Renal Cancer Stem Cells: Characterization and Targeted Therapies

Renal cell carcinoma (RCC) is a major neoplasm with high incidence in western countries. Tumors are heterogeneous and are composed of differentiated cancer cells, stromal cells, and cancer stem cells (CSCs). CSCs possess two main properties: self-renewal and proliferation. Additionally, they can generate new tumors once transplanted into immunodeficient mice. Several approaches have been described to identify them, through the expression of cell markers, functional assays, or a combination of both. As CSCs are involved in the resistance mechanisms to radio- and chemotherapies, several new strategies have been proposed to directly target CSCs in RCC. One approach drives CSCs to differentiate into cancer cells sensitive to conventional treatments, while the other proposes to eradicate them selectively. A series of innovative therapies aiming at eliminating CSCs have been designed to treat other types of cancer and have not been experimented with on RCC yet, but they reveal themselves to be promising. In conclusion, CSCs are an important player in carcinogenesis and represent a valid target for therapy in RCC patients.

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An Uncemented Spreading Stem for the Fixation in the Metaphyseal Femur: A Preliminary Report

Surgical treatment to restore full range of motion and full weight bearing after extensive femoral bone resection in patients with primary or metastatic femoral tumours is individually challenging. Especially when the remaining distal or proximal bone is very short, a rigid fixation of an implant is difficult to achieve due to the reverse funnel shape of the metaphysis. Herein, we present a novel implant design using a spreading mechanism in the distal part of the prosthesis for rigid, uncemented fixation in the remaining femoral bone after extensive tumour resection of the femur. We present the outcome of 5 female patients who underwent implantation of this spreading stem after extensive proximal or distal femoral bone resection. There was no radiological or clinical loosening or implant-related revision surgery in our follow-up (mean 21.46 months, range 3.5–46 months). This uncemented spreading stem may therefore represent an alternative option for fixation of a prosthetic device in the remaining metaphyseal femur.

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Diagnostic Performance of McMonnies Questionnaire as a Screening Survey for Dry Eye: A Multicenter Analysis

Purpose. To evaluate the diagnostic performance of the McMonnies questionnaire as a screening survey for dry eye in Chinese outpatients. Methods. The questionnaire was self-administered by 27,999 patients with dry eye symptoms. A thorough ophthalmic examination including tear break-up time (TBUT), fluorescein staining, and Schirmer I test was completed to make a clinical diagnosis of dry eye. Reliability, validity, and accuracy of the McMonnies questionnaire were assessed. Results. The McMonnies questionnaire showed poor internal consistency (Cronbach ), but excellent validity as the scores correlated with TBUT (Spearman test, , ) and Schirmer I test (Spearman’s test, , ), and significantly differed between the dry eye and control groups (2-sample t-test, , ). The area under the receiver-operating characteristics (ROC) curve (AUC) was 0.729, suggesting moderate accuracy in identifying dry eye and non-dry eye patients. However, the AUCs varied significantly in different gender and age subgroups (z test, ), as the discriminating ability declined with age. Analysis of the ROC curves also revealed that different cut-off points should be employed for each subgroup to achieve the same level of accuracy. Conclusions. The McMonnies questionnaire demonstrates moderate diagnostic value, and different cut-off points should be selected for various study populations.

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(Collage: Tablet Magazine) - Tablet Magazine

Tablet Magazine

(Collage: Tablet Magazine) Tablet Magazine Sometime after age 50, depending on personal genetics and life history, our gums withdraw, we lose our hair, our saliva glands falter, and our teeth grow brittle and break off or fall out. ... Irving Weissman M.D., Ludwig professor for Clinical ...

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Human papillomavirus promotes Epstein-Barr virus maintenance and lytic reactivation in immortalized oral keratinocytes.

Human papillomavirus promotes Epstein-Barr virus maintenance and lytic reactivation in immortalized oral keratinocytes.

Virology. 2016 May 11;495:52-62

Authors: Makielski KR, Lee D, Lorenz LD, Nawandar DM, Chiu YF, Kenney SC, Lambert PF

Abstract
Epstein-Barr virus and human papillomaviruses are human tumor viruses that infect and replicate in upper aerodigestive tract epithelia and cause head and neck cancers. The productive phases of both viruses are tied to stratified epithelia highlighting the possibility that these viruses may affect each other's life cycles. Our lab has established an in vitro model system to test the effects of EBV and HPV co-infection in stratified squamous oral epithelial cells. Our results indicate that HPV increases maintenance of the EBV genome in the co-infected cells and promotes lytic reactivation of EBV in upper layers of stratified epithelium. Expression of the HPV oncogenes E6 and E7 were found to be necessary and sufficient to account for HPV-mediated lytic reactivation of EBV. Our findings indicate that HPV increases the capacity of epithelial cells to support the EBV life cycle, which could in turn increase EBV-mediated pathogenesis in the oral cavity.

PMID: 27179345 [PubMed - as supplied by publisher]

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Renal clear cell carcinoma metastasis to salivary glands - a series of 9 cases: clinico-pathological study.

Renal clear cell carcinoma metastasis to salivary glands - a series of 9 cases: clinico-pathological study.

Pol J Pathol. 2016;67(1):39-45

Authors: Majewska H, Skálová A, Radecka K, Stodulski D, Hyrcza M, Stankiewicz C, Biernat W

Abstract
Metastatic tumors involving salivary glands arising from the non-head and neck area are very rare. Renal cell carcinoma (RCC) is known for its high propensity for metastasis to unusual localizations. RCC metastasis to the maxillofacial area is an uncommon event (16%), but metastasis to salivary glands is extremely rare. We report a series of 9 such cases retrieved from two institutions. The group included 6 females and 3 males. The age at diagnosis ranged from 60 to 97 years (mean 72.6 years). The tumors involved the parotid gland in 7 cases, and the submandibular and small salivary gland of the oral cavity in 1 case each. The size of tumors ranged from 0.4 to 5 cm. Total parotidectomy with selective neck dissection was performed in 4 cases, while superficial parotidectomy was performed in 1 case and simple resection in 3 cases. Histologically, all the tumors were clear cell renal cell carcinomas, and therefore the differential diagnosis mainly included clear cell variants of salivary gland carcinomas. The parotid gland was the initial manifestation of renal malignancy in 4 of the cases, while in the remaining 5 cases a history of RCC had been known. The salivary gland involvement developed from 11 months to 13 years after the time of diagnosis of the primary tumor. In 2 cases it was the first site of dissemination. Pathologists need to maintain a high index of suspicion for the possibility of metastasis when confronted with oncocytic or clear cell neoplasms developing in salivary glands. RCC, although rare, should be included in this differential diagnosis.

PMID: 27179273 [PubMed - as supplied by publisher]

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2-Deoxy-d-glucose Suppresses the In Vivo Antitumor Efficacy of Erlotinib in Head and Neck Squamous Cell Carcinoma Cells.

2-Deoxy-d-glucose Suppresses the In Vivo Antitumor Efficacy of Erlotinib in Head and Neck Squamous Cell Carcinoma Cells.

Oncol Res. 2016;24(1):55-64

Authors: Sobhakumari A, Orcutt KP, Love-Homan L, Kowalski CE, Parsons AD, Knudson CM, Simons AL

Abstract
Poor tumor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a significant challenge for effective treatment of head and neck squamous cell carcinoma (HNSCC). Therefore, strategies that may increase tumor response to EGFR TKIs are warranted in order to improve HNSCC patient treatment and overall survival. HNSCC tumors are highly glycolytic, and increased EGFR signaling has been found to promote glucose metabolism through various mechanisms. We have previously shown that inhibition of glycolysis with 2-deoxy-d-glucose (2DG) significantly enhanced the antitumor effects of cisplatin and radiation, which are commonly used to treat HNSCC. The goal of the current studies is to determine if 2DG will enhance the antitumor activity of the EGFR TKI erlotinib in HNSCC. Erlotinib transiently suppressed glucose consumption accompanied by alterations in pyruvate kinase M2 (PKM2) expression. 2DG enhanced the cytotoxic effect of erlotinib in vitro but reversed the antitumor effect of erlotinib in vivo. 2DG altered the N-glycosylation status of EGFR and induced the endoplasmic reticulum (ER) stress markers CHOP and BiP in vitro. Additionally, the effects of 2DG + erlotinib on cytotoxicity and ER stress in vitro were reversed by mannose but not glucose or antioxidant enzymes. Lastly, the protective effect of 2DG on erlotinib-induced cytotoxicity in vivo was reversed by chloroquine. Altogether, 2DG suppressed the antitumor efficacy of erlotinib in a HNSCC xenograft mouse model, which may be due to increased cytoprotective autophagy mediated by ER stress activation.

PMID: 27178822 [PubMed - in process]

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Cutaneous manifestations associated with malignancy of the head and neck.

Cutaneous manifestations associated with malignancy of the head and neck.

Semin Oncol. 2016 Jun;43(3):353-8

Authors: Lorimer P, Milas Z

Abstract
Most cutaneous malignancies of the head and neck (HN) are non-melanoma skin cancers, predominantly basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Less common entities include Merkel cell carcinoma (MCC), sebaceous carcinoma (SC), and angiosarcoma. Treatment is based on histology subtype, stage, and extent of involvement. Surgery is the primary means of treatment and includes wide local excision, Mohs micrographic surgery, sentinel lymph node biopsy, and cervical lymphadenectomy. Multidisciplinary management including radiation and targeted chemotherapy are critical adjuncts to surgery. Surgical planning must balance oncologic, functional, and cosmetic considerations. This review addresses cutaneous manifestations of primary malignancies of the HN and dermatologic complications of small molecule inhibitors used for targeted therapy. A working knowledge of both the cutaneous malignancies (CM) in the head and neck as well as the secondary dermatologic manifestations is relevant to multiple disciplines including dermatology, medical oncology, radiation oncology, and surgical oncology.

PMID: 27178688 [PubMed - in process]

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Non-epithelial tumors of the larynx: a single institution review.

Non-epithelial tumors of the larynx: a single institution review.

Am J Otolaryngol. 2016 May-Jun;37(3):279-85

Authors: Karatayli-Ozgursoy S, Bishop JA, Hillel AT, Akst LM, Best SR

Abstract
AIM: Non-epithelial tumors of the larynx are rare and encompass a wide range of pathology. We present the decade-long experience of a single institution to define clinical presentations and outcomes.
MATERIAL AND METHODS: This is a ten year retrospective chart review of a tertiary head and neck cancer center. Index patients were identified from a review of a pathology database, and patient demographics, presenting signs and symptoms, treatment modalities, and clinical outcomes were extracted from electronic medical records. Epithelial tumors (squamous cell carcinoma, spindle cell carcinoma, and salivary tumors), granulomas, sarcoidosis, papilloma, and amyloidosis were all excluded.
RESULTS: Twenty-four patients with ages ranging from 2months-old to 84years were identified. Malignant lesions (11) included chondrosarcoma (6), Kaposi's sarcoma (2), metastatic melanoma, synovial cell sarcoma, and T cell neoplasm. Six were operated upon endolaryngeally, but four required either upfront or salvage total laryngectomy. Two received adjuvant therapy. Benign lesions (13) included hemangioma (4), granular cell tumor (3), myofibroblastic tumor (2), schwannoma (2), chondroma, and ossifying fibromyxoid tumor. Nine underwent endolaryngeal operations, and four were managed medically or with observation. None have required aggressive open resection or total laryngectomy.
CONCLUSION: Treatment approach of non-epithelial tumors of the larynx depends on the site and extent of the tumor, histology, and sensitivity of adjuvant therapy. Benign tumors can be managed without need for aggressive resection thereby sparing laryngeal function.

PMID: 27178524 [PubMed - in process]

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Ex vivo ovine model for head and neck surgical simulation.

Ex vivo ovine model for head and neck surgical simulation.

Am J Otolaryngol. 2016 May-Jun;37(3):272-8

Authors: Ianacone DC, Gnadt BJ, Isaacson G

Abstract
OBJECTIVE: To evaluate a fresh, ovine/sheep head and neck tissue model to teach otolaryngology-head and neck surgical techniques.
STUDY DESIGN: Observational animal study.
SETTING: A university animal resource facility.
METHODS: Tissue was collected from pre-pubescent sheep (n=10; mean age: 4months; mean mass: 28kg) following humane euthanasia at the end of an in vivo protocol. No live animals were used in this study. The head and neck of the sheep were disarticulated and stored at 5°C for 1-5days. The tissues were tested in a variety of simulated procedures by a medical student and four fellowship-trained otolaryngology faculty. Practicality and similarity to human surgeries were assessed.
RESULTS: While ovine head and neck structures are proportionally different, the consistencies of skin, subcutaneous tissues and bone are remarkably similar to that seen in human dissection. Particularly useful were the eyelids and orbits, facial nerve and parotid gland, mandible, anterior neck and submandibular triangle. Surgeries performed included blepharoplasty, ptosis repair, orbital floor exploration, facial nerve dissection and repair, mandibular plating, tracheotomy, laryngofissure, tracheal resection and laryngectomy. The model was also useful for flexible and microsuspension laryngoscopy.
CONCLUSION: Fresh, ovine tissue provides a readily available, anatomically compatible, affordable, model for training in otolaryngology-head and neck surgery. The use of sheep tissues carries a low risk for disease transmission and is ethically defensible. Structural variations in the sheep temporal bone, paranasal sinuses and skull base anatomy limit the usefulness of the model for surgical training in these areas.

PMID: 27178523 [PubMed - in process]

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Multiple cranial neuropathies following etanercept administration.

Multiple cranial neuropathies following etanercept administration.

Am J Otolaryngol. 2016 May-Jun;37(3):259-62

Authors: Hunter JB, Rivas A

Abstract
There have been recent reports of sarcoid-like granulomatosis development following the administration of tumor necrosis factor (TNF) inhibitors. To date, only four cases of neurosarcoidosis have been reported in association with TNF inhibitors, two of which were attributed to etanercept. We present the first case of etanercept-induced neurosarcoidosis involving multiple cranial neuropathies, including the trigeminal, facial, and vestibulocochlear nerves, while also highlighting the differential diagnoses of multiple cranial neuropathies and the association of TNF inhibitors and neurosarcoidosis.

PMID: 27178520 [PubMed - in process]

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Initial radiographic tumor control is similar following single or multi-fractionated stereotactic radiosurgery for jugular paragangliomas.

Initial radiographic tumor control is similar following single or multi-fractionated stereotactic radiosurgery for jugular paragangliomas.

Am J Otolaryngol. 2016 May-Jun;37(3):255-8

Authors: Schuster D, Sweeney AD, Stavas MJ, Tawfik KY, Attia A, Cmelak AJ, Wanna GB

Abstract
OBJECTIVE: To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS).
STUDY DESIGN: Retrospective chart review.
SETTING: Tertiary academic referral center.
PATIENTS: Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18months of post-treatment follow up (FU).
INTERVENTION: Patients were treated with either single fraction or fractionated SRS.
MAIN OUTCOME MEASURE: Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression.
RESULTS: Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55years (range 35-79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15-18Gy), and 9 (64.3%) fractionated therapy (dose 3-7Gy×3-15 fractions). Median tumor volume was 3.78cm(3) (range 1.15-30.6). Median FU was 28.8months (range 18.6-56.1), with a mean of 31.7months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p=0.88) or progression (p=0.48) rates between groups (unpaired t-test).
CONCLUSIONS: At a median follow up of 28months, both single fraction and fractionated SRS appear to have comparable radiographic tumor control outcomes and toxicity profiles.

PMID: 27178519 [PubMed - in process]

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Evaluation of a laryngopharyngeal reflux management protocol.

Evaluation of a laryngopharyngeal reflux management protocol.

Am J Otolaryngol. 2016 May-Jun;37(3):245-50

Authors: Gupta N, Green RW, Megwalu UC

Abstract
PURPOSE: To evaluate the effectiveness of a protocol for management of patients with laryngopharyngeal reflux (LPR) in a multi-provider clinic.
MATERIALS AND METHODS: This is a retrospective cohort study of 188 patients treated for LPR. A standardized clinical protocol for diagnosis and management was instituted in 2012. Two cohorts were established: those managed according to the protocol, and those who were not. For patients managed with the LPR protocol, diagnosis was made using clinical judgment, guided by the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS). Patients were treated with proton pump inhibitors (PPI) with the goal of weaning therapy after symptom resolution. Response to therapy was rated using a global rating scale with three response levels: no response, partial response, and complete response. The primary outcome measure was complete response to therapy and the secondary outcome measures were any response (complete or partial) and successful wean off PPI therapy.
RESULTS: The patients treated with the LPR protocol had higher rates of complete response (p<0.001). There was no statistically significant difference in rates of any response (complete or partial) between the two groups (p=0.08). Patients treated using the LPR protocol were more likely to be successfully weaned off PPI therapy (p=0.006).
CONCLUSIONS: The use of an LPR protocol improved treatment effectiveness in our clinic, highlighting the role of clinical protocols in reducing variability in care, thereby improving patient outcomes.

PMID: 27178517 [PubMed - in process]

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Treatment of Meniere's disease with intratympanic dexamethazone plus high dosage of betahistine.

Treatment of Meniere's disease with intratympanic dexamethazone plus high dosage of betahistine.

Am J Otolaryngol. 2016 May-Jun;37(3):225-30

Authors: Albu S, Nagy A, Doros C, Marceanu L, Cozma S, Musat G, Trabalzini F

Abstract
PURPOSE: The aim of the present study was to assess if the combined therapy of intratympanic dexamethasone (ITD) and high dosage of betahistine (HDBH) is able to provide increased vertigo control compared to ITD alone in patients suffering from definite unilateral Meniere's disease (MD).
MATERIALS AND METHODS: Consecutive MD patients were enrolled and randomly divided in two groups, each comprising 33 cases. Group A received a combination of ITD and identical-appearing placebo pills while Group B received a combination of ITD and HDBH. ITD protocol consisted of three consecutive daily injections. HDBH comprised 144mg/day (48mg tid). The main outcome measures were: 1) vertigo class, pure tone average (PTA), speech discrimination score (SDS) and Functional Level Score (FLS) according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; 2) complete and substantial vertigo control according to the Kaplan-Meier survival method.
RESULTS: Sixty two patients completed the 24-month follow-up. A complete vertigo control was achieved in 14 patients (44%) from Group A and in 22 patients (73.3%) from Group B, statistically significant (p=0.01). Complete vertigo relief is also significant according to the Kaplan-Meier method: p=0.027, log rank test. Substantial vertigo control was obtained in 21 patients (65.6%) in Group A and 27 patients (90%) in Group B. The difference is statistically significant, p=0.02. The difference is significant according to the Kaplan-Meier method: p=0.035, log rank test. No significant differences between hearing levels and tinnitus scores were demonstrated between the groups.
CONCLUSIONS: Our preliminary results demonstrate that complete and substantial vertigo control is significantly higher in patients treated with a combination of HDBH and ITD.

PMID: 27178513 [PubMed - in process]

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Leiomyoma of the sternothyroid muscle.

Leiomyoma of the sternothyroid muscle.

Am J Otolaryngol. 2016 May-Jun;37(3):217-20

Authors: Rowe ME, Khorsandi AS, Guerrero DR, Brett EM, Sarlin J, Urken ML

Abstract
BACKGROUND: Leiomyomas are benign cutaneous tumors of smooth muscle origin. Only a small percentage of leiomyomas arise in the head and neck region. We present the first case of leiomyoma arising in the sternothyroid muscle of the neck.
CASE REPORT: We analyze the clinical presentation, pathology, and histology for a single case study. The histologic findings of the tumor located in the sternothyroid muscle support the diagnosis of leiomyoma.
DISCUSSION: This is the first case of leiomyoma arising in the sternothyroid muscle, and only the second reported case of leiomyoma in the strap muscles of the neck.
CONCLUSION: Leiomyoma should be included in the differential diagnosis of soft tissue tumors in the head and neck region. A histological analysis is essential in determining both tumor type and subtype, which will inform the proper course of treatment.

PMID: 27178511 [PubMed - in process]

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Resident fatigue in otolaryngology residents: a Web based survey.

Resident fatigue in otolaryngology residents: a Web based survey.

Am J Otolaryngol. 2016 May-Jun;37(3):210-6

Authors: Nida AM, Googe BJ, Lewis AF, May WL

Abstract
IMPORTANCE: Resident fatigue has become a point of emphasis in medical education and its effects on otolaryngology residents and their patients require further study.
OBJECTIVE: The purpose of our study was to evaluate the prevalence and nature of fatigue in otolaryngology residents, evaluate various quality of life measures, and investigate associations of increased fatigue with resident safety.
STUDY DESIGN: Anonymous survey.
SETTING: Internet based.
PARTICIPANTS: United States allopathic otolaryngology residents.
INTERVENTION: None.
MAIN OUTCOME(S) AND MEASURES: The survey topics included demographics, residency structure, sleep habits and perceived stress. Responses were correlated with a concurrent Epworth Sleep Scale questionnaire to evaluate effects of fatigue on resident training and quality of life.
RESULTS: 190 residents responded to the survey with 178 completing the Epworth Sleep Scale questionnaire. Results revealed a mean Epworth Sleep Scale score of 9.9±5.1 with a median of 10.0 indicating a significant number of otolaryngology residents are excessively sleepy. Statistically significant correlations between Epworth Sleep Scale and sex, region, hours of sleep, and work hours were found. Residents taking in-house call had significantly fewer hours of sleep compared to home call (p=0.01). Residents on "head and neck" (typically consisting of a large proportion of head and neck oncologic surgery) rotations tended to have higher Epworth Sleep Scale and had significantly fewer hours of sleep (p=.003) and greater work hours (p<.001). Additionally, residents who reported no needle stick type incidents or near motor vehicle accidents had significantly lower mean Epworth Sleep Scale scores. Only 37.6% of respondents approve of the most recent Accreditation Council for Graduate Medical Education work hour restrictions and 14% reported averaging greater than 80hours of work/week.
CONCLUSION AND RELEVANCE: A substantial number of otolaryngology residents are excessively sleepy. Our data suggest that the effects of fatigue play a role in resident well-being and resident safety.

PMID: 27178510 [PubMed - in process]

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Oropharyngeal stenosis: A rare complication following adenotonsillectomy.

Oropharyngeal stenosis: A rare complication following adenotonsillectomy.

Am J Otolaryngol. 2016 May-Jun;37(3):207-9

Authors: Eleff DJ, Tien DA, Anne S

PMID: 27178509 [PubMed - in process]

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Ultrasonic bone aspirator assisted endoscopic dacryocystorhinostomy.

Ultrasonic bone aspirator assisted endoscopic dacryocystorhinostomy.

Am J Otolaryngol. 2016 May-Jun;37(3):202-6

Authors: Steele TO, Wilson M, Strong EB

Abstract
OBJECTIVE: To evaluate the ultrasonic bone aspirator versus traditional powered drill technique for use in endoscopic dacryocystorhinostomy.
STUDY DESIGN: Retrospective chart review.
SETTING: Academic institution.
SUBJECTS AND METHODS: A retrospective chart review of all patients undergoing endoscopic dacryocystorhinostomy from June 2010 through May 2014 was performed. Data were collected from 63 eyes of 63 patients. Recorded data points include: age, gender, etiology of epiphora, procedure type, success rate, need for septoplasty, and length of follow-up. Surgical failure was defined as no improvement in epiphora, postoperative dacryocystitis, or inability to irrigate the lacrimal system post-operatively.
RESULTS: Sixty three consecutive patients underwent endonasal endoscopic dacryocystorhinostomy. Twenty nine patients underwent powered microdrill DCR (pDCR); 34 patients underwent ultrasonic bone aspirator DCR (uDCR). There was no statistically significant difference between groups in terms of age or gender. The success rates were: pDCR 86.2% and uDCR 94.1% (p=0.4). Concurrent septoplasty was performed in 48% of pDCR patients and 21% of uDCR patients (p=0.03) There was no significant difference in surgical success when septoplasty was controlled for (p=0.39).
CONCLUSION: Ultrasonic bone aspirator dacryocystorhinostomy has a similar success rate to traditional powered microdrill dacryocystorhinostomy.

PMID: 27178508 [PubMed - in process]

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Investigation of the Immediate Effects of Humming on Vocal Fold Vibration Irregularity Using Electroglottography and High-speed Laryngoscopy in Patients With Organic Voice Disorders.

Investigation of the Immediate Effects of Humming on Vocal Fold Vibration Irregularity Using Electroglottography and High-speed Laryngoscopy in Patients With Organic Voice Disorders.

J Voice. 2016 May 10;

Authors: Vlot C, Ogawa M, Hosokawa K, Iwahashi T, Kato C, Inohara H

Abstract
OBJECTIVES: The study aimed to investigate whether humming can immediately improve the regularity of vocal fold vibration on electroglottography (EGG) and laryngeal high-speed digital imaging (HSDI) in patients with organic dysphonia (OD).
METHODS: In a series of 49 dysphonic patients who were diagnosed to have benign mass lesions in the vocal folds and an equal number of non-dysphonic speakers, perturbation parameters were calculated on the acoustic (Ac) and EGG signals during natural and humming phonation. In addition, 11 OD patients and as many non-dysphonic speakers underwent simultaneous EGG and HSDI video recording under laryngofiberscopy while performing the two tasks. The perturbation parameters of the EGG signals as well as the glottal area waveforms (GAW), which were extracted from the HSDI movies, were calculated, and the correlations between both perturbation parameters were analyzed.
RESULTS: Humming achieved significant improvements in the EGG perturbation parameters in both groups. More than half of the OD patients showed decreased EGG perturbation parameters to the level of those during natural phonation in the control group. With respect to the GAW analysis, moderate correlations were observed between both period and amplitude perturbation parameters (period: r = 0.63, amplitude: r = 0.41). Humming decreased both GAW perturbation parameters significantly in the OD and control subjects combined.
CONCLUSIONS: These results demonstrate that in OD patients, humming has a potential to improve voice quality by stabilizing the vocal fold oscillation, and suggest that humming can remove the functional component in the vocal disturbance instead of the mechanical effect of the mass lesions.

PMID: 27178453 [PubMed - as supplied by publisher]

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A controlled study of use of patient-reported outcomes to improve assessment of late effects after treatment for head-and-neck cancer.

A controlled study of use of patient-reported outcomes to improve assessment of late effects after treatment for head-and-neck cancer.

Radiother Oncol. 2016 May 10;

Authors: Kjaer T, Dalton SO, Andersen E, Karlsen R, Nielsen AL, Hansen MK, Frederiksen K, Johansen C

Abstract
BACKGROUND AND PURPOSE: To test the effect of longitudinal feedback on late effects reported by survivors of head-and-neck cancer (HNC) to clinicians during regular follow-up.
MATERIAL AND METHODS: A total of 266 participants were sequentially assigned to either control or intervention group and filled in electronic versions of the EORTC QLQ C-30, H&N35, HADS and a study-specific list of symptoms at up to two consecutive follow-up visits. Participants' symptoms displayed according to severity were provided to the clinician for the intervention group but not for the control group. Linear mixed-effects models were used to examine the number of symptoms assessed by clinicians (primary outcome). Multivariate linear regression models examined participants' long-term symptom control and QoL (secondary outcome).
RESULTS: More symptoms were assessed by clinicians in the intervention group at all three visits (P<0.001, <0.001, and P=0.04). No effect was observed on most patient outcomes. When prompted by patient-reported outcomes at consultations, clinicians and patients were in better agreement about the occurrence of severe symptoms at all three visits.
CONCLUSION: Timely patient-reported outcomes to clinicians in routine follow-up of HNC survivors enhanced clinicians' rates of assessment of late symptoms. Giving reports of patient-reported outcome to clinicians had limited impact on participants' QoL or symptom burden.

PMID: 27178143 [PubMed - as supplied by publisher]

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The price of robustness; impact of worst-case optimization on organ-at-risk dose and complication probability in intensity-modulated proton therapy for oropharyngeal cancer patients.

The price of robustness; impact of worst-case optimization on organ-at-risk dose and complication probability in intensity-modulated proton therapy for oropharyngeal cancer patients.

Radiother Oncol. 2016 May 10;

Authors: van de Water S, van Dam I, Schaart DR, Al-Mamgani A, Heijmen BJ, Hoogeman MS

Abstract
PURPOSE: To quantify the impact of the degree of robustness against setup errors and range errors on organ-at-risk (OAR) dose and normal tissue complication probabilities (NTCPs) in intensity-modulated proton therapy for oropharyngeal cancer patients.
MATERIAL AND METHODS: For 20 oropharyngeal cases (10 unilateral and 10 bilateral), robust treatment plans were generated using 'minimax' worst-case optimization. We varied the robustness against setup errors ('setup robustness') from 1 to 7mm and the robustness against range errors ('range robustness') from 1% to 7% (+1mm). We evaluated OAR doses and NTCP-values for xerostomia, dysphagia and larynx edema.
RESULTS: Varying the degree of setup robustness was found to have a considerably larger impact than varying the range robustness. Increasing setup robustness from 1mm to 3, 5, and 7mm resulted in average NTCP-values to increase by 1.9, 4.4 and 7.5 percentage point, whereas they increased by only 0.4, 0.8 and 1.2 percentage point when increasing range robustness from 1% to 3%, 5% and 7%. The degree of setup robustness was observed to have a clinically significant impact in bilateral cases in particular.
CONCLUSIONS: For oropharyngeal cancer patients, minimizing setup errors should be given a higher priority than minimizing range errors.

PMID: 27178142 [PubMed - as supplied by publisher]

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Electron Beam Melting Manufacturing Technology for Individually Manufactured Jaw Prosthesis: A Case Report.

Electron Beam Melting Manufacturing Technology for Individually Manufactured Jaw Prosthesis: A Case Report.

J Oral Maxillofac Surg. 2016 May 10;

Authors: Suska F, Kjeller G, Tarnow P, Hryha E, Nyborg L, Snis A, Palmquist A

Abstract
In the field of maxillofacial reconstruction, additive manufacturing technologies, specifically electron beam melting (EBM), offer clinicians the potential for patient-customized design of jaw prostheses, which match both load-bearing and esthetic demands. The technique allows an innovative, functional design, combining integrated porous regions for bone ingrowth and secondary biological fixation with solid load-bearing regions ensuring the biomechanical performance. A patient-specific mandibular prosthesis manufactured using EBM was successfully used to reconstruct a patient's mandibular defect after en bloc resection. Over a 9-month follow-up period, the patient had no complications. A short operating time, good esthetic outcome, and high level of patient satisfaction as measured by quality-of-life questionnaires-the European Organisation for Research and Treatment of Cancer QLQ-C30 (30-item quality-of-life core questionnaire) and H&N35 (head and neck cancer module)-were reported for this case. Individually planned and designed EBM-produced prostheses may be suggested as a possible future alternative to fibular grafts or other reconstructive methods. However, the role of porosity, the role of geometry, and the optimal combination of solid and porous parts, as well as surface properties in relation to soft tissues, should be carefully evaluated in long-term clinical trials.

PMID: 27178123 [PubMed - as supplied by publisher]

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Surgical Anatomy of the Pyramidal Lobe (Lobe of Lalouette): A Tertiary Care Cancer Centre Experience.

Surgical Anatomy of the Pyramidal Lobe (Lobe of Lalouette): A Tertiary Care Cancer Centre Experience.

Int J Surg. 2016 May 10;

Authors: Irawati N, Vaish R, Chaukar D, Deshmukh A, D'Cruz A

Abstract
INTRODUCTION: To study the characteristics of pyramidal lobe (PL) in cancer patients with emphasis on its involvement in patients subjected to thyroidectomy at a tertiary care cancer centre.
METHODS: Retrospective review of prospectively maintained data of 103 patients (33 males and 70 females) who underwent thyroidectomy from January 1(st) 2011 - August 31(st) 2013. Surgery was performed by single surgeon, findings recorded by the lead author and all measurements taken with specimen in situ prior to mobilization of thyroid gland with intact anatomy. Thyroid specimens were examined for presence, location, length and histology of PL.
RESULTS: PL was identified in 38 (36.89%) of patients. PL was commoner on left 27 (71.05%) compared to 11 (28.95%) on right side. The frequency of PL was higher in males 51.51% compared to females 30%. The length varied from 4 to 35 mm. The mean length was 18.0±12.4 mm. In 10.53% cases PL contained deposits of papillary carcinoma of thyroid.
DISCUSSION: Meticulous clearance of disease is of utmost importance in thyroid cancer surgery in order to prevent recurrence and ensure reliable follow up with serum thyroglobulin. PL is a common site of residual thyroid tissue which if involved by cancer can be a cause of local recurrence.
CONCLUSIONS: PL is a well established entity which is present in over one third of patients. Efforts should be made to identify PL during surgery given its bearing on the management of thyroid carcinoma as one third of these will be site of multifocal papillary carcinoma.

PMID: 27177982 [PubMed - as supplied by publisher]

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Multifocal myositis ossoficans in masticatory muscles 30 years after gunshot wound: case report and literature review.

Multifocal myositis ossoficans in masticatory muscles 30 years after gunshot wound: case report and literature review.

Braz J Otorhinolaryngol. 2016 Apr 30;

Authors: Cavalheiro BG, Cernea CR, Brandão LG

PMID: 27177980 [PubMed - as supplied by publisher]

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Histopathological and Digital Morphometrical Evaluation of Uterine Leiomyoma in Brazilian Women

The current study aims to evaluate histopathological and digital morphometrical aspects associated with uterine leiomyomas in one hundred and fifty (150) patients diagnosed with leiomyoma. Uterine tissues were subjected to the histopathological and digital morphometric analyses of the interstitial collagen distribution. The analysis of medical records indicates that most of the women diagnosed with uterine leiomyomas (68.7%) are between 37 and 48 years old. As for the anatomic location of the tumors, approximately 61.4% of the patients had intramural and subserosal lesions. In 50% of the studied cases, the patients developed uterine leiomyomatosis (with more than eight tumors). As for the morphometric study, the average size of the interstitial collagen distribution held approximately 28.53% of the capture area, whereas it was of 7.43% in the normal tissue adjacent to the tumor. Another important aspect observed in the current study was the high rate of young women subjected to total hysterectomy, a fact that resulted in early and definitive sterility.

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Prevalence of Peripheral Arterial Disease among Adult Patients Attending Outpatient Clinic at a General Hospital in South Angola

Background. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis, whose prevalence is increasing worldwide, and is associated with all-cause mortality. However, no study has assessed this disease in Huambo. The aim of this study was to evaluate the prevalence of PAD in patients attending an outpatient clinic at a general hospital in Huambo, South Angola. Methods. A cross-sectional study, including 115 patients aged 40 years and older attending an outpatient service. The evaluation included a basic questionnaire for lifestyle and medical history and ankle-brachial index (ABI) measurement using hand-held Doppler. PAD was defined as an ABI ≤0.9 in either lower limb. Results. Of 115 patients, 62.60% were women with a median age of 52.5 (range of 40 to 91) years. The prevalence of PAD was 42.6% (95% confidence intervals [CI]: 95%: 33.91–52.17%). Among patients with PAD, 95.92% had mild disease and 4.08% moderate to severe disease. The main risk factor for PAD was age (≥60 years) (, ). The prevalence was slightly higher in men and hypertensive subjects, but without statistical significance with ORs of 1.5 (95% CI: 0.69–3.21) and 1.42 (95% CI: 0.64–3.17), respectively. Hypertension was also high in the group (66.95%). Conclusion. The prevalence of PAD was 42.6%, higher in those aged 60 years and older. More studies, with representative samples, are necessary to clarify PAD prevalence and associated risk factors.

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Neurochemical Plasticity of the Coeliac-Superior Mesenteric Ganglion Complex Neurons Projecting to the Prepyloric Area of the Porcine Stomach following Hyperacidity

This study was designed to determine neurochemical properties of the coeliac-superior mesenteric ganglion (CSMG) neurons supplying the prepyloric area of the porcine stomach in physiological state and following experimentally induced hyperacidity. To localize sympathetic neurons innervating the studied area of stomach, the neuronal retrograde tracer Fast Blue (FB) was applied to control animals and hydrochloric acid infusion (HCl) groups. After 23 days, animals of the HCl group were reintroduced into a state of general anesthesia and intragastrically given 5 mL/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were sacrificed. The CSMG complexes were then collected and processed for double-labeling immunofluorescence. In the control animals, FB-positive perikarya displayed immunoreactivity to tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), neuropeptide Y (NPY), and galanin (GAL). Experimentally induced gastric hyperacidity changed the neurochemical phenotype of the studied neurons. An upregulated expression of GAL and NPY and the de novo synthesis of neuronal nitric oxide synthase (nNOS) and leu5-enkephalin (LENK) as well as downregulated expression of TH and DβH in the stomach-projecting neurons were observed. These findings enrich existing knowledge about the participation of these active substances in adaptive mechanism(s) of the sympathetic neurons during pathological processes within the gastrointestinal tract.

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Smoking-related cancer in military veterans: retrospective cohort study of 57000 veterans and 173000 matched non ... - BMC Blogs Network

Smoking-related cancer in military veterans: retrospective cohort study of 57000 veterans and 173000 matched non ... BMC Blogs Network By 2004 clear evidence had been established of an association between smoking and many other cancers including larynx, oropharynx, oesophagus, stomach, bladder and, more recently recognised, colon and rectum [3]. Tobacco smoking has been shown ...

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Next-Generation Stereo Endoscopes are Opening Surgeons' Eyes - Photonics.com

Photonics.com

Next-Generation Stereo Endoscopes are Opening Surgeons' Eyes Photonics.com In the course of attempting to locate and remove a tumor via a 15-mm incision — rather than through a partial skull removal — these surgeons have mostly seen a world that was flat. Behind these 2D imaging limitations are single-lens endoscopes ...

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Immunomodulatory Effects of a Bioactive Compound Isolated from Dryopteris crassirhizoma on the Grass Carp Ctenopharyngodon idella

In the present study, we investigated effects of compound kaempferol 3-a-L-(4-O-acetyl)rhamnopyranoside-7-a-L-rhamnopyranoside (SA) isolated from Dryopteris crassirhizoma during immune-related gene expression in Ctenopharyngodon idella head kidney macrophages (CIHKM). The expression of immune-related genes (IL-1β, TNF-α, MyD88, and Mx1) were investigated using real-time PCR at 2 h, 8 h, 12 h, and 24 h after incubation with 1, 10, and 50 μg mL−1 of SA. Furthermore, fish were injected intraperitoneally with 100 μL of SA, and immune parameters such as lysozyme activity, complement C3, SOD, phagocytic activity, and IgM level were examined at 1, 2, and 3 weeks after injection. The differential expression of cytokines was observed after exposure to SA. IL-1β genes displayed significant expression at 2 and 8 h after exposure to 1–10 μg mL−1 of SA. SA also induced gene expression of cytokines such as MyD88, Mx1, and TNF-α. Furthermore, enhanced immune parameters in grass carp confirmed the immunomodulatory activity of SA. Interestingly, this compound has no toxic effect on CIHKM cells as tested by MTT assay. In addition, fish immunised with 10 μg mL−1 of SA exhibited maximum resistance against Aeromonas hydrophila infection. These results suggest that SA has the potential to stimulate immune responses in grass carp.

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Arabic Translation and Psychometric Evaluation of the Depression Literacy Questionnaire among Adolescents

Background. Depression is a serious mental health disease. Globally, it is estimated that almost 350 million people suffer from depression. It is important to assess depression literacy including knowledge and beliefs about mental disorders among adolescents. Objective. This study was conducted to validate the Arabic version of the Depression Literacy Questionnaire (D-Lit) among adolescents. Methods. A cross-sectional study was conducted among a sample size of 120 adolescents. Statistical analysis included face validation, confirmatory factor analysis, and reliability testing. A test-retest was carried out within a two-week interval. Results. The mean score for depression literacy among participants was 8.6 (SD = 4.48), the median was 8, and the interquartile range was 7. Preliminary construct validation analysis confirmed that factor analysis was appropriate for the Arabic version of D-Lit. The total internal consistency was measured by Cronbach’s alpha coefficient and split-half test and the results were 0.78 and 0.71, respectively. The test-retest reliability measured by Pearson’s correlation was 0.92 and spearman rho was equal to 0.91. Conclusions. Face validity, construct validity, and reliability analysis were found satisfactory for the Arabic version of D-Lit. The Arabic D-Lit was found valid and reliable to be used in the future studies.

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Immunological Evasion in Glioblastoma

Glioblastoma is the most aggressive tumor in Central Nervous System in adults. Among its features, modulation of immune system stands out. Although immune system is capable of detecting and eliminating tumor cells mainly by cytotoxic T and NK cells, tumor microenvironment suppresses an effective response through recruitment of modulator cells such as regulatory T cells, monocyte-derived suppressor cells, M2 macrophages, and microglia as well as secretion of immunomodulators including IL-6, IL-10, CSF-1, TGF-β, and CCL2. Other mechanisms that induce immunosuppression include enzymes as indolamine 2,3-dioxygenase. For this reason it is important to develop new therapies that avoid this immune evasion to promote an effective response against glioblastoma.

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Diverse Features of the Multiwavelength Afterglows of Gamma-Ray Bursts: Natural or Special?

The detection of optical rebrightenings and X-ray plateaus in the afterglows of gamma-ray bursts (GRBs) challenges the generic external shock model. Recently, we have developed a numerical method to calculate the dynamics of the system consisting of a forward shock and a reverse shock. Here, we briefly review the applications of this method in the afterglow theory. By relating these diverse features to the central engines of GRBs, we find that the steep optical rebrightenings would be caused by the fall-back accretion of black holes, while the shallow optical rebrightenings are the consequence of the injection of the electron-positron-pair wind from the central magnetar. These studies provide useful ways to probe the characteristics of GRB central engines.

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Voltage Balancing Method on Expert System for 51-Level MMC in High Voltage Direct Current Transmission

The Modular Multilevel Converters (MMC) have been a spotlight for the high voltage and high power transmission systems. In the VSC-HVDC (High Voltage Direct Current based on Voltage Source Converter) transmission system, the energy of DC link is stored in the distributed capacitors, and the difference of capacitors in parameters and charge rates causes capacitor voltage balance which affects the safety and stability of HVDC system. A method of MMC based on the expert system for reducing the frequency of the submodules (SMs) of the IGBT switching frequency is proposed. Firstly, MMC with 51 levels for HVDC is designed. Secondly, the nearest level control (NLC) for 51-level MMC is introduced. Thirdly, a modified capacitor voltage balancing method based on expert system for MMC-based HVDC transmission system is proposed. Finally, a simulation platform for 51-level Modular Multilevel Converter is constructed by using MATLAB/SIMULINK. The results indicate that the strategy proposed reduces the switching frequency on the premise of keeping submodule voltage basically identical, which greatly reduces the power losses for MMC-HVDC system.

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Approximation of the Monte Carlo Sampling Method for Reliability Analysis of Structures

Structural load types, on the one hand, and structural capacity to withstand these loads, on the other hand, are of a probabilistic nature as they cannot be calculated and presented in a fully deterministic way. As such, the past few decades have witnessed the development of numerous probabilistic approaches towards the analysis and design of structures. Among the conventional methods used to assess structural reliability, the Monte Carlo sampling method has proved to be very convenient and efficient. However, it does suffer from certain disadvantages, the biggest one being the requirement of a very large number of samples to handle small probabilities, leading to a high computational cost. In this paper, a simple algorithm was proposed to estimate low failure probabilities using a small number of samples in conjunction with the Monte Carlo method. This revised approach was then presented in a step-by-step flowchart, for the purpose of easy programming and implementation.

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Improvement of the Texture of Yogurt by Use of Exopolysaccharide Producing Lactic Acid Bacteria

19 Streptococcus thermophilus with high exopolysaccharide production were isolated from traditional Chinese fermented dairy products. The exopolysaccharide and viscosity of milk fermented by these 19 isolates were assayed. The strains of Streptococcus thermophilus zlw TM11 were selected because its fermented milk had the highest exopolysaccharide content (380 mg/L) and viscosity (7716 mpa/s). Then Streptococcus thermophilus zlw TM11 was combined with Lactobacillus delbrueckii subsp. bulgaricus 3 4.5 and the combination was named SH-1. The quality of the yogurt fermented by SH-1 and two commercial starter cultures (YO-MIX 465, YF-L711) were compared. It was shown that the exopolysaccharide content of yogurt fermented by SH-1 was similar to that of yogurt fermented by YF-L711 and significantly higher than YO-MIX 465 (). In addition, the yogurt fermented by SH-1 had the lowest syneresis (8.5%) and better texture and sensory than the samples fermented by YO-MIX 465 and YF-L711. It manifested that the selected higher exopolysaccharide production starter SH-1 could be used as yogurt starter and reduce the amount of adding stabilizer, which can compare with the imported commercial starter culture.

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Evaluation of Risk Factors for Peste des Petits Ruminants Virus in Sheep and Goats at the Wildlife-Livestock Interface in Punjab Province, Pakistan

Peste des petits ruminants virus (PPRV) is causing infectious disease with high morbidity and mortality rate in domestic and wild small ruminants of Pakistan with valuable economical losses. The present study was carried out to investigate risk factors of PPRV in domestic small ruminants which were present in the vicinity of wildlife parks. A total of 265 sera samples (27 wild ruminants and 238 domesticated small ruminants) from apparently healthy animals from two different wildlife parks were collected and analysed for PPRV antibodies. Also, 20 nasal swabs from domestic small ruminants showing respiratory signs were collected to check for presence of PPRV antigen. Competitive ELISA revealed highest proportions of anti-PPRV antibodies in domestic small ruminants around the Wildlife Park at Lahore (35%) as compared to Faisalabad (13%), with no existence of PPRV antibodies in tested serum of wild ruminants at these parks. Higher seropositivity was observed in females (25.6%) than in males (5.1%) and in goats (34.5%) compared to sheep (11.2%). The results of N-gene based RT-PCR highlight the absence of PPRV due to lack of current PPR outbreak in the region during study period. Even though grazing was not a significant risk factor, there is still a possibility of wildlife-livestock interactions for feed and water reservoirs, resulting in spillover of PPR to wildlife. Keeping in view the high seropositivity and risk of PPR, vaccination should be adopted to avoid circulation of PPRV among wild and domestic small ruminants (sheep and goats).

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Metastatic Granulosa Cell Tumor of the Testis: Clinical Presentation and Management

Granulosa cell tumors (GCTs) of the testis are rare sex cord-stromal tumors that are present in both juvenile and adult subtypes. While most adult GCTs are benign, those that present with distant metastases manifest a grave prognosis. Treatments for aggressive GCTs are not well established. Options that have been employed in previous cases include retroperitoneal lymph node dissection (RPLND), radiation, chemotherapy, or a combination thereof. We describe the case of a 57-year-old man who presented with a painless left testicular mass and painful gynecomastia. Serum tumor markers (alpha fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) and computed tomography of the chest and abdomen were negative. The patient underwent left radical orchiectomy. Immunohistochemical staining was consistent with a testicular GCT. He underwent a left-template laparoscopic RPLND which revealed 2/19 positive lymph nodes. Final pathological stage was IIA. He remains free of disease 32 months after surgery.

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Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines as In Vitro Cytotoxic and Antimicrobial Candidates

The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for their in vitro cytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs 33, 34, and 37 emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione 30 together with its alkylthio derivatives 33 and 34 stemmed as the most active antimicrobial members being equipotent to ampicillin against S. aureus, E. coli, and P. aeruginosa, together with a noticeable antifungal activity against C. albicans. Compounds 33 and 34 could be considered as a promising template for possible dual antimicrobial-anticancer candidates.

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Functional characterisation of human synaptic genes expressed in the Drosophila brain [METHODS [amp ] TECHNIQUES]

Lysimachos Zografos, Joanne Tang, Franziska Hesse, Erich E. Wanker, Ka Wan Li, August B. Smit, R. Wayne Davies, and J. Douglas Armstrong

Drosophila melanogaster is an established and versatile model organism. Here we describe and make available a collection of transgenic Drosophila strains expressing human synaptic genes. The collection can be used to study and characterise human synaptic genes and their interactions and as controls for mutant studies. It was generated in a way that allows the easy addition of new strains, as well as their combination. In order to highlight the potential value of the collection for the characterisation of human synaptic genes we also use two assays, investigating any gain-of-function motor and/or cognitive phenotypes in the strains in this collection. Using these assays we show that among the strains made there are both types of gain-of-function phenotypes investigated. As an example, we focus on the three strains expressing human tyrosine protein kinase Fyn, the small GTPase Rap1a and human Arc, respectively. Of the three, the first shows a cognitive gain-of-function phenotype while the second a motor gain-of-function phenotype. By contrast, Arc, which has no Drosophila ortholog, shows no gain-of-function phenotype.

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Garlic exerts allelopathic effects on pepper physiology in a hydroponic co-culture system [RESEARCH ARTICLE]

Haiyan Ding, Zhihui Cheng, Menglong Liu, Sikandar Hayat, and Han Feng

A hydroponic co-culture system was adopted to determine the allelopathic potential of garlic on the growth of pepper plants. Different numbers of garlic plants (0, 2, 4, 8 and 12) were hydroponically co-cultured with two pepper plants to investigate allelopathic effects on the growth attributes and antioxidative defense system of the test pepper plants. The responses of the pepper plants depended on the number of garlic plants included in the co-culture system, indicating an association of pepper growth with the garlic root exudate concentration. When grown at a pepper/garlic ratio of 1:1 or 1:2, the pepper plant height, chlorophyll content, and peroxidase (POD), catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were significantly increased after 30 days of co-culture; in contrast, reduction in methane dicarboxylic aldehyde (MDA) content was observed. However, when the pepper/garlic ratio was 1:4 or higher, these morphological indices and protective enzyme activities were significantly inhibited, whereas MDA levels in the pepper leaves were significantly increased due to severe membrane lipid peroxidation. The results indicate that although low concentrations of garlic root exudates appear to induce protective enzyme systems and promote pepper growth, high concentrations have deleterious effects. These findings suggest that further investigations should optimize the co-culture pepper/garlic ratio to reduce continuous cropping obstacles in pepper production.

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C. elegans flavin-containing monooxygenase-4 is essential for osmoregulation in hypotonic stress [RESEARCH ARTICLE]

Nisha Hirani, Marcel Westenberg, Paul T. Seed, Mark I. R. Petalcorin, and Colin T. Dolphin

Studies in Caenorhabditis elegans have revealed osmoregulatory systems engaged when worms experience hypertonic conditions, but less is known about measures employed when faced with hypotonic stress. Inactivation of fmo-4, which encodes flavin-containing monooxygenase-4, results in dramatic hypoosmotic hypersensitivity; worms are unable to prevent overwhelming water influx and swell rapidly, finally rupturing due to high internal hydrostatic pressure. fmo-4 is expressed prominently in hypodermis, duct and pore cells but is excluded from the excretory cell. Thus, FMO-4 plays a crucial osmoregulatory role by promoting clearance of excess water that enters during hypotonicity, perhaps by synthesizing an osmolyte that acts to establish an osmotic gradient from excretory cell to duct and pore cells. C. elegans FMO-4 contains a C-terminal extension conserved in all nematode FMO-4s. The coincidently numbered human FMO4 also contains an extended C-terminus with features similar to those of FMO-4. Although these shared sequence characteristics suggest potential orthology, human FMO4 was unable to rescue the fmo-4 osmoregulatory defect. Intriguingly, however, mammalian FMO4 is expressed predominantly in the kidney – an appropriate site if it too is, or once was, involved in osmoregulation.

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Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization [RESEARCH ARTICLE]

Gianluca Polese, Carla Bertapelle, and Anna Di Cosmo

The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens.

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Feliform carnivores have a distinguished constitutive innate immune response [RESEARCH ARTICLE]

Sonja K. Heinrich, Bettina Wachter, Ortwin H. K. Aschenborn, Susanne Thalwitzer, Jörg Melzheimer, Heribert Hofer, and Gabor A. Czirjak

Determining the immunological phenotype of endangered and threatened populations is important to identify those vulnerable to novel pathogens. Among mammals, members of the order Carnivora are particularly threatened by diseases. We therefore examined the constitutive innate immune system, the first line of protection against invading microbes, of six free-ranging carnivore species; the black-backed jackal (Canis mesomelas), the brown hyena (Hyena brunnea), the caracal (Caracal caracal), the cheetah (Acinonyx jubatus), the leopard (Panthera pardus) and the lion (Panthera leo) using a bacterial killing assay. The differences in immune responses amongst the six species were independent of their foraging behaviour, body mass or social organisation but reflected their phylogenetic relatedness. The bacterial killing capacity of black-backed jackals, a member of the suborder Caniformia, followed the pattern established for a wide variety of vertebrates. In contrast, the five representatives of the suborder Feliformia demonstrated a killing capacity at least an order of magnitude higher than any species reported previously, with a particularly high capacity in caracals and cheetahs. Our results suggest that the immunocompetence of threatened felids such as the cheetah has been underestimated and its assessment ought to consider both innate and adaptive components of the immune system.

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Is delight or devil in the detail of this hedgerow homage?

A Natural History of the Hedgerow explains everything you ever wanted to know about this classic feature of rural Britain – and perhaps a fair bit besides

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Mycobacterium tuberculosis and Dual M. tuberculosis/M. bovis Infection as the Cause of Tuberculosis in a Gorilla and a Lioness, Respectively, in Ibadan Zoo, Nigeria

Tuberculosis (TB) in zoo animals is an important public health problem in places where it occurs. This is even very important in countries where there is little public health awareness about the disease; thus confined animals in the zoo can be infected directly or indirectly by infected humans and vice versa. In Nigeria, the problem of TB is a major concern among both humans and cattle. Here, we present cases of Mycobacterium tuberculosis and M. tuberculosis/M. bovis infections in a female gorilla and a lioness, respectively, in a zoo in Ibadan, Nigeria. These cases were confirmed after bacteriological examinations and DNA from granulomatous lesions of the animals’ carcasses were subjected to the Hain and spoligotyping techniques. Our findings reveal the first documented report of TB infections in a gorilla and a lioness in zoo animals in Nigeria. The public health risks of tuberculosis in zoological settings are therefore reemphasized.

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A Study of Structural and Photoluminescence for Al-Doped CdO Thin Films

Al-doped CdO thin films were prepared by radio frequency magnetron sputtering at different deposition time and substrate temperature. X-ray diffraction showed that the changes in the intensities of the (200), (220), and (311) planes followed a similar trend with increase in deposition time. The surface of the thin film was examined by scanning electron microscopy. Grain sizes of Al-doped CdO thin films increased significantly with increasing deposition time. The film thicknesses were 0.09, 0.12, 0.20, and 0.225 μm for the deposition times of 1, 2, 3, and 4 h, respectively. The photoluminescence spectra of the Al-doped CdO thin films were measured at room temperature. The photoluminescence wavelength changed in the sequence, green, blue, green, and blue, with increasing deposition time, which indicates that blue light emitting films can be fabricated by adjusting the processing parameters.

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Stem Cell Therapy for Treatment of Ocular Disorders

Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

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Laparoscopic Treatment of Type III Mirizzi Syndrome by T-Tube Drainage

Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann’s pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests.

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Linfangioma: cos'è, sintomi e cause - Tanta Salute

Tanta Salute

Linfangioma: cos'è, sintomi e cause Tanta Salute Cos'è il linfangioma? Questa malattia provoca sintomi caratteristici da non trascurare. Quali sono le sue cause? Si tratta di un tumore benigno che interessa i vasi linfatici di alcune zone del corpo, come quella del collo, delle ascelle, dell'inguine ...

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