Intraoperative Techniques for the Plastic Surgeon to Improve Pain Control in Breast Surgery

Summary: In recent years, there has been a growing emphasis placed on reducing length of hospital stay and health costs associated with breast surgery. Adequate pain control is an essential component of enhanced recovery after surgery. Postoperative pain management strategies include use of narcotic analgesia, non-narcotic analgesia, and local anesthetics. However, these forms of pain control have relatively brief durations of action and multiple-associated side effects. Intraoperative regional blocks have been effectively utilized in other areas of surgery but have been understudied in breast surgery. The aim of this article was to review various intraoperative techniques for regional anesthesia and local pain control in breast surgery and to highlight areas of future technique development.

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Pemetrexed-induced painful erythematous nodules in both legs in a patient with recurrent mesothelioma

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Resuscitative endovascular balloon occlusion of the aorta may increase the bleeding of minor thoracic injury in severe multiple trauma patients: a case report

The resuscitative endovascular balloon occlusion of the aorta, because of its efficacy and feasibility, has been widely used in treating patients with severe torso trauma. However, complications developing aro...

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Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases

Publication date: Available online 13 December 2017
Source:Progress in Neurobiology
Author(s): Mithilesh Kumar Jha, Jong-Heon Kim, Gyun Jee Song, Won-Ha Lee, In-Kyu Lee, Ho-Won Lee, Seong Soo A. An, SangYun Kim, Kyoungho Suk
Astrocytes, which are homeostatic cells of the central nervous system (CNS), display remarkable heterogeneity in their morphology and function. Besides their physical and metabolic support to neurons, astrocytes modulate the blood-brain barrier, regulate CNS synaptogenesis, guide axon pathfinding, maintain brain homeostasis, affect neuronal development and plasticity, and contribute to diverse neuropathologies via secreted proteins. The identification of astrocytic proteome and secretome profiles has provided new insights into the maintenance of neuronal health and survival, the pathogenesis of brain injury, and neurodegeneration. Recent advances in proteomics research have provided an excellent catalog of astrocyte-secreted proteins. This review categorizes astrocyte-secreted proteins and discusses evidence that astrocytes play a crucial role in neuronal activity and brain function. An in-depth understanding of astrocyte-secreted proteins and their pathways is pivotal for the development of novel strategies for restoring brain homeostasis, limiting brain injury/inflammation, counteracting neurodegeneration, and obtaining functional recovery.

Graphical abstract

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The forgotten organ

Publication date: Available online 13 December 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): L.M. Roussel, C. Escalard, M. Hitier




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Considerations in Setting Up and Planning a Graft Processing Facility

Publication date: Available online 13 December 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Mickey B.C. Koh




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Sclerosing lipogranuloma presenting as movable masses induced by large doses of progesterone injection

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Early cutaneous eruptions after oral hydroxychloroquine in a lupus erythematosus patient: A case report and review of the published work

Abstract

Hydroxychloroquine (HCQ) is an effective treatment of lupus erythematosus. Although adverse effects, mainly gastrointestinal and cutaneous manifestations, are rare, they may result in the cessation of medication in some patients with severe reactions. Therefore, the evaluation of a patient's condition is important for a dermatologist to decide whether to cease or continue HCQ. We herein report a case of a 36-year-old Japanese woman with systemic lupus erythematosus and cutaneous eruptions caused by the p.o. administration of HCQ. Because she wanted to continue the medication and had only mild cutaneous eruptions without any adverse effects in other organs, we continued HCQ with careful monitoring. All cutaneous eruptions disappeared within 1 week. We also reviewed published case reports on skin lesions that developed after HCQ treatments, and propose strategies for early cutaneous eruptions after HCQ treatments. When the cutaneous reactions are mild without any reactions in other organs, withdrawal of the drug is not required. However, when cutaneous eruptions are accompanied by some common reactions, HCQ needs to be stopped for a period of time and may subsequently be carefully re-administrated.

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When Clarity Is Crucial: Regulating Ocular Surface Immunity

Publication date: Available online 14 December 2017
Source:Trends in Immunology
Author(s): William Foulsham, Giulia Coco, Afsaneh Amouzegar, Sunil K. Chauhan, Reza Dana
The ocular surface is a unique mucosal immune compartment in which anatomical, physiological, and immunological features act in concert to foster a particularly tolerant microenvironment. These mechanisms are vital to the functional competence of the eye, a fact underscored by the devastating toll of excessive inflammation at the cornea – blindness. Recent data have elucidated the contributions of specific anatomical components, immune cells, and soluble immunoregulatory factors in promoting homeostasis at the ocular surface. We highlight research trends at this distinctive mucosal barrier and identify crucial gaps in our current knowledge.



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Hypoxia Inducible Factors Modify Collagen I Fibers in MDA-MB-231 Triple Negative Breast Cancer Xenografts

Publication date: February 2018
Source:Neoplasia, Volume 20, Issue 2
Author(s): Eibhlin Goggins, Samata Kakkad, Yelena Mironchik, Desmond Jacob, Flonne Wildes, Balaji Krishnamachary, Zaver M. Bhujwalla
Hypoxia inducible factors (HIFs) are transcription factors that mediate the response of cells to hypoxia. HIFs have wide-ranging effects on metabolism, the tumor microenvironment (TME) and the extracellular matrix (ECM). Here we investigated the silencing effects of two of the three known isoforms, HIF-1α and HIF-2α, on collagen 1 (Col1) fibers, which form a major component of the ECM of tumors. Using a loss-of-function approach for HIF-1α or 2α or both HIF-1α and 2α, we identified a relationship between HIFs and Col1 fibers in MDA-MB-231 tumors. Tumors derived from MDA-MB-231 cells with HIF-1α or 2α or both HIF-1α and 2α silenced contained higher percent fiber volume and lower inter-fiber distance compared to tumors derived from empty vector MDA-MB-231 cells. Depending upon the type of silencing, we observed changes in Col1 degrading enzymes, and enzymes involved in Col1 synthesis and deposition. Additionally, a reduction in lysyl oxidase protein expression in HIF-down-regulated tumors suggests that more non-cross-linked fibers were present. Collectively these results identify the role of HIFs in modifying the ECM and the TME and provide new insights into the effects of hypoxia on the tumor ECM.



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A Low-Toxicity DNA-Alkylating N-Mustard-Quinoline Conjugate with Preferential Sequence Specificity Exerts Potent Antitumor Activity Against Colorectal Cancer

Publication date: February 2018
Source:Neoplasia, Volume 20, Issue 2
Author(s): Tai-Lin Chen, Yi-Wen Lin, Yan-Bo Chen, Jing-Jer Lin, Tsann-Long Su, Chia-Ning Shen, Te-Chang Lee
Efficacy and safety are fundamental prerequisites for anticancer drug development. In the present study, we explored the anti–colorectal cancer (CRC) activity of SL-1, a DNA-directed N-mustard-quinoline conjugate. The N-mustard moiety in SL-1 induced DNA strand breaks, interstrand cross-links (ICLs), G2/M arrest, and apoptosis, whereas its quinoline moiety preferentially directed SL-1 to target the selective guanine sequence 5′-G-G/C-N-G-C/T-3′. Notably, SL-1 was highly cytotoxic to various CRC cell lines. Experiments using xenograft models revealed that SL-1 was more potent than 5-fluorouracil (5-FU) and oxaliplatin for suppressing the growth of RKO and RKO-E6 (oxaliplatin-resistant subline) cells as well as metastatic SW620 cells. In addition, SL-1 combined with 5-FU was more effective than oxaliplatin and 5-FU for suppressing RKO or SW620 cell growth in mice. Significantly, compared with cisplatin, oxaliplatin, or 5-FU, SL-1 alone or in combination with 5-FU did not cause obvious kidney or liver toxicity in ICR mice. In summary, SL-1, a DNA-directed alkylating agent, is established as an anti-CRC agent with high efficacy and low toxicity and thus warrants further development for the treatment of CRC patients.



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Antibiotic Prophylaxis After Immediate Breast Reconstruction: The Reality of its Efficacy

Purpose: Numerous techniques are used to prevent infection after immediate implant-based breast reconstruction. Postoperative antibiotic prophylaxis (PAP) is commonly prescribed to decrease the risk of reconstructive failure, despite conflicting evidence regarding its effectiveness. We sought to determine whether PAP decreases the risk of infection-related explantation in the setting of immediate prosthesis-based breast reconstruction. Methods: Using Truven MarketScan databases, we identified all patients who underwent immediate implant reconstruction between 1/2010-6/2014 with at least 6 months of follow-up. PAP was defined as any oral antibiotic course to be taken postoperatively based on prescriptions filled within 14 days prior to surgery through 24 hours post-discharge. Reconstructive failure defined as explantation due to infection was the primary outcome. Secondary outcomes of interest included wound complications, infection, and readmission for infection. Multivariable regression analyses controlled for demographic variables/comorbidities. Results: Of the 7,443 patients, 6,049 (81%) filled prescriptions for PAP. These patients were equally likely to develop a wound complication (OR=0.93 95%CI:0.71-1.23), infection (OR=0.89 95%CI:0.70-1.14), undergo explantation due to infection (OR=0.82 95%CI: 0.57-1.18), or require readmission for infection (OR=1.21 95%CI:0.82-1.78) compared to those who did not receive PAP. There was no significant difference in the risk of infection-related outcomes based on PAP duration. Conclusion: PAP was not associated with a reduced risk of infection or explantation following prosthesis-based breast reconstruction. Given rising rates of antibiotic resistance, focusing instead on technical considerations and the management of comorbid conditions may more effectively enhance the safety of breast reconstruction. Disclosure: This research was supported by a Mentored Clinical Investigator Award to Dr. Waljee through the Agency for Healthcare Research and Quality (1K08HS023313-01). Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 2K24-AR053120-06 (Dr. Kevin Chung). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was funded by the Chang Gung Memorial Hospital (project CORPG3G0111 and CORPG3G0161). This work was presented at the annual Plastic Surgery Research Council in 2017. Corresponding Author: Jennifer F. Waljee MD, MPH, MS, Michigan Medicine, Section of Plastic Surgery,, 2130 Taubman Center, SPC 5340, Ann Arbor, MI, 48109-5340, filip@med.umich.edu, Phone 734-998-6022, Fax 734-798-6696 ©2017American Society of Plastic Surgeons

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Absorbable Antibiotic Beads Prophylaxis in Immediate Breast Reconstruction

Background: Breast reconstruction with tissue expander is the most common mode of reconstruction following mastectomy. Infection necessitating tissue expander removal is a significant complication leading to patient distress as well as increased health care costs. Methods: Over 3 years, 127 breast reconstructions with tissue expanders were performed by a single surgeon. Fifty-nine of these reconstructions were performed using a standardized protocol in which patients washed with chlorhexidine several days prior to surgery and received intravenous antibiotics preoperatively. Intraoperatively, the submuscular pocket was irrigated with triple antibiotic solution and the skin was re-prepped with povidone iodine prior to expander placement. This group was referred to as the preintervention group. Sixty-eight of the reconstructions were performed using the standardized protocol with the addition of biodegradable antibiotic beads (Stimulan ® with vancomycin and gentamicin) in the submuscular pocket. This group made up the post intervention group. The primary outcome was the rate of infection necessitating tissue expander removal. Results: Tissue expander loss due to infection was 11.9% in preintervention group and 1.5% in the post intervention group, (p=0.024). Higher body mass index was associated with a statistically significant increase in infections necessitating implant removal. Conclusions: The use of absorbable antibiotic beads in the submuscular pocket reduced the risk of periprosthetic implant infection necessitating implant removal by 8-fold. Financial Disclosure Statement: The authors have the following to disclose: Nothing Presented at (if applicable): Robert Ivy Plastic Surgery Meeting, Philadelphia, PA on April 22 2017 Absorbable Antibiotic Beads Prophylaxis in Immediate Breast Reconstruction Corresponding Author: Kenna M. Denise M.D F.A.C.S , 2350 Freedom Way Ste 107, York, PA. USA. e-mail address: dmkenna@comcast.net ©2017American Society of Plastic Surgeons

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Indocyanine Green Angiography Use in Breast Reconstruction: A National Analysis of Outcomes and Cost in 110,320 Patients

Background: Indocyanine Green (ICG) angiography has gained popularity in breast reconstruction due to its ability to assess the viability of both mastectomy skin and tissue flaps. We aim to analyze trends and outcomes associated with the use of ICG angiography in breast reconstruction. Methods: Using 2012-2014 data from the Healthcare Cost and Utilization Project National Inpatient Sample, Agency for Healthcare Research and Quality, we identified breast reconstructions that were performed with or without the use of ICG angiography. Trends over time were assessed using the Cochran-Armitage test. Outcomes were assessed using logistic regression and generalized linear modeling. Results: Over the study period, 110,320 patients underwent breast reconstruction: 107,005 (97.0%) without the use of ICG and 3,315 (3.0%) with the use of ICG angiography. Indocyanine green angiography use increased over time: 750 patients (1.9%) in 2012, increasing to 1,275 patients (3.7%) in 2013 (p

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Low Dose Insulin as an Anti-Scarring Therapy in Breast Surgery: A Randomised Controlled Trial

Background: The role of insulin in expediting wound healing is firmly established within the context of major trauma and burns however only limited clinical evidence exists as to its effects upon scar formation. This study aims to build upon previous laboratory work to examine the potential anti-scarring properties of insulin in a clinical environment. Methods: 91 patients undergoing bilateral aesthetic breast surgeries were recruited to receive low-dose insulin and placebo injections to the medial 3cm of their sub-mammary incisions within the context of a randomised, intra-patient, placebo controlled trial and scar quality was assessed at 3, 6, and 12-month reviews using the Manchester Scar Scale. Results: Across the cohort at 12-month review the insulin-treated scars had lower scar scores (p=0.055) compared to placebo. Sub-group analysis of individuals with heavier scars showed median scar scores were significantly lower for the insulin-treated scars in regards to both scar contour (p=0.048) and scar distortion (p=0.045). Conclusions: Sub-cutaneous insulin injections reduced the appearance of scarring in this study when compared to placebo. The greatest effect was seen in those participants who showed heavier scars and as such insulin has a role as an antiscarring therapy in individuals likely to be affected by heavier scarring. Further research is required to more precisely delineate what subjects may benefit most from this treatment. Acknowledgments: Jon Pleat. Director at Restore Burn & Research Foundation Di Lawrence-Watt. Emeritus Professor Brighton & Sussex Medical School Financial Disclosure Statement: None of the authors have anything to disclose and no funding was received for this article. Presented at: 2016 Winter BAPRAS meeting, London Trial Identification: South East Research Ethics Committee (REC reference 10/H1102/67). Corresponding Author:MJ Hallam, M.D, MRCS, BM, Department of Plastic Surgery, St John's Hospital, Livingston, Edinburgh, EH54 6PP, UK. mj_hallam@hotmail.co.uk ©2017American Society of Plastic Surgeons

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The “Boomerang Lift”: A 3-Step Compartment Based Approach to the Youthful Cheek

Background: Autologous fat grafting (AFG) is an important tool for plastic surgeons treating the aging face. Malar augmentation with fat is often targeted to restore the youthful facial contour and provides support to the lower eyelid. The existence of distinct facial fat compartments suggests a step-wise approach may be appropriate in this regard [1]. Here we describe a three-step approach to malar augmentation using targeted deep malar fat compartmental augmentation, termed the "Boomerang Lift". Methods: Clinical patients undergoing AFG for malar augmentation were injected in three distinct deep malar fat compartments: 1. the lateral sub-orbicularis oculi fat (LSOOF), medial sub-orbicularis oculi fat (MSOOF), and lastly to the deep medial cheek (DMC) (n=9). Intra-operative 3D images were taken at baseline and following compartmental injections(Canfield® VECTRA H1). Images were overlaid between the augmented and baseline captures, and the 3D surface changes were analyzed, which represented the resulting "augmentation zone" (AZ). Results: 3D analysis of patients (n=9) demonstrated a unique pattern for AZ consistent across patients. The AZ resembled a boomerang, with the short tail supporting the medial lower lid, and the long tail extending laterally along the zygomatic arch. The upper border was restricted by the level of the naso-jugal interface, and the lower border was defined medially by the nasolabial fold and laterally by the level of the zygomatico-cutaneous ligament. Injections to the lateral and medial SOOF defined the boundaries of the boomerang shape, while the injection to the deep medial cheek provided maximum projection. Conclusions: This is the first description of deep malar augmentation zones described in clinical patients. 3D surface imaging was an ideal method for analyzing the surface change in response to targeted facial fat grafting. Our technique resulted in a reproducible surface shape, which we term the "Boomerang Lift". The authors of this study have no financial disclosures. Corresponding Author: Oren M. Tepper, MD, Assistant Professor, Division of Plastic and Reconstructive Surgery, Director of Aesthetic Surgery, Director of Craniofacial Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, 875 Park Avenue, New York, NY 10075, orenteppermd@yahoo.com ©2017American Society of Plastic Surgeons

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MRI screening of the internal auditory canal: Is gadolinium necessary to detect intralabyrinthine schwannomas?

Publication date: Available online 13 December 2017
Source:American Journal of Otolaryngology
Author(s): Johnathan C. Valesano, Carrie M. Carr, Laurence J. Eckel, Matthew L. Carlson, John I. Lane
ObjectiveNon-contrast MRI of the internal auditory canal (IAC) using high-resolution T2WI (T2 weighted image) has been proposed as the primary screening study in patients with sudden or asymmetric sensorineural hearing loss (ASNHL). However, there are concerns that non-contrast MRI may not detect labyrinthine pathology, specifically intralabyrinthine schwannomas (ILSs). The purpose of this study was to determine if non-contrast high-resolution T2WI alone are adequate to exclude these uncommon intralabyrinthine tumors.Methods31 patients with ILSs and 36 patients without inner ear pathology that had dedicated MRI of the IAC performed with both non-contrast T2WI and post-contrast T1WI (T1 weighted image) were identified. Three board-certified neuroradiologists reviewed only the T2WI from these 67 cases. When an ILS was identified, its location and size were recorded. Sensitivity, specificity, and accuracy were calculated using the post-contrast T1WI as the "gold standard." A consensus review of cases with discordant results was conducted.ResultsThe sensitivity, specificity, and accuracy were 1.0, 1.0, and 1.0 for Observer 1; 0.84, 1.0, and 0.96 for Observer 2; 0.90, 1.0, and 0.98 for Observer 3. The 5 ILSs with discordant results were correctly identified upon consensus review. The median size of the ILSs was 4.4mm (±2.9mm) and most (18/31) were intracochlear in location.ConclusionNon-contrast high-resolution T2WI alone can detect ILSs with 84–100% sensitivity, suggesting that gadolinium may be unnecessary to exclude ILSs on screening MRI. These findings have implications for reducing cost, time, and adverse events associated with gadolinium administration in patients presenting with sudden or ASNHL.Level of evidence4



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Combined use of a nanocarbon suspension and 99mTc-MIBI for the intra-operative localization of the parathyroid glands

Publication date: Available online 13 December 2017
Source:American Journal of Otolaryngology
Author(s): Jun Chen, Qinyi Zhou, Jialin Feng, Jiadong Wang
ObjectiveTo investigate the combined use of a nanocarbon (NC) suspension and low-dose ^99mTc-MIBI for parathyroid localization during surgery in patients with secondary hyperparathyroidism (sHPT).MethodsBetween March 2010 and September 2015, 40 patients with sHPT were enrolled in this study and were randomized to receive either low-dose ^99mTc-MIBI+NC (group I) or low-dose ^99mTc-MIBI (group II). Pre- and post-operative serum levels of intact PTH (iPTH), calcium and phosphorus between groups were compared and the intra-operative radioactive counts of the parathyroid glands were measured.ResultsThe post-operative iPTH level was significantly lower in patients of group I (24.2±31ng/L) than in those of group II (106±155ng/L) (P=0.03) while there were no significant differences in intra-operative parathyroid gland radioactive counts between the groups. The duration of the surgical procedure was shorter for patients of group I than patients of group II. There were no serious intra-operative or post-operative complications.ConclusionThe combined use of an NC suspension and ^99mTc-MIBI for patients with sHPT is strongly recommended for the localization of parathyroid glands during surgery and is likely to improve clinical outcomes for patients.



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Corrigendum to “A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report” [Eur J of Canc (2017) 206–225]

Publication date: Available online 14 December 2017
Source:European Journal of Cancer
Author(s): Astrid K. Gnekow, David A. Walker, Daniela Kandels, Susan Picton, Giorgio Perilongo, Jacques Grill, Tore Stokland, Per Eric Sandstrom, Monika Warmuth-Metz, Torsten Pietsch, Felice Giangaspero, René Schmidt, Andreas Faldum, Denise Kilmartin, Angela De Paoli, Gian Luca De Salvo




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Microinvasive parathyroidectomy: Incremental improvement in minimally invasive parathyroid surgery

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Nanoparticle delivery of RNA-based therapeutics to alter the vocal fold tissue response to injury

Objectives/Hypothesis

Our laboratory and others hypothesized that Smad3 is a principle mediator of the fibrotic phenotype in the vocal folds (VFs), and we further posited that alteration of Smad3 expression through short interfering (si)RNA holds therapeutic promise, yet delivery remains challenging. To address this issue, we employed a novel synthetic oligomer, lipitoid, complexed with siRNA to improve stability and cellular uptake with the goal of increased efficiency of RNA-based therapeutics.

Study Design

In vitro study and in vivo animal model.

Methods

In vitro, lipitoid cytotoxicity was quantified via colorimetric and LIVE/DEAD assays in immortalized human VF fibroblasts and primary rabbit VF fibroblasts. In addition, optimal incubation interval and solution for binding siRNA to lipitoid for intracellular delivery were determined. In vivo, a rabbit model of VF injury was employed to evaluate Smad3 knockdown following locally injected lipitoid-complexed siRNA.

Results

In vitro, lipitoid did not confer additional toxicity compared to commercially available reagents. In addition, 20-minute incubation in 1× phosphate-buffered saline resulted in maximal Smad3 knockdown. In vivo, Smad3 expression increased following VF injury. This response was significantly reduced in injured VFs at 4 and 24 hours following injection (P = .035 and .034, respectively).

Conclusions

The current study is the first to demonstrate targeted gene manipulation in the VFs as well as the potential utility of lipitoid for localized delivery of genetic material in vivo. Ideally, these data will serve as a platform for future investigation regarding the functional implications of therapeutic gene manipulation in the VFs.

Level of Evidence

NA Laryngoscope, 2017

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An innovative solution for T-tube obstruction: The tracheostomy–customized stent combination

The Montgomery T-tube (MTT) is a useful tool for post-tracheostomy tracheal stenosis. However, MTTs can get blocked. We present a case series of life-threatening MTT blockage, wherein a split-function option was implemented, which was a customized silicone Dumon stent above the tracheostomy to maintain both airway and phonation. This tracheostomy–customized stent combination serves the same function as an MTT, with a greater margin of safety due to the easy suctioning capacity of the tracheostomy. With a fenestrated tracheostomy and stent above, speech is effectively preserved. We recommend this strategy in severe MTT blockage as a superior option to regular tracheostomy. Laryngoscope, 2017

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Clinical implications of magnetic resonance imaging in temporomandibular disorders patients presenting ear fullness

Objectives/Hypothesis

The aim of this study was to investigate whether findings detected by temporomandibular joint magnetic resonance imaging (TMJ-MRI) can provide pathognomonic evidence of temporomandibular disorders (TMD) in patients with nonspecific ear fullness (EF). The association of nonspecific EF with clinical characteristics of TMD based on TMJ-MRI findings was examined.

Study Design

Retrospective analysis.

Methods

Thirty-four subjects (42 ears) who had no detectable otologic problems as a cause of EF were enrolled in this study. Each subject underwent TMJ-MRI to identify pathology of the TMJ as a possible cause of nonspecific EF. All subjects participated in the re-evaluation process following TMD treatment.

Results

Anatomical abnormalities in TMJ-MRI, irrespective of TMD signs, were observed in 34 of the 42 ears (80.9%), such as degenerative change of the TMJ (16 ears), articular disc displacement (11 ears), and joint effusion (seven ears). Specific abnormalities of the TMJ were associated with nonspecific EF, and this symptom showed improvement following individualized TMD treatment in those with internal derangement and/or effusion of the TMJ. However, abnormal TMJ-MRI findings were also observed in seven of nine ears with no TMD signs, and there was no significant association between the presence of TMD signs and abnormal TMJ-MRI findings (χ² = 0.075, P = .784).

Conclusions

Patients presenting with nonspecific EF may have TMD, which can be effectively diagnosed using TMJ-MRI. The present study revealed the causal relationship between nonspecific EF and abnormal TMJ findings based on MRI. Individualized TMD treatments based on TMJ-MRI led to improved treatment outcomes with special regard to nonspecific EF

Level of Evidence

4 Laryngoscope, 2017

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Brain volume changes in hyposmic patients before and after olfactory training

Objectives/Hypothesis

Olfactory dysfunction is thought to be associated with reduced gray matter (GM) volume in olfactory-related brain areas. The aim of this study was to determine GM structural changes within olfactory-related regions of the brain in patients with smell loss due to upper respiratory tract infection (URTI) before and after olfactory rehabilitation.

Study Design

Prospective intervention case-control study.

Methods

Magnetic resonance imaging structural brain images were collected from 30 patients with smell loss due to URTI and 31 controls. Patients exposed themselves to odors (olfactory training [OT]) over 12 weeks and then were rescanned. Olfactory testing was performed using the validated Sniffin' Sticks test. GM was investigated with voxel-based morphometry.

Results

GM volumes were found to be reduced in the limbic system and thalamus among pretraining patients compared to controls; in patients, OT was associated with a significant increase of GM volume in these two regions. The GM volume within other olfactory-related regions was not different between patients and controls. In addition, no relevant difference between the GM volume pre- and post-OT was observed in primary olfactory-related regions.

Conclusions

OT was associated with an increase in GM volume of the hippocampus and the thalamus, possibly pointing toward a strategy for more effective exploitation of olfactory signals based on a higher degree of attention toward odors and association of memories with olfactory input.

Level of Evidence

3b Laryngoscope, 2017

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Use of autologous adipose-derived mesenchymal stem cells for creation of laryngeal cartilage

Objectives/Hypothesis

Adipose-derived mesenchymal stem cells (ASCs) are an exciting potential cell source for tissue engineering because cells can be derived from the simple excision of autologous fat. This study introduces a novel approach for tissue-engineering cartilage from ASCs and a customized collagen oligomer solution, and demonstrates that the resultant cartilage can be used for laryngeal cartilage reconstruction in an animal model.

Study Design

Basic science experimental design.

Methods

ASCs were isolated from F344 rats, seeded in a customized collagen matrix, and cultured in chondrogenic differentiation medium for 1, 2, and 4 weeks until demonstrating cartilage-like characteristics in vitro. Large laryngeal cartilage defects were created in the F344 rat model, with the engineered cartilage used to replace the cartilage defects, and the rats followed for 1 to 3 months. Staining examined cellular morphology and cartilage-specific features.

Results

In vitro histological staining revealed rounded chondrocyte-appearing cells evenly residing throughout the customized collagen scaffold, with positive staining for cartilage-specific markers. The cartilage was used to successfully repair large cartilaginous defects in the rat model, with excellent functional results.

Conclusions

This study is the first study to demonstrate, in an animal model, that ASCs cultured in a unique form of collagen oligomer can create functional cartilage-like grafts that can be successfully used for partial laryngeal cartilage replacement.

Level of Evidence

NA Laryngoscope, 2017

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When should a level IIB neck dissection be performed in treatment of head and neck squamous cell carcinoma?

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Effect of rural and urban geography on larynx cancer incidence and survival

Objectives/Hypothesis

Investigate the impact of rural geography on larynx cancer incidence and survival.

Study Design

Surveillance, Epidemiology, and End Results (SEER) database study.

Methods

Incidence and survival rates by Rural–Urban Continuum codes for larynx squamous cell carcinoma patients diagnosed from 2004 to 2012 were evaluated using SEER statistical software and Cox proportional hazards survival analysis.

Results

The lowest age-adjusted incidence rates for larynx cancer were seen in densely populated urban regions, with mean rates of 2.8 per 100,000 person years (95% confidence interval [CI]: 2.7-2.8); the highest were in the most rural areas, with mean rates of 5.3 per 100,000 person years (95% CI: 4.7-5.9). Nevertheless, of 23,659 larynx cancer patients diagnosed over this period, 19,556 (82.7%) arose in urban residents, compared with 1,428 or 6% from rural areas. Urban larynx cancer patients more likely lived in counties with an American College of Surgeons–approved cancer center and/or a fourfold greater otolaryngology physician supply. Nevertheless, frequency of advanced stage at initial presentation was similar. Cause-specific and overall survival were no different, both on univariable and multivariable analyses.

Conclusions

Compared with urban populations, Rural populations are at greater risk of developing larynx cancer, but initial stage and survival after diagnosis are comparable. Priority should be given to prevention strategies to decrease incidence rates.

Level of Evidence

4 Laryngoscope, 2017

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Trial of hyperthermic treatment for Bowen's disease with disposable chemical pocket warmers: A report of two cases

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Relationship between serum anti-varicella zoster virus antibody titer and time from onset of herpes zoster

Abstract

Herpes zoster is an internal reactivation of varicella zoster virus, and its onset depends on immunity against this virus. We have previously reported that antiviral antibody titers are inversely correlated with patient numbers. In this study, we hypothesized that patients with higher titers may be late visitors to the clinic, whose antibodies were already boosted at presentation because of the time lapse between onset of zoster and measurement of antibodies. We analyzed antibody titers of patients with acute herpes zoster who visited Fukuoka University Hospital from January 2009 to May 2016 (n = 141, 62 males and 79 females). Varicella zoster virus-specific immunoglobulin G, M and complement fixation tests were positive in 93.9%, 12.0% and 64.2% of the patients, respectively. Immunoglobulin G and complement fixation titers were strongly correlated (Spearman's r = 0.8634, P < 0.0001). Patients with high immunoglobulin G and complement fixation titers were immunoglobulin M-negative. Unexpectedly, immunoglobulin G and complement fixation titers showed large inter-subject variation, and were only weakly correlated with onset–measurement time lapse. Patients with consecutive tests tended to show increasing immunoglobulin G and complement fixation titers. Our data suggest that herpes zoster preferentially occurs in patients with low immunoglobulin G and complement fixation titers, and subsequently causes antibody elevation. However, the timing of elevation varies and can be as late as 10 days after zoster. The large variation in antibody titer over the time from onset to testing suggests that some mechanism exists that resists the local breakthrough of virus in the skin, and so delays the onset of blisters.

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Postmenopausal craniofacial hyperhidrosis

Summary

Hyperhidrosis is a condition marked by excessive sweating, which can either be localized or generalized. Primary focal hyperhidrosis (PFH) can arise from the palms, plantar feet, axillae and also from the face and scalp. PFH primarily affects a younger population of children and young adults, with the majority presenting before the age of 25 years. We report a distinct subtype of craniofacial hyperhidrosis in 20 postmenopausal women; this subtype is often under-recognized.

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Postmenopausal craniofacial hyperhidrosis

Summary

Hyperhidrosis is a condition marked by excessive sweating, which can either be localized or generalized. Primary focal hyperhidrosis (PFH) can arise from the palms, plantar feet, axillae and also from the face and scalp. PFH primarily affects a younger population of children and young adults, with the majority presenting before the age of 25 years. We report a distinct subtype of craniofacial hyperhidrosis in 20 postmenopausal women; this subtype is often under-recognized.

http://ift.tt/2zbe0zJ

Editorial overview: Glial biology

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Alison C Lloyd, Beth Stevens




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Contents page

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47





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Editorial Board

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47





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Time-varying causality between energy consumption, CO 2 emissions, and economic growth: evidence from US states

Abstract

This study is the first attempt to investigate the relationship between CO₂ emissions, energy consumption, and economic growth at a state level, for the 50 US states, through a time-varying causality approach using annual data over the periods 1960–2010. The time-varying causality test facilitates the better understanding of the causal relationship between the covariates owing to the fact that it might identify causalities when the time-constant hypothesis is rejected. Our findings indicate the existence of a time-varying causality at the state level. Specifically, the results probe eight bidirectional time-varying causalities between energy consumption and CO₂ emission, six cases of two-way time-varying causalities between economic growth and energy consumption, and five bidirectional time-varying causalities between economic growth and CO₂ emission. Moreover, we examine the traditional environmental Kuznets curve hypothesis for the states. Notably, our results do not endorse the validity of the EKC, albeit the majority of states support an inverted N-shaped relationship. Lastly, we can identify multiple policy implications based on the empirical results.

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Choroidal metastases as the presenting feature of adenocarcinoma of the lung: A case report and an overview of the role of radiotherapy in its management

Krishna Sharan, S Shailaja, Vijaya H Pai, Donald J Fernandes

Journal of Cancer Research and Therapeutics 2017 13(6):1062-1064

Although metastasis to the eye is the most common ophthalmic malignancy, it is usually asymptomatic and rarely a presenting symptom that leads to the diagnosis of a primary. Here, we report a patient who was evaluated for visual symptoms and was eventually diagnosed to have disseminated adenocarcinoma of the lung. He was treated with external radiotherapy to the choroidal metastasis, attaining an excellent response that was sustained until his death. A brief review on the role of radiotherapy in the management of uveal metastases is also presented.

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Diagnosis and management of gastrointestinal stromal tumors: An up-to-date literature review

Ayman El-Menyar, Ahammed Mekkodathil, Hassan Al-Thani

Journal of Cancer Research and Therapeutics 2017 13(6):889-900

Gastrointestinal stromal tumors (GISTs) are rare life-threatening forms of cancer that may arise anywhere in the GI tract. Herein, we aimed to review the literature to describe the incidence, management, and outcomes of GISTs. We conducted a traditional narrative review using PubMed and EMBASE, searching for English-language publications for GISTs between January 2001 and January 2016 using keywords ""gastrointestinal" "stromal tumors." Among 4582 retrieved articles, 50 articles were relevant over the last 15 years. Several risk stratification systems exist to predict the outcomes of GISTs based on certain criteria such as the primary site of occurrence, size of the tumor, mitotic activity, staining for proliferating cells, and tumor necrosis. Risk stratification is crucial in the management and outcomes of the disease. Surgical resection remains the gold standard option of GISTs treatment. Complete resection of the tumor is the main predictor of the postoperative patient's survival. Laparoscopic resections are associated with less intraoperative blood loss, early return of bowel function, early resumption of diet, and short hospital stay. However, laparoscopy is difficult to perform in large and unfavorably placed GISTs and may result in disease progression, recurrence, and poor survival. Robot-assisted laparoscopic resections provide instruments for surgeons to perform technically demanding operations. Moreover, extensive research work including large clinical trials is ongoing to establish promising role of the adjuvant and neo-adjuvant therapy for better disease- free survival in GIST patients.

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Expression of WW domain-containing protein 2 is correlated with pathological grade and recurrence of glioma

Jun Liang, Wei-Feng Qi, Shao Xie, Wei-Feng Wang, Xian-Li Zhang, Xiu-Ping Zhou, Qiong-Shi , Jin-Xia Hu, Ru-Tong Yu

Journal of Cancer Research and Therapeutics 2017 13(6):1032-1037

Objective: WW domain-containing protein 2 (WWP2) is an E3 ubiquitin ligase, which belongs to the NEDD4-like protein family. Recently, it is reported to play a key role in tumorigenesis and development of tumors such as prostate and lung cancer. However, there has been not related report on glioma until now. The aim of this study is to detect the expression of WWP2 and analyze its correlation to the pathological grade and tumor recurrence in patients with glioma. Materials and Methods: Western blot and immunohistochemistry were separately used to detect the expression of WWP2 protein in 31 brain glioma tissue samples and 80 brain glioma paraffin specimens. The method of Kaplan–Meier was used to analyze the correlation between the WWP2 expression and glioma recurrence. Results: The protein expression level of WWP2 in glioma tissue was significantly higher than that in nontumorous brain tissue (P < 0.05), and the protein expression level of WWP2 in high-grade glioma (Grade III–IV) was significantly higher than that in low-grade glioma (Grade I–II) (P < 0.05). Kaplan–Meier analysis indicated that the patients with high WWP2 expression had significantly shorter tumor recurrence time than the patients with low WWP2 expression (P < 0.05). Conclusion: Our study suggests that WWP2 may play a role in the genesis and development of glioma; it may be a potential biomarker to predict pathological grade and tumor recurrence in patients with glioma.

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Occupational doses of cardiologists in cath labs and simulation method

Reza Fardid, Fatemeh Mirzadeh, Hadi Rezaei

Journal of Cancer Research and Therapeutics 2017 13(6):901-907

In recent years, using the ionizing radiation in the interventional cardiology has been increased; this is because of the rapid growth of the number of interventional procedures and the high levels of radiation dose in these examinations. Therefore, it is necessary to develop procedures for managing the use of fluoroscopy radiation to ensure that patients and personnel are not exposed to excessive levels of radiation. It seems that by the new generation devices of fluoroscopy that are equipped with a real dosimeters or dose area product (DAP)-meter which are able to record the produced dose rate in the area of patient's body in each procedure, it is possible to calculate the cardiologist dose with simulation. In addition, a relationship can be made between the patient DAP and cardiologist dose that is defined as an appropriate conversion factor. Hence, in each procedure, besides the record of patient's DAP, the cardiologist dose is recorded as well.

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Extramedullary sarcomatoid variant of plasmablastic plasmacytoma

Urmila Majhi, Shirley Sundersingh, Kanchan Murhekar, Krishnamurthy Radha

Journal of Cancer Research and Therapeutics 2017 13(6):1078-1079



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Optical diagnostics in oral cancer: An update on Raman spectroscopic applications

Aditi Sahu, C Murali Krishna

Journal of Cancer Research and Therapeutics 2017 13(6):908-915

Raman spectroscopy (RS) is a sensitive vibrational spectroscopic method that can detect even subtle biochemical changes during the onset of disease. Consequently, RS has been extensively investigated for disease diagnosis, including cancers. Oral cancers are known to suffer from dismal survival rates, which have not improved for several decades. As delayed diagnosis contributes to the low disease-free survival rate observed in oral cancers, RS has also been explored for the early diagnosis of oral cancers. This review summarizes the major developments in the field, including diagnosis, surgical margin assessment and prediction of treatment response, and in the overall management of oral cancers. The article comprises an overview of epidemiology, diagnosis, treatment, and recently introduced diagnostic adjuncts for oral cancers, the basic principle, instrumentation of RS, multivariate analysis that impart objectivity to the approach, and finally a discussion on the recent applications in oral cancers. PubMed and Google Scholar database have been used to compile information available online till December 2015.

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Intrarectal fixative for positioning of the prostate for intensity modulated radiotherapy

Janos Stumpf, Subathira Balasundaram, P. G. G. Kurup, Rathnadevi Ramadas, Murali Venkatraman, Karthikeyan Perumal

Journal of Cancer Research and Therapeutics 2017 13(6):1050-1052

Dose escalation improves local control in carcinoma prostate, but rectal toxicity remains a concern. Various techniques have been there to reduce the dose to the rectum. Mobility of the prostate results in a necessary expansion of the target volume. We describe a new intrarectal fixative, developed in-house with transrectal ultrasonography through the fixative itself for localization of the organ by reporting a case with early carcinoma prostate. Concerns of rectal toxicity limit dose escalation in the treatment of prostate cancer. Intra- and interfraction prostate motion is a concern in dose conformity techniques. The intrarectal fixative system developed in-house physically separates the prostate and rectum during radiation treatment. Thus, both intra- and inter-fractional movement of the organ are addressed, therefore planning target volume expansion can be kept minimal.

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Cancer-related fatigue treatment: An overview

Hemanth Mohandas, Saravana Kumar Jaganathan, Mohan Prasath Mani, Manikandan Ayyar, GV Rohini Thevi

Journal of Cancer Research and Therapeutics 2017 13(6):916-929

Cancer-related fatigue is a symptom of cancer where most patients or the general practitioners tend to misinterpret due to the insufficient understanding or knowledge of cancer-related fatigue (CRF). This paper will provide a better perspective for the patients and the health professionals on how to manage and handle CRF for both mild and severe fatigue patients. Articles were selected from the searches of PubMed database that had the terms "randomized controlled trials," "cancer," "fatigue," "pharmacologic treatment," and "nonpharmacologic treatment" using both Mesh terms and keywords. The authors have reviewed the current hypothesis and evidence of the detailed etiology of the CRF present in the literature for healthier management, directives, and strategies to improve the treatment of cancer-related fatigue. An algorithm has been blueprinted on screening, and management, of the CRF, and various kinds of effective treatments and assessment tools have been briefly studied and explained. Although many strategies seemed promising, the quality of randomized controlled trials is generally quite low in studies, making it difficult to draw conclusions about the effectiveness of each self-care strategies. Therefore, future studies require better design and reporting of methodological issues to ensure evidence-based self-care recommendations for people receiving cancer treatment.

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Neurofibromatosis type-1 in a patient with ataxia-telangiectasia

Serhan Kupeli

Journal of Cancer Research and Therapeutics 2017 13(6):1073-1074



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Quantitative determination of tumor platinum concentration of patients with advanced Breast, lung, prostate, or colorectal cancers undergone platinum-based chemotherapy

Hesameddin Mostaghimi, Ali Reza Mehdizadeh, Mohammad Jahanbakhsh, Amir Reza Dehghanian, Ramin Askari

Journal of Cancer Research and Therapeutics 2017 13(6):930-935

Context: Previous studies have reported direct relationship between tumor reduction and its platinum concentration following platinum-based (Pt-based) chemotherapy. However, quantitative data of tumor platinum concentration have not yet been reported for the most common cancers. Aims: Determination of tumor platinum concentration of breast, lung, prostate, and colorectal cancers after Pt-based chemotherapy; and evaluation of the influence of chemo drug type, chemotherapy regimen, and time lapse from last chemotherapy on tumor platinum concentration. Materials and Methods: Tumor samples of patients with advanced breast, lung, prostate, and colorectal cancers undergone Pt-based chemotherapy were collected from pathology collection of various hospitals. The platinum concentration of each sample was measured by inductively coupled plasma optical emission spectrometry. The data were categorized by drug type, time lapse from last chemotherapy, and regimen type to evaluate their effects on platinum concentration. Statistical Analysis: ANOVA, Mann–Whitney U and Kruskal–Wallis tests were used. Results: Tumor platinum concentrations of breast, lung, prostate, and colorectal cancers were all obtained in the range of 1–10 μg/g tumor tissue. Large values of P (>0.05) indicate no significant differences between various chemo drug, regimen, and time groups. Conclusions: In general, the platinum concentration was higher in prostate and lower in lung tumors. The type of Pt-based chemo drug, time lapse from the last chemotherapy, and concurrency of other antineoplastic agents administered with Pt-based chemo drugs had no significant effect on tumor platinum concentration.

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Agreement analysis between three different short geriatric screening scales in patients undergoing chemotherapy for solid tumors

Amit Joshi, Nidhi Tandon, Vijay M Patil, Vanita Noronha, Sudeep Gupta, Atanu Bhattacharjee, Kumar Prabhash

Journal of Cancer Research and Therapeutics 2017 13(6):1023-1026

Background: Comprehensive geriatric assessment (CGA) in routine practice is not logistically feasible. Short geriatric screening tools are available for selecting patients for CGA. However none of them is validated in India. In this analysis we aim to compare the level of agreement between three commonly used short screening tools (Flemish version of TRST (fTRST), G8 and VES-13. Methods: Patients ≥65 years with a solid tumor malignancy undergoing cancer directed treatment were interviewed between March 2013 to July 2014. Geriatric screening with G8, fTRST and VES-13 tools was performed in these patients. G8 score ≤14, fTRST score ≥1 and VES-13 score ≥3 were taken as indicators for the presence of a high risk geriatric profile respectively. R version 3.1.2 was used for analysis. Cohen kappa agreement statistics was used to compare the agreement between the 3 tools. p value of 0.05 was taken as significant. Results: The kappa statistics value for agreement between G8 score and fTRST, between VES-13 and fTRST and between VES-13 and G8 were 0.12 (P = 0.04), 0.16 (P = 0.07) and 0.05 (P = 0.45) respectively. It was found that maximum agreement was observed for VES-13 and fTRST. The agreement value of VES-13 and fTRST observed was 59.44 %(39.63% for high risk profile and 19.81% for low risk profile). The agreement value of G-8 and fTRST was 39.62% (2.83% only for high risk profile and 36.79% for low risk profile). The lowest agreement was between G8 and VES-13, 35.84% (7.54% for high risk detection and 28.30% for low risk detection). Conclusion: There was poor agreement (in view of kappa value been below 0.2) between the 3 short geriatric screening tools. Research needs to be directed to compare the agreement level between these 3 scales and CGA, so that the appropriate short screening tool can be selected for routine use.

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Assessment of the scatter correction procedures in single photon emission computed tomography imaging using simulation and clinical study

Mehravar Rafati, Hemmatollah Rouhani, Ahmad Bitarafan-Rajabi, Mahsa Noori-Asl, Bagher Farhood, Hadi Taleshi Ahangari

Journal of Cancer Research and Therapeutics 2017 13(6):936-942

Background: Compton-scattered photons transfer incorrect spatial information. These photons are detected in used photo-peak energy window. In this study, three scatter correction procedures including dual-energy window (DEW), three energy window (TEW), and new approach were evaluated, and then the best procedure based on simulation and clinical conditions introduced. Materials and Methods: In this study, simulation projections and three-dimensional nonuniform rational B-spline–based Cardiac-Torso phantoms were produced by GEANT4 application for emission tomography simulation code. For clinical study, 2-day stress/rest myocardial perfusion imaging (MPI) protocol was performed with 99m Tc-sestamibi for 46 patients. Image quality parameters including contrast, signal-to-noise ratio (SNR), and relative noise of the background (RNB) were evaluated. Results: The simulation results showed that contrast values for DEW, TEW, and new approach were (0.45 ± 0.07, 0.5 ± 0.08, and 0.63 ± 0.09), SNR values (4.74 ± 0.94, 5.58 ± 1.08, and 6.56 ± 1.24), and RNB values (0.33 ± 0.06, 0.33 ± 0.07, and 0.33 ± 0.05), respectively. In clinical study, the contrast values for DEW, TEW, and new approach were 0.53 ± 0.03, 0.57 ± 0.07, and 0.62 ± 0.04 in rest MPI and were 0.52 ± 0.04, 0.57 ± 0.06, and 0.6 ± 0.05 in stress MPI, respectively. Moreover, for the rest images, the SNR values were 7.65 ± 1.9, 9.08 ± 2.2, and 10.2 ± 1.75 and for stress images were 7.76 ± 1.99, 9.12 ± 2.25, and 10.17 ± 2.04, respectively. Finally, RNB values for rest and stress images were 0.12 ± 0.03, 0.13 ± 0.03, and 0.13 ± 0.03, respectively. Conclusion: The simulation and the clinical studies showed that the new approach could be better performance than DEW, TEW methods, according to values of the contrast, and the SNR for scatter correction.

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Detection of balanced translocations in acute lymphoblastic leukemia by a novel multiplex reverse transcriptase reverse transcription-polymerase chain reaction

Jyoti Kotwal, Madakshira Gopal Manoj, Rajan Kapoor

Journal of Cancer Research and Therapeutics 2017 13(6):1042-1046

Fusion transcripts detection is essential for subtyping and diagnosis of acute lymphoblastic leukemia (ALL). This enables institution of appropriate therapy and provides a parameter to monitor disease progression and response to therapy. This study endeared to detect and analyze various balanced translocations known in ALL by using a novel polymerase chain reaction (PCR) method. A pilot study was done in which 16 consecutive cases of ALL were analyzed and followed-up for a period of 1 year. Diagnosis of ALL was established after subjecting blood/bone marrow aspirate samples to morphological examination, immunophenotyping, and detection of fusion transcripts by multiplex reverse transcription (RT)-PCR using HemaVision kit. Results were analyzed by correlating with morphology, immunophenotype, and response to therapy. Epi-Info statistical software was used. 43% (seven cases) showed balanced translocations, with all seven cases being B-ALL and t(9;22) being the most common. There was a consistent association of CD25 cases with t(9;22). Analyses of relation to other parameters were as expected by their respective WHO 2008 subtype. No significant correlation in terms of survival benefit was seen between cases with and without balanced translocations (P = 0.7472). The study demonstrated the utility of multiplex RT-PCR in the initial evaluation, subtyping, and monitoring minimal residual disease in ALL cases with balanced translocations, thereby guiding both therapy and prognosis. The consistent association of CD25 in cases of t(9;22) ALL indicated that CD25 could be used as a surrogate marker.

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Accelerated hypofractionation (OCTA SHOT): Palliative radiation schedule in advanced head and neck carcinoma

Shankar Lal Jakhar, Ramesh Purohit, Akankhsha Solanki, P Murali, Trupti Kothari, Neeti Sharma, Harvinder Singh Kumar

Journal of Cancer Research and Therapeutics 2017 13(6):943-946

Background: Head and neck cancers are attributed to be the most common type of malignancy in the developing countries with most cases presenting in advanced stage. This pilot study was performed to evaluate the effect of an accelerated hypofractionated 4 days schedule (octa shot) in providing palliation to such advanced cases of head and neck cancer. Materials and Methods: Twenty-two patients with advanced (Stage VIB-IVB) squamous cell carcinoma of head and neck region were enrolled in the study. All these patients were planned for radiotherapy at Cobalt Unit with a fractionation schedule of 3.5 Gy/fraction, 2 fractions/day with 6 h interval between two fractions, for four days (28 Gy/8Fr/4 days). Patients were reviewed at 2 and 4 weeks to assess change in tumor size, any symptomatic relief, or toxicity. The tumor response, dermal, and mucosal toxicities were assessed using WHO criteria. Results: Median age of these 22 patients (17M male + 5F female) in the study was 59.8 years. After completion of radiotherapy, first response evaluation done at 15th day showed ≥50% objective response in 14 patients. At 1 month, this response increased to ≥75% in 16 patients and 50%–75% in three patients. None of the patients had disease progression. Improvement in symptoms was reported with respect to pain and dysphagia by patients subjectively. Only two patients reported Grade III mucositis; remaining patients had mucositis and dermatitis up to Grade II. Conclusion: The study concludes that this "octa shot" is an effective palliative radiotherapy schedule. With a decreased duration of hospital stay, it is also favorable for outpatients.

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Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous lesion

Namrata Punit Awasthi, Sumaira Qayoom, Sunil Dabadghao

Journal of Cancer Research and Therapeutics 2017 13(6):1056-1058

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy, recognized as a distinct entity in the WHO 2008 classification of hematolymphoid neoplasm. Described for the first time in 1994 as CD4+ cutaneous lymphoma with high expression of CD56, BPDCN has been known previously with various names such as blastic natural killer (NK) leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm, and agranular CD4+ NK cell leukemia. This disease usually presents with cutaneous involvement as the first manifestation, with subsequent or simultaneous spread to bone marrow and peripheral blood. Leukemia as the first presenting symptom without any cutaneous involvement is a rare finding and can masquerade as acute undifferentiated leukemia. We present here such a case of a 59-year-old male who presented as leukemia without any cutaneous lesion but subsequently developed a scalp nodule.

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Utility of the laminin immunohistochemical stain in distinguishing invasive from noninvasive urothelial carcinoma

Dinesh Pradhan, Milon Amin, Shveta Hooda, Rajiv Dhir, Sheldon Bastacky, Anil V Parwani

Journal of Cancer Research and Therapeutics 2017 13(6):947-950

Background: To study the utility of the laminin immunostain in distinguishing invasive from noninvasive urothelial carcinoma (UC). The distinction is difficult but clinically significant as it can affect the decision to administer intravesical Bacillus Calmette–Guerin or can even lead to cystectomy. Materials and Methods: Representative sections of the transurethral resection of bladder tumor specimens from 25 cases of formalin-fixed paraffin-embedded invasive UCs and 25 cases of noninvasive UCs were selected for immunohistochemical (IHC) staining with laminin (Ventana, Oro Valley, AZ, USA). These cases were selected using a computer-assisted search of our laboratory information system (Cerner CoPath). Tissue from five paraffin-embedded tissue blocks containing unremarkable urothelial-lined bladder parenchyma was chosen as controls. Results: All five control cases demonstrated crisp linear staining of the basement membrane underlying the unremarkable urothelium. Similar findings were also noted in the 25 cases of noninvasive UC. All 25 cases of the invasive UC demonstrated a complete absence of the staining around invasive and malignant urothelial cells. Laminin staining was also noted in both the muscularis mucosae and the detrusor muscle, although the pattern of staining in these areas was granular and was distinguishable from the crisp linear staining of the basement membrane. Conclusion: Laminin IHC staining can be useful in differentiating invasive from noninvasive UC.

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Incision site metastasis: Adding insult to injury

Ranil Johann Boaz, Tanush Vig, Ramani Manojkumar, Antony Devasia

Journal of Cancer Research and Therapeutics 2017 13(6):1068-1069

Incision site metastasis is a rare yet well-recognized complication of oncologic operations. We describe the case of a 60-year-old man with a large mass at the site of abdominal incision for a nephrectomy. The operation was performed for infection in an obstructed kidney, which in retrospect harbored malignancy. Percutaneous core biopsy of the mass revealed metastatic conventional renal cell carcinoma (RCC). Surgical resection was obviated by the presence of nodal disease on imaging. Palliative targeted therapy with tyrosine kinase inhibitor was initiated. RCC can not only mimic an inflammatory renal mass radiologically but also coexist with infective renal conditions. Diligent histopathological examination as a routine following nephrectomy for complicated diagnoses is imperative.

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Efficacy of centrifuged liquid-based cytology over conventional cytology: A comparative study

Veda Hegde, Shwetha Nambiar, Nikhil Yadav

Journal of Cancer Research and Therapeutics 2017 13(6):951-955

Background: Exfoliative cytology is the microscopic examination of a shed or desquamated cells from the epithelial surface. Centrifuged liquid-based cytology (CLBC) is a modified technique that is used in the current study. Aims: To compare the efficacy of CLBC with conventional cytology in apparently normal mucosa and histologically proven cases of oral squamous cell carcinoma after staining with Papanicolaou stain. Materials and Methods: The study sample was collected from fifty individuals with no habits and apparently normal oral mucosa (Group 1) and forty cases of histologically proven cases of oral squamous cell carcinoma (Group 2). One smear was taken and spread on the slide by a conventional technique. The second sample was flushed out in a suspending solution, centrifuged, and the cell pellet obtained was used to make the smear. The stained smears were compared for nine parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, cellular elongation, mucus, inflammatory blood, and microbial colonies. Chi-square test was used for statistical analysis and P ≤ 0.05 was considered statistically significant. Results: There was a statistically significant result with parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, and cellular elongation in CLBC technique, in comparison with the conventional technique. The presence of mucus, microbial colonies, and inflammatory cells were also less in CLBC technique in comparison with the conventional technique. Conclusion: CLBC has better efficacy over conventional method in all the parameters analyzed.

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The feasibility of smoker's surcharge policy in tobacco control

Eby Aluckal, Sanju Lakshmanan

Journal of Cancer Research and Therapeutics 2017 13(6):1075-1076



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The effect of ciprofloxacin on the growth of B16F10 melanoma cells

Dalal Fares Jaber, Mary-Ann Nabil Jallad, Alexander Micheal Abdelnoor

Journal of Cancer Research and Therapeutics 2017 13(6):956-960

Objective: The antitumor effect of ciprofloxacin has been widely assessed in-vitro, and positive results have been reported. The aim of this study was to investigate the influence of ciprofloxacin treatment on the growth of B16F10 melanoma cells both in-vitro and in-vivo. Materials and Methods: Groups of C57BL/6 female mice challenged with B16F10 melanoma cells were kept untreated or were treated with sterile water, intraperitoneal ciprofloxacin, or ciprofloxacin through drinking water for 10 days. The serum levels of vascular endothelial growth factor (VEGF) were measured by ELISA 1 and 3 h after the last dose of ciprofloxacin. Mice were monitored for an additional 10 days for survival assessment. Moreover, B16F10 melanoma cells were cultured in 24-well plates and exposed to different concentrations of ciprofloxacin (10–1000 μg/ml). Viability was determined, after 24 and 48 h, using trypan blue. Results: The serum levels of VEGF significantly decreased in ciprofloxacin-treated mice when compared to the controls. None of the control mice survived beyond day 8, whereas 16.67% of those treated with ciprofloxacin survived up to 18 days. In addition, the viability of B16F10 melanoma cells, in-vitro, significantly decreased with increasing concentrations of ciprofloxacin after 24 and 48 h. Conclusion: Ciprofloxacin seems to exhibit antitumor activity both in-vivo and in-vitro. This effect might be explained by several mechanisms such as directly inducing cancer cell death or altering the immune response through the modification of the normal microbiota.

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IL-25 is involved in CTCL progression by establishing Th2-dominant microenvironment

Summary

Background

Interleukin (IL)-25 is a member of the IL-17 family which can promote and augment T-helper type (Th) 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases.

Objective

To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL).

Methods

Expression and localization of IL-25 in lesional skin was investigated using immunohistochemistry. The effect of various cytokines on IL-25 production from normal human epidermal keratinocytes was assessed by quantitative reverse-transcription real-time polymerase chain reaction. Serum IL-25 levels were measured by enzyme-linked immunosorbent assay. The direct effect of IL-25 on tumor cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in Sézary syndrome patients.

Results

IL-25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL-4 and IL-13, and periostin induced IL-25 expression by normal human epidermal keratinocytes. Serum IL-25 levels were increased in patients with advanced CTCL (stage IIB-IV) and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL-25R and its expression was augmented by stimulation with IL-25. IL-25 enhanced IL-13 production from MyLa cells via phosphorylation of STAT6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL-25R and showed increase of IL-13 production by IL-25.

Conclusions

Th2 cytokines highly expressed in CTCL lesional skin induce IL-25 production by epidermal keratinocytes, which may in turn lead to formation of Th2-dominant microenvironment through the direct induction of IL-13 by tumor cells.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nX849Y

IL-25 is involved in CTCL progression by establishing Th2-dominant microenvironment

Summary

Background

Interleukin (IL)-25 is a member of the IL-17 family which can promote and augment T-helper type (Th) 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases.

Objective

To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL).

Methods

Expression and localization of IL-25 in lesional skin was investigated using immunohistochemistry. The effect of various cytokines on IL-25 production from normal human epidermal keratinocytes was assessed by quantitative reverse-transcription real-time polymerase chain reaction. Serum IL-25 levels were measured by enzyme-linked immunosorbent assay. The direct effect of IL-25 on tumor cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in Sézary syndrome patients.

Results

IL-25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL-4 and IL-13, and periostin induced IL-25 expression by normal human epidermal keratinocytes. Serum IL-25 levels were increased in patients with advanced CTCL (stage IIB-IV) and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL-25R and its expression was augmented by stimulation with IL-25. IL-25 enhanced IL-13 production from MyLa cells via phosphorylation of STAT6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL-25R and showed increase of IL-13 production by IL-25.

Conclusions

Th2 cytokines highly expressed in CTCL lesional skin induce IL-25 production by epidermal keratinocytes, which may in turn lead to formation of Th2-dominant microenvironment through the direct induction of IL-13 by tumor cells.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nX849Y

Evaluation of zinc oxide nanoparticles on lettuce ( Lactuca sativa L.) growth and soil bacterial community

Abstract

The wide spread of nanoparticles (NPs) has caused tremendous concerns on agricultural ecosystem. Some metallic NPs, such as zinc oxide (ZnO), can be utilized as a nano-fertilizer when used at optimal doses. However, little is known about the responses of plant development and concomitant soil bacteria community to ZnO NPs. The present pot experiment studied the impacts of different doses of ZnO NPs and bulk ZnO (0, 1, 10, 100 mg ZnO/kg), on the growth of lettuce (Lactuca sativa L.) and the associated rhizospheric soil bacterial community. Results showed that at a dose of 10 mg/kg, ZnO NPs and bulk ZnO, enhanced the lettuce biomass and the net photosynthetic rate; whereas, the Zn content in plant tissue was higher in NPs treatment than in their bulk counterpart at 10 mg/kg dose or higher. For the underground observations, 10 mg/kg treatment doses (NPs or bulk) significantly changed the soil bacterial community structure, despite the non-significant variations in alpha diversity. Taxonomic distribution revealed that some lineages within Cyanobacteria and other phyla individually demonstrated similar or different responses to ZnO NPs and bulk ZnO. Moreover, some lineages associated with plant growth promotion were also influenced to different extents by ZnO NPs and bulk ZnO, suggesting the distinct microbial processes occurring in soil. Collectively, this study expanded our understanding of the influence of ZnO NPs on plant performance and the associated soil microorganisms.

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Modeling the impacts of ambient temperatures on cardiovascular mortality in Yinchuan: evidence from a northwestern city of China

Abstract

No evidence is available on whether cardiovascular mortality is affected by the ambient temperatures in Yinchuan, which is located in the northwestern region of China, with a typical continental semi-humid semi-arid climate. Daily data on cardiovascular mortality and meteorological factors was collected from Yinchuan city for the period of 2010–2015. A distributed lag non-linear model with quasi-Poisson link was used to assess the association between daily temperatures and cardiovascular deaths, after controlling for seasonality, day of the week, atmospheric pressure, humidity, sunshine duration, and wind speed. The relationship between ambient temperature and cardiovascular mortality was non-linear, with a U-shaped exposure-response curve. For all cardiovascular mortality, the effects of high temperatures appeared at lag 2–5 days, with the largest hot effect at lag 3 day (RR 1.082, 95% CI 1.021–1.146), while the effects of cold temperatures were insignificant. Both cold and high temperatures have more serious influence on the elderly (age ≥ 65) and males than the youth and females, respectively. The study has shown that both cold and high temperatures affect cardiovascular mortality. The findings may be helpful to identify the susceptible subgroups of cardiovascular mortality induced by temperatures, and to provide useful information for establishing public health programs that would better protect local population health from ambient temperatures.

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Increased anti-biofilm efficacy of toluidine blue on Staphylococcus species after nano-encapsulation

Publication date: Available online 13 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Bishakh Rout, Chi-Hsien Liu, Wei-Chi Wu
BackgroundPhotodynamic therapy has been studied by many studies as a method for inactivating bacterial growth. Workers have used planktonic bacterial as well as biofilm bacterial cultures to evaluate the potential of photodynamic therapy in inactivating bacteria. However, almost all the studies use a photosensitiser in aqueous solution, which could be detrimental to the efficiency of photodynamic therapy.MethodsIn this study, the photodynamic killing effect of toluidine blue O (TBO) has been investigated on Staphylococcal biofilms in −vitro. The sensitivity of the in-vitro biofilms to photodynamic killing action was compared using different formulations of TBO, different dosages of photosensitiser and different light irradiation strengths. Effect of TBO formulations on bacterial quorum sensing system was evaluated using a colorimetric assay. Finally, dual staining using hoechst and propidium iodide stains was carried out on the photodynamically treated biofilms to visualise and compare the effects of photodynamic therapy. Scanning electron microscope imagery was also carried out to evaluate the photodynamic killing effect on the in-vitro biofilms.ResultsThe sensitivity of biofilms to the photodynamic killing effect increased proportionally with the photosensitiser dosage and the light irradiation duration. TBO encapsulated in microemulsion was more effective in killing the biofilm bacteria than only TBO in water. The combination of TBO in microemulsion with EDTA was another effective way of increasing the photodynamic killing effect on the bacterial biofilms. Effect of encapsulated TBO on the quorum sensing system of bacteria was greater than the effect of aqueous solution of TBO. The in-vitro Staphylococcal biofilms could thus be inhibited by the photodynamic effect, and TBO encapsulated in microemulsion was much more effective than only TBO in water.ConclusionsThe encapsulation of a photosensitiser is an effective way of increasing the likelihood of the complete and successful inactivation of the biofilm growth. The encapsulated photosensitiser achieves higher inactivation of the bacterial biofilm than that of the aqueous solution of a photosensitiser.



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The problem of lack of normative data in paediatric EMG and possible solutions

Publication date: Available online 13 December 2017
Source:Clinical Neurophysiology
Author(s): Matthew C Pitt, Joe Jabre




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Abnormal somatosensory temporal discrimination in Parkinson’s disease: Pathophysiological correlates and role in motor control deficits

Publication date: Available online 13 December 2017
Source:Clinical Neurophysiology
Author(s): Myung Sik Lee, Myung Jun Lee, Antonella Conte, Alfredo Berardelli
ObjectiveThe somatosensory temporal discrimination threshold (STDT), defined as the shortest time interval required for two tactile stimuli to be perceived as separate, is longer in patients with Parkinson's disease (PD). In this review, we discuss STDT findings in healthy subjects and in PD patients and the relationship between altered STDT and motor disturbances.MethodsA search was conducted on PubMed for papers dealing with PD and temporal discrimination published from January 1990 to July 2017.ResultsAbnormal STDT in PD correlates with disease duration, disease severity and degree of nigrostriatal dopamine loss, and responds to dopaminergic medication. In PD, a prolonged STDT does not correlate, or only marginally correlates, with clinically assessed bradykinesia of finger tapping. By contrast, a prolonged STDT correlates with the variability in amplitude and speed of finger tapping as assessed by means of neurophysiological techniques and may contribute to impaired finger dexterity in PD.ConclusionsWe suggest that abnormal temporal processing of sensory information in PD generates incorrect signals for the execution and control of voluntary movements.SignificanceThis review sheds light on unsolved questions regarding the relationship between STDT alterations and motor disturbances in PD and proposes directions for future research on this topic.



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Non-invasive brain stimulation and neuro-enhancement in aging

Publication date: Available online 13 December 2017
Source:Clinical Neurophysiology
Author(s): Carl-Johan Boraxbekk




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Diaphragm Motor Responses to phrenic nerve stimulation in ALS: Surface and Needle Recordings

Publication date: Available online 13 December 2017
Source:Clinical Neurophysiology
Author(s): Mamede de Carvalho, Susana Pinto, Michael Swash
ObjectiveIn studies of phrenic nerve (PN) conduction in amyotrophic lateral sclerosis (ALS) both motor response amplitude and latency have been reported as abnormal. However, correlation with diaphragm motor unit loss, and with diaphragmatic function has not been fully evaluated.MethodsWe studied 83 patients with ALS, and 21 patients referred with clinically suspected phrenic nerve lesions whose studies were normal. PN responses elicited by percutaneous electrical stimulation in the neck were recorded using superficial electrodes placed at the surface markings of the diaphragm on the chest wall, and a concentric needle electrode inserted into the diaphragmatic costal fibres. Electromyography of diaphragm was performed to analyse motor unit morphology and recruitment.ResultsThe 21 controls and 83 ALS patients were matched for age. In controls, the only significant correlation between surface and needle recording was for negative-peak amplitude (p=0.03). In ALS patients, amplitudes and negative-peak area were highly correlated (p<0.001), as were PN motor latencies (p=0.002). Forced vital capacity (FVC) was highly correlated with both amplitude (p<0.001) and PN latency (p<0.02), whichever electrode was used. PN amplitude recording with needle electrode was consistent with EMG findings in the diaphragm.ConclusionIn ALS, PN motor amplitude/area and latency measurements recorded by surface electrodes are highly correlated with needle EMG findings in the diaphragm. CMAP amplitude/area measurements showed high correlation with FVC.SignificanceIn ALS, amplitude/area of the motor PN response, recorded by surface or needleelectrodes, correlates with dysfunction of the diaphragm.



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Diminished EEG Habituation to Novel Events Effectively Classifies Parkinson’s Patients

Publication date: Available online 13 December 2017
Source:Clinical Neurophysiology
Author(s): James F. Cavanagh, Praveen Kumar, Andrea A. Mueller, Sarah Pirio Richardson, Abdullah Mueen
ObjectivesWe aimed to test if EEG responses to novel events reliably dissociated individuals with Parkinson's disease and controls, and if this dissociation was sensitive and specific enough to be a candidate biomarker of cognitive dysfunction in Parkinson's disease.MethodsParticipants included N=25 individuals with Parkinson's disease and an equal number of well-matched controls. EEG was recorded during a three-stimulus auditory oddball paradigm both ON and OFF medication.ResultsWhile control participants showed reliable EEG habituation to novel events over time, individuals with Parkinson's did not. In the OFF condition, individual differences in habituation correlated with years since diagnosis. Pattern classifiers achieved high sensitivity and specificity in discriminating patients from controls, with a maximum accuracy of 82%. Most importantly, the confidence of the classifier was related to years since diagnosis, and this correlation increased as the time course of differential habituation increasingly distinguished the groups.ConclusionsThese findings identify systemic alteration in an obligatory neural mechanism that may contribute to higher-level cognitive dysfunction in Parkinson's disease.SignificanceThese findings suggest that EEG responses to novel events in this rapid, simple, and inexpensive test have tremendous promise for tracking individual trajectories of cognitive dysfunction in Parkinson's disease.



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Green electrochemical modification of RVC foam electrode and improved H 2 O 2 electrogeneration by applying pulsed current for pollutant removal

Abstract

The performance of cathode on H₂O₂ electrogeneration is a critical factor that limits the practical application of electro-Fenton (EF) process. Herein, we report a simple but effective electrochemical modification of reticulated vitreous carbon foam (RVC foam) electrode for enhanced H₂O₂ electrogeneration. Cyclic voltammetry, chronoamperometry, and X-ray photoelectron spectrum were used to characterize the modified electrode. Oxygen-containing groups (72.5–184.0 μmol/g) were introduced to RVC foam surface, thus resulting in a 59.8–258.2% higher H₂O₂ yield. The modified electrodes showed much higher electrocatalytic activity toward O₂ reduction and good stability. Moreover, aimed at weakening the extent of electroreduction of H₂O₂ in porous RVC foam, the strategy of pulsed current was proposed. H₂O₂ concentration was 582.3 and 114.0% higher than the unmodified and modified electrodes, respectively. To test the feasibility of modification, as well as pulsed current, EF process was operated for removal of Reactive Blue 19 (RB19). The fluorescence intensity of hydroxybenzoic acid in EF with modified electrode is 3.2 times higher than EF with unmodified electrode, illustrating more hydroxyl radicals were generated. The removal efficiency of RB 19 in EF with unmodified electrode, modified electrode, and unmodified electrode assisted by pulsed current was 53.9, 68.9, and 81.1%, respectively, demonstrating that the green modification approach, as well as pulsed current, is applicable in EF system for pollutant removal.

Graphical abstract

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Metal-tolerant thermophiles: metals as electron donors and acceptors, toxicity, tolerance and industrial applications

Abstract

Metal-tolerant thermophiles are inhabitants of a wide range of extreme habitats like solfatara fields, hot springs, mud holes, hydrothermal vents oozing out from metal-rich ores, hypersaline pools and soil crusts enriched with metals and other elements. The ability to withstand adverse environmental conditions, like high temperature, high metal concentration and sometimes high pH in their niche, makes them an interesting subject for understanding mechanisms behind their ability to deal with multiple duress simultaneously. Metals are essential for biological systems, as they participate in biochemistries that cannot be achieved only by organic molecules. However, the excess concentration of metals can disrupt natural biogeochemical processes and can impose toxicity. Thermophiles counteract metal toxicity via their unique cell wall, metabolic factors and enzymes that carry out metal-based redox transformations, metal sequestration by metallothioneins and metallochaperones as well as metal efflux. Thermophilic metal resistance is heterogeneous at both genetic and physiology levels and may be chromosomally, plasmid or transposon encoded with one or more genes being involved. These effective response mechanisms either individually or synergistically make proliferation of thermophiles in metal-rich habitats possibly. This article presents the state of the art and future perspectives of responses of thermophiles to metals at genetic as well as physiological levels.

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Proteomic analysis of six- and twelve-month hippocampus and cerebellum in a murine Down syndrome model

Publication date: March 2018
Source:Neurobiology of Aging, Volume 63
Author(s): Guido N. Vacano, David S. Gibson, Abdullah Arif Turjoman, Jeremy W. Gawryluk, Jonathan D. Geiger, Mark Duncan, David Patterson
This study was designed to investigate the brain proteome of the Ts65Dn mouse model of Down syndrome. We profiled the cerebellum and hippocampus proteomes of 6- and 12-month-old trisomic and disomic mice by difference gel electrophoresis. We quantified levels of 2082 protein spots and identified 272 (170 unique UniProt accessions) by mass spectrometry. Four identified proteins are encoded by genes trisomic in the Ts65Dn mouse. Three of these (CRYZL11, EZR, and SOD1) were elevated with p-value <0.05, and 2 proteins encoded by disomic genes (MAPRE3 and PHB) were reduced. Intergel comparisons based on age (6 vs. 12 months) and brain region (cerebellum vs. hippocampus) revealed numerous differences. Specifically, 132 identified proteins were different between age groups, and 141 identified proteins were different between the 2 brain regions. Our results suggest that compensatory mechanisms exist, which ameliorate the effect of trisomy in the Ts65Dn mice. Differences observed during aging may play a role in the accelerated deterioration of learning and memory seen in Ts65Dn mice.



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Regulation of MAVS activation through post-translational modifications

Bingyu Liu | Chengjiang Gao

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Adaptive cortical parcellations for source reconstructed EEG/MEG connectomes

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Seyedeh-Rezvan Farahibozorg, Richard N. Henson, Olaf Hauk
There is growing interest in the rich temporal and spectral properties of the functional connectome of the brain that are provided by Electro- and Magnetoencephalography (EEG/MEG). However, the problem of leakage between brain sources that arises when reconstructing brain activity from EEG/MEG recordings outside the head makes it difficult to distinguish true connections from spurious connections, even when connections are based on measures that ignore zero-lag dependencies. In particular, standard anatomical parcellations for potential cortical sources tend to over- or under-sample the real spatial resolution of EEG/MEG. By using information from cross-talk functions (CTFs) that objectively describe leakage for a given sensor configuration and distributed source reconstruction method, we introduce methods for optimising the number of parcels while simultaneously minimising the leakage between them. More specifically, we compare two image segmentation algorithms: 1) a split-and-merge (SaM) algorithm based on standard anatomical parcellations and 2) a region growing (RG) algorithm based on all the brain vertices with no prior parcellation. Interestingly, when applied to minimum-norm reconstructions for EEG/MEG configurations from real data, both algorithms yielded approximately 70 parcels despite their different starting points, suggesting that this reflects the resolution limit of this particular sensor configuration and reconstruction method. Importantly, when compared against standard anatomical parcellations, resolution matrices of adaptive parcellations showed notably higher sensitivity and distinguishability of parcels. Furthermore, extensive simulations of realistic networks revealed significant improvements in network reconstruction accuracies, particularly in reducing false leakage-induced connections. Adaptive parcellations therefore allow a more accurate reconstruction of functional EEG/MEG connectomes.

Graphical abstract

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Unfolding the hippocampus: An intrinsic coordinate system for subfield segmentations and quantitative mapping

Publication date: 15 February 2018
Source:NeuroImage, Volume 167
Author(s): Jordan DeKraker, Kayla M. Ferko, Jonathan C. Lau, Stefan Köhler, Ali R. Khan
The hippocampus, like the neocortex, has a morphological structure that is complex and variable in its folding pattern, especially in the hippocampal head. The current study presents a computational method to unfold hippocampal grey matter, with a particular focus on the hippocampal head where complexity is highest due to medial curving of the structure and the variable presence of digitations. This unfolding was performed on segmentations from high-resolution, T2-weighted 7T MRI data from 12 healthy participants and one surgical patient with epilepsy whose resected hippocampal tissue was used for histological validation. We traced a critical image feature composed of the hippocampal sulcus and stratum radiatum lacunosum-moleculare, (SRLM) in these images, then employed user-guided semi-automated techniques to detect and subsequently unfold the surrounding hippocampal grey matter. This unfolding was performed by solving Laplace's equation in three dimensions of interest (long-axis, proximal-distal, and laminar). The resulting 'unfolded coordinate space' provides an intuitive way of mapping the hippocampal subfields in 2D space (long-axis and proximal-distal), such that similar borders can be applied in the head, body, and tail of the hippocampus independently of variability in folding. This unfolded coordinate space was employed to map intracortical myelin and thickness in relation to subfield borders, which revealed intracortical myelin differences that closely follow the subfield borders used here. Examination of a histological resected tissue sample from a patient with epilepsy reveals that our unfolded coordinate system has biological validity, and that subfield segmentations applied in this space are able to capture features not seen in manual tracing protocols.



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Influence of diabetes on the foreign body response to nitric oxide-releasing implants

Publication date: March 2018
Source:Biomaterials, Volume 157
Author(s): Robert J. Soto, Elizabeth P. Merricks, Dwight A. Bellinger, Timothy C. Nichols, Mark H. Schoenfisch
The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8–630.0 pmol cm⁻² s⁻¹ and 2–13 d, respectively). The NO-releasing materials were implanted in the subcutis for 3, 10, or 25 d for histological and immunohistochemical evaluation of the FBR. A delayed, more severe inflammatory response to control (i.e., non-NO-releasing) implants was observed in diabetic pigs relative to healthy swine. Regardless of the animal disease state, each NO-releasing implant tested elicited reduced inflammation compared to controls at both 3 and 10 d. However, only the NO-release materials capable of releasing low NO fluxes (0.8–3.3 pmol cm⁻² s⁻¹) for 7–13 d durations mitigated the inflammatory response at 25 d. Using immunohistochemical staining for the endothelial cell surface marker CD-31, we also observed poor blood vessel development at non-NO-releasing implants in diabetic swine. Relative to controls, NO-releasing implants with the longest NO-release duration (13 d) increased blood vessel densities by 47.1 and 70.4% in the healthy and diabetic pigs, respectively. In the healthy model, tissues surrounding the long NO-release materials contained sparse amounts of collagen, whereas implants with shorter NO-release durations (2, 3, and 7 d) were characterized with a dense collagen encapsulation layer, similar to controls. Collagen deposition in diabetic swine was inhibited, and unaffected by NO. These results emphasize several key differences in the FBR in the setting of acute onset diabetes. The observation that NO release counteracts the more severe FBR in diabetic swine while simultaneously promoting tissue integration may help guide the design of medical implants (e.g., glucose sensors) with improved performance for diabetes management.



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Magnesium phosphate ceramics incorporating a novel indene compound promote osteoblast differentiation in vitro and bone regeneration in vivo

Publication date: March 2018
Source:Biomaterials, Volume 157
Author(s): Ju Ang Kim, Hui-suk Yun, Young-Ae Choi, Jung-Eun Kim, So-Young Choi, Tae-Geon Kwon, Young Kyung Kim, Tae-Yub Kwon, Myung Ae Bae, Nak Jeong Kim, Yong Chul Bae, Hong-In Shin, Eui Kyun Park
Incorporating bioactive molecules into synthetic ceramic scaffolds is challenging. In this study, to enhance bone regeneration, a magnesium phosphate (MgP) ceramic scaffold was incorporated with a novel indene compound, KR-34893. KR-34893 induced the deposition of minerals and expression of osteoblast marker genes in primary human bone marrow mesenchymal stem cells (BMSCs) and a mouse osteoblastic MC3T3-E1 cell line. Analysis of the mode of action showed that KR-34893 induced the phosphorylation of MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase, and subsequently the expression of bone morphogenetic protein 7, accompanied by SMAD1/5/8 phosphorylation. Accordingly, KR-34893 was incorporated into an MgP scaffold prepared by 3D printing at room temperature, followed by cement reaction. KR-34893-incorporated MgP (KR-MgP) induced the expression of osteoblast differentiation marker genes in vitro. In a rat calvaria defect model, KR-MgP scaffolds enhanced bone regeneration and increased bone volume compared with MgP scaffolds, as assessed by micro-computed tomography and histological analyses. In conclusion, we developed a method for producing osteoinductive MgP scaffolds incorporating a bioactive organic compound, without high temperature sintering. The KR-MgP scaffolds enhanced osteoblast activation in vitro and bone regeneration in vivo.



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Optical molecular imaging for tumor detection and image-guided surgery

Publication date: March 2018
Source:Biomaterials, Volume 157
Author(s): Chensu Wang, Zhaohui Wang, Tian Zhao, Yang Li, Gang Huang, Baran D. Sumer, Jinming Gao
We have witnessed rapid development of fluorescence molecular imaging of solid tumors for cancer diagnosis and image-guided surgery in the past decade. Many biomarkers unique to cancer cells or tumor microenvironment, such as cell surface receptors, hypoxia, secreted proteases and extracellular acidosis have been characterized, and can be used to distinguish cancer from normal tissue. A variety of optical imaging probes have been developed to target these biomarkers to improve tumor contrast over the background tissue. Unlike conventional anatomical and molecular imaging technologies, fluorescent imaging method benefits from its safety, high-spatial resolution and real-time capability, and therefore, has become a highly adoptable imaging method for tumor detection and image-guided surgery in clinics. In this review, we summarize recent progress in 'always-ON' and stimuli-activatable fluorescent imaging probes, and discuss their potentials in tumor detection and image-guided surgery.

Graphical abstract

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Methotrexate and azathioprine in severe atopic dermatitis: a 5-year follow up study of a randomised controlled trial

Summary

Background

Systemic treatment is indicated for moderate-to-severe atopic dermatitis (AD), refractory to topical treatment. Long-term evidence, up to 5 years, of off-label prescribed methotrexate (MTX) and azathioprine (AZA) is lacking.

Objectives

To investigate long-term effectiveness, safety and drug survival of MTX and AZA.

Methods

In an open-label follow up phase of a clinical trial patients were seen every 3 months for 5 years. MTX and AZA doses could be in- or decreased concurrent with daily clinical practice. Primary effectiveness outcomes were mean absolute and relative reduction in SCORing Atopic Dermatitis (SCORAD) index and Investigator Global Assessment (IGA) after 5 years compared to baseline. For safety type, frequency, severity and relatedness to treatment of adverse events were investigated. Drug survival was analysed by Kaplan-Meier curves.

Results

Thirty-five of 43 originally included patients participated, of which 27 completed follow up. At year 5 mean relative reduction in SCORAD index was similar in MTX and AZA group: 52.8% and 53.8% by descriptive analysis. Eleven serious adverse events occurred in 5 years; for three there was a possible causal relationship. Drug survival demonstrated a longer survival for MTX, but survival in both groups was low after 5 years (MTX n=5, AZA n=1).

Conclusion

Based on this relatively small pragmatic study, MTX and AZA seem to be effective and safe as maintenance treatments in moderate-to-severe AD up to 5 years. Few patients in both groups survive on their originally allocated drug although some discontinued due to controlled AD.

This article is protected by copyright. All rights reserved.

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