Head and Neck Diseases by Alexandros G.Sfakianakis: 05/03/18

Πέμπτη 3 Μαΐου 2018

Spontaneous Medial Cribriform CSF Leak: Endoscopic Surgical Repair with Free Mucosal Graft—Our Experience

Abstract

Cribriform plate is the commonest site of spontaneous CSF leak, the fragility of the plate and juxtaposition of arachnoid's investment to the bone, where the olfactory nerve pierces the skull made this area, a vulnerable site for CSF leak. Transnasal endoscopic approach has gained popularity for CSF leak repair over the years. To describe the 5 year experience of spontaneous medial cribriform CSF leak repair with free mucosal graft in a tertiary medical centre. All patients who underwent transnasal endoscopic repair with free mucosal graft for spontaneous medial cribriform CSF leak in our institution between 2011 and 2016 were reviewed. Twelve patients were identified, all were women with a mean age of 44.5 years. The defect was localised by preoperative computed tomography scans with 1 mm cuts and MR cisternography. Via medial approach, the mucosa surrounding the entire defect was denuded and the defect was closed with free mucosal graft harvested either from the middle turbinate or from the nasal septum and middle turbinate was finally sutured with septum to stabilise the repair. The overall success rate was 100% with the first attempt with no recurrence or postoperative complications. Follow up ranged from 1 to 5 years. The endoscopic transnasal technique with free mucosal graft for the repair of spontaneous medial cribriform CSF rhinorrhoea is associated with a very high success rate and it should be considered for majority of cases.

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The 5th IEEE International Conference on Renewable Energy Research and Applications (ICRERA 2016)

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Histoplasmosis: An Emerging Endemic Mycosis

A. Pulido Pérez
Actas Dermosifiliogr.2018;109:295

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Risk of Skin Cancer Associated With Narrowband UV-B Phototherapy

J. Aguilera
Actas Dermosifiliogr.2018;109:296

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Improving the Quality of Life of Patients With Actinic Keratosis

N. Blázquez-Sánchez
Actas Dermosifiliogr.2018;109:296-7

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Lymphadenectomy After a Positive Sentinel Lymph Node Biopsy in Melanoma: A Paradigm Shift

Á. Pizarro
Actas Dermosifiliogr.2018;109:298-302

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Morphea in Childhood: An Update

B. Aranegui, J. Jiménez-Reyes
Actas Dermosifiliogr.2018;109:312-22

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Quality of Life, Behaviour and Attitudes towards Actinic Keratosis in Spain: The PIQA Study

I. Longo, C. Serra-Guillén
Actas Dermosifiliogr.2018;109:331-9

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Electrosurgery for the Treatment of Moderate or Severe Rhinophyma

L.F. González, H. Herrera, A. Motta
Actas Dermosifiliogr.2018;109:e23-6

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Mucocutaneous Manifestations of Infection by Histoplasma capsulatum in HIV-Negative Immunosuppressed Patients

L.V. Gómez-Santana, A.C. Torre, B.A. Hernández, V.I. Volonteri, B. Laura, R. Luis-Galimberti
Actas Dermosifiliogr.2018;109:e27-32

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Painful Ulcer in a Black Man

I. Latour-Álvarez, M. Arteaga-Henriquez, A. de Andrés-del Rosario
Actas Dermosifiliogr.2018;109:351-2

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Umbilicated Papules on the Elbows of a Woman With Systemic Vasculitis

C. Lloret-Ruiz, N. Barrado-Solís, E. Quecedo-Estébanez
Actas Dermosifiliogr.2018;109:353-4

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Ulcerative nodules on the perineum

C.-F. Yen, K.-L. Chen, T.-F. Tsai
Actas Dermosifiliogr.2018;109:355-6

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Proliferating Pilomatricoma Mimicking a Malignant Tumor

P. García-Montero, J.B. Repiso-Jiménez, I. Fernández-Canedo
Actas Dermosifiliogr.2018;109:359

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Cutaneous Metastases From Adenocarcinoma of the Prostate

M.Á. Flores-Terry, R. Cruz-Conde de Boom, M. García-Arpa, I.M. de Lara-Simón
Actas Dermosifiliogr.2018;109:360

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Folliculitis Decalvans Caused by Bacterial Superinfection Secondary to Erlotinib

A. Sahuquillo-Torralba, B. Escutia-Muñoz, M. Rodríguez-Serna, R. Botella-Estrada
Actas Dermosifiliogr.2018;109:363-4

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Evaluation of bone repair after application of a norbixin membrane scaffold with and without laser photobiomodulation (λ 780 nm)

Abstract

Biocompatible membranes are widely used in medicine to stimulate bone repair. Several studies have demonstrated that laser photobiomodulation (PBM) also stimulates osteoblast proliferation and osteogenesis at the fracture site, leading to a greater deposition of bone mass and accelerating the process of bone consolidation. This work assessed the therapeutic effect of 780-nm laser PBM and a polystyrene membrane coated with norbixin and collagen (PSNC) on bone healing in rats with calvarial bone defect. Histological staining, Raman spectroscopy, and scanning electron microscopy (SEM) were used to evaluate the bone repair process. Four experimental treatment groups were compared: C, control; M, membrane only; L, laser PBM only; and ML, membrane + laser PBM. A bone defect was created in the calvaria of each animal, with each group subdivided into two subgroups that underwent euthanasia after 15 and 30 days treatment. The L and ML groups were irradiated (λ = 780 nm, ED = 6 J/cm², P = 60 mW, t = 4 s) postoperatively on alternate days until they were euthanized. The bone concentration of hydroxyapatite (CHA) showed a clear gradation with increasing phosphate area in the order B (normal cortical bone) > L > M > ML > C for both periods. The PSNC membrane was effective in reducing the inflammatory process and served as a scaffold for bone repair. The laser PBM also showed positive effects on the bone repair process with increased deposition and organization of the newly formed bone. However, laser PBM failed to improve the bioactive properties of the membrane scaffold.

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When and how to treat women with HER2-positive, small (pT1a-b), node-negative breast cancer?

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Stefania Gori, Monica Turazza, Alessandra Modena, Simona Duranti, Giuseppe Zamboni, Filippo Alongi, Giovanni Carbognin, Alberto Massocco, Matteo Salgarello, Alessandro Inno
Small (pT1a-b), node-negative (pN0) breast cancer generally has a good prognosis. However, HER2-positive status is associated with an increased risk of relapse and decreased survival even in these tumors. Although there are only few data from prospective randomized trials, results of retrospective studies suggest adjuvant chemotherapy plus trastuzumab may improve outcomes of patients with pT1a-b pN0 HER2-positive breast cancer. On the other hand, trastuzumab is potentially associated with increased cardiac toxicity, especially when combined with anthracycline-based chemotherapy. A valid strategy for improving cardiac safety is the addition of trastuzumab to non-anthracycline chemotherapy, whereas a shorter duration of trastuzumab should be not routinely considered although might represent an option for selected patients at low risk of relapse and very high risk of cardiac events. Therefore, the choice of adjuvant treatment for patients with pT1a-b pN0 HER2-positive breast cancer should be done on individual basis, carefully weighing benefits and risks.

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Cochlear implants in developing countries: practical and ethical considerations

No abstract available

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Editorial introductions

No abstract available

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Perspectives on voice treatment for unilateral vocal fold paralysis

Purpose of review Unilateral vocal fold paralysis (UVFP) is a common cause of neurogenic dysphonia resulting in glottal insufficiency. To restore glottal sufficiency and reduce the presenting dysphonia, treatment involving either surgical intervention, voice therapy or a combination of the two is typically provided. Currently, there is no consensus for the most effective voice treatment for UVFP. This results in an inability to compare current studies, and a lack of treatment effectiveness for the management of UVFP. This study aims to review the most recent literature for the management of dysphonia due to UVFP to establish the current evidence base for voice treatment options. Recent findings There was found to be a lack of consistency in the rationale, selection and timing of the surgical intervention and/or voice therapy being provided for patients with UVFP. Summary Further consensus is required for the rationale and selection of voice treatment prescriptions for the management of UVFP in order to improve treatment effectiveness and voice outcomes in patients with UVFP.

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Developing competent videofluoroscopic swallowing study analysts

Purpose of review This review examines the recent literature concerning the development of VFSS analysts. Recent findings Face-to-face and blended methods of training improve reliability and accuracy of VFSS analysis. However, with the exception of the literature describing the MBSImP training, most studies investigate relatively brief training for specific VFSS rating tools. The influence of training mode and trainee factors has received limited attention. Summary There is a lack of controlled studies investigating the influences of training methods for VFSS analysis. Pilot data is emerging concerning VFSS analysis training 'packages' but without information about the relative influence of training mode, it is difficult to determine the most efficient and cost-effective way of training VFSS analysts. Future research should investigate the contribution of trainee-related factors to succeed in VFSS analysis training, and the relative benefits and disadvantages of online, peer, independent, and blended modes of training.

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Managing the late effects of chemoradiation on swallowing: bolstering the beginning, minding the middle, and cocreating the end

Purpose of review Late dysphagia has a profound impact on quality of life in patients treated with chemoradiation therapy for advanced head and neck cancer and the number of survivors is growing. Traditional treatment methods are not uniformly successful in reducing the swallow impairment in these patients. Recent findings Manifestations of late dysphagia are complex and do not follow a uniform trajectory. Patient's experience of eating and engagement in treatment is critical given the complex, variable nature of late dysphagia. Novel swallow treatment methods target respiratory function including coordination and strength as well as patient adherence. Summary Head and neck cancer survivors deserve routine and fastidious surveillance beyond the 5-year survival point with respect to swallow function if the enormous biopsychosocial burden of late dysphagia is to be addressed.

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A comparison of neuromuscular electrical stimulation and traditional therapy, versus traditional therapy in patients with longstanding dysphagia

Purpose of review Dysphagia in adults arises from a range of causes including acquired neurological disorders and some cancers. Previous research has suggested that treatment using neuromuscular electrical stimulation (NMES) when used in conjunction with conventional therapy is effective. This review describes the recent literature and a small prospective case series carried out in the United Kingdom. This study contributed to support National Institute of Clinical Excellence (NICE) guidance for clinicians who wish to include NMES in a rehabilitation programme for dysphagic patients, specifically with reference to safety and the impact on swallowing function of this intervention. Recent findings In 2014, the UK NICE issued guidelines enabling UK therapists to trial the use of NMES, but the guidelines also sought additional evidence on the impact on swallowing function of NMES and the incidence of side effects. This small prospective case series investigated both of these aspects with a group of patients with dysphagia of neurological origin who had not achieved adequate swallowing function with traditional therapy alone. This study recruited 10 adult patients with dysphagia of neurological origin. All had previously received traditional swallowing therapy for at least 6 months but only achieved a Functional Oral Intake Scale of 4 or less (a scale for amounts and types of oral intake). The total study period was 10 weeks for each subject comprising 5 weeks of traditional therapy delivered three times a week followed by 5 weeks of NMES concurrent with traditional therapy (NMES + traditional therapy) delivered three times a week using the VitalStim stimulator (VitalStim Therapy, UK). In addition, the Quality of Life in Swallowing and Eating Assessment Tool 10 (quality of life scales) were determined to allow comparison between studies. Nine subjects achieved an improvement in swallowing function after NMES + traditional therapy was measured using the Functional Oral Intake Scale, giving a statistically significant improvement (P

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Cost-effectiveness of CI in developing countries

Purpose of review Cost-effectiveness of cochlear implants is a major concern for expanding these services to low-income and middle-income developing countries. Recent findings Recent studies have applied appropriate methodology to make determination of cost-effectiveness for cochlear implants in developing countries. In addition, important parameters that effect cost-effectiveness have been reviewed in a systematic way. The combination of these new studies along with existing reports of cochlear implant programmes in developing countries allows for a discussion of cost and outcomes determinants that drive cost-effectiveness in these environments. Summary Cochlear implants are a very cost-effective treatment for profound hearing loss in all high-resource countries and in many low-income and middle-income developing countries. A number of cost considerations affect cost-effectiveness of cochlear implants in developing countries including device cost and device-related expenses such as power consumption and reliability, but also including rehabilitation and access-related expenses. Large-scale programmes confer an advantage for cost-effectiveness, primarily through device-related savings.

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Clinical presentation, assessment, and management of inducible laryngeal obstruction

Purpose of review Many aspects of inducible laryngeal obstruction (ILO) are still poorly understood. However, in recent years there have been advances made and an international consensus has achieved a standardized taxonomy. This review will synthesize recent research; specifically, relating to clinical presentation, assessment, and therapeutic interventions. Recent findings The evidence base is growing but still limited for ILO and mostly comprises retrospective reviews, case studies, and anecdotal reports. The proposed relationship between ILO and other manifestations of laryngeal dysfunction via laryngeal hypersensitivity and hyperresponsiveness warrants further investigation. Progress has been made with guidelines published on laryngoscopy reporting procedures and validated symptom questionnaires produced for clinical use, although diagnostic algorithms are yet to be established. Emerging conservative and surgical interventions show promise, although as yet there are no randomized controlled trials investigating treatment efficacy. Summary The field is in an embryonic state and key research priorities, acknowledged in the current literature, need to be addressed to positively impact patient care.

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Overcoming developing-world challenges in cochlear implantation: a South American perspective

Purpose of review Effective hearing rehabilitation with cochlear implantation is challenging in developing countries, and this review focuses on strategies for childhood profound sensorineural hearing loss care in South America. Recent findings Most global hearing loss exists in developing countries; optimal cost-effective management strategies are essential in these environments. This review aims to assess and discuss the challenges of cochlear implantation effectiveness in South America. The authors searched electronic databases, bibliographies, and references for published and unpublished studies. Sensitivity analysis was performed to evaluate the effect of device cost, professional salaries, annual number of implants, and failure rate. Costs were obtained from experts in South America using known costs and estimations whenever necessary. Recent studies reported several challenges in unilateral or bilateral cochlear implants: cochlear implant costs, deaf education costs, increasing need for cochlear implant capacity, and training and increasing longevity. Summary Cochlear implantation was very cost-effective in all South American countries. Despite inconsistencies in the quality of available evidence, the robustness of systematic review methods substantiates the positive findings of the included studies, demonstrating that unilateral cochlear implantation is clinically effective and likely to be cost-effective in developing countries.

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Income as a moderator of psychological stress and nicotine dependence among adult smokers

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): Andréa L. Hobkirk, Nicolle M. Krebs, Joshua E. Muscat
BackgroundPerceived stress and psychological distress are associated with more cigarette craving and withdrawal, higher nicotine dependence, and less success during quit attempts. Low income smokers have disproportionately higher rates of smoking and may be particularly vulnerable to the effects of stress on smoking dependence. The aim of the current study was to assess if lower income smokers have a stronger association between stress and nicotine dependence than higher income smokers.MethodsData were obtained from the Pennsylvania Adult Smoking Study, which included 351 daily smokers. Subjects completed PhenX Toolkit and other self-report measures of socioeconomic factors, the 10-item Perceived Stress Scale, Kessler Psychological Distress Scale (K6), Fagerstrom Test for Nicotine Dependence (FTND), and the Hooked on Nicotine Checklist (HONC). Moderation analyses using linear regression examined income-related differences in the association between stress and nicotine dependence.ResultsIncome groups were categorized by an annual household income of $50,000 based on visual-inspection of scatter plots of income by nicotine dependence. Compared to higher income smokers, lower income smokers had significantly higher mean levels of nicotine dependence on the FTND [3.74 vs. 4.79, p < 0.001], perceived stress [15.63 vs. 17.95, p = 0.004], and psychological distress [5.30 vs. 6.86, p = 0.001], respectively. There were interaction effects, such that lower income smokers had a strong, positive associations between FTND and perceived stress (B = −0.11, CI = −0.17 to −0.04, p = 0.002) and psychological distress (B = −0.13, CI = −0.25 to −0.02, p = 0.022) whereas no association was found in higher income smokers. No significant moderation effects were found for the HONC or when income groups were categorized by U.S. federal poverty level.ConclusionsThe results highlight that the relationship between increasing stress and FTND was found in lower but not higher income groups. Future research should examine socioeconomic, environmental and psychosocial factors that may facilitate increased smoking during stress-induced craving.

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Sound source localization

Publication date: Available online 3 May 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): M. Risoud, J.-N. Hanson, F. Gauvrit, C. Renard, P.-E. Lemesre, N.-X. Bonne, C. Vincent
Sound source localization is paramount for comfort of life, determining the position of a sound source in 3 dimensions: azimuth, height and distance. It is based on 3 types of cue: 2 binaural (interaural time difference and interaural level difference) and 1 monaural spectral cue (head-related transfer function). These are complementary and vary according to the acoustic characteristics of the incident sound. The objective of this report is to update the current state of knowledge on the physical basis of spatial sound localization.

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French Society of ENT (SFORL) guidelines (short version) on the roles of the various treatment options in childhood obstructive sleep apnea-hypopnea syndrome

Publication date: Available online 3 May 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): B. Pateron, R. Marianowski, P.-J. Monteyrol, V. Couloigner, M. Akkari, F. Chalumeau, P. Fayoux, N. Leboulanger, P. Franco, M. Mondain
ObjectiveThe authors present the guidelines of the French Society of ENT and Head & Neck Surgery (SFORL) on the role of the ENT physician in childhood obstructive sleep apnea-hypopnea syndrome (OSAHS). This section of the guidelines concerns the roles of the various medical and surgical treatment options.MethodA multidisciplinary work-group was entrusted with a review of the scientific literature on the topic. Based on the retrieved articles and the group members' own experience, guidelines were drawn up, then read over by a reading group independent of the work-group. An editorial meeting then produced the final text.ResultsAdenotonsillectomy is the reference treatment for childhood OSAHS with adenotonsillar hypertrophy. Respiratory assistance is recommended in children with severe OSAHS without nasal and/or oropharyngeal obstacle, after surgery in case of persistent OSAHS, in case of contraindications to surgery, in complex obstruction related to pharyngolaryngeal or laryngeal pathology or comorbidity, or as an alternative to tracheotomy. Nasal route corticosteroids may be used in childhood OSAHS in with associated nasal obstruction.

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Elucidation of the TMab-6 Monoclonal Antibody Epitope Against Telomerase Reverse Transcriptase

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.

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Custom designing laryngoplasty implant using actual size CT scan images on a mobile device

Clinical Otolaryngology, EarlyView.

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Synthesis and characterization of anthill-eggshell composite adsorbent for removal of hexavalent chromium from aqueous solution

Abstract

In this study, adsorption behavior of anthill-eggshell composite (AEC) for the removal of hexavalent chromium (Cr⁶⁺) from aqueous solution was investigated. The raw AEC sample was thermally treated at 864 °C for 4 h and characterized using Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and X-ray fluorescence (XRF) techniques. The effects of adsorption process variables including initial Cr⁶⁺ concentration, contact time, and adsorbent dosage on the Cr⁶⁺ removal efficiency were investigated using central composite design (CCD) of response surface methodology (RSM). Equilibrium adsorption isotherm and kinetic were also studied. From the analysis of variance (ANOVA), the three variables proved to be significant and the optimum conditions for Cr⁶⁺ adsorption were obtained to be 150 mg/L initial Cr⁶⁺ concentration, 45.04-min contact time, and 0.5 g adsorbent dosage, which resulted in 86.21% of Cr⁶⁺ adsorbed. Equilibrium isotherm study showed that Freundlich model fitted well to the experimental data. The pseudo-second-order kinetic model appeared to better describe the experimental data. The study showed that mixed anthill-eggshell is a promising adsorbent for removing Cr⁶⁺ from aqueous solution.

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The predominant phytoplankton of Pseudoanabaena holding specific biosynthesis gene-derived occurrence of 2-MIB in a drinking water reservoir

Abstract

With the increasing occurrence of water eutrophication and blooms, earthy-musty odor problems caused by cyanobacteria have been more and more apparent. These problems have a serious impact on aquatic ecosystems and drinking water safety and become one of the priorities of the water environment researches and managements. In the present study, genes associated with 2-MIB synthesis in cyanobacteria were studied by systematic investigation on molecular characterization and quantity of 2-MIB-producing cyanobacteria in China. Our results founded that Pseudoanabaena is an important 2-MIB-producing phytoplankton and predominant in summer in Qingcaosha reservoir, and the copy number of mic and 2-MIB concentration have strongly positive correlation. We also demonstrated that abundance of mic in water was significant correlation with that in sediment. These results will help us to understand the main taxa of the odoriferous cyanobacteria in the water bodies in China, understand the genetic basis of the odor substances in the cyanobacteria. Rapid, reliable monitoring and ecological research methods for the production of odor cyanobacteria in water bodies can be established based on these results.

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Interobserver variations in the delineation of target volumes and organs at risk and their impact on dose distribution in intensity-modulated radiation therapy for nasopharyngeal carcinoma

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Ying-lin Peng, Li Chen, Guan-zhu Shen, Ya-ning Li, Ji-jin Yao, Wei-wei Xiao, Lin Yang, Shu Zhou, Jia-xin Li, Wan-qin Cheng, Ying Guan, Hai-qun Xia, Shuai Liu, Chong Zhao, Xiao-wu Deng
ObjectiveThis study aimed to (a) assess the differences in the delineation of target volumes and organs-at-risk (OARs) by different physicians designing an intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and (b) analyze the impact of these differences on the treatment plan optimization.Materials and methodsThe planning target volumes (PTVs) and OARs for radiotherapy were manually delineated from computed tomography images of a patient with NPC, and a standard delineation was determined using the STAPLE algorithm of ABAS software. IMRT was designed using one standard plan and 10 individual plans based on the same constraints and field conditions. The maximum/minimum ratio (MMR) of the PTV and OAR volumes and the coefficient of variation (CV) for the different groups were evaluated and compared to the volume of the standard contour.ResultsSignificant differences were seen in the PTVs of the nasopharynx (PTVnx), neck lymph node (PTVnd) and the OARs manually delineated by different physicians. Compared to the standard plan, the mean dose-related parameters of various OARs in different individual plans were not significantly different, while that of most organs in different individual plans were reduced. However, a significant difference in the dose at each organ was noted in different individual plans.ConclusionSignificant differences were noted in the PTV and OAR delineations by different physicians in radiotherapy of NPC, and their dosimetric parameters were significantly different from the standard planned parameters. Therefore, multicenter trials should pay attention to the impact of these differences on the clinical evaluation.

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Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control

Publication date: Available online 3 May 2018
Source:Cell Metabolism
Author(s): Louise Lang Lehrskov, Mark Preben Lyngbaek, Line Soederlund, Grit Elster Legaard, Jan Adam Ehses, Sarah Elizabeth Heywood, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst, Kristian Karstoft, Bente Klarlund Pedersen, Helga Ellingsgaard
Gastric emptying is a critical regulator of postprandial glucose and delayed gastric emptying is an important mechanism of improved glycemic control achieved by short-acting glucagon-like peptide-1 (GLP-1) analogs in clinical practice. Here we report on a novel regulatory mechanism of gastric emptying in humans. We show that increasing interleukin (IL)-6 concentrations delays gastric emptying leading to reduced postprandial glycemia. IL-6 furthermore reduces insulin secretion in a GLP-1-dependent manner while effects on gastric emptying are GLP-1 independent. Inhibitory effects of IL-6 on gastric emptying were confirmed following exercise-induced increases in IL-6. Importantly, gastric- and insulin-reducing effects were maintained in individuals with type 2 diabetes. These data have clinical implications with respect to the use of IL-6 inhibition in autoimmune/inflammatory disease, and identify a novel target that could be exploited pharmacologically to delay gastric emptying and spare insulin, which may be beneficial for the beta cell in type 2 diabetes.

Graphical abstract

Teaser

Lehrskov et al. show that acutely elevated IL-6 in humans delays gastric emptying, reduces postprandial blood glucose, and reduces insulin secretion. The delay in gastric emptying and the reduced meal-stimulated insulin secretion are maintained in individuals with type 2 diabetes and may contribute to long-term preservation of beta cell function.

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The application of Mir-183 family and mesenchymal stem cells: A possibility for restoring hearing loss

Mohammad Reza Mahmoudian-Sani, Ameneh Mehri-Ghahfarrokhi, Ghollam Reza Poorshahbazi, Majid Asadi-Samani

Indian Journal of Otology 2017 23(4):217-221

Hearing loss as one of the most common disabilities approximately over 5% of the world's population – 360 million people – has disabling hearing loss (328 million adults and 32 million children). Recent developments in stem cell technology provide new opportunities for the treatment of deafness. miRNAs are essential factors of an extensively conserved posttranscriptional process controlling gene expression at mRNA level. Various biological processes such as growth and differentiation are regulated by miRNAs. In this review paper we have discussed about the application of miR-183 family and mesenchymal stem cells as a possibility for restoring hearing loss. In this regards, the web of Science and PubMed databases were searched using the Endnote software for the publications about the application of miR-183 family and mesenchymal stem cells (MSCs) to study hearing loss published from 2000 to 2016. The miR-183 family (miR-183, miR-96, and miR-182) is expressed abundantly in sensory cells in inner ear. miR-183 family is significant for the development and persistence of auditory neurons and hair cell. These four genes, i.e. Sox2, Notch1, Jag1, and Hes1, are potentially the targets of miR-183 family. In studies on animal models such as mouse and zebrafish, the time of Atoh1 expression in the hair cells was found to be the E12/5-E14/5 day, and miR-183 family was reported to begin to express on the E14/5 day. Use of human MSCs in differentiating into hair cells has been investigated, demonstrating that MSCs have neuroregenerative capacity. Cell therapy-targeting regeneration of the auditory neurons and hair cell may therefore be a powerful strategy to cure hearing loss that cannot be reversed by current therapies. A combination of the MSCs, specific growth factors and miR-183 cluster (96-182-183) can increase the potential to differentiate into the auditory neurons and hair cell.

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Glass ionomer cement: An attractive alternative for the reconstruction of incudostapedial joint discontinuity

BS Yogeesha, K Rohit, Nagaraj Maradi

Indian Journal of Otology 2017 23(4):222-225

Background: Chronic suppurative otitis media (CSOM) is a rampant clinical entity in India, and hearing loss is a very debilitating condition which is treatable. Hence, ossiculoplasty is a frequently combined operation with myringoplasty to reconstruct the hearing apparatus of a CSOM patient. Ossiculoplasty can be accomplished through autograft, homograft, and allograft materials. The glass ionomer cement (GIC) included under bone cement is biocompatible and easily available, for restoring the ossicular continuity, more specifically, the incudostapedial joint. Objective: The purpose of this study is to evaluate hearing improvement after repair of ossicular discontinuity between the incus and stapes with GIC. Materials and Methods: This prospective clinical study was conducted in a tertiary care hospital. CSOM patients found to have incudostapedial joint discontinuity intraoperative underwent ossiculoplasty with GIC. Postoperatively, hearing was evaluated at 1 month and 3 months. Audiometric pure-tone threshold by air conduction (AC) was recorded at 0.5, 1, 2, 3, 4, 6, and 8 kHz and by bone conduction at 0.5, 1, 2, 3, and 4 kHz. As per the AAO-CHE guidelines, thresholds at 0.5, 1, 2, and 3 kHz were used to calculate the Pure Tone Average (PTA). The air-bone gap (ABG) was calculated for each patient and the results were tabulated. Results: At the end of each predesignated PTA evaluation, postoperatively, the patients showed improvement in AC thresholds and narrowing of ABG, which was statistically significant. In our study, after applying GIC, the mean AC was 30.89 dB at the end of 3rd month which was significant improvement. Eighteen patients (66.67%) had closure of ABG <20 dB. Interpretation and Conclusion: The current study reveals that tympano-ossicular reconstruction using GIC is a simple, cost-effective method which gives definite good postoperative hearing improvement. Other advantages are more physiological continuity between the incus and stapes, technically easier application, nonextrusion.

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Tuberculous otomastoiditis: A therapeutic and diagnostic challenge

Rohit Verma

Indian Journal of Otology 2017 23(4):260-263

Context and Aims: Tuberculosis (TB) has affected mankind since time immemorial. Extrapulmonary TB poses special diagnostic and therapeutic challenges. Temporal bone is an extremely rare target organ for tuberculous infection. It constitutes just 0.05%–0.9% of all chronic middle ear otitis cases. However, because of its rarity, it is often missed as a diagnosis, and thus there is a significant delay in initiating the treatment. The aim of this study was to identify the cases of tuberculous otomastoiditis (TOM) in patients undergoing middle ear surgery in a tertiary care hospital. Settings and Design: This was a retrospective chart review carried out in a tertiary care hospital. Materials and Methods: Nine hundred and fifty charts of patients undergoing middle ear surgery were studied. Three cases of TOM were identified. Results: All the patients had painless otorrhea and hearing loss as the presenting feature. Only one patient had facial nerve palsy. During the initial phase of management, TB was not suspected in any of the patients. Histopathological examination (HPE) of the tissue obtained at surgery provided the diagnosis in all the cases. The response to antitubercular treatment (ATT) was satisfactory in all three cases. Conclusions: TB should always be kept as a differential diagnosis in case of chronic middle ear infection, especially if there is a poor response to antibacterial treatment. HPE of the tissue and specific microbiological testing are the gold standard for diagnosis. The primary treatment in these cases is ATT with a limited role of surgery.

https://ift.tt/2JMMWsY

Hyperuricemia effects auditory functions

Amit Saini, Jagdeep S Thakur, Gaveshna Saini, Dev Raj Sharma, Narinder K Mohindroo

Indian Journal of Otology 2017 23(4):226-229

Aim: The aim of this article is to study the effect of hyperuricemia on auditory functions. Materials and Methods: This was an academic institution (Indira Gandhi Medical College, Shimla, HP, India)-based, prospective, observational case–control study with 25 hyperuricemic individuals. Individuals with any confounding factor were excluded from the study. Cochlear functions were evaluated using pure tone audiometry, transient evoked otoacoustic emission (TEOAE), and distortion product otoacoustic emission (DPOAE). Results: This study found reduced responses at higher frequencies on DPOAE and TEOAE in the case group. On TEOAE, statistically significant difference was observed in the signal-noise ratio at 4 and 3 KHz with P < 0.001. Signal-noise ratio of DPOAE was also found statistically significant at 5 and 6 KHz. Conclusions: This study found association of asymptomatic hyperuricemia and hearing loss, especially at high frequencies. In our opinion, hyperuricemia causes cochlear damage through crystal formation and minor vessel atherosclerosis.

https://ift.tt/2Ibcpzq

Bacteriology and drug susceptibility in chronic suppurative otitis media in Ear, Nose, and Throat outpatient and inpatient department of tertiary care Hospital, Bhavnagar

TU Samanth, Sushil G Jha, Vikas Sinha, Swati Dadhich

Indian Journal of Otology 2017 23(4):252-255

Background: The diagnosis of Chronic Suppurative otitis media (CSOM) implies a permanent abnormality of the pars tensa or flaccida, most likely a result of earlier acute otitis media or negative middle ear pressure. Changes in the microbiological flora following the advent of sophisticated synthetic antibiotics increase the relevance of antibiotic sensitivity to plan a general outline of treatment for a patient with a chronically discharging ear. Aim: To evaluate the bacteriological causes of CSOM. To know their antibiotic sensitivity pattern to commonly used antibiotics. Study Design: Prospective Observational Study. Materials and Methods: Sixty patients of Suppurative otitis media both unilateral and bilateral who present with active purulent discharge for to Ear, Nose and Throat (ENT) Department will be prospectively studied. Patients were of all age group, both sexes and had symptoms of active ear discharge for more than 6 weeks. Patients suffering from SOM who are on systemic antibiotics and on topical medications to the ear were not included in the study. Results: Of the 60 patients 64% were males with maximum incidence in 26-50 y age group.55% of patients were from lower Socio Economic Status.Of the organisms isolated Staph. Aureus(35%) was most predominant followed by Pseudomonas(31%).All gram positive organisms were susceptible to Co-trimoxazole, Vancomycin , Gentamycin and all Gram negative to Meropenam, Aztreonam, Piperacillin. Conclusion: The patients should also be advised to take the drugs for the complete prescribed duration. This will not only help in minimizing the complications, but also help in preventing the emergence of resistant strains.

https://ift.tt/2JP0KTW

Effect of practicing yoga on functioning of efferent auditory system

Shubhaganga Dhrruva Kumar, Tejaswini Shambhu, Prashanth Prabhu

Indian Journal of Otology 2017 23(4):230-232

Introduction: The present study attempted to determine the effect of practicing Yoga on the functioning of the efferent auditory system using contralateral suppression of otoacoustic emissions (OAE). Method: The efferent suppression of transient evoked OAE (TEOAE), and distortion product OAE (DPOAE) was recorded from 40 participants (20 who practice Yoga regularly and 20 who do not practice yoga regularly). Results: The results of this study showed that there was an increase in the amount of suppression of both TEOAE and DPOAE in individuals who practice Yoga. The result suggests that Yoga enhances the sensory perception and improves auditory attention. The constant practice of Yoga could have led to the plasticity of the efferent auditory system. Conclusions: Thus, the practice of Yoga may be used to strengthen the efferent auditory system. However, further studies on a larger group of the population are essential for better clinical applicability of the results.

https://ift.tt/2I9R614

Role of antivirals in treatment of vertigo due to vestibulopathies

Zafarullah Beigh, Tabish Maqbool, Rauf Ahmad

Indian Journal of Otology 2017 23(4):233-236

Objective: The objective of this study is to study the role of antiviral medication on treatment of recurrent vertigo due to various vestibulopathies. Materials and Methods: Sixty-six adult patients of vestibular neuronitis (VN), Meniere's disease (MD), and benign paroxysmal positional vertigo were enrolled in this study, patients in each disorder where distributed randomly in two groups, Group A (antiviral) and Group B (nonantiviral). All Patients were assessed on the basis of reduction in dose of vestibular sedative drugs needed for control of vertigo on 1st, 3rd, and 5th day of treatment. Results: Statistically significant reduction in dose of labyrinthine sedatives was found to control vertigo in Group A patients as compared to Group B patients in both VN and MD. This reduction in dose of labyrinthine sedatives was seen on day 3 as well as on day 5 of treatment. Conclusion: This study shows that use of antiviral drugs significantly reduces the dose of vestibular sedatives needed for control of vertigo in MD and VN and hence should be used on a regular basis to treat these ailments.

https://ift.tt/2rjOHr0

Efficacy of vestibulo-ocular reflex gain and refixation saccades of video head impulse test in identifying vestibular pathologies

Niraj Kumar Singh, Rajeshwari Govindaswamy, Nirmala Jagadish

Indian Journal of Otology 2017 23(4):247-251

Aim: Video head impulse test is a clinical tool found useful for assessment of each of the 6 semicircular canals independent of each other. However there is little known about relative efficacy of the two measures, vestibulo-ocular reflex gain and refixation saccade, in identifying the presence of a vestibular pathology. The present study therefore aimed at investigating the utility of each of these measures in identifying vestibular pathology. Materials and Methods: Twenty subjects with normal audio-vestibular system and 20 subjects with vestibulopathies underwent video head impulse testing. Results: The VOR gain was significantly higher in lateral and posterior canals and presence of refixation saccades was in significantly higher proportion of individuals with vestibulopathies than the controls (p < 0.05). When presence of either refixation saccades or reduced VOR gain was considered an abnormal result, the sensitivity was ~71% and ~43% and specificity was ~92% and ~82% for lateral and posterior canals respectively. When presence of either refixation saccades or reduced VOR gain for either of the two canals was considered an abnormal result, the sensitivity shot up to reach ~86% whereas the specificity plummeted slightly to drop to75%. Conclusion: The video head impulse test can differentiate vestibulopathies from normal individuals and hence a clinically useful tool.

https://ift.tt/2JRoc2Y

GSTP1 levels in cisplatin-induced rat cochlea after alpha lipoic acid and oxytocin treatment

Sedat Aydin, Mehmet Gökhan Demir, Serpil Oguztüzün, Niyazi Altintoprak, Eda Bekmez Bilmez, Aylin Ege Gül, Arzu Kaya Kocdogan

Indian Journal of Otology 2017 23(4):237-240

Introduction: Cisplatin is a well-known chemotherapeutic agent used in many cancer treatments. Several antioxidant agents are used for diminishing the toxic side effects of the cisplatin therapy. Alpha-lipoic acid (α-LA) and oxytocin (OT) are antioxidant agents that can be used in toxicity. Our aim is to investigate the effect of these antioxidants in cisplatin-induced ototoxicity in tissue level. Materials and Methods: Forty Wistar albino rats divided into five groups as control, cisplatin, cisplatin + intraperitoneal (IP) OT, cisplatin + intratympanic (IT) OT, and cisplatin + IT α-LA. The drug administration is applied for 4 days, and at the end of the procedure, the cochleas are harvested. After tissue preparation, GSTP1 levels are investigated and the intensity of the reaction is scored as negative (−), weak (1+), moderate (2+), or strong (3+). Results: Group 4 has a moderate staining which can be interpreted as high immunoreaction. When we compare with Group 1, this staining difference is statistically significant (P < 0.02). When we observe the Group 3, we cannot detect any difference with Group 1 in immunoreactivity. Conclusion: α-LA and OT are antioxidants effective against cisplatin ototoxicity. The expression of GSTP1 isozyme is increased in antioxidant-treated groups. Increased levels of these isozymes proved the increased healing response in tissue levels. Antioxidant agents can be used for adverse effects during cisplatin treatment. IT route is effective as IP systemic route.

https://ift.tt/2IfaycP

Inflammation-Based prognostic factor in different forms of chronic suppurative otitis media

Hatice Terzi, Kasım Durmuş, Tuba Doğan Karataş, Mehmet Şencan, Emine Elif Altuntaş

Indian Journal of Otology 2017 23(4):256-259

Objective: The aim of the present study was to investigate whether several blood tests could be used as inflammatory indicators in active or inactive chronic suppurative otitis media patients. Methods: Between 2007 to 2014, this study was conducted in 358 consecutive patients having chronic suppurative otitis media were included in the present retrospective clinical study. Patients were divided into two groups based on the clinical history, otologic examination, audiological evaluation and intraoperative finding. Group 1 consisted of 163 patients who had inactive chronic suppurative otitis media, while group 2 was comprised of 195 patients who had active chronic suppurative otitis media and cholesteatomatous otitis media. Results: With respect to the neutrophil-lymphocyte ratio (P = 0 .001), the platelet-lymphocyte ratio (P = 0 .001), absolute lymphocytes (P = 0.001), absolute neutrophil (P = 0.001), platelet (P = 0,001) and white blood cell (P = 0,02), Group 1 and Group 2 showed statistically significant differences. Conclusion: The results we obtained showed that markers such as neutrophil-lymphocyte ratio, the platelet-lymphocyte ratio, platelet, absolute neutrophil and white blood cell could be used as guide in evaluation of the prognosis of chronic suppurative otitis media.

https://ift.tt/2JRaGMQ

Risk factors and identifiable causes of hearing impairment among pediatric age group in Kaduna, Nigeria

Musa Thomas Samdi, Abdullahi Musa Kirfi, Umaru Sambo Grema, Alfred Nicholas Bemu

Indian Journal of Otology 2017 23(4):241-243

Background: Most of the cases of pediatric hearing loss are avoidable through primary prevention. This study aims to identify the common risk factors/identifiable causes and type of hearing loss among the pediatric age group in the study location. Methods: A retrospective study of pediatric patients diagnosed with hearing loss. The clinical records of these patients seen at the study center from 2009 to 2012 were reviewed. Demography, histories of risk factors, and type of hearing loss were obtained from the record. The data collected were analyzed using IBM SPSS version 16. Results: Three hundred and twenty-one (10.33%) children were diagnosed with hearing loss with a male-to-female ratio 1.8:1. Average age at diagnosis was 2.65 and 3.35 years for bilateral and unilateral hearing losses, respectively, bilateral hearing loss, 304 (94.70%), and unilateral hearing loss, 17 (5.29%). Furthermore, 235 (73.20%) children had predisposing risk factors while 86 (26.79%) had no identifiable risk factor. The most common risk factor was febrile illness and its treatment in 163 (50.7%), followed by middle ear infections in 29 (9.03%). A family history of hearing loss, prematurity, or complicated perinatal course was found in 17 (5.29%) patients. Seven (2.18%) cases had sickle cell disease. Sensorineural hearing loss was observed in 228 (71.0%) on the right ear and 222 (69.2%) on the left ear while conductive hearing loss accounted for 21 (6.54%) and 25 (7.78%), respectively, while mixed hearing loss was 9 (3.1%). Conclusion: Hearing loss constitutes about 10.33% of all pediatric ear, nose, and throat diseases within the period under review. There were more males than females. Febrile illnesses and their treatment are the most common risk factors. The most common cause of these fevers was meningitis, measles, malaria, mumps, and sepsis. Sensorineural hearing loss is also the most common type of hearing loss.

https://ift.tt/2I9QRDc

A rare complication of tuning fork test

Rajinder Singh Hardyal Singh, Hasme Zam Hashim, Irfan Mohamad

Indian Journal of Otology 2017 23(4):264-266

Incidence of tuning fork-related complication is extremely rare. Here, we report a case of an 18-year-old gentleman who presented with a recurrent left ear discharge with a central perforation for the past 7-year duration. Left myringoplasty was performed after the ear condition was permissible. One week after surgery, he presented with an erythematous lesion over his forehead secondary to a tuning fork test which was done prior discharge.

https://ift.tt/2JRkpCy

Optimizing outcomes in pediatric cochlear implant recipients with coexisting attention deficit hyperactive disorder

Ruchika Mittal, Poonam Raj

Indian Journal of Otology 2017 23(4):244-246

Introduction: Speech language outcomes are often variable in hearing impaired children managed with cochlear Implantation. Co-existing Attention Deficit Hyperactive Disorder may be responsible in some cases. Active management of these cases may result in improved outcomes in terms of better speech language acquisition. This study compared the progress in speech language acquisition in paediatric cochlear implant recipients with coexisting ADHD before and after intervention with Behaviour Modification Therapy (BMT) and /or pharmacological treatment. Materials and Methods: The study group was of 20 hearing impaired children post cochlear implant with co-existing ADHD who did not show expected results with regular AVT for 3 months post implant. Management of ADHD was instituted as per laid down protocol and CAP scores were compared at 0, 3, 6, 9 and 12 months post implantation. The scores obtained were subjected to a Wilcoxon sign rank test and P value derived. Results: The CAP scores after the inclusion of treatment for ADHD showed a definite improvement with a highly significant P value. Conclusions: Variables such as co-existent ADHD must be actively looked for in hearing impaired children prior to surgery and. Appropriate treatment in the form of BMT and / or medication should be instituted to improve the performance.

https://ift.tt/2rleMG7

Aural melanocytic nevi presented as polypoidal mass

Jeyasakthy Saniasiaya, Mohd Khairi Md Daud, Ramiza Ramza Ramli, Hilma Hazmi, Hasnan Jaafar

Indian Journal of Otology 2017 23(4):270-272

Nevus is a benign melanocytic tumor which occurs anywhere in the skin and is considered to be the most common type of skin tumor. Albeit rare, its manifestation over the external auditory canal has been reported. Herein, we present a case of a previously healthy middle-aged female who presented with insidious onset of left-sided aural fullness and tinnitus. Otoscopic finding revealed a peculiar-looking blackish polypoidal mass occupying left ear canal. Histopathological examination of the excised polypoidal mass turned out to be intradermal melanocytic nevi. Melanocytic nevi in the ear canal may presents as polypoidal mass in a long-standing case. Any suspicious mass over the external auditory canal warrants excision along with histopathological examination of the excised mass as to exclude the possibility of malignancy.

https://ift.tt/2JPV7ot

Gallium spreads itself thin

Publication date: Available online 3 May 2018
Source:Nano Today

https://ift.tt/2FHn0wr

Principal component analysis of personalized biomolecular corona data for early disease detection

Publication date: Available online 3 May 2018
Source:Nano Today
Author(s): Massimiliano Papi, Giulio Caracciolo
Today, early disease detection (EDD) is a matter of more importance than ever in medicine. Upon interaction with human plasma, nanoparticles are covered by proteins leading to formation of a biomolecular corona (BC). As the protein patterns of patients with conditions differ from those of healthy subjects, current research into technologies based on the exploitation of personalized BC patterns could be a turning point for early disease detection. Here, we present a framework based on principal component analysis of large personalized BC datasets. We comment on how principal component analysis of personalized BC data is a fundamental step towards turning the output of basic research into fast, safe and inexpensive technologies with superior prediction ability than current methods.

Graphical abstract

https://ift.tt/2KwU6mq

Infant and childhood diet at the passage tomb of Alto de la Huesera (north‐central Iberia) from bone collagen and sequential dentine isotope composition

International Journal of Osteoarchaeology, EarlyView.

https://ift.tt/2rjwVEp

Time-course transcriptome analysis of medullary thymic epithelial cells in the early phase of thymic involution

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Haoming Wu, Xiaodan Qin, Hui Dai, Yu Zhang
Degeneration of the thymic epithelium is believed to be the primary cause of age-associated thymic involution. In order to investigate the molecular events during the early phase of thymic involution, RNA-seq was performed to gain the transcriptional profiles of medullary thymic epithelial cells (mTEC) from mice of 2, 6 and 10 weeks of age. We confirmed and extended the previous observation of declined expression of cell cycle-related genes and diminished E2F3 activity during thymic involution, showing that it occurred as early as 2–6 weeks after birth. Moreover, we demonstrated that mTEC aging was coupled with augmented expression of inflammatory chemokines and cytokines, reminiscent of the senescence-associated secretory phenotype. Impaired cell cycling and proinflammatoty response therefore represent two predominant transcriptional signatures during the very early phase of thymic involution. Taken together, the present study provides not only complimentary information about, but also new insight into the molecular mechanisms underlying age-related degeneration of thymic epithelial cells.

https://ift.tt/2I8voKX

Increased plasmatic soluble HLA-G levels in endometrial cancer

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Hamza Ben Yahia, Wafa Babay, Daria Bortolotti, Nadia Boujelbene, Ahmed Baligh Laaribi, Nour Zidi, Mehdi Kehila, Hanène Chelbi, Abdellatif Boudabous, Karima Mrad, Amel Mezlini, Dario Di Luca, Hadda-Imene Ouzari, Roberta Rizzo, Inès Zidi
Human Leukocyte Antigen-G (HLA-G) is known as an immune suppressive molecule; it interacts with several immune cells and inhibits their functions. HLA-G molecule is highly represented in pathological conditions including malignant transformation. To the best of our knowledge this is the first study that focuses on the expression of soluble HLA-G (sHLA-G) in endometrial cancer (EC). We aimed at exploring sHLA-G plasma levels and its prognostic value in EC.We examined total sHLA-G expression as well as the sHLA-G1 and HLA-G5 isoforms expression in plasma samples from 40 patients with EC and 45 healthy controls by a specific sandwich ELISA. Immunoprecipitation and Coomassie blue staining were performed to explore the presence of plasmatic sHLA-G monomers and dimers.sHLA-G plasma level was significantly enhanced in patients with EC compared to healthy controls (p = 0.028). Additionally, HLA-G5 molecules were highly represented than sHLA-G1 molecules in EC, at the borderline of significance (p = 0.061). Interestingly, sHLA-G has been shown to be increased in early stages (Stages I and II) as well as in high grade EC (Grade 3) that is associated with rapid spread of the disease (p = 0.057). sHLA-G ^positive EC plasma were majorly in monomeric form (75%). Clinically, all the HLA-G dimers were detected in early stages and in high grade of EC.Our data strengthen the implication of HLA-G molecules in EC etiology and especially in progression.

https://ift.tt/2HRGZKW

Insect (food) allergy and allergens

Publication date: Available online 3 May 2018
Source:Molecular Immunology
Author(s): Steffie de Gier, Kitty Verhoeckx
Insects represent an alternative for meat and fish in satisfying the increasing demand for sustainable sources of nutrition. Approximately two billion people globally consume insects. They are particularly popular in Asia, Latin America, and Africa. Most research on insect allergy has focussed on occupational or inhalation allergy. Research on insect food safety, including allergenicity, is therefore of great importance. The objective of this review is to provide an overview of cases reporting allergy following insect ingestion, studies on food allergy to insects, proteins involved in insect allergy including cross-reactive proteins, and the possibility to alter the allergenic potential of insects by food processing and digestion. Food allergy to insects has been described for silkworm, mealworm, caterpillars, Bruchus lentis, sago worm, locust, grasshopper, cicada, bee, Clanis bilineata, and the food additive carmine, which is derived from female Dactylopius coccus insects. For cockroaches, which are also edible insects, only studies on inhalation allergy have been described. Various insect allergens have been identified including tropomyosin and arginine kinase, which are both pan-allergens known for their cross-reactivity with homologous proteins in crustaceans and house dust mite. Cross-reactivity and/or co-sensitization of insect tropomyosin and arginine kinase has been demonstrated in house dust mite and seafood (e.g. prawn, shrimp) allergic patients. In addition, many other (allergenic) species (various non-edible insects, arachnids, mites, seafoods, mammals, nematoda, trematoda, plants, and fungi) have been identified with sequence alignment analysis to show potential cross-reactivity with allergens of edible insects. It was also shown that thermal processing and digestion did not eliminate insect protein allergenicity. Although purified natural allergens are scarce and yields are low, recombinant allergens from cockroach, silkworm, and Indian mealmoth are readily available, giving opportunities for future research on diagnostic allergy tests and vaccine candidates.

https://ift.tt/2HMxzEv

Time-course transcriptome analysis of medullary thymic epithelial cells in the early phase of thymic involution

Increased plasmatic soluble HLA-G levels in endometrial cancer

Insect (food) allergy and allergens

Spectrophotometric photodynamic diagnosis of prostate cancer cells excreted in voided urine using 5-aminolevulinic acid

Abstract

To evaluate the feasibility of photodynamic diagnosis using 5-aminolevulinic acid (PDD-ALA) for detection of prostate cancer (PCa) cells in urine samples after prostate massage in patients who were suspected to have PCa. One hundred and eighty-nine patients with abnormal digital rectal examination and/or an elevated prostate-specific antigen (PSA) level who underwent initial prostate biopsy were recruited. After prostate massage, the first 60 mL of voided urine was collected. For PDD-ALA, 50 mL was used. The rest of collected urine was used for polymerase chain reaction (PCR) of PSA and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). After incubation for 2 h, the intensity was measured at 635 nm under a 405-nm wavelength excitation. The results of PDD-ALA were compared with those of an initial transrectal ultrasound (TRUS)–guided prostate biopsy. Overall, 126/189 (67%) samples that showed bands of both PSA and GAPDH on PCR in urine samples were analyzed. The area under the curve, sensitivity, and specificity of PDD-ALA were 0.74, 77, and 67%, respectively. The value of PDD-ALA was significantly higher in patients with Gleason scores of 6 (p = 0.03), 7 (p = 0.005), and 8–10 (p = 0.0002) than in those with negative biopsy results. In the multivariate analysis, high PSA density, abnormal findings on TRUS, and a high value of PDD-ALA were significant markers for prediction of positive biopsy results. PDD-ALA was useful to predict positive biopsy results in patients who underwent initial prostate biopsy with suspected PCa. This PCa-detection method has potential for clinical use.

https://ift.tt/2FFHPIW

Adoptive T cell therapy: points to consider

Cassian Yee

https://ift.tt/2wbWThJ

The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer

Abstract

Background:

Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.

Objective:

The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.

Methods:

The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.

Results:

The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.

https://ift.tt/2Ibnws1

Stability of fumonisin B 1 , deoxynivalenol, zearalenone, and T-2 toxin during processing of traditional Nigerian beer and spices

Abstract

The stability of the Fusarium mycotoxins fumonisin B₁, deoxynivalenol, T-2 toxin, and zearalenone during processing of Nigerian traditional spices (dawadawa, okpehe, and ogiri) and beer (burukutu) using artificially contaminated raw materials was investigated. Results revealed the reduction of these toxins in all the final products. Boiling played a significant role (p < 0.05) in Fusarium mycotoxin reduction in the traditional spices. The highest percentage reduction of deoxynivalenol (76%) and zearalenone (74%) was observed during okpehe processing (boiled for 12 h). Dehulling and fermentation further demonstrated a positive influence on the reduction of these toxins with a total reduction ranging from 85 to 98% for dawadawa, 86 to 100% for okpehe, and 57 to 81% for ogiri. This trend was also observed during the production of traditional beer (burukutu), with malting and brewing playing a major impact in observed reduction. In addition, other metabolites including deoxynivalenol-3-glucoside, 15-acetyl-deoxynivalenol, α-zearalenol, and β-zearalenol which were initially not present in the raw sorghum were detected in the final beer product at the following concentrations 26 ± 11, 16 ± 7.7, 22 ± 18, and 31 ± 16 μg/kg, respectively. HT-2 toxin was also detected at a concentration of 36 ± 13 μg/kg along the processing chain (milled malted fraction) of the traditional beer. For the traditional spices, HT-2 toxin was detected (12 μg/kg) in ogiri. Although there was a reduction of mycotoxins during processing, appreciable concentrations of these toxins were still detected in the final products. Thus, the use of good quality raw materials significantly reduces mycotoxin contamination in final products.

https://ift.tt/2riwcDc

Identifying β-thalassemia carriers using a data mining approach: The case of the Gaza Strip, Palestine

Publication date: Available online 3 May 2018
Source:Artificial Intelligence in Medicine
Author(s): Alaa S. AlAgha, Hossam Faris, Bassam H. Hammo, Ala' M. Al-Zoubi
Thalassemia is considered one of the most common genetic blood disorders that has received excessive attention in the medical research fields worldwide. Under this context, one of the greatest challenges for healthcare professionals is to correctly differentiate normal individuals from asymptomatic thalassemia carriers. Usually, thalassemia diagnosis is based on certain measurable characteristic changes to blood cell counts and related indices. These characteristic changes can be derived easily when performing a complete blood count test (CBC) using a special fully automated blood analyzer or counter. However, the reliability of the CBC test alone is questionable with possible candidate characteristics that could be seen in other disorders, leading to misdiagnosis of thalassemia. Therefore, other costly and time-consuming tests should be performed that may cause serious consequences due to the delay in the correct diagnosis. To help overcoming these challenging diagnostic issues, this work presents a new novel dataset collected from Palestine Avenir Foundation for persons tested for thalassemia. We aim to compile a gold standard dataset for thalassemia and make it available for researchers in this field. Moreover, we use this dataset to predict the specific type of thalassemia known as beta thalassemia (β-thalassemia) based on hybrid data mining model. The proposed model consists of two main steps. First, to overcome the problem of the highly imbalanced class distribution in the dataset, a balancing technique called SMOTE is proposed and applied to handle this problem. In the second step, four classification models, namely k-nearest neighbors (k-NN), naïve Bayesian (NB), decision tree (DT) and the multilayer perceptron (MLP) neural network are used to differentiate between normal persons and those patients carrying β-thalassemia. Different evaluation metrics are used to assess the performance of the proposed model.The experimental results show that the SMOTE oversampling method can effectively improve the identification ratio of β-thalassemia carriers in a highly imbalanced class distribution. The results reveal also that the NB classifier achieved the best performance in differentiating between normal and β-thalassemia carriers at oversampling SMOTE ratio of 400%. This combination shows a specificity of 99.47% and a sensitivity of 98.81%.

https://ift.tt/2riZ7ar

Leveraging Wikipedia knowledge to classify multilingual biomedical documents

Publication date: Available online 3 May 2018
Source:Artificial Intelligence in Medicine
Author(s): Marcos Antonio Mouriño García, Roberto Pérez Rodríguez, Luis Anido Rifón
This article presents a classifier that leverages Wikipedia knowledge to represent documents as vectors of concepts weights, and analyses its suitability for classifying biomedical documents written in any language when it is trained only with English documents. We propose the cross-language concept matching technique, which relies on Wikipedia interlanguage links to convert concept vectors between languages. The performance of the classifier is compared to a classifier based on machine translation, and two classifiers based on MetaMap. To perform the experiments, we created two multilingual corpus. The first one, Multi-Lingual UVigoMED (ML-UVigoMED) is composed of 23,647 Wikipedia documents about biomedical topics written in English, German, French, Spanish, Italian, Galician, Romanian, and Icelandic. The second one, English-French-Spanish-German UVigoMED (EFSG-UVigoMED) is composed of 19,210 biomedical abstract extracted from MEDLINE written in English, French, Spanish, and German. The performance of the approach proposed is superior to any of the state-of-the art classifier in the benchmark. We conclude that leveraging Wikipedia knowledge is of great advantage in tasks of multilingual classification of biomedical documents.

https://ift.tt/2HU3vTC

Reduced protein expression of the phosphodiesterases PDE4A4 and PDE4A8 in AIP mutation positive somatotroph adenomas

Publication date: Available online 3 May 2018
Source:Molecular and Cellular Endocrinology
Author(s): Mariana Ferreira Bizzi, Sergio Veloso Brant Pinheiro, Graeme B. Bolger, Junia Ribeiro de Oliveira Longo Schweizer, Alexandre V. Giannetti, Mary N. Dang, Antonio Ribeiro-Oliveira, Márta Korbonits
Type 4 phosphodiesterases (PDE4s) of the large PDE enzyme superfamily have unique specificity for cAMP and may, therefore, be relevant for somatotroph tumorigenesis. Somatotroph adenomas typically overexpress PDEs probably as part of a compensatory mechanism to reduce cAMP levels. The rat PDE4A5 isoform (human homolog PDE4A4) interacts with the AIP protein, coded by a tumour suppressor gene mutated in a subgroup of familial isolated pituitary adenomas (FIPAs). PDE4A8 is the closest related isoform of PDE4A4. We aimed to evaluate the expression of both PDE4A4 and PDE4A8 in GH cells of AIP-mutated adenomas and compare their expression with that in GH cells from sporadic AIP-mutation negative GH-secreting adenomas, where we had shown previously that both PDE4A4 and PDE4A8 isoforms had been over-expressed. Confocal immunofluorescence analysis showed that both PDE4A8 and PDE4A4 had lower expression in AIP-mutated somatotropinoma samples compared to sporadic GH-secreting tumours (P < 0.0001 for both). Based on the association of low PDE4A4 and PDE4A8 expression with germline AIP-mutations positive samples we suggest that lack of AIP hinders the upregulation of PDE4A8 and PDE4A4 protein seen in sporadic somatotrophinomas. These data point to a unique disturbance of the cAMP-PDE pathway in AIP-mutation positive adenomas, which may help to explain their well-described poor response to somatostatin analogue.

https://ift.tt/2wdfLwW

Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet

Publication date: Available online 3 May 2018
Source:Molecular and Cellular Endocrinology
Author(s): Biljana Bursać, Ana Djordjevic, Nataša Veličković, Danijela Vojnović Milutinović, Snježana Petrović, Ana Teofilović, Ljupka Gligorovska, Frederic Preitner, Luc Tappy, Gordana Matić
Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats.We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Δ9 desaturase activity.The results showed that fructose diet increased blood triglycerides and Δ9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetyl-CoA carboxylase mRNA level and with increased 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein.In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction.

Graphical abstract

https://ift.tt/2rp0iVV

The role of bisphosphonates or denosumab in light of the availability of new therapies for prostate cancer

Publication date: Available online 3 May 2018
Source:Cancer Treatment Reviews
Author(s): Fred Saad, Cora N Sternberg, Peter FA Mulders, Daniela Niepel, Bertrand F Tombal
Most men with advanced prostate cancer will develop bone metastases, which have a substantial impact on quality of life. Bone metastases can lead to skeletal-related events (SREs), which place a burden on patients and healthcare systems. For men with castration-resistant prostate cancer (CRPC) and bone metastases, the treatment landscape has evolved rapidly over the past few years. The relatively recent approvals of the hormonal agents abiraterone acetate and enzalutamide, second-line chemotherapy cabazitaxel, and the radiopharmaceutical radium-223 dichloride (radium-223), have provided clinicians with a greater choice of treatments. These compounds have benefits in terms of overall survival based on the results of pivotal phase 3 studies. The bisphosphonate zoledronic acid and the RANK ligand inhibitor denosumab are indicated for the prevention of SREs in men with metastatic CRPC but studies of these compounds have not demonstrated a survival benefit. The important question of the role of bisphosphonates or denosumab in combination with these new agents has thus materialised. Current and emerging evidence from clinical studies of abiraterone acetate, enzalutamide and radium-223, suggest that addition of bisphosphonates or denosumab to these new therapies may provide further clinical benefits for patients with prostate cancer and bone metastases. This evidence may help to shape clinical practice but are based largely on post hoc analyses of clinical trial data. It is therefore apparent that further data are required from both clinical studies and real-world settings to enable physicians to understand the efficacy and safety of combination therapy with the new agents plus bisphosphonates or denosumab.

https://ift.tt/2JToczz

Treatment of Advanced HER2-positive Breast Cancer: 2018 and Beyond

Publication date: Available online 2 May 2018
Source:Cancer Treatment Reviews
Author(s): Noam Pondé, Mariana Brandão, Georges El-Hachem, Emilie Werbrouck, Martine Piccart
In the 1980s the importance of HER2 signalling to the aberrant behaviour of a subset of breast cancer cells was recognized for the first time and, consequently, a hitherto unknown subtype of breast cancer – HER2-positive (HER2+) breast cancer was identified. The development of the anti-HER2 class of drugs, first with trastuzumab, followed closely by lapatinib, pertuzumab, and T-DM1, has improved outcomes dramatically. Nevertheless, metastatic HER2+ breast cancer remains an incurable disease and new therapeutic options are needed. Additionally, the rapid changes in treatment standards 5 years ago have left unanswered numerous questions, including the "real-life" benefit of pertuzumab and T-DM1, since both the CLEOPATRA and EMILIA trials were conducted in populations that no longer exist in practice and, moreover, on the role of endocrine therapy in HER2+ disease. Furthermore, despite significant research efforts, including translational efforts and new imaging techniques, no predictive biomarkers have been clinically validated and therefore a more refined approach to treatment tailoring remains beyond our reach. Finally, a better understanding of resistance to currently existing anti-HER2 agents and of the role played by the microenvironment (e.g. immune system) and of interconnected signalling pathways (e.g. PI3K-mTOR-AKT) is at the core of clinical trials exploring new drugs and new regimens. These include the combination of anti-HER2 agents and anti-PD-1/PDL-1, PI3K inhibitors and CDK 4/6 inhibitors, as well as a host of new panHER inhibitors, drug antibody conjugates and anti-HER antibodies, which may, in coming years further push the boundaries of what we can do for our patients.

https://ift.tt/2JSUYRt

The Role of PARP Inhibition in Triple-Negative Breast Cancer: Unraveling the Wide Spectrum of Synthetic Lethality

Publication date: Available online 2 May 2018
Source:Cancer Treatment Reviews
Author(s): Marios Papadimitriou, Giannis Mountzios, Christos A. Papadimitriou
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by a lack of immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PR) and HER2. TNBC is associated with poor long-term outcomes compared with other breast cancer subtypes. Many of these tumors are also basal-like cancers which are characterized by an aggressive biological behavior with a distant recurrence peak observed early at 3 years following diagnosis. Furthermore, metastatic TNBC bears a dismal prognosis with an average survival of 12 months. Although the prevalence of genetic alterations among women with TNBC differs significantly by ethnicity, race and age, BRCA mutations (including both germline mutations and somatic genetic aberrations) are found in up to 20-25% of unselected patients and especially in those of the basal-like immunophenotype. Therefore, defects in the DNA repair pathway could represent a promising therapeutic target for this subgroup of TNBC patients. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in BRCA1 or BRCA2 mutation carriers. Several PARP inhibitors are currently being evaluated in the adjuvant, neo-adjuvant, and metastatic setting for the treatment of breast cancer patients with a deficient homologous recombination pathway. In this article, we review the major molecular characteristics of TNBC, the mechanisms of homologous recombination, and the role of PARP inhibition as an emerging therapeutic strategy.

https://ift.tt/2risNUW

Cardiotoxicity associated with radiotherapy in breast cancer: A question-based review with current literatures

Publication date: Available online 2 May 2018
Source:Cancer Treatment Reviews
Author(s): Qian Zhu, Youlia M. Kirova, Lu Cao, Alexandre Arsene-Henry, Jiayi Chen
Radiotherapy is an indispensable unit of multidisciplinary treatment of breast cancer. Although the application of modern techniques has led to a significantly reduction in radiation-induced heart disease, it is still recognized as the leading causes of morbidity and mortality among breast cancer survivors. With the growing number of long-term survivors, it is important to understand the cardiovascular risks associated with radiotherapy. Questions exist regarding the existence or not of a safe radiation threshold dose that the heart (or its substructures) can receive and strategies to minimize risk of radiation. This paper aims to review the current understanding of radiation-induced cardiotoxicity and try to give answers to those unsettled issues based on current literatures.

https://ift.tt/2JMxAok

Metabolomics in breast cancer: a decade in review

Publication date: Available online 3 May 2018
Source:Cancer Treatment Reviews
Author(s): Amelia McCartney, Alessia Vignoli, Laura Biganzoli, Richard Love, Leonardo Tenori, Claudio Luchinat, Angelo Di Leo
Breast cancer (BC) is a heterogeneous disease which has been characterised and stratified by many platforms such as clinicopathological risk factors, genomic assays, computer generated models, and various "-omic" technologies. Genomic, proteomic and transcriptomic analysis in breast cancer research is well established, and metabolomics, which can be considered a downstream manifestation of the former disciplines, is of growing interest. The past decade has seen significant progress made within the field of clinical metabolomic BC research, with several groups demonstrating results with significant promise in the setting of BC screening and biological characterisation, as well as future potential for prognostic metabolomic biomarkers.

https://ift.tt/2I9DFhE

The current evidence for a biomarker-based approach in cancer of unknown primary

Publication date: Available online 2 May 2018
Source:Cancer Treatment Reviews
Author(s): Elie El Rassy, Nicholas Pavlidis
Cancer of unknown primary (CUP) accounts for the seventh to eighth most frequently diagnosed cancer yet its prognosis remains poor with conventional chemotherapy. The spectrum of therapeutic management includes both locoregional and systemic therapy and should intend to offer optimal benefit to favorable CUP patients and palliative care to unfavorable cases. The recent molecular advances have revolutionized the armamentarium of cancer treatments though a biomarker-based approach. Unfortunately, solid data in CUP is lacking in the absence of a CUP-specific driver molecular signature. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of the biomarker-based approach in CUP patients. In this review, we will summarize the available evidence for the applicability of targeted therapies in CUP.

https://ift.tt/2JPROxv

Renal Cell Carcinoma in one year: going inside the news of 2017

Publication date: Available online 2 May 2018
Source:Cancer Treatment Reviews
Author(s): Claudia Mosillo, Chiara Ciccarese, Davide Bimbatti, Emanuela Fantinel, Alberto Dalla Volta, Iolanda Bisogno, Ilaria Zampiva, Matteo Santoni, Francesco Massar, Matteo Brunelli, Rodolfo Montironi, Giampaolo Tortora, Roberto Iacovelli
Very interesting issues regarding RCC treatment have been raised during 2017. We analysed the main news that may potentially modified clinical practice. Conflicting data came from trials testing targeted therapies in the adjuvant setting, supporting the necessity of further investigations. One of the key goals of RCC research is focused on the first-line therapy, with particular interest focus on immunotherapy combinations. Redefine the standard of care with the aim of improving patients' survival represents an imperative need. Enhancing immunotherapy antitumor activity by combining immune checkpoint inhibitors with anti-angiogenetic therapies is a noteworthy research field, with promising results. In addiction, we analysed in the metastatic setting data about the role of cytoreductive nephrectomy and the possibility of delay the start of first-line therapy after an active surveillance period. Based on recent developments, the paper outlines future prospective of RCC research.

https://ift.tt/2rjjKDr

Suspected severe acute food protein-induced enterocolitis syndrome caused by cow's milk through breast milk

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated gastrointestinal food hypersensitivity, characterized by profuse vomiting, frequently associated to pallor or/and lethargy that appears within 1 to 3 hours after ingestion of the offending food. Severe cases with protracted emesis develop dehydration, hypotension and acidosis.

https://ift.tt/2FFDnda

Angioedema: systemic activation process during prodromes

The present observation sheds new light on the pathogenesis of bradykinin-mediated angioedema by showing that local involvement occurs hours after systemic kallikrein-kinin activation. Therefore, biological diagnostic workup is of greatest value when performed at the very early phase of the attack.

https://ift.tt/2KzKHdJ

The impact of patient autonomy on older adults with asthma

Understanding patient preferences and desire for involvement in making medical decisions is important when managing chronic conditions. Previous studies have utilized the Autonomy Preference Index (API) in younger asthmatic patients to evaluate these preferences.

https://ift.tt/2FFzTag

Harmine, a small molecule derived from natural sources, inhibits enterovirus 71 replication by targeting NF-κB pathway

Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Deyan Chen, Xiaoyan Tian, Xue Zou, Shijie Xu, Huanru Wang, Nan Zheng, Zhiwei Wu
Enterovirus 71 (EV71) infection of young children can cause neurological manifestations, which is mainly responsible for the fatality. Although a vaccine is recently available for preventing enterovirus 71 infection, its efficacy remains to be seen. Therefore, there is a pressing need for anti-viral agents for the treatment of EV71 infection. By screening a natural compound library for inhibitory activity of EV71 replication, we identified a small molecule, harmine, that inhibited EV71 replication by targeting NF-κB signaling pathway. Harmine is a β-carboline alkaloid found in the medicinal plant Peganum harmala, which is used as a folk antitumor medicine in China and other parts of the Asia. The estimated EC50 value for harmine to block EV71 infection was 20 μM, while the CC50 was estimated at 500 μM in vitro. Harmine inhibited replication of EV71, as evidenced by its ability to diminish plague formation induced by EV71 and to reduce the level of viral RNA and protein. Mechanistic studies indicated that harmine suppressed EV71 replication through inhibition of NF-κB signaling pathway. Harmine treatment also reduced EV71-induced reactive oxygen species (ROS) formation, which was associated with a decline in EV71-associated NF-κB activation. In addition, the harmine treatment could protect AG129 mice against EV71 replication in vivo. These findings suggest that harmine may present as a candidate antiviral drug for the treatment of EV71 infection.

https://ift.tt/2rnFcX8

Progressive increase in allergen concentration abrogates immune tolerance in ovalbumin-induced murine model of chronic asthma

Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Gurupreet S. Sethi, Amarjit S. Naura
Persistent inflammation and remodeling of airways are the major hallmarks of asthma. Though airway inflammation diminishes in ovalbumin (OVA)-based mouse model of chronic asthma owing to immune-tolerance linked with repeated allergen exposure, which limits the application of the disease model. Accordingly, the present study was designed to develop a murine model of chronic asthma which presents persistent airway inflammation coupled with remodeling traits. Herein, OVA-sensitized BALB/c mice were challenged with increasing (modified protocol) or constant concentration (conventional protocol) of the allergen for 6 weeks; 3 times/week. The results, indeed, revealed that mice subjected to modified protocol demonstrate an improved response to the allergen as reflected by the significant increase in inflammatory cells particularly, eosinophils in bronchoalveolar lavage fluid compared to conventional protocol. Moreover, the expression of Th2 cytokines and their responsible transcription factors (GATA-3 and STAT-6) was markedly enhanced in lungs. The increase in inflammation was further accompanied by a marked increase in mucus production, collagen deposition, and the expression of allied factors (Muc5ac, Col1α1, and α-SMA). Interestingly, pre-treatment of dexamethasone, a corticosteroid (0.5 mg/kg b.wt., i.p.), suppressed the allergen-induced airway inflammation and mucus production without altering collagen deposition. Failure of dexamethasone seems to be related to their ineffectiveness to modulate the expression of TGF-β, MMP-9, COL1α1, and α-SMA. Overall, our results strongly suggest that mice underwent modified chronic protocol bears more resemblance with asthmatics as it imitates persistent airway inflammation allied with steroid-refractory remodeling traits; hence, may be useful for the evaluation of new/alternative drugs in steroid-refractory asthmatic conditions.

Graphical abstract

https://ift.tt/2KulDVL

New peptide MY1340 revert the inhibition effect of VEGF on dendritic cells differentiation and maturation via blocking VEGF-NRP-1 axis and inhibit tumor growth in vivo

Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Zheng Mo, Fei Yu, Su Han, Songhua Yang, Liangliang Wu, Peng Li, Shunchang Jiao
The development and clinical application of immunostimulatory therapy provides us a new and exciting strategy in cancer treatment of which the agents act on crucial receptors. Given the fact that Neuropilin-1(NRP-1) is essential for vascular endothelial growth factor (VEGF) to inhibit LPS-dependent maturation of dendritic cells (DCs), it may present a potentially meaningful target in cancer immunotherapy. To explore this hypothesis, we synthesized a novel polypeptide called MY1340 consist of 32 amino acids with the aim of targeting VEGF–NRP-1 axis. Pull-down assay coupled with liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) was firstly conducted to identify NRP-1 as a potential MY1340 interacting protein, and the interaction between them was further confirmed by western blot. The competitive enzyme-linked immunosorbent assay (ELISA) results revealed that MY1340 was able to inhibit the binding between NRP-1 and VEGF with IC50 7.42 ng/ml, better than that of Tuftsin, although a natural ligand reportedly specific for the NRP-1 receptor. The presence of VEGF significantly reduced the expression of human leukocyte antigen-DR (HLA-DR), CD86 and CD11C on DCs, and this effect was reverted by MY1340-augment p65 NF-κB and ERK1/2 phosphorylation. We also present evidence that MY1340 is remarkably efficacious in the treatment of mice bearing subcutaneous liver cancer and induced DC maturation in the tumor environment in vivo. Taken together, these results indicate that MY1340 may represent a potential efficient immune therapeutic compound within disease that are rich in VEGF.

https://ift.tt/2rktkF9

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Πέμπτη 3 Μαΐου 2018

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