the products. Current hPSC culture methods do not fulfill these requirements because of a lack of proper extracellular matrices (ECMs) and cell culture wares. We developed a layered nano-on-micro fibrous cellular matrix mimicking ECM, named "fiber-on-fiber (FF)" matrix, which enables easy handling and manipulation of cultured cells. While non-woven sheets of cellulose and polyglycolic acid were used as a microfiber layer facilitating mechanical stability, electrospun gelatin nanofibers were crosslinked on the microfiber layer, generating a mesh structure with connected nanofibers facilitating cell adhesion and growth. Our results showed that the FF matrix supports effective hPSC culture with maintenance of their pluripotency and normal chromosomes over two months, as well as effective scaled-up expansion, with fold increases of 54.1 ± 15.6 and 40.4 ± 8.4 in cell number per week for H1 human embryonic stem cells and 253G1 human induced pluripotent stem cells, respectively. This simple approach to mimick the ECM may have important implications after further optimization to generate lineage-specific products.



http://ift.tt/2kk8Ckc

Positioning metal-organic framework nanoparticles within the context of drug delivery – A comparison with mesoporous silica nanoparticles and dendrimers

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Stefan Wuttke, Marjorie Lismont, Alberto Escudero, Bunyarat Rungtaweevoranit, Wolfgang J. Parak
Nanotechnology enables the creation of delivery vehicles able to overcome physiologically imposed barriers, allowing new approaches for reducing the unwanted side effects of systemic delivery of drug, increasing targeting efficiency and so improving therapy efficacy. Owing to the considerable advances in material sciences and pharmaceutics, a broad range of different inorganic or organic drug nanocarriers have been developed. Furthermore, researchers have shown that the combination of inorganic and organic chemistries in one single material, named metal-organic framework (MOF), offers structural designability at the molecular level together with tunable porosity and chemical functionalisability. While the MOF size can be controlled at the nanometer scale, these features are of paramount interest in the development of the next generation of drug delivery systems. After a short state-of-the-art about MOF technology and within the drug delivery context, this paper discusses the benefits of using MOF nanoparticles compared to dendrimers and mesoporous silica nanoparticles in order to understand the challenges that must still be overcome.



http://ift.tt/2khdI0o

Shape-controlled fabrication of magnetite silver hybrid nanoparticles with high performance magnetic hyperthermia

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Qi Ding, Dongfang Liu, Dawei Guo, Fang Yang, Xingyun Pang, Renchao Che, Naizhen Zhou, Jun Xie, Jianfei Sun, Zhihai Huang, Ning Gu
Superparamagnetic Fe3O4 nanoparticles (NPs)-based hyperthermia is a promising non-invasive approach for cancer therapy. However, the heat transfer efficiency of Fe3O4 NPs is relative low, which hinders their practical clinical applications. Therefore, it is promising to improve the magnetic hyperthermia efficiency by exploring the higher performance magnetic NPs-based hybrid nanostructures. In the current study, it presents a straightforward in situ reduction method for the shape-controlled preparation of magnetite (Fe3O4) silver (Ag) hybrid NPs designed as magnetic hyperthermia heat mediators. The magnetite silver hybrid NPs with core-shell (Fe3O4@Ag) or heteromer (Fe3O4-Ag) structures exhibited a higher biocompatibility with SMMC-7721 cells and L02 cells than the individual Ag NPs. Importantly, in the magnetic hyperthermia, with the exposure to alternating current magnetic field, the Fe3O4@Ag and Fe3O4-Ag hybrid NPs indicated much better tumor suppression effect against SMMC-7721 cells than the individual Fe3O4 NPs in vitro and in vivo. These results demonstrate that the hybridisation of Fe3O4 and Ag NPs could greatly enhance the magnetic hyperthermia efficiency of Fe3O4 NPs. Therefore, the Fe3O4@Ag and Fe3O4-Ag hybrid NPs can be used to be as high performance magnetic hyperthermia mediators based on a simple and effective preparation approach.



http://ift.tt/2k0Muil

Antibacterial effects of titanium embedded with silver nanoparticles based on electron-transfer-induced reactive oxygen species

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Guomin Wang, Weihong Jin, Abdul Mateen Qasim, Ang Gao, Xiang Peng, Wan Li, Hongqing Feng, Paul K. Chu
Although titanium embedded with silver nanoparticles (Ag-NPs@Ti) are suitable for biomedical implants because of the good cytocompatibility and antibacterial characteristics, the exact antibacterial mechanism is not well understood. In the present work, the antibacterial mechanisms of Ag-NPs@Ti prepared by plasma immersion ion implantation (PIII) are explored in details. The antibacterial effects of the Ag-NPs depend on the conductivity of the substrate revealing the importance of electron transfer in the antibacterial process. In addition, electron transfer between the Ag-NPs and titanium substrate produces bursts of reactive oxygen species (ROS) in both the bacteria cells and culture medium. ROS leads to bacteria death by inducing intracellular oxidation, membrane potential variation, and cellular contents release and the antibacterial ability of Ag-NPs@Ti is inhibited appreciably after adding ROS scavengers. Even though ROS signals are detected from osteoblasts cultured on Ag-NPs@Ti, the cell compatibility is not impaired. This electron-transfer-based antibacterial process which produces ROS provides insights into the design of biomaterials with both antibacterial properties and cytocompatibility.



http://ift.tt/2kkocMq

Expression of metallothionein in dimethylhydrazine-induced colonic precancerous and cancerous model in rat

Pamela Christudoss, Geeta Chacko, Ratnasamy Selvakumar, Jude Joseph Fleming, Srinivasan Pugazhendhi, George Mathew

Journal of Cancer Research and Therapeutics 2016 12(4):1307-1312

Aim: Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess the MT mRNA gene expression as well as the MT protein content by immunohistochemistry and radioimmunoassay (RIA) in 1,2-dimethylhydrazine (DMH)-induced precancerous and cancerous colonic tissue in rats. Materials and Methods: Six-week-old rats were given subcutaneous injections of DMH twice a week for 3 months and sacrificed at 4 months (precancerous model) and 6 months (cancerous model). We determined MT mRNA expression by reverse transcription polymerase chain reaction and MT protein content by both immunohistochemical expression and cadmium-109 RIA. Results: MT mRNA expression in the large intestine showed statistically significant decrease in the precancerous (P < 0.01) and the cancerous (P < 0.001) model as compared with controls. Immunohistochemical expression of MT showed statistically significant decrease (P < 0.05) in the colonic cancerous tissue. MT content in the large intestine showed statistically significant decrease in precancerous (P < 0.005) and cancerous (P < 0.001) model as compared with controls. Conclusion: This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.

http://ift.tt/2kpyCga

Adjuvant treatment for Stage I seminoma: Why radiotherapy is better than carboplatin

Prahlad H Yathiraj, Krishna Sharan, Donald J Fernandes, MS Vidyasagar

Journal of Cancer Research and Therapeutics 2016 12(4):1216-1219

Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.

http://ift.tt/2kFPUo4

Synergistic induction of apoptosis in B-cell chronic lymphocytic leukemia cells after treatment with all-trans retinoic acid in combination with interleukin-21 and rituximab

Kazem Abbaszadeh-Goudarzi, Fazel Shokri, Mostafa Hosseini, Farhad Jadidi-Niaragh, Ghasem Ghalamfarsa, Ali Akbar Saboor-Yaraghi

Journal of Cancer Research and Therapeutics 2016 12(4):1278-1283

Aim: B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world and characterized by the progressive expansion of malignant B lymphocytes in peripheral blood. In spite of advances in sciences to recognize the number of effective agents for the treatment of chronic lymphocytic leukemia (CLL), this leukemia is thought as incurable one. Introducing a new therapy that has a direct effect on B-CLL lymphocytes and no cytotoxic effects on the other cells is a great wish. Materials and Methods: Twenty-one patients with B-CLL were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood samples and were further treated with all-tans retinoic acid (ATRA), interleukin (IL-21), and rituximab at concentrations of 30 ng/ml, 25 ng/ml, and 4 μg/ml, respectively. ATRA, IL21, and rituximab were used alone or in various combinations and their effects on apoptosis were measured using annexin V-fluorescein isothiocyanate apoptosis detection kit. Result: Treatment of the patients' cells with IL21 and rituximab showed a synergistic effect on the induction of apoptosis, in comparison with untreated CLL cells (P < 0.05). The induction of apoptosis by ATRA in combination with IL21 and rituximab were significantly increased compared to untreated CLL cells as a negative control (P < 0.01). Conclusion: Treatment of patients' PBMCs by ATRA in combination with IL21 and rituximab and also IL21 in combination with rituximab showed synergistic induction of apoptosis compared to untreated CLL cells as a negative control (P < 0.01). It seems that ATRA in combination with IL21 and rituximab activate different pathways of apoptosis (extrinsic pathway, intrinsic pathway, and granzyme B pathway).

http://ift.tt/2kpK2Rn

Palbociclib: A new hope in the treatment of breast cancer

R Priyadharsini Palanisamy

Journal of Cancer Research and Therapeutics 2016 12(4):1220-1223

Breast cancer being one of the common cancers has high morbidity and mortality. Despite the conventional treatment, the burden of the disease increases year after year. There is a need for newer drugs that target the different mechanisms in the pathogenesis. The interaction of cyclins with cyclin dependent kinases (CDKs) plays a major role in the abnormal cell cycle in cancer and it is considered to be an important target. Palbociclib is a CDK inhibitor currently approved for the treatment of breast cancer. The preclinical studies with breast cancer lines were sensitive to palbociclib and the clinical trials phase I, phase II (PALOMA 1), and phase III (PALOMA 2, 3, PENTELOPE, PEARL) showed that the drug was efficacious when combined other conventional drugs for breast cancer. Palbociclib was also been tested in various other germ cell tumors, melanoma, multiple myeloma, glioblastoma multiforme etc., The major adverse effect of the drug includes hematological toxicity mainly neutropenia, gastrointestinal adverse effects.

http://ift.tt/2kFuuY1

A case of unilateral atypical orofacial pain with Eagle's syndrome

GV Sowmya, Mohit Pal Singh, BS Manjunatha, Prashant Nahar, Madhusudan Astekar

Journal of Cancer Research and Therapeutics 2016 12(4):1323-1323

Eagle's syndrome is not an uncommon condition, but less known to physicians, where an elongated styloid process or calcified stylohyoid ligament compresses the adjacent anatomical structures leading to orofacial pain. Diagnosis is made with appropriate radiological examination. Nonsurgical treatment options include reassurance, analgesia, and anti.inflammatory medications; and the surgical option includes a transoral or external approach. Here, we present a case report of a male patient, of age38 years, with a chief complaint of unilateral atypical orofacial pain on the right side of his face radiating to the neck region, for the last two months.

http://ift.tt/2kpyA82

Membrane-bound versus soluble major histocompatibility complex Class I-related chain A and major histocompatibility complex Class I-related chain B differential expression: Mechanisms of tumor eradication versus evasion and current drug development strategies

PK Suresh

Journal of Cancer Research and Therapeutics 2016 12(4):1224-1233

Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor. Among the evasion strategies developed by tumors, the metalloprotease-dependent shedding of MICA/MICB from tumors (either the free or the exosome form) can contribute to the inhibition of cytolysis by the immune effector cells (all NK cells, most NKT cells; γδ CD8+ T cells and αβ CD8+ T cells, as well as some αβ CD4+ T cells). There are micro-RNA clusters that regulate surface expression and shedding. Polymorphic variants can be used as susceptibility/associative markers and can also possibly be used to correlate with tumor survival as well as staging/grading of tumors. Variations in the expression level require quantification of this marker for diagnostic/prognostic and therapeutic purposes. Mechanism-based studies would provide a better tumor-specific understanding of their relative roles in the processes of tumor cell elimination versus growth and progression. Last but not least, conventional, interlaboratory validated assays (for, e.g., antibody-based methods) should be replaced by robust, reproducible, feasible biophysics-based methods using tumor biopsies. Further, correlative DNA polymorphism-based studies can be done using biological fluids (for, e.g., human saliva) that can be sampled by minimally invasive means.

http://ift.tt/2kFxYKb

Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma

Rongna Wei, Zhiqun Shang, Jing Leng, Lihong Cui

Journal of Cancer Research and Therapeutics 2016 12(4):1291-1297

Purpose: Although high-mobility group A2 (HMGA2) protein has been reported to participate in cancer progression and metastasis, its clinical relationship with tumor invasion, lymph node metastasis, and prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to analyze the clinical and prognostic significance of HMGA2 in ESCC patients after curative resection. Materials and Methods: The expression of HMGA2 protein was evaluated by using immunohistochemistry in a tissue microarray (TMA) containing ESCC lesions and adjacent normal esophageal epithelial tissues from 96 patients who had undergone curative resection. TMA was constructed by Shanghai Biochip Co. Ltd., Shanghai, China. The relationship between HMGA2 expression and clinicopathological parameters and prognosis was further analyzed. Results: HMGA2 expression was significantly higher in ESCC tissues compared with that of the adjacent noncancerous tissues (P < 0.001). High expression of HMGA2 was significantly related to tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage (P < 0.05). Patients with low expression of HMGA2 had a better prognosis than those with high expression (χ2 = 5.069, P = 0.024). Univariate analysis showed that age (P = 0.041), depth of tumor invasion (P = 0.031), lymph node status (P = 0.001), and HMGA2 expression (P = 0.024) were correlated with prognosis. Multivariate analysis showed that HMGA2 expression (hazard ratio [HR]: 0.539; 95% confidence interval [95% CI]: 0.302–0.963, P = 0.037) and lymph node metastasis (HR: 0.504; 95% CI: 0.310–0.820, P = 0.006) were independent prognostic factors for overall survival. Conclusions: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.

http://ift.tt/2kpCHB7

Prophylactic role of some plants and phytochemicals against radio-genotoxicity in human lymphocytes

Mohsen Cheki, Ehsan Mihandoost, Alireza Shirazi, Aziz Mahmoudzadeh

Journal of Cancer Research and Therapeutics 2016 12(4):1234-1242

Genotoxicity in lymphocytes of cancer patients undergoing radiotherapy can lead to lymphocytopenia. Lymphocytopenia induced by radiotherapy is one of the most unfavorable prognostic biological markers in cancer patients, since it has been accepted to be associated with poor prognosis in terms of both survival time and response to cancer therapy. Therefore, reduction in lymphocytopenia may increase treatment efficiency. Research endeavors with synthetic radioprotectors in the past have met with little success primarily due to toxicity-related problems. These disadvantages have led to interest on the use of some plants and phytochemicals as radioprotector. The aim of this paper is to review protective role of some plants and phytochemicals against genotoxicity-induced by ionizing radiation in human blood lymphocytes. Therefore, current review may help the future researches to decrease lymphocytopenia in radiotherapeutic clinical trials.

http://ift.tt/2kFNNAy

The diagnosis of mesenteric fibromatosis: A 90-month five patients case report

Peixin Li, Zhongtao Zhang, Shengqi Qin, Jianshe Li

Journal of Cancer Research and Therapeutics 2016 12(4):1318-1320

Mesenteric fibromatosis (MF) is a rare tumor (2–4 cases per 1 million people annually) with few presented features. In this case study, we reported five MF patients, one of whom suffered a recurrence. Patients received renogram, colonoscopy, cystoscopy, and gastrointestinal examinations. Histology and immunohistochemistry evaluations were performed after the surgical resection. Hormone levels were measured before and after the surgery. It was found that clinical imaging readily confirmed an abnormal mass but was unable to distinguish MF from other tumors. Histology and immunohistochemistry were definitive diagnoses because the tissue was vimentin ± β–catenin ± CD117−/CD34−. Furthermore, the patient who suffered a recurrence showed an elevated estrogen level. A 6-month postoperative administration of letrozole drove the estrogen down to normal level. Our study showed that vimentin, β–catenin, CD117, and CD34 were the markers for MF whereas medical imaging, and estrogen level could be used for the complimentary purpose.

http://ift.tt/2kpK2AR

Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy

Douglas E Holt, Mark E Bernard, Kimmen Quan, David A Clump, Johnathan A Engh, Steven A Burton, Dwight E Heron

Journal of Cancer Research and Therapeutics 2016 12(4):1243-1248

Background: Glioblastoma multiforme (GBM) carries a poor prognosis with high recurrence rates. Salvage stereotactic radiosurgery (SRS) may be an effective treatment option. Methods: We retrospectively reviewed 34 patients (41 lesions) treated with salvage SRS for recurrent GBM between 2004 and 2012. Initial surgical treatments were gross total resection (58%), subtotal resection (STR) (24%), and biopsy (18%). All patients were treated with prior radiation therapy. Recurrent disease was treated with salvage SRS with a median dose and fractions of 23.4 Gy (range, 12–30) and 3 (range, 1–3), respectively. Cox proportional hazards regression was conducted to establish predictive factors (P ≤ 0.05) Results: Median follow-up from salvage SRS was 10.8 months (interquartile range [IQR], 7.0–15.6). The median time from initial radiation therapy to salvage SRS was 13.7 months (IQR, 2.9–25.0). The 6- and 12-month overall survival from salvage SRS were 84.9% and 42.5%, respectively. On univariate analysis, STR was associated with inferior survival from salvage SRS (P ≤ 0.05). The 6- and 12-month local control (LC) estimates were 63.1% and 16.4%, respectively. On univariate analysis, higher biological effective dose and prior temozolomide were associated with superior LC. Concerning toxicity, there were 4 (12%) grade 2 and 1 (3%) grade 3 adverse events within this patient series. No grade 4 or grade 5 toxicities were observed. Conclusion: Our outcomes suggest that SRS is a feasible treatment option with acceptable salvage survival rates, given the poor prognosis of this disease.

http://ift.tt/2kFxX95

One last time

Nagraj Huilgol

Journal of Cancer Research and Therapeutics 2016 12(4):1215-1215



http://ift.tt/2kpHZwr

Prediction of heterogeneity in breast cancer immunophenotype at ductal carcinoma in situ stage?

Manish Rohilla, Amanjit Bal, Gurpreet Singh, Kusum Joshi

Journal of Cancer Research and Therapeutics 2016 12(4):1249-1256

Introduction: Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage. Materials and Methods: Precise prevalence of molecular subtypes of pure DCIS and DCIS component of infiltrating duct carcinoma (IDC) was evaluated using immunohistochemistry and correlated with known prognostic factors. Results: DCIS cases were classified as luminal A (46.6% in each group), luminal B (pure DCIS 20% and DCIS component of IDC 13.3%), HER2 overexpressing, basal and nonbasal (pure DCIS 3.3% and 26.6% and DCIS component of IDC 3.3% and 33.3%, respectively), and triple negative, nonbasal (pure DCIS and DCIS component of IDC 3.3% each). The molecular phenotype of DCIS correlated well with that of the coexisting IDC. Conclusions: This study demonstrated molecular heterogeneity in DCIS; however, similar molecular phenotypes were seen in the coexisting IDC suggesting that DCIS is a precursor lesion and can predict phenotype of the invasive component. This also suggests that the invasiveness of DCIS is not dependent solely on the molecular character of the tumor epithelial cells, but factors such as tumor microenvironment may play a role.

http://ift.tt/2kFI1ik

Enhanced cytotoxic activity of endophytic bacterial extracts from Adhatoda beddomei leaves in A549 lung cancer cell lines

Y Swarnalatha, Bhaswti Saha

Journal of Cancer Research and Therapeutics 2016 12(4):1284-1290

Aim of the Study: The current study is aimed to isolate and study the efficacy of the anticancer activity of endophytic bacteria from adhatoda beddomei leaves. Endophytic bacteria, microorganisms can found in the plant tissues, like leaves, branches and roots and able to produce various novel secondary metabolites for the medicinal applications. Methodology: Endophytic bacteria were isolated from the leaves of the adhatoda beddomei leaves. The extract from the culture was tested for the cytotoxicity in A549 cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay, dual staining and nuclear staining. Results: The expression of the apoptotic and proliferative genes were assessed with the reverse transcriptase polymerase chain reaction (RT-PCR) comparing with the control gene. The inhibitory concentration (IC50) of the bacterial extract was found to be 43.97 μg/ml. With the dual staining the apoptotic cell percentage was significantly increased (P < 0.001) and with the 40μg/ml and 80μg/ml concentration the apoptotic percentages observed as 67% and 89% respectively. Similar concentrations were used for the nuclear fragmentation (PI) and the cell cycle analysis (FACS) using WinMDI 2.9 software. During cell cycle analysis the accumulation of the cells at G0-G1 stage was observed with increasing concentrations of the chi-alg encophytic bacterial extract nanoparticles. Finally the proapoptotic and proliferative gene expression for the bax, Bcl-2 and caspase was significantly regulated (P < 0.01; P < 0.05). The Bax and Caspase were up-regulated and Bcl-2 was down regulated. Conclusion: The results conclude that enophytic bacterial extract possess good cytotoxic activity.

http://ift.tt/2kpDrXb