Biomedical Microdevices

Inkjet printed microfluidic paper-based analytical device (μPAD) for glucose colorimetric detection in artificial urine Abstract This article introduces a novel inkjet printing method for the fabrication of a microfluidic paper-based analytical device (μPADs) with improved analytical performance for colorimetric measurements. Firstly, a hydrophobic boundary was created by wax printing on chromatography paper. Then, chitosan (CHI), 3,3′,5,5'-Tetramethylbenzidine (TMB) and enzymatic mixture solvent (glucose oxidase (GOx) and horseradish peroxidase (HRP)) were sequentially printed in the sensing zone. Polyethylene glycol (PEG6000) was mixed with the bienzymatic solution to act as an enzyme stabilizer, forming the printable ink. The resulting μPADs exhibited a linear relationship between color intensity and glucose concentration from 0.0 25 mg/ml to 0 .5mg/ml. The detectable glucose concentration was in a clinically relevant range from 0.01 mg/ml to 4 mg/ml. The limit of detection (LOD) was achieved at 0.01 mg/ml. After 60-day storage under 4 °C, the color intensity at the testing zone retained over 80% of the original intensity. In addition, a smartphone application was developed for in situ colorimetric image processing, and the colorimetric analysis results were compared with those from the use of a scanner followed by processing using ImageJ. Furthermore, the development of this ink printing method also provides a point of care (POC) platform for other substances detection purposes.

Advanced implantable drug delivery technologies: transforming the clinical landscape of therapeutics for chronic diseases Abstract Chronic diseases account for the majority of all deaths worldwide, and their prevalence is expected to escalate in the next 10 years. Because chronic disorders require long-term therapy, the healthcare system must address the needs of an increasing number of patients. The use of new drug administration routes, specifically implantable drug delivery devices, has the potential to reduce treatment-monitoring clinical visits and follow-ups with healthcare providers. Also, implantable drug delivery devices can be designed to maintain drug concentrations in the therapeutic window to achieve controlled, continuous release of therapeutics over extended periods, eliminating the risk of patient non-compliance to oral treatment. A higher local drug concentration can be achieved if the device is implanted in the affected tissue, reducing systemic adverse side effects and decreasing the challenges and discomfort of parenteral treatment. Although implantable drug delivery devices have existed for some time, interest in their therapeutic potential is growing, with a global market expected to reach over $12 billion USD by 2018. This review discusses implantable drug delivery technologies in an advanced stage of development or in clinical use and focuses on the state-of-the-art of reservoir-based implants including pumps, electromechanical systems, and polymers, sites of implantation and side effects, and deployment in developing countries.

Organotropic drug delivery: Synthetic nanoparticles and extracellular vesicles Abstract Most clinically approved drugs (primarily small molecules or antibodies) are rapidly cleared from circulation and distribute throughout the body. As a consequence, only a small portion of the dose accumulates at the target site, leading to low efficacy and adverse side effects. Therefore, new delivery strategies are necessary to increase organ and tissue-specific delivery of therapeutic agents. Nanoparticles provide a promising approach for prolonging the circulation time and improving the biodistribution of drugs. However, nanoparticles display several limitations, such as clearance by the immune systems and impaired diffusion in the tissue microenvironment. To overcome common nanoparticle limitations various functionalization and targeting strategies have been proposed. This review will discuss synthetic nanoparticle and extracellular vesicle delivery strategies that exploit organ-specific features to enhance drug accumulation at the target site.

Polymers for extended-release administration Abstract Developing strategies to deliver the required dose of therapeutics into target tissues and cell populations within the body is a principal aim of controlled release and drug delivery. Specifically, there is an interest in developing formulations that can achieve drug concentrations within the therapeutic window, for extended periods of time, with tunable release profiles, and with minimal complication and distress for the patient. To date, drug delivery systems have been developed to serve as depots, triggers, and carriers for therapeutics including small molecules, biologics, and cell-based therapies. Notably, the efficacy of these systems is intricately tied to the manner in which they are administered. For example, systemic and oral routes of administration are common, but both can result in rapid clearance from the organism. Towards this end, what formulation and administration route strategies are available to prolong the bioavailability of therapeutics? Here, we discuss historical and modern drug delivery systems, with the intention of exploring how properties including formulation, administration route and chemical structure influence the ability to achieve extended-release drug release profiles within the body.

A quantitative approach for determining the role of geometrical constraints when shaping mesenchymal condensations Abstract In embryogenesis, mesenchymal condensation is a critical event during the formation of many organ systems, including cartilage and bone. During organ formation, mesenchymal cells aggregate and undergo compaction while activating developmental programmes. The final three-dimensional form of the organ, as well as cell fates, can be influenced by the size and shape of the forming condensation. This process is hypothesized to result from multiscale cell interactions within mesenchymal microenvironments; however, these are complex to investigate in vivo. Three-dimensional in vitro models that recapitulate key phenotypes can contribute to our understanding of the microenvironment interactions regulating this fundamental developmental process. Here we devise such models by using image analysis to guide the design of polydimethylsiloxane 3D microstructures as cell culture substrates. These microstructures establish geometrically constrained micromass cultures of mouse embryonic skeletal progenitor cells which influence the development of condensations. We first identify key phenotypes differentiating face and limb bud micromass cultures by linear discriminant analysis of the shape descriptors for condensation morphology, which are used to guide the rational design of a micropatterned polydimethylsiloxane substrate. High-content imaging analysis highlights that the geometry of the microenvironment affects the establishment and growth of condensations. Further, cells commit to establish condensations within the first 5 h; condensations reach their full size within 17 h; following which they increase cell density while maintaining size for at least 7 days. These findings elucidate the value of our model in dissecting key aspects of mesenchymal condensation development.

In situ three-dimensional printing for reparative and regenerative therapy Abstract Three-dimensional (3D) bioprinting is an emerging biofabrication technology, driving many innovations and opening new avenues in regenerative therapeutics. The aim of 3D bioprinting is to fabricate grafts in vitro, which can then be implanted in vivo. However, the tissue culture ex vivo carries safety risks and thereby complicated manufacturing equipment and practice are required for tissues to be implanted in the humans. The implantation of printed tissues also adds complexities due to the difficulty in maintaining the structural integrity of fabricated constructs. To tackle this challenge, the concept of in situ 3D bioprinting has been suggested in which tissues are directly printed at the site of injury or defect. Such approach could be combined with cells freshly isolated from patients to produce custom-made grafts that resemble target tissue and fit precisely to target defects. Moreover, the natural cellular microenvironment in the body can be harnessed for tissue maturation resulting in the tissue regeneration and repair. Here, we discuss literature reports on in situ 3D printing and we describe future directions and challenges for in situ 3D bioprinting. We expect that this novel technology would find great attention in different biomedical fields in near future.

A tissue chamber chip for assessing nanoparticle mobility in the extravascular space Abstract Although a plethora of nanoparticle configurations have been proposed over the past 10 years, the uniform and deep penetration of systemically injected nanomedicines into the diseased tissue stays as a major biological barrier. Here, a 'Tissue Chamber' chip is designed and fabricated to study the extravascular transport of small molecules and nanoparticles. The chamber comprises a collagen slab, deposited within a PDMS mold, and an 800 μm channel for the injection of the working solution. Through fluorescent microscopy, the dynamics of molecules and nanoparticles was estimated within the gel, under different operating conditions. Diffusion coefficients were derived from the analysis of the particle mean square displacements (MSD). For validating the experimental apparatus and the protocol for data analysis, the diffusion D of FITC-Dextran molecules of 4, 40 and 250 kDa was first quantified. As expected, D reduces with the molecular weight of the dextran molecules. The MSD-derived diffusion coefficients were in good agreement with values derived via fluorescence recovery after photobleaching (FRAP), an alternative technique that solely applies to small molecules. Then, the transport of six nanoparticles with similar hydrodynamic diameters (~ 200 nm) and different surface chemistries was quantified. Surface PEGylation was confirmed to favor the diffusion of nanoparticles within the collagen slab, whereas the surface decoration with hyaluronic acid (HA) chains reduced nanoparticle mobility in a way proportional to the HA molecular weight. To assess further the generality of the proposed approach, the diffusion of the six nanoparticles was also tested in freshly excised brain tissue slices. In these ex vivo experiments, the diffusion coefficients were 5-orders of magnitude smaller than for the Tissue Chamber chip. This was mostly ascribed to the lack of a cellular component in the chip. However, the trends documented for PEGylated and HA-coated nanoparticles in vitro were also confirmed ex vivo. This work demonstrates that the Tissue Chamber chip can be employed to effectively and efficiently test the extravascular transport of nanomedicines while minimizing the use of animals.

Hang on tight: reprogramming the cell with microstructural cues Abstract Cells interact intimately with complex microdomains in their extracellular matrix (ECM) and maintain a delicate balance of mechanical forces through mechanosensitive cellular components. Tissue injury results in acute degradation of the ECM and disruption of cell-ECM contacts, manifesting in loss of cytoskeletal tension, leading to pathological cell transformation and the onset of disease. Recently, microscale hydrogel constructs have been developed to provide cells with microdomains to form focal adhesion binding sites, which enable restoration of cytoskeletal tension. These synthetic anchors can recapitulate the complex 3D architecture of the native ECM to provide microtopographical cues. The mechanical deformation of proteins at the cell surface can activate signaling cascades to modulate downstream gene-level transcription, making this a unique materials-based approach for reprogramming cell behavior. An overview of the mechanisms underlying these mechanosensitive interactions in fibroblasts, stem and other cell types is provided to review their effects on cellular reprogramming. Recent investigations on the fabrication, functionalization and implementation of these materials and microtopographical features for drug testing and therapeutic applications are discussed.

Investigation of parameters that determine Nano-DC vaccine transport Abstract Effective migration of dendritic cells into the lymphatic system organs is the prerequisite for a functional dendritic cell vaccine. We have previously developed a porous silicon microparticle (PSM)-based therapeutic dendritic cell vaccine (Nano-DC vaccine) where PSM serves both as the vehicle for antigen peptides and an adjuvant. Here, we analyzed parameters that determined dendritic cell uptake of PSM particles and Nano-DC vaccine accumulation in lymphatic tissues in a murine model of HER2-positive breast cancer. Our study revealed a positive correlation between sphericity of the PSM particles and their cellular uptake by circulating dendritic cells. In addition, the intravenously administered vaccines accumulated more in the spleens and inguinal lymph nodes, while the intradermally inoculated vaccines got enriched in the popliteal lymph nodes. Furthermore, mice with large tumors received more vaccines in the lymph nodes than those with small to medium size tumors. Information from this study will provide guidance on design and optimization of future therapeutic cancer vaccines.

Mathematical modeling in cancer nanomedicine: a review Abstract Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine has made significant progress, but challenges remain that impede its clinical translation. Several biophysical barriers to the transport of nanocarriers to the tumor exist, and a much deeper understanding of nano-bio interactions is necessary to change the status quo. Mathematical modeling has been instrumental in improving our understanding of the physicochemical and physiological underpinnings of nanomaterial behavior in biological systems. Here, we present a comprehensive review of literature on mathematical modeling works that have been and are being employed towards a better understanding of nano-bio interactions for improved tumor delivery efficacy.

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

6948891480

alsfakia@gmail.com

Auris Nasus Larynx

Long-term efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell carcinoma Publication date: Available online 5 June 2019 Source: Auris Nasus Larynx Author(s): Hiroshi Okuda, Masami Ohnishi, Hiroki Takahashi, Chiaki Takagi, Natsuki Takada, Toshimitsu Ohashi Abstract Objective The present study aimed to retrospectively analyze the long-term efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell carcinoma. Methods The study enrolled 53 patients (23 with stage II disease, 13 with stage III disease, and 17 with stage IV disease). S-1 was administered orally twice a day for 14 days, followed by a two-week rest period. Nedaplatin was intravenously administered on day 4. Where possible, two courses of chemotherapy were performed. Radiotherapy was started with the administration of S-1. We analyzed the clinical response, survival rate, acute adverse events, and late swallowing toxicity. Results The complete response rates for the primary tumor and neck lymph node metastases were 94.3% and 79.3%, respectively. The five-year overall survival rate was 79.5%, the five-year disease-specific survival rate was 84.8%, and the five-year relapse-free survival rate was 73.7%. The main acute adverse events were leukopenia, neutropenia, mucositis, and dermatitis. No patient had severe nephrotoxicity. Late swallowing toxicity was observed in 13 patients. Conclusions The low toxicity, and low nephrotoxicity of chemoradiotherapy with nedaplatin and S-1 have a positive impact on long-term survival. The combination of nedaplatin and S-1 can be used instead of cisplatin and 5-fluorouracil as a safer regimen, especially in patients with some complications and those requiring treatment in an outpatient setting.

Corrigendum to "Environmental factors associated with allergic rhinitis symptoms in Japanese university students: A cross-sectional study" [Auris Nasus Larynx 45 (2018) 1006–1013] Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Hironobu Nishijima, Sayaka Suzuki, Kenji Kondo, Tatsuya Yamasoba, Shintaro Yanagimoto

Cancer of the mandibular gingiva metastasizing to the small intestine Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Takeshi Okamura, Takeshi Beppu, Takao Tokumaru, Masato Yamada, Tomonori Sugiyama, Nobuaki Koide, Miyuki Tani, Masayuki Kaneko, Atsumori Hamahata, Yu Nishimura, Takashi Fukuda Abstract Head and neck cancer metastasizing to the small intestine is very rare. Here we report a case of cancer of the mandibular gingiva metastasizing to the small intestine. The patient was an 82-year-old man who had squamous cell carcinoma of the mandibular gingiva staged as T2N2bM0. Two months after surgery, he presented with lower abdominal pain accompanied by signs of peritoneal irritation. Urgent abdominal surgery was performed, during which a crater-shaped perforation was noted on the wall of the ileum. Microscopic findings at this site confirmed a diagnosis of metastatic squamous cell carcinoma in the small intestine from the mandibular gingiva. To our knowledge, this is the first case report of oral cancer metastasizing to the small intestine. If gastrointestinal symptoms appear in a patient with advanced oral cancer, a differential diagnosis of metastasis to the gastrointestinal tract should be kept in mind.

Laryngeal fractures treated with titanium mesh fixation Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Taku Sato, Takaharu Nito, Rumi Ueha, Takao Goto, Tatsuya Yamasoba Abstract The larynx plays a vital role in respiration, swallowing, and vocal function. Thus, laryngeal fractures that are not appropriately managed may lead to permanent dyspnea, dysphagia, and voice disorders. In cases of laryngeal fractures, surgical repair by internal fixation has been performed with materials such as thread, steel wire, and titanium miniplates. However, thyroid and cricoid cartilage have a complicated morphology, and ossification at each site in the cartilage is not uniform; thus, in some cases it is difficult to perform internal fixation with conventional methods. In this case report, we describe two patients who underwent successful fixation of fractures in their laryngeal cartilage after trauma by using titanium mesh with thread and screws. Since optimal reduction and fixation of fractured laryngeal cartilage cannot be performed with conventional methods in patients with unossified cartilage, titanium mesh may be considered a safe and reliable alternative.

Neck stiffness in a post-irradiated nasopharyngeal carcinoma adult: An unusual diagnosis Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Kang Ni Lorna Ting, Yew Toong Liew, Zulkiflee Abu Bakar, Prepageran Narayanan Abstract Nasopharyngeal carcinoma is a neoplasm commonly found in population of South East Asia. The mainstay of treatment is high dose irradiation. Complications from radiotherapy are not uncommon especially to those nearby structures such as vertebrae and spinal cord. A 57 year-old gentleman with nasopharyngeal carcinoma (NPC) who was treated with chemo-radiation (total of 35 fractions,70 Gy) presented to us 6 months post therapy with bilateral nasal discharge and progressive neck stiffness. Nasoendoscopy showed inflamed nasophayngeal mucosa and Computed Tomography (CT) brain and cervical spine showed retropharyngeal and anterior epidural collection with extension into atlantoaxial bone and spinal cord compression. Histopathological specimen revealed features of chronic inflammations with multiple actinomycetes colonies. Our patient suffered severe neck stiffness and loss of sensations on both upper limbs. He was treated conservatively with Halo vest and intravenous antibiotics for 8 weeks and recovered fully. Irradiation in NPC is known to cause devastating complications to cervical spine such as osteoradionecrosis, osteomyelitis. It also renders tissues hypoxic and risk of getting rare infection like actinomycosis. This report can represent a great diagnostic and therapeutic challenge with differentials of tumor recurrence, osteoradionecrosis or osteomyelitis. Patients must be regularly followed up to look for possible cervical complications as a result from irradiation, to prevent devastating outcome or prognosis.

The inflammatory pseudotumor presenting periodic acid-Schiff-positive inclusions with acute unilateral facial nerve palsy Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Akira Inagaki, Masaomi Motegi, Yuji Sato, Hideo Hattori, Shingo Murakami Abstract Although most acute peripheral facial palsies can be attributed to Bell's palsy, other factors, such as infection, trauma, and neoplasm, can cause facial palsy as well. Among these, facial nerve tumors are rare but should be considered in the differential diagnosis of facial palsy. Palsies due to facial nerve tumors usually present with slow onset but occasionally present as acute episodes. In such cases, facial nerve decompression is the treatment of choice to allow the tumor room to grow without compressing the nerve or its blood supply. We describe a case of severe, acute facial palsy presenting with a spindle-shaped bone erosion on the mastoid portion of the facial canal. Although facial neuroma was suspected preoperatively, emergency decompression surgery revealed that an unusual inflammatory pseudotumor was responsible for the finding. Postoperative histological analysis revealed extensive destruction of the nerve fibers, with extensive infiltration of foamy macrophages containing characteristic, diastase-resistant, periodic acid-Schiff (PAS)-positive inclusions, which are hallmark of the uncommon bacterial infections. This was a case of facial palsy with an unusual etiology. The case shows the benefit of decompression surgery not only as treatment for the palsy but also as exploratory surgery in cases of facial nerve tumor.

Risk factors and distribution features of level IB lymph nodes metastasis in nasopharyngeal carcinoma Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Lei Zeng, Qin Zhang, Fan Ao, Chun-Ling Jiang, Yun Xiao, Hong-Hui Xie, Yi-Qiang Tang, Xiao-Chang Gong, Jin-Gao Li Abstract Objective The objective of this study is to investigate the risk factors and distribution features for level IB metastasis in nasopharyngeal carcinoma (NPC) and provide clinical evidence for defining the indications and clinical target volume (CTV) of prophylactic level IB irradiation. Methods We retrospectively analyzed 798 patients with newly-diagnosed, non-metastatic and histologically confirmed NPC underwent intensity-modulated radiation therapy (IMRT). Two sides of neck in each patient have been analyzed separately. The correlations of level IB metastasis and the clinical risk factors were analyzed with Chi-square test and logistic regression model. The risk score model (RSM) of level IB metastasis was calculated by totaling up the scores of each independent variable. We divided level IB into three areas, including anterolateral space of submandibular glands, medial space of the submandibular glands and submandibular glands. Results Maximal axial diameter (MAD) of level IIA nodes >20 mm or extra capsular spread (ES) of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression were independently significantly risk factors for level IB lymph nodes (LNs) metastasis at diagnosis. Two groups based on RSM were obtained: low risk (total score = 0–2.5); high risk (4–8.5). The incidence of IB LNs metastasis at diagnosis of the two groups were 0.9% and 6.3%, respectively (P < 0.001). The cervical lymph nodes of level IB were distributed in the anterolateral space of submandibular glands. There was no positive/negative LNs inside or medial space of the submandibular glands. Conclusion Level IB LNs metastasis is associated with MAD of level IIA nodes >20 mm or ES of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression in NPC patients. Omission of level IB irradiation may be feasible for patients with low-risk IB LNs metastasis at diagnosis. The submandibular gland should not be included in level IB.

Evaluation of folded amniotic membrane and injectable amniotic membrane pieces as soft tissue filler materials Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Mustafa Caglar Buday, Murat Ozturk Abstract Objective The search for safe and effective tissue fillers has been an ongoing effort for many years. Obtaining biological materials from patients can require additional incisions and brings surgical and cosmetic risks as a major disadvantage. The aim of this experimental study was, therefore, to evaluate the efficacy of folded amniotic membrane as a soft tissue filler and to assess its volume, and to investigate the possible usage of injectable amniotic membrane for augmentation. Methods Multi-layer amniotic membranes are transplanted to the subcutaneous tunnels created in the rat's back, and the amniotic membrane transformed into the injection material is inoculated transcutaneously under the rat's skin. At the end of two months, the amount of volume loss and histopathological changes in the grafts were examined under light microscope. Results The multi-layer amniotic membrane grafts maintain its volume around 92%. It has been shown that the injectable amniotic membrane maintains its presence in the tissue, can augment it, and can be used as a soft tissue filler. The availability of using amniotic membrane for injection material is shown. No foreign body reaction to the amnion grafts, fibrosis, and necrosis were observed in our study. Conclusion According to our study results, multi-layer amnion graft and amnion injection seem to be used as camouflage grafts and soft tissue augmentation materials. Although further clinical trials are mandatory before considering the use of amniotic membrane as a tissue filler material in humans, we are hopeful about its long-term safety and efficacy.

Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Tomomi Aga, Kazuhira Endo, Akira Tsuji, Mitsuharu Aga, Makiko Moriyama-Kita, Takayoshi Ueno, Yosuke Nakanishi, Miyako Hatano, Satoru Kondo, Hisashi Sugimoto, Naohiro Wakisaka, Tomokazu Yoshizaki Abstract Objectives A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC. Methods The expression of Beclin 1 and microtubule-associated protein light chain 3 (LC3), a marker of autophagy, was determined by immunohistochemistry in the biopsy samples of patients with NPC before and after the first course of chemotherapy. Additionally, to investigate in the effect of autophagy suppression in chemotherapy, NPC cell line C666-1 cells were treated with cisplatin and/or chloroquine, an inhibitor of autophagy. Results The expression of Beclin 1 increased after chemotherapy in all patients. In NPC cell line C666-1, compared to cisplatin alone, combination therapy (cisplatin and chloroquine) reduced cell viability, and promoted cell apoptosis. Conclusions These results suggest that autophagy, represented by Beclin 1, is upregulated after chemotherapy in both in vitro and in vivo NPC studies. Inhibition of autophagy could therefore be new strategy for NPC treatment.

Clinical features of poorly differentiated thyroid papillary carcinoma Publication date: June 2019 Source: Auris Nasus Larynx, Volume 46, Issue 3 Author(s): Masaaki Higashino, Yusuke Ayani, Tetsuya Terada, Yoshitaka Kurisu, Yoshinobu Hirose, Ryo Kawata Abstract Objective To investigate the clinical feature of the poorly differentiated thyroid papillary carcinoma. Methods We investigate retrospectively 276 thyroid papillary carcinoma patients who underwent initial treatment at our Department who underwent initial treatment at our Department during the 13-year period from 2000 to 2012. We examine the pathological samples of papillary carcinoma retrospectively to investigate the prevalence of a poorly differentiated component in the tumor. Then the disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate were compared between patients with or without a poorly differentiated component. In addition, well differentiated carcinoma and poorly differentiated carcinoma were compared in relation to the age, sex, TNM stage, and recurrent laryngeal nerve infiltration. Results It was considered appropriate to define tumors with a poorly differentiated component of 10% or more as poorly differentiated carcinoma. There was a significant difference of the T classification but not the N classification between well and poorly differentiated thyroid papillary carcinomas. The disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate of patients with poorly differentiated carcinoma was significantly lower than that of patients with well differentiated carcinoma, and we considered that this might be due to the higher frequency of local infiltration in patients with poorly differentiated tumors. Conclusion The higher relapse rate compared with well differentiated carcinoma suggests that careful postoperative follow-up of patients with poorly differentiated carcinoma is important, particularly surveillance of distant metastasis.

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

6948891480

alsfakia@gmail.com

Nitric Oxide

Compensatory mechanisms in myoglobin deficient mice preserve NO homeostasis Publication date: 1 September 2019 Source: Nitric Oxide, Volume 90 Author(s): Ji Won Park, Barbora Piknova, Soumyadeep Dey, Constance T. Noguchi, Alan N. Schechter Abstract The mechanism for nitric oxide (NO) generation from reduction of nitrate (NO3−) and nitrite (NO2−) has gained increasing attention due to the potential beneficial effects of NO in cardiovascular diseases and exercise performance. We have previously shown in rodents that skeletal muscle is the major nitrate reservoir in the body and that exercise enhances the nitrate reduction pathway in the muscle tissue and have proposed that nitrate in muscle originates from diet, the futile cycle of nitric oxide synthase 1 (NOS1) and/or oxidation of NO by oxymyoglobin. In the present study, we tested the hypothesis that lack of myoglobin expression would decrease nitrate levels in skeletal muscle. We observed a modest but significant decrease of nitrate level in skeletal muscle of myoglobin deficient mice compared to littermate control mice (17.3 vs 12.8 nmol/g). In contrast, a NOS inhibitor, L-NAME or a low nitrite/nitrate diet treatment led to more pronounced decreases of nitrate levels in the skeletal muscle of both control and myoglobin deficient mice. Nitrite levels in the skeletal muscle of both types of mice were similar (0.48 vs 0.42 nmol/g). We also analyzed the expression of several proteins that are closely related to NO metabolism to examine the mechanism by which nitrate and nitrite levels are preserved in the absence of myoglobin. Western blot analyses suggest that the protein levels of xanthine oxidoreductase and sialin, a nitrate transporter, both increased in the skeletal muscle of myoglobin deficient mice. These results are compatible with our previously reported model of nitrate production in muscle and suggest that myoglobin deficiency activates compensatory mechanisms to sustain NO homeostasis. Graphical abstract

Nitric oxide releasing two-part creams containing S-nitrosoglutathione and zinc oxide for potential topical antimicrobial applications Publication date: 1 September 2019 Source: Nitric Oxide, Volume 90 Author(s): Joshua C. Doverspike, Yang Zhou, Jianfeng Wu, Xiaojuan Tan, Chuanwu Xi, Mark E. Meyerhoff Abstract Currently, most antimicrobial topical treatments utilize antibiotics to prevent or treat infection at a wound site. However, with the ongoing evolution of multi-drug resistant bacterial strains, there is a high demand for alternative antimicrobial treatments. Nitric oxide (NO) is an endogenous gas molecule with potent antimicrobial activity, which is effective against a wide variety of bacterial strains. In this study, the potential for creating NO releasing creams containing the naturally occurring NO carrier, S-nitrosoglutathione (GSNO), are characterized and evaluated. GSNO is shown to have prolonged stability (>300 days) when mixed and stored within Vaseline at 24 °C. Further, enhanced proliferation of NO from GSNO using zinc oxide nanoparticles (ZnO) is demonstrated. Triggering NO release from the GSNO/Vaseline mixture using a commercial zinc oxide-containing cream exhibits first-order NO release kinetics with the highest %NO release over the first 6 h. Significant killing effects against S. aureus, S. epidermidis, and P. aeruginosa are demonstrated for the GSNO/Vaseline/ZnO cream mixtures in a proportional manner dependent upon the concentration of GSNO in the final mixture. Graphical abstract

The role of nitric oxide signaling in pulmonary circulation of high- and low-altitude newborn sheep under basal and acute hypoxic conditions Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Emilio A. Herrera, Germán Ebensperger, Ismael Hernández, Emilia M. Sanhueza, Aníbal J. Llanos, Roberto V. Reyes Abstract Nitric oxide (NO) is the main vasodilator agent that drives the rapid decrease of pulmonary vascular resistance for the respiratory onset during the fetal to neonatal transition. Nevertheless, the enhanced NO generation by the neonatal pulmonary arterial endothelium does not prevent development of hypoxic pulmonary hypertension in species without an evolutionary story at high altitude. Therefore, this study aims to describe the limits of the NO function at high-altitude during neonatal life in the sheep as an animal model without tolerance to perinatal hypoxia. We studied the effect of blockade of NO synthesis with l-NAME in the cardiopulmonary response of lowland (580 m) and highland (3600 m) newborn lambs basally and under an episode of acute hypoxia. We also determined the pulmonary expression of proteins that mediate the actions of the NO vasodilator pathway in the pulmonary vasoactive tone and remodeling. We observed an enhanced nitrergic function in highland lambs under basal conditions, evidenced as a markedly greater increase in basal mean pulmonary arterial pressure (mPAP) and resistance (PVR) under blockade of NO synthesis. Further, acute hypoxic challenge in lowland lambs infused with l-NAME markedly increased their mPAP and PVR to values greater than baseline, whilst in highland animals under NO synthesis blockade, these variables did not show additional increase in response to low PO2. Highland animals showed increased pulmonary RhoA expression, decreased PSer188-RhoA fraction, increased PSer311-p65-NFқβ fraction and up-regulated smooth muscle α-actin, relative to lowland controls. Taken together our data suggest that NO-mediated vasodilation is important to keep a low pulmonary vascular resistance under basal conditions and acute hypoxia at low-altitude. At high-altitude, the enhanced nitrergic signaling partially prevents excessive pulmonary hypertension but does not protect against acute hypoxia. The decreased vasodilator efficacy of nitrergic tone in high altitude lambs could be in part due to increased RhoA signaling that opposes to NO action in the hypoxic pulmonary circulation.

Targeting nitric oxide as a key modulator of sepsis, arthritis and pain Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Fernando Spiller, Rodrigo Oliveira Formiga, Jonathan Fernandes da Silva Coimbra, Jose Carlos Alves-Filho, Thiago Mattar Cunha, Fernando Queiroz Cunha Abstract Nitric oxide (NO) is produced by enzymatic activity of neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS) and modulates a broad spectrum of physiological and pathophysiological conditions. The iNOS isoform is positively regulated at transcriptional level and produces high levels of NO in response to inflammatory mediators and/or to pattern recognition receptor signaling, such as Toll-like receptors. In this review, we compiled the main contributions of our group for understanding of the role of NO in sepsis and arthritis outcome and the peripheral contributions of NO to inflammatory pain development. Although neutrophil iNOS-derived NO is necessary for bacterial killing, systemic production of high levels of NO impairs neutrophil migration to infections through inhibiting neutrophil adhesion on microcirculation and their locomotion. Moreover, neutrophil-derived NO contributes to multiple organ dysfunction in sepsis. In arthritis, NO is chief for bacterial clearance in staphylococcal-induced arthritis; however, it contributes to articular damage and bone mass degradation. NO produced in inflammatory sites also downmodulates pain. The mechanism involved in analgesic effect and inhibition of neutrophil migration is dependent on the activation of the classical sGC/cGMP/PKG pathway. Despite the increasing number of studies performed after the identification of NO as an endothelium-derived relaxing factor, the underlying mechanisms of NO in inflammatory diseases remain unclear.

Nitric oxide and interactions with reactive oxygen species in the development of melanoma, breast, and colon cancer: A redox signaling perspective Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Hugo P. Monteiro, Elaine G. Rodrigues, Adriana K.C. Amorim Reis, Luiz S. Longo, Fernando T. Ogata, Ana I.S. Moretti, Paulo E. da Costa, Ana C.S. Teodoro, Maytê S. Toledo, Arnold Stern Abstract Cancer development is closely related to chronic inflammation, which is associated with identifiable markers of tumor progression, such as uncontrolled cell proliferation, angiogenesis, genomic instability, chemotherapeutic resistance, and metastases. Redox processes mediated by reactive oxygen species (ROS) and nitric oxide (NO) within the inflammatory tumor microenvironment play an essential role in directly influencing intercellular and intracellular signaling. These reactive species originating in the cancer cell or its microenvironment, mediate the epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET). However, intracellular interactions between NO and ROS must be controlled to prevent cell death. Melanoma, breast, and colon cancer cells have developed a mechanism to survive and adapt to oxidative and nitrosative stress. The mechanism involves a spatial-temporal fine adjustment of the intracellular concentrations of NO and ROS, thereby guaranteeing the successful development of cancer cells. Physiological concentrations of NO and supra physiological concentrations of ROS are prevalent in cancer cells at the primary site. The situation reverses in cancer cells undergoing the EMT prior to being released into the blood stream. Intracellular supra physiological concentrations of NO found in circulating cancer cells endow them with anoikis resistance. When the anoikis-resistant cancer cells arrive at a metastatic site they undergo the MET. Endogenous supra physiological concentrations of ROS and physiological NO concentrations are prevalent in these cells. Understanding tumor progression from the perspective of redox signaling permits the characterization of new markers and approaches to therapy. The synthesis and use of compounds with the capacity of modifying intracellular concentrations of NO and ROS may prove effective in disrupting a redox homeostasis operative in cancer cells.

Delivery of carbon monoxide via halogenated ether anesthetics Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Christopher P. Hopper, Jakob Wollborn

Light-induced release of nitric oxide from the nitric oxide-bound CDGSH-type [2Fe–2S] clusters in mitochondrial protein Miner2 Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Yiming Wang, Jeonghoon Lee, Huangen Ding Abstract Human mitochondrial matrix protein Miner2 hosts two [2Fe–2S] clusters via two CDGSH (Cys-Asp-Gly-Ser-His) motifs. Unlike other iron-sulfur clusters in proteins, the reduced CDGSH-type [2Fe–2S] clusters in Miner2 are able to bind nitric oxide (NO) and form stable NO-bound [2Fe–2S] clusters without disruption of the clusters. Here we report that the NO-bound Miner2 [2Fe–2S] clusters can quickly release NO upon the visible light excitation. The UV–visible and Electron Paramagnetic Resonance (EPR) measurements show that the NO-bound Miner2 [2Fe–2S] clusters are converted to the reduced Miner2 [2Fe–2S] clusters upon the light excitation under anaerobic conditions, suggesting that NO binding in the reduced Miner2 [2Fe–2S] clusters is reversible. Additional studies reveal that binding of NO effectively inhibits the redox transition of the Miner2 [2Fe–2S] clusters, indicating that NO may modulate the physiological activity of Miner2 in mitochondria by directly binding to the CDGSH-type [2Fe–2S] clusters in the protein.

Nitric oxide and abscisic acid protects against PEG-induced drought stress differentially in Brassica genotypes by combining the role of stress modulators, markers and antioxidants Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Seema Sahay, Ehasanullah Khan, Meetu Gupta Abstract The present study was designed to see the effect of exogenous nitric oxide (NO) and abscisic acid (ABA) and their interaction on physiological and biochemical activities in leaves and roots of two Indian mustard (Brassica juncea) cultivars [cv. Pusa Jagannath (PJN) and Varuna (VAR)] exposed to polyethylene glycol (PEG)-induced drought stress. Seven days old hydroponically grown seedlings were treated with PEG (10%), sodium nitroprusside, a NO donor [NO (100 μM)] and abscisic acid [ABA (10 μM)], using different combinations as: Control, ABA, NO, PEG, PEG + ABA, PEG + NO, and PEG + NO + ABA. Results revealed that in response to PEG-induced drought stress leaf relative water content, chlorophyll, carotenoid and protein content decreased with increased production of O2−●, MDA, H2O2, cysteine content and non-enzymatic antioxidants (including proline, flavonoid, phenolic, anthocyanin, and ascorbic acid), whereas, the enzymatic antioxidants (including SOD, CAT, APX, GR) showed the response range from no effect to increase or decrease in certain enzymes in both Brassica cultivars. The application of NO or/and ABA in PEG-stressed cultivars showed that both enzymatic and non-enzymatic antioxidants responded differently to attenuate oxidative stress in leaves and roots of both cultivars. Overall, PJN had the antioxidant protection mainly through the accumulation of non-enzymatic antioxidants, whereas VAR showed tolerance by the enhancement of both enzymatic and non-enzymatic antioxidant activities. Altogether, the study concluded that the independent NO and its interaction with ABA (PEG + NO and PEG + NO + ABA) were much effective than independent ABA (PEG + ABA) in lowering PEG-drought stress in Brassica cultivars.

Exogenous l-ARGININE does not stimulate production OF NO or cGMP within the rat corporal smooth muscle cells in culture Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Monica G. Ferrini, Andrea Abraham, Sabine Nguyen, Robert Luna, Manuel Flores, Jorge N. Artaza, Leslie Graciano, Jacob Rajfer Abstract Background and aim Nitric oxide (NO) is the intracellular chemical responsible for initiating a penile erection. Despite conflicting clinical data, it continues to be publicized and promoted that orally administered l-arginine, the putative substrate for NO, enhances the erectile response presumably by stimulating NO production by the corporal tissues resulting in an increase in cGMP production. To shed light on this issue, an in vitro study was conducted to explore the effect of direct exogenous administration of l-arginine as well as its precursor and metabolite, l-citrulline, on the NO-cGMP pathway within the cavernosal smooth muscle (CSM) cell. Materials and methods CSM cells obtained from 8 to 10 week old Sprague-Dawley rats were grown in Dulbecco media with 20% fetal calf serum and then incubated with or without l-arginine (L-ARG) or l-citrulline (L-CIT) in a time course and dose-response manner. Sildenafil (0.4 mM), IBMX (1 mM), l-NAME (3 μM), ODQ (5 μM) and Deta Nonoate (10 μM) were used as either inhibitors or stimulators of the NO-cGMP pathway. mRNA and protein were extracted and used for the determination of the phosphodiesterase 5 (PDE5). PDE5 activity was determined by luminometry. cGMP content was determined by ELISA. Nitrite formation, an indicator of NO production, was measured in the cell culture media by a colorimetric assay. The cationic (CAT-1) and neutral (SNAT-1) amino acid transporters for L-ARG and L-CIT, respectively, were determined by Western blot. Results When compared to untreated CSM cells, incubation with 0.25–4.0 mM of L-ARG or 0.3–4.8 mM of L-CIT anywhere between 3 and 24 h did not result in any additional nitrite or cGMP production. The addition of l-NAME, IBMX or ODQ to these L-ARG and L-CIT treated cells did not alter these results. L-CIT but not L-ARG increased PDE5 mRNA and protein content as well as the activity of the PDE5 enzyme. Both CAT-1 and SNAT-1 were expressed in the CSM cells. Conclusions This in vitro study demonstrates that exogenous administration of L-ARG or L-CIT failed to stimulate production of either NO or cGMP by the corporal CSM cells. A re-evaluation of the presumptive role of the exogenous administration of L-ARG in improving the synthesis of NO at least at the level of the CSM cells appears warranted.

Dietary nitrate supplementation alters the oral microbiome but does not improve the vascular responses to an acute nitrate dose Publication date: 1 August 2019 Source: Nitric Oxide, Volume 89 Author(s): Mia Burleigh, Luke Liddle, David J. Muggeridge, Christopher Monaghan, Nicholas Sculthorpe, John Butcher, Fiona Henriquez, Chris Easton Abstract Nitrate (NO3−) contained in food and beverages can transiently increase nitric oxide (NO) availability following a stepwise reduction to nitrite (NO2−) by commensal bacteria in the oral cavity. We tested the hypothesis that regular ingestion of dietary NO3− would influence the oral microbiome, the capacity to reduce NO3− to NO2− in saliva, and the vascular responses to an acute dose of NO3−. The abundance of bacterial species on the tongue, the availability of NO markers, and vascular function were assessed in 11 healthy males before and after 7 days of supplementation with NO3−-rich beetroot juice and a NO3−-depleted placebo. As expected, saliva and plasma NO2− and NO3− were significantly elevated after NO3− supplementation (all P < 0.05) but not placebo. We found that NO3− supplementation increased salivary pH (7.13 ± 0.54 to 7.39 ± 0.68, P = 0.043) and altered the abundance of some bacteria previously implicated in NO3− reduction: Neisseria (from 2% ± 3%–9% ± 5%, P < 0.001), Prevotella (from 34% ± 17%–23% ± 11%, P = 0.001) and Actinomyces (from 1% ± 1%–0.5% ± 0.4%). Despite these alterations to the oral microbiota, an acute dose of NO3− increased salivary and plasma NO2−, reduced systolic blood pressure and increased the response to flow mediated dilation to a similar extent before and after 7 days of supplementation (P > 0.05). Our study establishes that supplementing the diet with NO3− for a sustained period can alter the oral environment in favour of health but does not impact the response to an acute NO3− dose. Acute ingestion of NO3− results in transient improvements in vascular function but the dietary induced adaptations to the oral bacteria did not enhance these effects.

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

6948891480

alsfakia@gmail.com

Oral Surgery, Oral Medicine, Oral Pathology ,Oral Radiology

Congenital nonvascular neck masses: A retrospective analysis Publication date: Available online 12 June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Matteo Brucoli, Paolo Boffano, Arnaldo Benech, Silvia Rosa, Massimiliano Garzaro, Paolo Aluffi Valletti ABSTRACT Introduction Congenital nonvascular neck masses are a challenge in head and neck diagnosis and management. The aim of this study was to analyze the clinical and epidemiological findings in patients who were diagnosed for congenital nonvascular neck masses. Methods All patients with congenital nonvascular neck masses who were treated between 1996 and 2018 were reviewed. The following data were recorded: age, gender, final pathological diagnosis (thyroglossal duct cysts, branchial cleft cysts, dermoid cysts), side of the lesion, subtype according to branchial arch (for branchial cleft cysts), and need for second surgery. Results 226 patients were included, with 100 thyroglossal duct cysts, 97 branchial cysts, and 29 dermoid cysts. Excision surgery was performed in all cases. Recurrence and subsequent second surgery was necessary in 5 cases out of 226. Conclusions An appropriate knowledge of clinical and epidemiological data regarding congenital nonvascular neck masses is crucial. Surgical resection is the optimal choice of therapy. Early referral of these patients to a head and neck surgeon is crucial for a timely treatment.

Endoscopic-assisted Enucleation of Large Mandibular Odontogenic Cysts Publication date: Available online 6 June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Yan Wang, Shao-hai Chang, Zhao-yu Lin, Rui Chen, Zhiquan Huang Abstract Purpose Traditional enucleation of large mandibular odontogenic cysts is an invasive method that might be associated with several complications. The purpose of this study was to evaluate the clinical outcome of endoscope-assisted enucleation of large mandibular cysts. Materials and Methods Fifty-seven patients with large mandibular odontogenic cysts were enrolled in this study. Patients were divided into 2 groups as follows: 25 patients were treated by traditional enucleation and 32 underwent endoscope-assisted enucleation. Allogeneic bone grafting was applied in all patients. Results All patients successfully underwent the operation. The follow-up period ranged from 16 to 28 months. Recurrence was found in 2 patients (8%) in the traditional enucleation group. In addition, no recurrence was observed in patients in the endoscope-assisted enucleation group. Permanent mandibular nerve palsy was found in 2 patients in the traditional enucleation group. In addition, only 2 cases of temporary mandibular nerve palsy were observed in the endoscope-assisted enucleation group. Conclusion Endoscopically assisted enucleation of large mandibular odontogenic cysts proved to be an effective treatment method, which provides complete enucleation of the cystic lesion while preserving surrounding tissue.

Automatic detection and classification of radiolucent lesions in the mandible on panoramic radiographs using a deep learning object detection technique Publication date: Available online 6 June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Yoshiko Ariji, Yudai Yanashita, Syota Kutsuna, Chisako Muramatsu, Motoki Fukuda, Yoshitaka Kise, Michihito Nozawa, Chiaki Kuwada, Hiroshi Fujita, Akitoshi Katsumata, Eiichiro Ariji Abstract Objective To investigate whether a deep learning object detection technique can automatically detect and classify radiolucent lesions in the mandible on panoramic radiographs. Study Design Panoramic radiographs of patients with mandibular radiolucent lesions of 10 mm or more, including ameloblastomas, odontogenic keratocysts, dentigerous cysts, radicular cysts, and simple bone cysts, were included. Lesion labels including region of interest coordinates were created in text format. In total, 210 training images and labels were imported into the 'DIGITS' deep learning training system. A learning model was created using the deep neural network 'DetectNet'. Two testing datasets (testing 1 and 2) were applied to the learning model. Similarities and differences between the prediction and ground-truth images were evaluated using Intersection over Union (IoU). Sensitivity and false positive rate per image were calculated using an IoU threshold of 0.6. The detection performance for each disease was assessed using multi-class learning. Results Sensitivity was 0.88 for both testing 1 and 2. False positive rate per image was 0.00 for testing 1 and 0.04 for testing 2. The best combination of detection and classification sensitivity occurred with dentigerous cysts. Conclusion Radiolucent lesions of the mandible can be detected with high sensitivity using deep learning.

Morphological changes in idiopathic condylar resorption with different degrees of bone loss Publication date: Available online 6 June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Yifan He, Han Lin, Qiuping Lin, Lin Lu, Mingyu Li, Qianli Li, Jingyi Xue, Yue Xu Abstract Objective The aim of this case control study was to investigate sizes, shapes, and angles of condyles exhibiting idiopathic condylar resorption (ICR) with different degrees of condylar bone loss, and to provide additional information for the diagnosis of ICR. Study Design In total, 154 condyles from ICR patients and 42 healthy condyles were included. The ICR group was further divided into three subgroups (ICR I, ICR II, and ICR III) based on the morphology of the condyle. 3D models of the condyles were measured and analyzed using the Mimics software based on cone beam computed tomography (CBCT) data. Results The condylar anteroposterior diameter, transverse diameter, height, superficial area, volume, articular surface angles, condylar neck angle, maximal sectional area, and condylar neck sectional area were all significantly different in the ICR group compared with the control group (P < 0.05). There were also significant differences among the three subgroups in many of these parameters (P < 0.05). Conclusions Morphologic changes in ICR become worse as the disease progresses, with significant differences between diseased and normal condyles. Many changes were significant between the subgroups. Posteriorly inclined condylar neck and slender condylar neck may be associated with ICR.

Multiphase Contrast-Enhanced CT Imaging Features of Salivary Duct Carcinoma: Differentiation from Other Salivary Gland Malignancies Publication date: Available online 6 June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Wen-li Wu, Cheng-long Wang, Dan Li, Jin Luo, Jun-yong Ye, Sheng-sheng Xu Abstract Objective To investigate the CT imaging features of salivary duct carcinoma (SDC) with multiphase contrast-enhanced CT (CECT) scanning and to compare them to mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and acinic cell carcinoma (AcCC). Study design A total of 63 patients with histologically diagnosed salivary gland malignancies underwent preoperative multiphase CECT. Clinical information, location, size, mass pattern, enhancement pattern, borders, invasion of adjacent tissues, and lymph node metastasis were evaluated. CT number attenuation patterns were calculated. Results SDCs were significantly more common in males and in the parotid gland (p≤0.018). They were more likely to invade into adjacent tissues and metastasize to lymph nodes (p≤0.032). Six SDCs (66.7%) had comedonecrosis as detected on histopathological examination, and 3 lesions presented cribriform necrosis on CECT. CT numbers during delayed-phase scanning were significantly higher in SDC than ACC (p=0.031). Significant differences were discovered between MEC and ACC for CT numbers during arterial-phase scanning (p=0.047) and in the ratio of CT numbers (p=0.018). Conclusion SDC exhibits some specific CT features, and multiphase CECT imaging is useful in the differential diagnosis of salivary gland malignancies.

Subjective analysis of the application of enhancement filters on magnetic resonance imaging of the temporomandibular joint Publication date: June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 6 Author(s): Gonzalo André Montesinos, Sérgio Lucio Pereira de Castro Lopes, Tarcila Trivino, José Andrés Sánchez, Fernando Akio Maeda, Claudio Fróes de Freitas, Andre Luiz Ferreira Costa Objective The aim of this study was to investigate the effect of enhancement filters on magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ). Study Design In total, 66 MRI scans of the TMJ were analyzed without filtration and with the application of 2 filters: Sharpen 1 and Sharpen 2 (OnDemand software). Two dentomaxillofacial radiologists examined the original and filtered images individually. Intra- and interobserver concordance was measured by using generalized estimating equations. The observers evaluated the subjective image quality and the visibility of 3 components of the TMJ: disk, condyle, and articular eminence. The images were ranked on a 4-point scale, from poor to excellent. The image quality of all filtered images was compared by using the χ2 test and Bonferroni correction for multiple comparisons. Results Intra- and interobserver concordance was good. The images filtered with Sharpen 1 and Sharpen 2 provided better definition of the structures compared with nonfiltered images, providing the highest scores for subjective image quality for all structures (P < .0001). Conclusions The use of enhancement filters led to improved subjective quality and may improve the diagnostic efficacy of MRI in TMJ evaluation.

Acinetobacter baumannii orofacial cellulitis: report of 2 cases Publication date: June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 6 Author(s): Thaís dos Santos Fontes Pereira, Denise Vieira Travassos, Raissa Cristina Costa Silva, Laiz Fernandes Mendes Nunes, Maria Edileusa Santos, Célia Regina Lanza, Gabriela Assunção Goebel, Fabiana Maria Kakehasi, Tarcília Aparecida Silva Acinetobacter baumannii infection of skin and soft tissues is uncommon and usually associated with trauma. The present report describes 2 pediatric cases of cellulitis in the orofacial region, caused by A. baumanniiinfection with a fatal outcome. A 12-year-old male patient, diagnosed with acute promyelocytic leukemia, presented with an ulcerated lesion on the lip suggestive of local trauma. The condition progressed to cellulitis, epithelial necrosis, and nonspecific vesicles and blisters. The second case occurred in a 10-year-old male patient with a diagnosis of Burkitt lymphoma. The patient's condition progressed to World Health Organization Grade IV mucositis and cellulitis. In both cases, hemoculture was positive for multidrug-resistant A. baumannii. In conclusion, A. baumannii should be considered a potentially multidrug-resistant pathogen in the presence of skin and soft tissue cellulitis. Ulcerated oral lesions may place hospitalized pediatric patients at risk for A. baumannii infection.

Association between biomarkers and medication-related osteonecrosis of the jaws: a systematic review Publication date: June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 6 Author(s): Vittorio Moraschini, Daniel Costa Ferreira de Almeida, Carlos Marcelo Figueredo, Monica Diuana Calasans-Maia Objectives Our aim was to conduct a systematic review (SR) of the literature assessing the role of human biomarkers in the diagnosis or prognostication of medication-related osteonecrosis of the jaws (MRONJ). Study Design An electronic search without date or language restriction was carried out in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Web of Science, and LILACS for publications until March 2018. In addition, a manual search in the gray literature was conducted. The search process was performed by 2 independent reviewing authors. Eligibility criteria included randomized and nonrandomized clinical trials, prospective or retrospective cohorts, case controls, and case series evaluating the association between biomarkers and MRONJ. The protocol of this SR was registered in PROSPERO under number CRD42018095886. Results The search and selection process yielded 19 studies (2 case series, 6 case-control studies, 9 prospective cohort studies, and 2 retrospective studies) published between 2008 and 2018. Twenty-four biomarkers collected from serum, saliva, and urine were investigated by these studies. Eleven biomarkers were possibly related to MRONJ; however, no consensus is observed in the literature with regard to the sensitivity and clinical effectiveness of these biomarkers. Conclusions Although many biomarkers have been associated with MRONJ, the present SR found scarce clinical evidence supporting the use of these biomarkers for the diagnosis and prognosis of MRONJ.

Diagnostic delay and suboptimal management in persistent idiopathic facial pain and persistent dentoalveolar pain; a cross-sectional study Publication date: June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 6 Author(s): Yazan Hassona, Ahmad El- Ma'aita, Jacqueline Amarin, Anas Al Taee Objectives The aim of this study was to explore the diagnostic and therapeutic challenges encountered by patients with persistent idiopathic facial pain (PIFP) and to investigate factors influencing its delayed diagnosis. Study Design In this cross-sectional study, 34 patients with newly diagnosed PIFP were interviewed. Data about diagnostic delay, number and nature of previous consultations, and previous medical and surgical interventions were recorded. Pearson's correlation and Student t test were used to examine the differences among the variables in relation to diagnostic delay. Results The average time between the onset of symptoms to correct diagnosis was 19.3 ± 11.1 months. Diagnostic delay was significantly longer in patient with pain localized to intraoral sites (22.6 ± 7.4) compared with patients with extraoral pain (16.1 ± 9.3). The average number of health care professionals consulted before correct diagnosis was 3.7 ± 2.3. General dental practitioners were the most commonly consulted health care professionals (n = 27; 79.4%). On average, patients were given 2.3 ± 0.24 misdiagnoses before the correct diagnosis was determined and were prescribed 3.5 ± 2.4 classes of drugs. Twenty-five patients (73.5%) underwent unnecessary surgical/dental interventions. Conclusions Patients with PIFP are frequently misdiagnosed, leading to prescription of ineffective medications and unnecessary investigations and surgical interventions. Educational efforts should emphasize on improving knowledge and awareness of this condition.

Association of geographic tongue and fissured tongue with ABO blood group among adult psoriasis patients: a novel study from a tertiary care hospital in Saudi Arabia Publication date: June 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 6 Author(s): Nabeeh A. Al Qahtani, Angeline Deepthi, Nada Mohammed Alhussain, Bashayer Ayesh Mohammed Al Shahrani, Hamza Alshehri, Amal Alhefzi, Betsy Joseph Objective We aimed to determine if there was any association between geographic tongue (GT) and fissured tongue with ABO blood group among adult psoriasis patients in Saudi Arabia. Study Design This hospital-based cross-sectional study included 100 consecutive new adult patients diagnosed with psoriasis and 100 case-matched participants in the control group (nonpsoriatic). Sociodemographic and dermatologic parameters, intraoral lesions (GT and fissured tongue), and ABO blood grouping and immunoglobulins were recorded and evaluated using χ2 or Fisher's exact test. Results A total of 74% of patients had an early age of onset, and 48% of them reported this disease in their parents. A total of 76% of those with generalized psoriasis had plaque type, whereas 78% with the localized type had pustular lesions. A total of 70% of psoriatic patients had O Rh-positive blood; 63% of tongue lesions seen in these patients were GT, and it was most prominent in O Rh-positive (64.28%) and O Rh-negative (62.50%) blood types. GT was prevalent among women (75.6%). Conclusions This study found a positive association of both GT and fissured tongue in this population of adult patients with psoriasis compared with a case-matched control population without psoriasis.

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

6948891480

alsfakia@gmail.com

Aggression and Violent Behavior

The conceptualization of gangs: Changing the focus Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Daniel Wegerhoff, Louise Dixon, Tony Ward Abstract Discussions about the gang construct and appropriate definitions have been pervasive throughout gang research. This paper seeks to shed light on these discussions by adopting a theoretical perspective to examine the suitability of 'gangs' as a target of explanation and the appropriateness of current definitional approaches. First, we examine the validity and utility of the gang construct. It is concluded that the gang label has poor construct validity and limited explanatory utility, thereby making it unsuitable for theoretical purposes. Instead, we suggest that researchers need to focus on what gangs are at a foundational level, namely groups, and that the group should be the target of explanation. Second, we consider the limitations of gang definitions for theory construction and instead offer a method known as three-tier analysis to comprehensively conceptualize groups without discussions of necessary and sufficient definitional boundaries. Finally, we produce a framework based on these findings and demonstrate how it facilitates understanding of a specific gang exemplar. In doing so, we bypass several theoretical roadblocks obstructing gang research and advance a way to explain the group and (by extension) gangs, thus improving our understanding of groups and gangs with the purpose of ultimately informing practice and policy initiatives.

Tracking narrative change in the context of extremism and terrorism: Adapting the Innovative Moments Coding System Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Raquel da Silva, Pablo Fernández-Navarro, Miguel M. Gonçalves, Catarina Rosa, Joana Silva Abstract Existing models of deradicalisation, countering violent extremism (CVE), and counter-terrorism (CT) have lacked a clear theory of change, as well as robust empirical methodologies. This paper proposes an empirically-based systematic and transparent methodology – the Innovative Moments Coding System (IMCS) – which is empirically sensitive, ethically defensible, and can be of use in the context of research to inform practitioner contexts. Through a case study of former violent militants, we explore the adaptation and usage of this instrument to identify and track self-narrative change in the processes of engagement and disengagement, as well as radicalisation and deradicalisation in the context of violent extremism and terrorism. We illustrate how this methodology has the potential to bring benefits to the work of researchers involved in producing guidelines for disengagement, deradicalisation or risk-reduction interventions.

Moving beyond prison rape: Assessing sexual victimization among youth in custody Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Eileen M. Ahlin Abstract This integrated literature review discusses the need to treat youth in custody distinctly from adult carceral populations when examining sexual victimization. Although the Prison Rape Elimination Act (PREA) mandates correctional facilities address sexual assault in both populations, the lack of available information on risk factors among youth may lead to practitioners and policy-makers becoming reliant on the adult literature when making decisions on preventative and reactive care for juveniles. Such extrapolation may lead to an inadequate or even inappropriate response for youth in custody. A research agenda using an ecological framework to determine youth-specific individual and structural level risk factors is proposed. Findings demonstrate differences in sexual victimization risk factors for adults in jails and prisons compared to youth in custody. This review serves as a foundation for moving research on this topic to juvenile custody settings while also acknowledging the challenges associated with conducting such research among youth in custody.

Neurobiological findings of the psychopathic personality in adults: One century of history Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Diana Moreira, Andreia Azeredo, Fernando Barbosa Abstract This review intends to produce a historical overview of the psychobiological bases of psychopathy from the first studies using biological or neuropsychological measures up to the present state of knowledge. The reviewed studies were retrieved from multiple databases, following the procedures of the Cochrane Collaboration. Of the 205 documents obtained, 49 were selected for further analysis and 31 were considered eligible for inclusion. Furthermore, eight studies were included through manual search. The objectives, sample (age, percentage of male, type of sample), country of origin of the studies, language, design, instruments, and results and main conclusions were extracted from each study. Overall, the results reinforce the idea that psychopathic traits are associated with abnormalities in the way the brain processes environmental emotional information, and that the fundamental cognitive properties related to attention maintain or worsen these abnormalities. In some cases, changes in attention explain, by themselves, the abnormalities in emotional processing. Future studies using neurophysiological paradigms would be a great asset to help differentiate, at a neurocognitive level, the personality structures characterized by pronounced antisocial behavior, in order to improve the understanding of their heterogeneous etiologies.

Measures for evaluating sex trafficking aftercare and support services: A systematic review and resource compilation Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Laurie M. Graham, Rebecca J. Macy, Amanda Eckhardt, Cynthia F. Rizo, Brooke L. Jordan Abstract Increasingly, organizations are providing services to promote the resilience and reintegration of persons trafficked for sexual exploitation. Unfortunately, services for survivors of trafficking have out-paced the evaluation of such services. However, formative studies exist on the needs and service outcomes of survivors of trafficking. We undertook a systematic summary of such studies with the aim of compiling the measures and constructs used in this literature. Of the 53 studies reviewed, 22 studies named 34 published measures used to collect data regarding survivors' coping; physical, mental, sexual, and reproductive health; substance use; social support; trafficking-related needs, strengths, and outcomes; and trauma and abuse experiences. Additionally, to gather information on constructs of interest, 18 of the 22 studies included supplemental questions that were not part of a specific measure. Results show sex trafficking research is strongly focused on the physical and mental health needs and service outcomes of survivors. Few studies incorporate holistic views of well-being. Moreover, measures used with this population often have not been tested with survivors of trafficking. We recommend testing measures with this population, conducting holistic assessment of the needs and outcomes of survivors of sex trafficking, and developing tailored measures for various subgroups within this diverse population.

Predicting domestic violence: A meta-analysis on the predictive validity of risk assessment tools Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Claudia E. van der Put, Jeanne Gubbels, Mark Assink Abstract Risk assessment tools are increasingly being used to guide decisions about supervision and treatment of domestic violence perpetrators. However, earlier review studies showed that the predictive validity of most of these tools is limited, and is reflected in small average effect sizes. The present study aimed to meta-analytically examine the predictive validity of domestic violence risk assessment tools, and to identify tool characteristics that positively moderate the predictive validity. A literature search yielded 50 independent studies (N = 68,855) examining the predictive validity of 39 different tools, of which 205 effect sizes could be extracted. Overall, a significant discriminative accuracy was found (AUC = 0.647), indicating a moderate predictive accuracy. Tools specifically developed for assessing the risk of domestic violence performed as well as risk predictions based on victim ratings and tools designed for predicting general/violent criminal recidivism. Actuarial instruments (AUC = 0.657) outperformed Structured Clinical Judgment (SCJ) tools (AUC = 0.580) in predicting domestic violence. The onset of domestic violence (AUC = 0.744) could be better predicted than recurrence of domestic violence (AUC = 0.643), which is a promising finding for early detection and prevention of domestic violence. Suggestions for the improvement of risk assessment strategies are presented.

The role of media exposure on relational aggression: A meta-analysis Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Nicole Martins, Andrew Weaver Abstract We conducted a meta-analysis of 33 studies that examined the effects of media exposure on relationally aggressive behaviors and cognitions (a total of 66 effect sizes, N = (20,990). Across all types of aggressive content, there was a small positive effect (r = 0.15) on relational aggression. However, a comparison of effects sizes demonstrate that exposure to relational aggression had the strongest effect (r = 0.21), whereas exposure to non-specific media content had the weakest effect (r = 0.08). Exposure to physical aggression fell in the middle of the two content types (r = 0.15). Potential explanations for these effects as well as moderators that could influence the results are considered, and the practical implications of these findings are discussed.

Emotional victims and the impact on credibility: A systematic review Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Janne van Doorn, Nathalie N. Koster Abstract Previous research suggests that a victim's emotional expression plays an important role in credibility judgments. However, victims show different emotional responses to the consequences of a crime. Previous research has shown that the emotionality of a victim's demeanor affects the perceived credibility of the victim, also known as the emotional victim effect (EVE). The current systematic review aims to critically scrutinize the current literature on the influence of a victim's emotional demeanor on credibility ratings of that same victim. A comprehensive literature search was performed using search term combinations including victim-related terms, emotion-related terms, and credibility-related terms. A total of 25 studies, published between 1981 and 2017, and in which the emotional demeanor of the victim was manipulated, were included in the systematic review. By using a systematic approach, both in search for studies and in reporting results, the current review provides an overview under what circumstances the EVE is present. This is important because credibility is a key determinant for case advancement in the criminal justice system. A synthesis of the literature suggests that the effect of a victim's emotionality on credibility is dependent upon several factors and almost exclusively found in student samples.

Suicide by abdominal wounds suggesting seppuku: Case reports from Romania and an international literature review Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Claudia Judea-Pusta, Alexandru Rusu, Andreea Camarasan Abstract Seppuku is a traditional suicide method practiced by honorable Japanese samurai. Today this method of suicide is rarely used in Japan or worldwide and may be exceptionally encountered in patients suffering from psychiatric disorders, the majority of them being older men. It is well known that clinical and cultural factors also play a role in practicing this method of suicide. The mortality rate is significantly higher in cases of abdominal wounds suggesting seppuku, compared to the mortality rate caused by simple stab wounds. Death can occur immediately through massive external or/and internal hemorrhage as well as later on through complications, often septic. In the Romanian forensic literature files, suicide by abdominal stabbing suggesting seppuku is rarely encountered and documented. When investigating violent deaths owing to sharp force, the role of the forensic pathologist is not only to establish the cause of death and the mechanism used for creating the lesions, but also to identify the object used for inflicting the injuries, the type of the injuries, allowing thus to formulate a conclusion from legal perspective upon the act itself: suicide or homicide? The present paper reviews the international literature and presents three cases of suicide by self- inflected abdominal stab wounds suggesting seppuku, autopsied at the Bihor County Forensic Service, Romania, during 2013–2017.

Biosocial studies of antisocial behavior: A systematic review of interactions between peri/prenatal complications, psychophysiological parameters, and social risk factors Publication date: July–August 2019 Source: Aggression and Violent Behavior, Volume 47 Author(s): Babette C.M. van Hazebroek, Hilde Wermink, Lieke van Domburgh, Jan W. de Keijser, Machteld Hoeve, Arne Popma Abstract In order to reduce antisocial behavior (ASB) and associated individual and societal problems, insight into determinants of ASB is warranted. Increasing efforts have been made to combine biological and social factors in explaining antisocial development. Two types of biological parameters have been studied vastly and provide the most compelling evidence for associations between biosocial interaction and ASB: peri/prenatal complications and psychophysiological parameters. A systematic review was conducted to synthesize empirical evidence on interactions between these biological measures and social risk factors in predicting ASB. In doing so, we aimed to (1) examine whether specific peri/prenatal and psychophysiological measures composite a vulnerability to social risk and increase risk for specific types of ASB, and (2) evaluate the application of divergent biosocial theoretical models. Based on a total of 50 studies (documented in 66 publications), associations between biological parameters and ASB were generally found to be stronger in the context of adverse social environments. In addition, associations between biosocial interaction and ASB were stronger for more severe and violent types of ASB. Further, in the context of social risk, under-arousal was associated with proactive aggression, while over-arousal was associated with reactive aggression. Empirical findings are discussed in terms of distinct biosocial theoretical perspectives that aim to explain ASB and important unresolved empirical issues are outlined.

Alexandros Sfakianakis
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alsfakia@gmail.com