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025% and CRE 1% in food) for 4 weeks or from controls that were fed a basal diet. We extracted RNAs from FFPE samples and RNA-Seq was performed on a MiniSeq (Illumina) using the TruSeq custom RNA panel. AAF induced remarkable differences in the expression of eight genes (Aen, Bax, Btg2, Ccng1, Gdf15, Mbd1, Phlda3 and Tubb4b) from that in the control group, while CRE only induced expression changes in Gdf15, as shown using Tukey's test. Gene expression profiles for nine genes (Aen, Bax, Btg2, Ccng1, Cdkn1a, Gdf15, Mbd1, Phlda3, and Plk2) differed.between samples treated with AAF and CRE. Finally, principal component analysis (PCA) of 12 genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2, and Tubb4b) using our previous Open TG-GATE data plus FFPE-AAF and FFPE-CRE successfully differentiated FFPE-AAF, as GTHC, from FFPE-CRE, as NGHTC. Conclusion Our results suggest that FFPE RNA-Seq and PCA are useful for evaluating typical rat GTHCs and NGTHCs. © The Author(s) 2020.Calcification of the ligamentum flavum (CLF), which is a rare disorder that can potentially cause myelopathy, occurs uncommonly in the thoracic spine. Here, we report a rare case of thoracic myelopathy caused by CLF in a 78-year-old man. Magnetic resonance imaging (MRI) showed posterior spinal cord compression by a hypo-signal intense mass, and computed tomography (CT) revealed CLF and vacuum disc phenomenon at T10/11. After undergoing posterior decompression and instrumented fusion (T9-T12), the patient's gait difficulties improved. The pathogenesis of CLF is largely unknown; however, it involves accumulation of calcium pyrophosphate dehydrate crystals (CPPD), and CLF from CPPD deposition tends to occur within a thickened and hypertrophic ligament. CLF occurs predominantly in the cervical spine and less frequently in the lumbar spine, with few cases involving the thoraco-lumbar spine. The thoracic spine is characterized by hypomobility; however, the thoraco-lumbar spine has a mobile segment which may potentiate CLF formation. Decompression with fusion surgery can be useful for treating patients with thoraco-lumbar CLF. ©2020 The Japanese Association of Rural Medicine.Although methemoglobinemia is rare in adulthood, it may have fatal consequences if unnoticed. We planned to implant an implantable cardioverter defibrillator ICD in a 50-year-old male patient for primary prevention. Following sterile draping, prilocaine 5 mg/kg (400 mg) was injected subcutaneously for local anesthesia. We injected an additional dose of 200 mg due to pain during subclavian vein puncture. A DDD-R ICD was placed successfully within approximately 40 minutes. The patient complained of sudden chest pain and dyspnea 15 minutes after bed rest and was transferred to the coronary care unit due to cyanosis and deterioration of general status. Physical examination revealed blood pressure of 110/80 mmHg, pulse rate of 110 bpm, and otherwise unremarkable signs. Peripheral oxygen saturation was determined as 83% by pulse oximeter. Possible pneumothorax and cardiac perforation were excluded by emergency chest radiograph and echocardiography. Blood gas analyses was performed to assess for methemoglobinemia, which revealed pH 7.41, pCO2 40 mmHg, oxygen saturation 98.2%, and methemoglobin 7.9% that peaked to 12.3%. Methylene blue (1%) was slowly injected over 10 minutes at a dose of 1 mg/kg. Cyanosis waned and methemoglobin values decreased to 4.1%, 2.1%, and 1.1% at 2, 8, and 16 hours following the administration, respectively. The patient was safely discharged 2 days after implantation of pacemaker. Methemoglobinemia should be considered in cases presenting with cyanosis, non-diagnostic ECG, and a discrepancy in oxygen saturation between pulse oximetry and blood gas analyses. ©2020 The Japanese Association of Rural Medicine.Owing to new surgical procedures and medications, more women who have undergone the Fontan procedure reach childbearing ages. We report five cases of pregnancy with Fontan circulation. Case 1 had subchorionic hematoma (SCH), fetal growth restriction (FGR), and preterm labor (PTL). She delivered a 1073 g infant via cesarean section at gestation week 28 because of hemorrhagic shock. Case 2 delivered 2142 g and 2232 g infants at gestation weeks 37 and 36, respectively. She had FGR, PTL, and postpartum hemorrhage (PPH). Case 3 had SCH, PTL, and heart failure. At 36 weeks, labor was induced and she delivered a 2546 g infant by vacuum extraction with epidural analgesia. Cases 4 and 5 resulted in miscarriage. All subjects experienced obstetrical complications. This report discusses pregnant women with Fontan circulation by focusing on affected Japanese women. . © 2019 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.Anticoagulation therapy is essential for preventing thrombus formation in the left atrial appendage (LAA) and subsequent ischemic strokes in patients with atrial fibrillation (AF). The complete disappearance of any existing LAA thrombi is crucial before AF ablation. Currently, warfarin and direct oral anticoagulants are widely used for this purpose. However, treatment strategies for anticoagulation-resistant LAA thrombi are not well established. Here, we present a case of an 85-year-old male who was scheduled to undergo AF ablation. He developed an LAA thrombus that was resistant to 300 mg/day of dabigatran. Low-dose pimobendan was prescribed in addition to dabigatran; three months later, the thrombus was dissolved successfully. This case demonstrates the potential efficacy of a low-dose oral inotrope for treating an anticoagulation-resistant LAA thrombus. . © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.Relative bradycardia (mild sinus bradycardia) is one of the major barriers for the effective treatment of hemodynamically unstable patients with heart failure and reduced cardiac output. We report a case of a man aged 58 years with an old broad anterior myocardial infarction and relative bradycardia (about 60 bpm) suffering from symptoms of congestive heart failure at rest in spite of optimal medical therapy, including the use of the inotropes. Transvenous atrial pacing during right heart catheterization indicated that an increase in heart rate (up to 80 bpm) improved hemodynamics immediately. Implantation of a pacemaker (atrial pacing of 80 bpm) was effective for stabilizing the heart failure symptoms. Transvenous atrial pacing during right heart catheterization is effective for estimating the optimal heart rate in patients with heart failure and relative bradycardia. . © 2019 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.Pacemaker implantations are minimally invasive procedures commonly used for patients with bradycardic arrhythmias. Takotsubo cardiomyopathy, which is usually induced by life-threatening stress hardly ever occurs after this minimally invasive procedure. Here, we experienced a patient who developed takotsubo cardiomyopathy leading to ventricular fibrillation the day after a pacemaker implantation. At that time, a cardiac echocardiogram and left ventriculogram revealed hypercontraction of the base of the heart and a decreased contraction of the apex. A coronary angiogram revealed no significant coronary stenosis. Ten days later, the electrocardiogram findings normalized, and an echocardiogram revealed that the left ventricular function had fully recovered. Therefore, we diagnosed this patient with takotsubo cardiomyopathy. In general, pacemaker implantations are routine procedures and fatal complications are low. We report a case that developed potentially fatal complications after a pacemaker implantation. . © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.Isolated congenital pulmonary valvular stenosis is a relatively common abnormality. A 52-year-old woman with an asymptomatic cardiac murmur since her childhood visited our hospital. The peak pressure gradient across the pulmonary valve (PV) was calculated 25 mmHg by Doppler velocity during the transthoracic echocardiography, the severity was graded into mild. The cardiac computed tomography indicated a dome-shaped PV with an equilateral triangle orifice without commissural fusion. No case has been described in a triangle orifice, it will be necessary to follow up carefully. . © 2019 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.Transcatheter closure is an established method to treat coronary artery fistula (CAF). We present transcatheter closure in a 6-year-old girl with CAF and anomalous aortic origin of the left main coronary artery from the right aortic sinus. The CAF originated from the left coronary artery (LCA), coursed through the interventricular septum (intraseptal course) with prominent dilation, and drained into the right ventricular outflow tract. She underwent transcatheter closure and was in a stable condition at the 3-year follow-up with regression of the dilated portion of the intraseptal-type LCA. Hence, transcatheter closure of CAF is feasible in patients with anomalous origins of coronary arteries. . © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.Myocarditis is an uncommon but potentially life-threatening disease. Clinical manifestations could range from subclinical disease to sudden death, due to fulminant heart failure and/or malignant ventricular arrhythmias. The most common cause of myocarditis is viral infection, including Epstein-Barr virus (EBV). Nevertheless, EBV rarely presents with cardiac involvement in immunocompetent hosts. We report a case of acute EBV-related myocarditis in a young female, complicated with malignant ventricular arrhythmias and cardiac arrest. After 20 days of hospitalization and treatment, the patient was fit for discharge on pharmacological therapy (tapering steroids, beta-blockers, amiodarone, angiotensin-converting enzyme inhibitors, and diuretics). Clinical course is described, cardiac magnetic resonance images are shown. This case underlines how myocarditis is a disease that should not be underestimated it could present with life-threatening complications such as malignant arrhythmias and/or severe systolic dysfunction. . © 2019 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.Coronary artery disease (CAD), the major reason of deaths worldwide is generally known as a disease of the elderly, however it is grasping the youth too. The most common etiology of young CAD is lifestyle changes, smoking, and development of other comorbid conditions such as diabetes and hypertension at an early age. There has been an upward trend in youngsters regarding consciousness about their body build and thus use of various protein supplements and anabolic steroids for faster results. The present case reports a young patient presenting with severe retrosternal left-sided chest pain for 15-20 min to the emergency department. His electrocardiogram was suggestive of acute anterolateral wall ST segment elevation myocardial infarction for which he underwent urgent coronary angiography and percutaneous coronary intervention. His personal history revealed a significant use of steroids, proteins, and other supplements in supraphysiological doses for instant body building efforts without any other significant past medical, surgical, or family history. He showed good recovery and was strongly recommended to stop steroids and protein supplements. In conclusion, supraphysiological doses of protein supplements, anabolic steroids, and other nutritional products bear a risk factor for CAD. . © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.Ascending aortic pseudoaneurysm is a rare pathology that could have multiple etiologies such as thoracic trauma, infection, and percutaneous or surgical procedures. In patients with aortic pseudoaneurysms, open surgical or endovascular interventions are always indicated, if feasible and independent of size. Several types of endovascular treatment have been reported in the literature, but they have been mostly restricted to those cases when traditional surgery has a prohibitive risk. We report the case of a 75-year-old man with a sinotubular junction pseudoaneurysm, likely developed after coronary artery bypass grafting, which was successfully treated by implanting a multifenestrated cribriform septal occluder, a device already used in few similar cases. . © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.Persistent Thebesian veins with the appearance of multiple coronary artery microfistulas are a rare finding and little is known about their physiologic and clinical features. In addition, few reports have demonstrated the perfusion status of patients with Thebesian veins. We report a 75-year-old woman referred for non-ST-elevation myocardial infarction due to prominent Thebesian veins who displayed a perfusion defect in cardiac magnetic resonance imaging. . © 2019 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.Acute aortic dissection (AAD) is a catastrophic cardiovascular disease with high disability and mortality due to multiple fatal complications. However, the molecular changes of the serum proteome after AAD are not very clear. Here, we performed isobaric tags for relative and absolute quantitation- (iTRAQ-) based comparative proteomic analysis to investigate the proteome profile changes after AAD by collecting plasma samples from 20 AAD patients and 20 controls. Out of the 345 identified proteins, 266 were considered as high-quality quantified proteins (95%confident peptides ≥ 2), of which 25 proteins were accumulated and 12 were reduced in AAD samples. Gene ontology enrichment analysis showed that the 25 AAD-accumulated proteins were enriched in high-density lipoprotein particles for the cellular component category and protein homodimerization acidity for the molecular function category. Protein-protein interaction network analysis showed that serum amyloid A proteins (SAAs), complement component proteins, and carboxypeptidase N catalytic chain proteins (CPNs) possessed the key nodes of the network. The expression levels of six selected AAD-accumulated proteins, B2-GP1, CPN1, F9, LBP, SAA1, and SAA2, were validated by ELISA. Moreover, ROC analysis showed that the AUCs of B2-GP1 and CPN1 were 0.808 and 0.702, respectively. Our data provide insights into molecular change profiles in proteome levels after AAD and indicate that B2-GP1 and CPN1 are potential biomarkers for AAD. Copyright © 2020 Na Cheng et al.The evolution of virtual reality (VR) technologies requires setting boundaries of its use. In this study, 3 female participants were experiencing VR scenarios with stressful content and their activity of the autonomic nervous system and EEG were recorded. It has been discovered that virtual reality can evoke acute stress reactions accompanied by activation of the sympathetic nervous system and a decrease in the activity of the parasympathetic nervous system. The high-stress response is accompanied by a decrease in the power of the EEG, and, on the contrary, the activation of the avoidance reaction is accompanied by an increase in the power of the EEG alpha waves. Therefore, the use of stressful VR content can cause high emotional stress to a user and restrictions should be considered. Copyright © 2020 Kirill A. Fadeev et al.Hexa-peri-hexabenzocoronene (HBC) is known to be a poorly soluble polycyclic aromatic hydrocarbon for which direct functionalization methods have been very limited. Herein, the synthesis of hexaborylated HBC from unsubstituted HBC is described. Iridium-catalyzed six-fold C-H borylation of HBC was successfully achieved by screening solvents. The crystal structure of hexaborylated HBC was confirmed via X-ray crystallography. Optoelectronic properties of the thus-obtained hexaborylated HBC were analyzed with the support of density functional theory calculations. The spectra revealed a bathochromic shift of absorption bands compared with unsubstituted HBC under the effect of the σ-donation of boryl groups. Copyright © 2020, Nagase et al.; licensee Beilstein-Institut.Direct arylation is an appealing method for preparing π-conjugated materials, avoiding the prefunctionalization required for traditional cross-coupling methods. A major effort in organic electronic materials development is improving the environmental and economic impact of production; direct arylation polymerization (DArP) is an effective method to achieve these goals. Room-temperature polymerization would further improve the cost and energy efficiencies required to prepare these materials. Reported herein is new mechanistic work studying the underlying mechanism of room temperature direct arylation between iodobenzene and indole. Results indicate that room-temperature, Pd/Ag-catalyzed direct arylation systems are radical-mediated. This is in contrast to the commonly proposed two-electron mechanisms for direct arylation and appears to extend to other substrates such as benzo[b]thiophene and pentafluorobenzene. Copyright © 2020, Mayhugh and Luscombe; licensee Beilstein-Institut.Diverse P,N-phosphine ligands reported to date have performed exceptionally well as auxiliary ligands in organometallic catalysis. Phosphines bearing 2-pyridyl moieties prominently feature in literature as compared to phosphines with five-membered N-heterocycles. This discussion seeks to paint a broad picture and consolidate different synthetic protocols and techniques for N-heterocyclic phosphine motifs. The introduction provides an account of P,N-phosphine ligands, and their structural and coordination benefits from combining heteroatoms with different basicity in one ligand. The body discusses the synthetic protocols which focus on P-C, P-N-bond formation, substrate and nucleophile types and different N-heterocycle construction strategies. Selected references are given in relation to the applications of the ligands. Copyright © 2020, Munzeiwa et al.; licensee Beilstein-Institut.Raw material from biomass and green preparation processes are the two key features for the development of green products. As a bio-lubricant in metalworking fluids, estolides of ricinoleic acid are considered as the promising substitute to mineral oil with a favorable viscosity and viscosity index. Thus, an efficient and sustainable synthesis protocol is urgently needed to make the product really green. In this work, an environment-friendly Brønsted acidic ionic liquid (IL) 1-butanesulfonic acid diazabicyclo[5.4.0]undec-7-ene dihydrogen phosphate ([HSO3-BDBU]H2PO4) was developed as the efficient catalyst for the production of oligomeric ricinoleic acid from ricinoleic acid under solvent-free conditions. The reaction parameters containing reaction temperature, vacuum degree, amount of catalyst and reaction time were optimized and it was found that the reaction under the conditions of 190 °C and 50 kPa with 15 wt % of the [HSO3-BDBU]H2PO4 related to ricinoleic acid can afford a qualified product with an acid value of 51 mg KOH/g (which corresponds to the oligomerization degree of 4) after 6 h. Furthermore, the acid value of the product can be adjusted by regulating the reaction time, implying this protocol can serve as a versatile method to prepare the products with different oligomerization degree and different applications. The other merit of this protocol is the facile product separation by stratification and decantation ascribed to the immiscibility of the product and catalyst at room temperature. It is also worth mentioning that the IL catalyst can be used at least for five cycles with high catalytic activity. As a result, the protocol based on the IL catalyst, i.e. [HSO3-BDBU]H2PO4 shows great potential in industrial production of oligomeric ricinoleic acid from ricinoleic acid. Copyright © 2020, You et al.; licensee Beilstein-Institut.A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure-activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as "synthetic nucleases", independently of oxygen and pH. Calf thymus-DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for "on demand" biotechnological applications in drug discovery and medicine. Copyright © 2020, Gritzapis et al.; licensee Beilstein-Institut.A series of optically active bisbenzofuro[2,3-b3',2'-e]pyridine (BBZFPy) derivatives was synthesized starting with the readily available (S)- and (R)-1,1'-bi-2-naphthols through a palladium-catalyzed multiple intramolecular C-H/C-H coupling as the key ring-closure step. The effect of terminal tert-butyl substituents on the BBZFPy skeleton was systematically investigated to uncover a unique aggregation-induced enhancement of CPL characteristics in the solid state. The crystal structures of the coupling products were also evaluated by single crystal X-ray analysis and the well-ordered intermolecular stacking arrangements appeared to be responsible for the enhanced CPL. Copyright © 2020, Takishima et al.; licensee Beilstein-Institut.Differently substituted thiophene-thiophene-alternating copolymers were formally synthesized employing a halo-bithiophene as a monomer. Nickel-catalyzed polymerization of bithiophene with substituents at the 3-position, including alkyl-, fluoroalkyl-, or oligosiloxane-containing groups, afforded the corresponding copolymers in good to excellent yield. The solubility test in organic solvents was performed to reveal that several copolymers showed a superior solubility. X-ray diffraction analysis of the thin film of the alternating copolymers composed of methyl and branched oligosiloxane substituents was also performed, and the results suggested the formation of a dual-layered film structure. Copyright © 2020, Mori et al.; licensee Beilstein-Institut.Copper catalysis and, more generally, copper chemistry are pivotal for modern organofluorine chemistry. Major advances have been made in the field of trifluoromethylselenolations of organic compounds where copper catalysis played a crucial role. Recent developments in this field are highlighted in this minireview. Copyright © 2020, Ghiazza and Tlili; licensee Beilstein-Institut.A pair of geometrically isomeric unsaturated keto fatty acids, (6E,8Z)- and (6E,8E)-5-oxo-6,8-tetradecadienoic acids (1 and 2), were isolated from the culture broth of an actinomycete of the genus Micrococcus, which was associated with a stony coral, Catalaphyllia sp. Their chemical structures were elucidated by spectroscopic analysis including NMR and MS, with special assistance of spin system simulation studies for the assignment of an E geometry at C8 in 2. As metabolites of microbes, compounds 1 and 2 are unprecedented in terms of bearing a 2,4-dienone system. Both 1 and 2 showed antibacterial activity against the plant pathogen Rhizobium radiobacter and the fish pathogen Tenacibaculum maritimum, with a contrasting preference that 1 is more effective to the former strain while 2 is so to the latter. In addition, compounds 1 and 2 displayed agonistic activity against peroxisome proliferator-activated receptors (PPARs) with an isoform specificity towards PPARα and PPARγ. Copyright © 2020, Sharma et al.; licensee Beilstein-Institut.Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs, thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery. In particular, intestinal carnitine/organic cation transporter 2 (OCTN2) and mono-carboxylate transporter protein 1 (MCT1) possess high transport capacities and complementary distributions. Therefore, we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review. First, basic information of the two transporters is reviewed, including their topological structures, characteristics and functions, expression and key features of their substrates. Furthermore, progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed, including improvements in the oral absorption of anti-inflammatory drugs, antiepileptic drugs and anticancer drugs. Finally, the potential of a dual transporter-targeting strategy is discussed. © 2020 Shenyang Pharmaceutical University. Published by Elsevier B.V.Introduction  Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is one of the six diagnostic categories of the Bethesda System for Reporting Thyroid Cytopathology. The prevalence of malignancy among Bethesda category III cytology is variable, ranging from 5% to 37% in the literature. Objective  To determine the rate of malignancy in thyroid nodules reported as Bethesda category III. Methods  A total of 495 patients underwent surgical intervention for thyroid nodules from January 2015 to December 2017. The present study included 81 cases reported as Bethesda category III, and their medical records were reviewed. Results  Out of 495 fine-needle aspiration cytology samples, 81 (16.4%) samples were labeled as AUS/FLUS. Among these 81 patients, the mean age was 43.0 years (± 13.9), with only 11 (14%) patients older than 55 years of age. Most of our patients were female ( n  = 69; 85.2%), and the rest were male. The rate of malignancy based on the final histology was of 33.3% ( n  = 27). The majority were 17 cases (21%) of papillary carcinoma, followed by follicular carcinoma ( n  = 6) (7.4%). Conclusion  The risk of malignancy can be higher than it is commonly believed, and guidelines should be based on the data from the institutions themselves for a better assessment of the outcomes.Introduction  Although computed tomography scanning is the most common method for the diagnosis of sinusitis today, X-ray imaging is still used in outpatient clinics. Because X-ray imaging is beneficial for patients with severe sinusitis but not for those with mild sinusitis, an alternative method to visualize sinusitis without X-ray imaging is desirable. Objective  To study the possibility of using thermography to visualize sinusitis. Methods  In the present study, heat distribution on the faces of individuals with and without sinusitis was studied using thermography. Overall, 10 control subjects and 20 patients with sinusitis were included. Original thermography data were cropped, resized, and converted to relative thermography data based on the average temperature for visualization and statistical analysis. Results  The shape of the maxillary and/or frontal sinuses was determined based on regions indicating increased temperature in patients with sinusitis. The region with increasing temperature was statistically visualized, and the significant side ( t test, p   less then  0.05) coincided with the maxillary shadow on X-ray imaging. Conclusion  Thermography demonstrates visually the correlation between the surface temperature of the face and inflammation patterns in the paranasal sinus. Therefore, our comparative study using thermography to visually differentiate individuals with and without sinusitis was effective, indicating that thermography is a possible alternative to X-ray imaging to detect sinusitis.Introduction  Tumors of the parotid gland are heterogeneous. The purpose of the drain placement is to evacuate fluid that has a potential to accumulate in the dead space and cause infection after parotidectomy. Objectives  To evaluate the factors associated with drain output among patients submitted to parotidectomy. Methods  A retrospective cohort study was conducted in the Department of Otolaryngology/Head and Neck Surgery at the Aga Khan University Hospital, Karachi, from January 1994 to December 2014. Patients who underwent parotidectomy were included in the study. Linear regression analysis was used to determine the factors associated with drain output. Results  A total of 193 patients were included in the study. The mean age of the patients was 46.3 years, and 57% of them were male. Length of surgery (β coefficient = 24.2; 95% confidence interval [95%CI] 4.94-85.26), type of neck dissection (modified radical neck dissection β = 93.9; 95% CI 30.47-157.38; selective neck dissection β = 79.9; 95%CI 29.04-126.85), and type of parotidectomy (total β = 45.1; 95%CI 4.94-85.26) were factors that significantly influenced drain output in patients submitted to parotidectomy with or without neck dissection. Conclusion  Neck dissection, total parotidectomy and length of surgery were predictors of postoperative neck drainage in our cohort. These factors can help predict postoperative neck drain output and help in patient counselling.Introduction  Knowing a concentration at which cytostatic drugs are toxic for the nasal fibroblasts will enable the use cytostatic drugs in the clinical practice to prevent excessive cicatrization. Objective  To determine the cytostatic concentrations of mitomycin С, doxorubicin, and 5-fluorouracil affecting nasal mucosa fibroblasts. Methods  We obtained material during an endonasal dacryocystorhinostomy with the patient's informed consent. The cells were cultivated. Second- to fourth-passage cells were used in the experiments. The cells were stained for vimentin and cluster of differentiation 90 (CD90). An MTS test 3 (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium); cell viability test was performed. Results  The cytostatic drugs have a toxic effect on cultivated fibroblasts of the nasal mucosa. This effect is dose-dependent. In terms of reducing the level of tissue fibrotisation in the nasal cavity, the most justified approach is to carry out an experimental study of the effect of mitomycin C, doxorubicin, and 5-fluorouracil at the concentrations of 0.25 mg/ml, 0.25 mg/ml, and 12.5 mg/ml respectively. Conclusion  The authors argue that it is inappropriate to use these cytostatic drugs to conduct studies with the goal of analyzing their antifibrotic effect on the nasal mucosa at concentrations that are either lower or higher than the aforementioned ones.Introduction  Despite much advancement in medicine, endocrine and metabolic diseases remain an important cause of morbidity and even mortality in children. Objective  The present study was planned to investigate the evaluation of hearing that also includes high frequencies, and the presence and degree of vertigo and tinnitus symptoms in pediatric patients diagnosed with endocrine diseases such as type 1 diabetes mellitus (DM), growth hormone deficiency (GHD), obesity, idiopathic short stature, and precocious puberty Methods  The present study included a patient group of 207 children patients diagnosed with endocrine disease (95 males, 112 females; mean age 9.71 years old [range 6-16 years old]) and a control group including 55 healthy children who do not have any kind of chronic disease (26 males, 29 females; mean age 9.33 years old [range 6-16 years old]). The subjects underwent a hearing test with frequencies between 250 and 20,000 Hz. The vestibular and tinnitus symptoms were evaluated with the Pediatric Vestibular Symptom Questionnaire. Results  Out of 207 patients in the patient group, 5 (2.4%) had hearing loss in pure tones, 10 (4.8%) had it in high frequencies, 40 (19.3%) had tinnitus symptoms, and 18 (8.7%) had vertigo symptoms. A total of 4 out of 207 patients in the study group (1.9%), 2 out of 59 with type 1 DM patients (3.4%), 1 out of 46 with GHD (2.2%), and 1 out of 43 obesity patients (2.3%) had hearing loss, vertigo, and tinnitus symptoms. Conclusions  Our results suggest that some childhood endocrine diseases can cause some changes in the inner ear, although the exact cause is unknown. Perhaps, a detailed hearing and balance examination should be a routine in a child diagnosed with an endocrine disease. We think it is necessary to work on more comprehensive patient groups and tests in the future.Introduction  Tinnitus, which is considered the third worst symptom for humans, is a common complaint among people living with hearing loss and may negatively affect the quality of life of those who have it. Objective  To analyze the perception of the handicap in patients with tinnitus and hearing loss as well as the possible associations between the variables hearing loss, loudness, onset, frequency and annoyance by tinnitus, and the correlation between the visual analogue scale (VAS) and the Tinnitus Handicap Inventory (THI). Methods  A total of 30 patients with complaints of tinnitus and the presence of sensorineural hearing impairment were selected for this cross-sectional, observational, and descriptive study. The loudness of the tinnitus was measured by a VAS and classified as mild, moderate, or severe. The THI was classified as slight, mild, moderate, severe, and catastrophic. Data were submitted to statistical analysis using the Fisher exact test and Spearman correlation coefficient. Results  Eleven male (36.7%) and 19 female (63.3%) subjects with a mean age of 56.5 years old were evaluated. There was no significant association between loudness, annoyance, time and frequency of tinnitus, nor between hearing loss and tinnitus. There was a significant association between the variables hearing loss and loudness, and a weak correlation between VAS and THI. Conclusion  Tinnitus has a practical impact in the lives of patients with hearing loss in terms of catastrophic, functional, and emotional aspects, regardless of loudness, frequency, or time of onset. Hearing loss was a factor that had an impact on the loudness of tinnitus. There was no statistically significant correlation between VAS and THI.Introduction  The mismatch negativity (MMN) is a long-latency auditory evoked potential related to a passive elicited auditory event. Objective  To verify the occurrence of MMN with different stimuli, to describe reference values in normal-hearing adults with verbal and nonverbal stimuli and to compare them with each other, besides analyzing the latency, area, and amplitude regarding gender and between the ears. Method  Normal-hearing individuals, aged between 18 and 59 years old, participated in the study. As inclusion criterion in the study, all of them underwent tone threshold audiometry, logoaudiometry, tympanometry, and the Dichotic Sentence Identification (DSI) test, and later the MMN with 4 different stimuli, being 2 verbal (da/ta and ba/di) and 2 nonverbal stimuli (750/1,000Hz and 750/4,000Hz), which are considered stimuli with low and high contrast. Results  A total of 90 individuals composed the sample, being 39 males and 51 females, with an average age of 26.9 years old. In the analysis of the latency, amplitude, and area of the four stimuli between the ears, they were not considered statistically different. There was a significant difference between all of the stimuli in terms of latency, amplitude and area, with the highest latency found in da/ta, and the greatest amplitude and area in ba/di. Regarding gender, there was only difference in the latency of the da/ta stimulus. Conclusion  The da/ta and 750/1,000Hz stimuli elicited the most MMN in the population of normal-hearing adults. Among the genders, there was difference only regarding the latency of the verbal stimulus da/ta, and there was no difference between the ears.Introduction   Streptococcus pneumoniae is a major pathogen of otogenic meningitis (OgM), the most commonly reported intra-cranial complication of otitis media (OM). Objectives  To study the changes in adult OgM patients in the pneumococcal conjugated vaccines (PCVs) era. Methods  Retrospective cohort of adults presenting with concurrent OM and meningitis in a secondary medical care center between 2005 and 2015. Data collected included demographics, OM-related symptoms, cerebrospinal fluid (CSF) and ear culture results, pre- and during hospitalization antibiotic treatment, imaging findings, and complications. We compared the pre-PCV years (2005-2009) with the post-PCV years (2010-2015). Outcomes were 1) incidence of all-cause adult OgM from the total meningitis cases; 2) impact of PCVs on the clinical presentation of OgM and bacteriology. Results  Otogenic meningitis was diagnosed in 26 out of 45 (58%) cases of all-cause meningitis admissions. Of those, 10 (38%) were male, with a mean age of 62.4 years old. Ear-related signs and symptoms were documented in 70% of the patients, and OgM was diagnosed following imaging studies in 6 out of 26 (23%) patients. All of the patients received intravenous antibiotic therapy, and 7 (27%) patients required surgical interventions 6 required myringotomy and 1 required mastoidectomy. There were 12 (46%) patients in the pre-PCV years and 14 (56%) in the post-PCV years. The positive pneumococcal CSF and ear culture rates remained high and unchanged (∼ 75%). There were no significant changes in the clinical presentation or mortality rates. Conclusion  Micro-otoscopy should be included in the routine work-up of any suspected adult meningitis, because OgM is underdiagnosed. Unlike their impact on pediatric otitis media, PCVs did not change the epidemiology and bacteriology of OgM.Introduction  Laryngeal cancer is the second most common head and neck cancer, but no study to date reports exclusively on the well-being of the caregivers of patients with laryngeal cancer treated by radiotherapy. Objective  The present prospective pilot study aims to describe the impact of the work on the well-being of the caregivers of patients with laryngeal cancer. Methods  The caregivers of patients undergoing radiotherapy with curative intent for laryngeal cancer were included in the present study, and they were asked to fill out a specific questionnaire, while the patients filled out the Hospital Anxiety and Depression Scale (HADS) following diagnosis but prior to treatment. Results  A total of 50 caregivers were included, 20% of which were male, and 80%, female. In total, 62% ( n  = 31) of the caregivers were spouses, while the remaining were daughters/sons ( n  = 11; 22%), siblings ( n  = 6; 12%), or they were classified as "other" ( n  = 2; 4%). The female caregivers scored lower (worse) on the depression/worry domain, and this was statistically significant ( p  = 0.047); they also reported a statistically significant higher negative impact on employment ( p  = 0.011) compared with the male caregivers. In general, the caregivers of patients with late-stage tumors tended to report lower (worse) scores on all domains (except hospital contact) compared with the caregivers of patients with early-stage tumors. No other differences were observed regarding the patients' age, gender, tumor site or their HADS score. Conclusion  The diagnosis and treatment of laryngeal cancer impacts the caregiver's psychological well-being, particularly that of female caregivers. This should be taken into consideration when the patients begin the hospital treatment pathway. However, larger studies are needed to target resources more appropriately.Introduction  The most common site of salivary gland tumors is the parotid gland. Computed tomography (CT), magnetic resonance imaging (MRI), and sonography are imaging modalities to differentiate benign from malignant parotid tumors. Objective  The aim of this study is the evaluation of the diagnostic value of perfusion CT for differentiating histological categorization of benign and malignant parotid tumors. Methods  A total of 29 patients with parotid neoplasms were enrolled in this study. Mean age and all CT perfusion variables (gradient and permeability, blood flow [BF], blood volume [BV], mean transit time [MTT], permeability surface [PS], maximum intensity projection [MIP], time-density curve [TDC], and time to peak [TTP]) were compared among three groups (malignant tumors [MTs], Warthin's tumor [WT] and pleomorphic adenomas [PA]). Results  The mean age of the patients was 55.9 ± 14.1 (26-77), and 15 of them were male (51.7%). Eleven lesions were PAs [37.9%], 8 lesions were WTs (27.6%0 and 10 lesions (34.5%) were MTs (6 acinic cell carcinomas [ACCs], 3 adenocystic carcinomas [AdCCs], and 1 mucoepidermoid carcinoma [MEC]). The mean age of the patients with WTs was 62 ± 7.5 years; 52 ± 14.2 for patients with Pas, and 55.2 ± 17.2 for those with MTs ( p  = 0.32). The mean MIP was 122.7 ± 12.2 in WT, while it was 80.5 ± 19.5 in PA, and 76.2 ± 27.1 in MTs ( p   less then  0.001); The mean MIP for WT was higher than for PAs and MTs; the values of MTs and PAs were not statistically different. The average of BF, BV, and curve peak were higher in WTs in comparison with the other two groups, and curve time 2 and TTP were higher in PAs in comparison with MTs. Conclusion  Based on this study, perfusion CT of the parotid gland and its parameters can distinguish between benign and malignant parotid masses.Introduction  Mismatch negativity (MMN) is a long latency auditory evoked potential, represented by a negative wave, generated after the potential N1 and visualized in a resulting wave. Objective  To identify the time of occurrence of MMN after N1, elicited with verbal and nonverbal stimuli. Methods  Ninety individuals aged between 18 and 56 years old participated in the study, 39 of whom were male and 51 female, with normal auditory thresholds, at least 8 years of schooling, and who did not present auditory processing complaints. All of them underwent audiologic anamnesis, visual inspection of external auditory meatus, pure tone audiometry, speech audiometry, acoustic immittance measures and the dichotic sentence identification test as a screening for alterations in auditory processing, a requirement to participate in the sample. The MMN was applied with two different stimuli, with these being da/ta (verbal) and 750 Hz and 1,000 Hz (nonverbal). Results  There was a statistically significant difference between the latency values of the N1 potential and the MMN with the two stimuli, as well as between the MMN with verbal and nonverbal stimuli, and the latency of the MMN elicited with da/ta being greater than that elicited with 750 Hz and 1,000 Hz, which facilitated its visualization. Conclusion  The time of occurrence of MMN after the N1 elicited with verbal stimuli was 100.4 ms and with nonverbal stimuli 85.5 ms. Thus, the marking of the MMN with verbal stimuli proved to be more distant from N1 compared with the nonverbal stimuli.Introduction  There are some discrepancies in the literature about the influence of vitiligo on auditory functions. According to some authors, vitiligo influences hearing, whereas others question such influence. Therefore, we conducted a study to evaluate audiological functions in vitiligo patients. Objectives  To determine the effect of vitiligo on auditory functions. Methods  A hospital-based observational study was done from January 2017 to July 2017. Clinically diagnosed cases of vitiligo were enrolled for the study. A complete otological examination was conducted in all patients. Results  Fifty-two patients (male female 2824) were included in the study. Ten patients (19.2%) had sensorineural hearing loss (SNHL). Seven patients (13.5%) had bilateral and 3 (5.7%) had unilateral SNHL. High frequency loss was seen in 17 out of 20 ears (10 affected patients), 6 ears had both low and high-frequency hearing loss. Of 12 ears with speech frequency involvement, mild hearing loss was seen in 5 and moderate to severe in 1 ear. Most cases of SNHL were detected in the age group 41 to 60 years old (63.6%), which was statistically significant ( p -value 0.00). Conclusion  The results of this study suggest that vitiligo patients require routine monitoring for auditory functions for early identification of SNHL. Older subjects with vitiligo might be at a higher risk for audiological abnormalities. These patients should also be informed regarding the associated risk with noise and ototoxic drug exposure.Introduction  Auditory neuropathy spectrum disorder (ANSD) features the presence of otoacoustic emissions, poor speech identification score and absent auditory brainstem response. Objective  The present study was designed to evaluate the functioning of all six semicircular canals in individuals with ANSD and to compare it with those of normal-hearing individuals. Methods  A total of 50 individuals participated in the present study, in which Group I comprised 25 normal-hearing individuals, and Group II comprised 25 individuals with ANSD. All of the participants underwent case history, pure tone audiometry, immittance, otoacoustic emissions, auditory evoked response and video head impulse test (vHIT). Results  The independent sample t-test revealed significantly lower vestibulo-ocular reflex gain values in individuals with ANSD. A presence of 100% corrective refixation saccades was observed in the same group. The Pearson correlation test revealed no significant correlation between vestibulo-ocular reflex (VOR) gain with duration of hearing loss and pure tone thresholds for any of the three orthogonal planes. The chi-squared test revealed no association between the VOR gain values and the presence or absence of saccades in any of the semicircular canals ( p  > 0.05). Conclusion  Huge percentages of individuals with ANSD have been found to have associated vestibular dysfunction as well. Therefore, the vHIT can be used as one of the important tests of the vestibular test battery to evaluate all six semicircular canals in individuals with ANSD.Introduction  Cochlear implantation has been considered a viable option to restore hearing perception in adults with severe to profound postlingual hearing loss. Objectives  To analyze behavioral hearing responses and P300 latency and amplitude measurements in adults with bilateral sensorineural hearing loss at two phases, first when they were using hearing aids (HAs) and, then, after 12 months of cochlear implant (CI) use. The association between behavioral and electrophysiological evaluations was explored, as it is believed that the study of auditory processing with different hearing devices can contribute to future CI adjustments and fittings, especially for patients who cannot give subjective feedback (such as small children and individuals with multiple disabilities). Methods  Prospective comparative study (Ethical approval 11489/2014). Twelve adults were assessed, 7 males and 5 females, in the 22 to 76 years old age range, who had undergone CI surgery after HA experience. Results  The analyses showed an improvement of hearing thresholds when patients started using CIs. Comparing data from P300 latency measurements, there was an increase of the P300 wave post-CI at Cz and Fz. Regarding the amplitude, P300 mean values decreased at Cz, but increased at Fz. There was no significant correlation between behavioral and electrophysiological assessment and the variables age, gender, auditory deprivation, and electronic device used. Conclusion  There was a significant improvement of hearing thresholds after twelve months of CI experience. The mean latency values of P300 after 12 months of CI use increased at Cz and Fz, while mean amplitude values decreased at Cz and increased at Fz.Introduction  The efficacy of sentinel node biopsy in early stage oral cancer is well established. Its evolving role can be reinforced by further studies. Objective  Analyzing the predictability of the levels of echelon nodes for various oral cavity tumor subsites on sentinel node biopsy. Methods  A prospective study of 20 patients with stage I/II oral squamous cell carcinoma who underwent sentinel node biopsy-guided neck dissection between January 2017 and 2018 at our institute. The procedure included radiotracer injection, imaging (lymphoscintigraphy, single photon emission computed tomography-computed tomography), and gamma probe application. Sentinel node detection on imaging and gamma probe were compared. Results  Out of 20 patients, 13 (65%) had carcinoma of the tongue, 6 (30%) had buccal mucosa carcinoma, and 1 (5%) had retromolar trigone carcinoma. The mean age of the patients was 52.3 years. A total of 13 (65%) patients were male, and 7 (35%) were female. The sentinel node identification rates with imaging and gamma probe were of 70% and 100% respectively. In tongue and retromolar trigone primaries, the most common first-echelon nodes in both modalities were levels IIA and IB respectively. For buccal mucosa primaries, first-echelon nodes were detected only with the gamma probe, which was level IB. On imaging, second-echelon nodes were detected only for tongue primaries, and had equivalent incidence of levels II, III, and IV. On the gamma probe, level IIA, followed by III, and IV for the tongue, and level IIA were the most common second-echelon nodes for the buccal mucosa. Third-echelon nodes were detected only with the gamma probe for tongue carcinoma at level IV. Conclusion  The combined use of imaging and gamma probe provides the best results, with high identification rate and predictability of echelon levels.[This corrects the article DOI 10.3892/ol.2012.934.]. Copyright © Fan et al.[This corrects the article DOI 10.3892/ol.2019.10834.]. Copyright © Zhao et al.Breast cancer is the second leading primary cause for cancer-related mortality among women and metastasis to the brain is a disastrous event for patients with increasing incidence. A previous study confirmed the critical function of RRM2 in breast cancer cell growth. Unfortunately, the role and fundamental molecular mechanism of RRM2 in breast cancer metastasis remains elusive. In the current study, higher RRM2 expression was validated in breast cancer tissues, especially in the brain metastasis group. Simultaneously, the expression of RRM2 was increased in breast cancer cells relative to the normal breast epithelial cell line MCF-10A, concomitant with higher levels of RRM2 in the highly metastatic MDA-MB-231 cell line relative to the weakly metastatic MCF-7 cell line. Knockdown of RRM2 by small interfering-RRM2 transfection notably suppressed the malignant metastatic behavior of breast cancer cells, including invasion and migration. Simultaneously, RRM2 downregulation also restrained the transcription and release of vascular endothelial growth factor (VEGF) in breast cancer cells.