OtoLaryngology New Articles

Dentistry, Medicine team on new program for underrepresented students The School of Dentistry is teaming with the UW School of Medicine on an initiative to draw more undergraduate students from disadvantaged and underrepresented backgrounds into careers in the health sciences. The post Dentistry, Medicine team on new program for underrepresented students appeared first on UW School of Dentistry. Read More » Mapping the Superficial Inferior Epigastric System and its Connection to the Deep System: An MRA Analysis The superficial inferior epigastric vasculature plays a critical role in free abdominal tissue transfer. However, its anatomic variations are incompletely characterized. Preoperative imaging from all patients undergoing free flap breast reconstruction by a single surgeon from 2008-2013 was examined. Patients receiving abdominal magnetic resonance angiogram (MRA) were included for analysis. The main trunk and primary branches from each patient's superficial inferior epigastric system were drawn onto a coordinate system. Read More » Palliative and end-of-life care for children with diffuse intrinsic pontine glioma: results from a London cohort study and international survey Background More than 90% of patients with diffuse intrinsic pontine glioma (DIPG) will die within 2 years of diagnosis. Patients deteriorate rapidly during the disease course, which severely impairs their quality of life. To date, no specific research on this clinically important subject has been conducted. This study aimed to compile an inventory of symptoms experienced, interventions applied, and current service provision in end-of-life care for DIPG. MethodsWe performed a retrospective cohort study of children with DIPG, aged 0–18 years, who received treatment under the care of 2 London hospitals. Symptoms, interventions, and services applied during the 12 weeks before death were analyzed. In addition, we conducted a global questionnaire-study among health care professionals. ResultsIn more than 78% of DIPG patients, problems concerning mobility, swallowing, communication, consciousness, and breathing arose during end-stage disease. Supportive drugs were widely prescribed. The use of medical aids was only documented in <15% of patients. Palliative and end-of-life care was mostly based on the health care professional's experience; only 21% of the questionnaire respondents reported to have a disease-specific palliative care guideline available. ConclusionsThis research assessed the current state of palliative and end-of-life care for children with DIPG. Our results show the variability and complexity of symptoms at end-stage disease and the current lack of disease-specific guidelines for this vulnerable group of patients. This first descriptive paper is intended to act as a solid basis for developing an international clinical trial and subsequent guideline to support high-quality palliative and end-of-life care. Read More » 20Q: The Cross-Check Principle in Pediatric Audiometry - Forty Years Later The cross-check principle, however, is not specifically unique to that time frame, as it more or less applies to all aspects of diagnostic audiology. Over time, the key measures used for the audiologic cross-check will change, but the principle remains the same. Unless you have one particular test with excellent sensitivity and specificity, it is considered good practice to "cross-check" your findings with another test. This is especially critical for pediatric audiology, where the findings for one of the tests might be ambiguous. And this principle isn't just for diagnostic audiology. With hearing aid fittings we frequently cross-check our probe-microphone real-ear findings with behavioral tests in the clinic or outcome measures in the real world. Read More » New Wireless, Binaural Processing Reduces Problems Associated with Wind Noise in Hearing Aids With today's hearing aid technology, we have become accustomed to providing significant aided benefit for our patients in a variety of listening conditions. Speech recognition in both quiet and in background noise is improved. Most patients have improved sound quality and spatial localization. Research also has shown that listening effort and fatigue is reduced when hearing aids are used. A lot of good things are happening. But what about listening outdoors when the wind is blowing? Paradoxically, this isn't a complaint you typically hear from patients before they start wearing hearing aids, but do you hear about it after they start using amplification? Much too often. Read More » NecroX-5 suppresses IgE/Ag-stimulated anaphylaxis and mast cell activation by regulating the SHP-1-Syk signaling module Abstract Background IgE/Ag-stimulated mast cells release various pro-allergic inflammatory mediators, including histamine, eicosanoids, and pro-inflammatory cytokines. NecroX-5, a cell permeable necrosis inhibitor, showed cytoprotective effects in both in vitro and in vivo models. However, the anti-allergic effect of NecroX-5 has not yet been investigated. The aims of this study were to evaluate the anti-allergic activity of NecroX-5 in vivo and to investigate the underlying mechanism in vitro. Methods The anti-allergic activity of NecroX-5 was evaluated in vitro using bone marrow-derived mast cells (BMMCs) and IgE receptor-bearing RBL-2H3 or KU812 cells, and in vivo using a mouse model of passive anaphylaxis. The evels of histamine, eicosanoids (PGD2 and LTC4), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using enzyme immunoassay kits. The mechanism underlying the action of NecroX-5 was investigated using immunoblotting, immunoprecipitation, and gene knockdown techniques. Results NecroX-5 markedly inhibited mast cell degranulation and the synthesis of eicosanoids, TNF-α, and IL-6 by suppressing activation of Syk, LAT, phospholipase Cγ1, MAP kinases, the Akt/NF-κB pathway, and intracellular Ca2+mobilization via activation of phosphatase SHP-1. Oral administration of NecroX-5 effectively suppressed mast cell-dependent passive cutaneous and systemic anaphylactic reactions in a dose-dependent manner. Conclusions NecroX-5 might be a potential candidate for the development of a novel anti-allergic agent that suppresses IgE-dependent mast cells signaling. This article is protected by copyright. All rights reserved. Read More » Quality of Life of Family Caregivers of Children with Orofacial Clefts in Nigeria: A Mixed Methods Study Abstract Background Orofacial clefts (OFCs) are common birth defects that may impose a large burden on the health and psychosocioeconomic well-being of affected individuals and families. The current study aims to identify qualitative factors that affect the quality of life (QOL) of family caregivers of children with OFCs. Methods A mixed method study in which family caregivers of OFCs children were consecutively recruited from cleft clinics over a 3-month period. Quantitative data was analyzed using SPSS version 17 and FGD by framework analysis. Results A total of 107 caregivers participated in the entire study and 24 caregivers participated in the focus group discussions. About 50% of the children had cleft lip and palate (CLP), 28% with cleft lips only (CL) and 23.4% with cleft palate only (CP). Poor access to specific information and lack of empathy of professionals affected the quality of life and delivery of family centered care. Conclusions To improve the quality of life of family caregivers, individual focused counseling sessions should be organized for caregivers soon after birth. This will provide an opportunity to discuss laid out plans for supportive care. It will also as an avenue to address arising social issues by health professionals and counselors. This article is protected by copyright. All rights reserved. Read More » Efficacy and safety of miconazole for oral candidiasis: a systematic review and meta-analysis Abstract Objectives To assess the efficacy and safety of miconazole for treating oral candidiasis. Methods Twelve electronic databases were searched for randomized controlled trials evaluating treatments for oral candidiasis and complemented by hand searching. The clinical and mycological outcomes, as well as adverse effects, were set as the primary outcome criteria. Results Seventeen trials were included in this review. Most studies were considered to have a high or moderate level of bias. Miconazole was more effective than nystatin for thrush. For HIV patients, there was no significant difference in the efficacy between miconazole and other antifungals. For denture wearers, microwave therapy was significantly better than miconazole. No significant difference was found in the safety evaluation between miconazole and other treatments. The relapse rate of miconazole oral gel may be lower than that of other formulations. Conclusions This systematic review and meta-analysis indicated that miconazole may be an optional choice for thrush. Microwave therapy could be an effective adjunct treatment for denture stomatitis. Miconazole oral gel may be more effective than other formulations with regard to long-term results. However, future studies that are adequately powered, large-scale, and well-designed are needed to provide higher-quality evidence for the management of oral candidiasis. This article is protected by copyright. All rights reserved. Read More » Recreational motor vehicle use and facial trauma Objectives/Hypothesis The use of recreational motorized vehicles (RMVs), including all-terrain vehicles (ATVs), snowmobiles, and go-carts, has increased in recent decades. Because RMVs are lightly regulated, there are numerous safety concerns. This analysis examines a nationally representative resource to estimate the incidence of craniofacial trauma secondary to RMV accidents, evaluating injury and demographic patterns. Methods The Consumer Product Safety Commission's National Electronic Injury Surveillance System was examined for facial trauma resulting in emergency department (ED) visits stemming from the use of ATVs, motorbikes/scooters, snowmobiles, and utility vehicles. Characteristics including demographics, anatomic sites, mechanism, and location of injury were evaluated, as well as details regarding helmet and alcohol use. Results There were 1,464 entries extrapolating to an estimated 61,312 ED visits over a 5-year period for facial trauma from RMV use. From 2009 to 2013, there was a 28% reduction in ED visits. The majority of patients were male, and the median age was 17 years. Lacerations (45.1%), contusions/abrasions (26.7%), and fractures (24%) were the most frequent injuries. Among fractures, the most common types were nasal (29%), followed by mandible (20%) and orbital (8%) fractures. All-terrain vehicles (62%) were the most common vehicles. Alcohol consumption resulted in a higher rate of facial fractures (48.5% vs. 22.8%). Conclusion As there is a significant potential for injury, familiarity with injury patterns associated with RMVs is useful in the management of facial trauma. Recreational motorized vehicles facial trauma results in tens of thousands of ED visits annually. This data reinforces the importance of pursuing further efforts to raise public awareness and improve safety measures. Level of Evidence 4. Laryngoscope, 2015 Read More » Subtalar fusion with iliac bone free flap after a recalcitrant nonunion: Report of two cases Fractures of the calcaneus are associated with secondary osteoarthritis of the subtalar joint. In a persistent nonunion, vascularized bone flaps offer superior biologic and mechanical properties as well as accelerates joint fusion and decreases morbidity. In this report, we present results of the use of vascularized iliac bone free flap for treating subtalar failed fusions in two patients. Two patients sustained calcaneal fractures due to foot trauma, which were initially or subsequently treated with subtalar arthrodesis. Case one developed septic subtalar nonunion during treatment and case two failed three attempts at subtalar arthrodeses. The iliac crest bone flap harvested measured 4 × 4 cm (case one) and 3 × 3 cm (case two). The flap was pedicled by the deep circumflex iliac artery, which was anastomosed to the anterior tibial artery at the recipient site. No flap donor or recipient site complications occurred. Fusion was confirmed on CT scan and weight bearing was initiated at 5–6 months. At latest follow up (1–2 years), no complications occurred. Our results show that subtalar nonunion treatment with a vascularized iliac bone flap may be feasible and such a reconstruction could be clinically successful. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015. Read More » Morphological and morphometric evaluation of the ilium, fibula, and scapula bones for oral and maxillofacial reconstruction Read More » The reconstruction of large laryngeal defect with medial condyle femur corticoperiosteal free flap—a case report The larynx is a complicated organ with very important functions. Reconstructive operations of the larynx often result in some function reduction caused by scars and stenoses. The aim of this report is to present the results of the one-stage reconstructive operation after a large excision of the chondrosarcoma of the larynx. The patient was male, aged 48 with the history of the operation of the highly mature cartilaginous sarcoma of the thyroid on the right side with tumor recurrence. The one-stage reconstructive surgery using medial condyle femur corticoperiosteal free flap which reshaped the cartilage scaffold and restored an inner layer as the mucosa was made. The flap survived without local and systemic complications. Six months follow-up revealed no local recurrence and good breathing results. There was no restriction of movement of the lower limbs. The patient returned to work previously performed. Results were shown in endoscopic examinations and computer tomography. The medial condyle femur corticoperiosteal free flap may be an option for reconstruction of large laryngeal defect with restoring its shape and inner layers. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015. Read More » Historical Semantic Chaining and Efficient Communication: The Case of Container Names Abstract Semantic categories in the world's languages often reflect a historical process of chaining: A name for one referent is extended to a conceptually related referent, and from there on to other referents, producing a chain of exemplars that all bear the same name. The beginning and end points of such a chain might in principle be rather dissimilar. There is also evidence supporting a contrasting picture: Languages tend to support efficient, informative communication, often through semantic categories in which all exemplars are similar. Here, we explore this tension through computational analyses of existing cross-language naming and sorting data from the domain of household containers. We find (a) formal evidence for historical semantic chaining, and (b) evidence that systems of categories in this domain nonetheless support near-optimally efficient communication. Our results demonstrate that semantic chaining is compatible with efficient communication, and they suggest that chaining may be constrained by the functional need for efficient communication. Read More » Temporal characteristics of Punjabi word-medial singletons and geminates Many studies have investigated the temporal characteristics of the word-medial singletons and geminates in Indo-Aryan languages. However, little is known about the acoustic cues distinguishing between the word-medial singletons and geminates of Punjabi. The present study examines the temporal characteristics of Punjabi word-medial singleton and geminate stops in a C1V1C2V2 template. The results from five Punjabi speakers showed that, unlike previous studies of Indo-Aryan languages, the durations of C2 and V2 are the most important acoustic correlates of singleton and geminate stops in Punjabi. These findings therefore point towards the cross-linguistic differences in the acoustic correlates of singletons and geminates. Read More » A real-time articulatory visual feedback approach with target presentation for second language pronunciation learning Articulatory information can support learning or remediating pronunciation of a second language (L2). This paper describes an electromagnetic articulometer-based visual-feedback approach using an articulatory target presented in real-time to facilitate L2 pronunciation learning. This approach trains learners to adjust articulatory positions to match targets for a L2 vowel estimated from productions of vowels that overlap in both L1 and L2. Training of Japanese learners for the American English vowel /æ/ that included visual training improved its pronunciation regardless of whether audio training was also included. Articulatory visual feedback is shown to be an effective method for facilitating L2 pronunciation learning. Read More » Combination of genetic variants in cyclin D1 and retinoblastoma genes predict clinical outcome in oral cancer patients Abstract Oral cancer is a dreadful disease with a wide variation in geographical distribution. In order to identify some useful biomarkers for the disease prognosis, the present study assessed the influence of single nucleotide polymorphisms (SNPs) in cell cycle genes on survival in a well-annotated set of patients with oral squamous cell carcinoma (OSCC). The study examined 12 sequence variants or SNPs in selected cell cycle genes, with prognostic outcomes in 311 oral cancer patients. Our analysis showed that SNPs in cyclin D1:rs9344 and retinoblastoma:rs427686 genes showed a strong correlation with disease-free survival. In addition, the cumulative effect of these SNPs significantly and independently predicts the survival. Thus, the current study identified genotypes (SNP signature), which can be used as novel prognostic biomarkers to stratify patients based on disease-free survival and therefore maybe helpful in therapeutic decision-making. Read More » Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival Abstract Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients' survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients' survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy. Read More » CD20-negative diffuse large B cell lymphoma: a comprehensive analysis of 695 cases Abstract CD20 expression is absent in a variety of diffuse large B cell lymphomas (DLBCLs), including plasmablastic lymphoma, primary effusion lymphoma, anaplastic lymphoma, kinase-positive DLBCL, and large B cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease. These rare and heterogeneous tumors are characterized by the presence of proliferating immunoblasts with similar transcriptional profiles as those of plasma cells and are typically associated with highly aggressive pathologies, with high levels of chemotherapy resistance and low survival rates; thus, they pose significant diagnostic and treatment challenges. We conducted a systematic literature review of the limited existing clinical data to summarize the current knowledge regarding the biological basis, diagnostic limits, and potential therapeutic targets of distinct variants of CD20-negative DLBCL. This review will hopefully increase the awareness of these rare disorders among clinicians and pathologists and prompt basic and clinical research. Read More » Plasma miR-940 may serve as a novel biomarker for gastric cancer Abstract It was reported that circulating microRNAs could be applied as non-invasive biomarkers for cancer monitoring. The purpose of this study was to identify plasma miRNA that may serve as a novel biomarker for gastric cancer and to evaluate its clinical application. MicroRNA profiles were generated from plasma samples of 5 patients with gastric cancer (GC) versus 5 healthy controls (HC). MicroRNA-940 (miR-940) was one of the most downregulated miRNAs with fold change of 0.164. It was revealed that the expression of miR-940 was downregulated in both the initial set (N = 30, P < 0.0001) and the validation set (N = 80, P < 0.0001) of plasma samples of patients with gastric cancer. The sensitivity was obviously higher than the current biomarkers CEA and CA19-9 (81.25 % vs. 22.54 % and 15.71 %). MiR-940 was also significantly downregulated in gastric cancer tissue samples (N = 34, P = 0.0015), as well as in cancer cell lines (N = 7). Importantly, miR-940 was significantly highly expressed in stomach tissue samples than in other types of tissue samples including the liver, breast, thyroid, and lung. Moreover, there was a trend of lower expression of miR-940 from early to advanced stage of gastric cancer. Target prediction suggested that miR-940 regulated cell signaling including NF-κB and Wnt/β-catenin, as well as pathways of cell communication and adhesion. These pathways play critical roles in gastric cancer initiation and progression. It is the first report that miR-940 may mainly express in the stomach. Downregulation of plasma miR-940 may serve as a novel biomarker for detection of gastric cancer. Read More » Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium Abstract Recurrences occur in 30 % of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7 % of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8 % in patients with isolated BCH (BCH + SM−; odds ratio (OR) 31.26, 95 % confidence interval (CI) 3.77–258.60; p = 0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM− (34.9 vs. 18.3 %; effect size 2.86, 95 % CI 2.23–3.47; p = 0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM− (14.4 vs. 9.6 %; effect size 1.22, 95 % CI 0.69–1.76; p = 0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM− (21.8 vs. 38.5 %; effect size −6.26, 95 % CI −7.31 to −5.22; p = 0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence. Read More » High scavenger receptor class B type I expression is related to tumor aggressiveness and poor prognosis in breast cancer Abstract Scavenger receptor class B type I (SR-BI) has been linked to the development and progression of breast cancer. However, its clinical significance in breast cancer remains unclear. Here, we evaluated SR-BI expression in a well-characterized breast cancer tissue microarray by immunohistochemistry. High SR-BI expression was observed in 54 % of all breast cancer cases and was significantly associated with advanced pTNM stage (P = 0.002), larger tumor size (P = 0.023), lymph node metastasis (P = 0.012), and the absence of ER (P = 0.014). The Kaplan–Meier survival analysis revealed that patients with high SR-BI expression had significantly shorter overall survival (OS) (P = 0.004). Moreover, multivariate analysis with adjustment for other prognostic factors confirmed that SR-BI was an independent prognostic factor for patient outcome (P = 0.017). Overall, our study demonstrated that high SR-BI expression was related to conventional parameters indicative of more aggressive tumor type and may serve as a new prognostic marker for poor clinical outcome in human breast cancer. Read More » Clinical influence of cancer stem cells on residual disease after preoperative chemoradiotherapy for rectal cancer Abstract We evaluated the clinical influence of cancer stem cells (CSCs) on residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were assessed. To identify CSCs, immunohistochemistry was performed using their surrogate makers (CD44 and aldehyde dehydrogenase 1 [ALDH1]) in full section tissues. Of the 145 cases, ALDH1 and CD44 positivity was found in 80.0 % (n = 116) and 47.6 % (n = 69), respectively; ALDH1 positivity showed weakly positive correlation with CD44 (r s  = 0.269, P = 0.002). ALDH1 and CD44 positivity was related to lower tumor regression grade (TRG) (P = 0.009 and 0.003, respectively). Additionally, ALDH1 positivity was associated with positive circumferential resection margin (P = 0.019). However, ALDH1 and CD44 positivity showed no relationship with KRAS or BRAF mutation. In univariate analysis, ALDH1 positivity was associated with short recurrence-free survival (RFS) (P = 0.005) and rectal cancer-specific survival (RCSS) (P = 0.043), but not CD44 positivity (RFS, P = 0.725; RCSS, P = 0.280). In multivariate analysis, ALDH1 positivity was an independent prognostic factor for poor RFS (P = 0.039; hazard ratio = 2.997; 95 % confidence interval = 1.059–8.478), but not RCSS (P = 0.571). The expression of ALDH1 assessment independently predicts RFS in patients with residual disease after CRT. These results suggest that targeting CSCs could be an effective therapeutic approach to rectal cancer patients receiving preoperative CRT. Read More » Downregulation of miR-329 promotes cell invasion by regulating BRD4 and predicts poor prognosis in hepatocellular carcinoma Abstract Increasing evidence indicates that abnormal microRNA (miRNA) expression is related to hepatocellular carcinoma (HCC) development. Our study aimed to elucidate the essential role of miR-329 in HCC progression. Real-time PCR was used to analyze miR-329 and bromodomain containing 4 (BRD4) expression in HCC samples (n = 135). Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were used to investigate cell proliferation and apoptosis. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter and western blot assays. Kaplan-Meier analysis was used to detect the function of miR-329 on the prognosis of HCC patients. miR-329 was decreased in HCC samples and was related to tumor development. Furthermore, miR-329 significantly regulated cell invasion by targeting BRD4 but had no effect on cell proliferation and apoptosis. Moreover, downregulation of miR-329 predicted poor prognosis of HCC patients. miR-329 could control cell invasion via regulating BRD4 expression and may be a prognostic marker in HCC. Read More » Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines Abstract Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by −2.9, −3.7, −1.7, −1.7, −2.0 and −1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by −5.1, −2.0, −2.4, −3.1, −1.5, −2.0 and −2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer. Read More » Spindle cell lipoma with predominant nerve sheath tumor-like areas: A potential diagnostic pitfall on aspiration cytology Spindle cell lipoma (SCL) is an uncommon variant of lipoma that usually is present in subcutaneous fat of adult men. This tumor has a low rate of local recurrence and no risk of malignant behavior. Although histological features of SCL are well documented, cytological descriptions have been few. We present the case of a 41-year man with a right arm swelling, which on fine-needle aspiration cytology showed adipose tissue fragments, spindle cell areas mimicking benign nerve sheath tumor, and bundles of ropy collagen in a myxoid background, suggesting a diagnosis of SCL. SCL with predominant spindle cell component may mimic benign nerve sheath tumor on aspiration cytology. Subtle cytological features like presence of adipose tissue, ropy collagen, and mast cells help in accurate diagnosis. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc. Read More » A clinicopathological study of peripheral lymph nodes in HIV-infected patients with special reference to CD4+ T-cell counts: Experience from a tertiary care institution in Darjeeling (India) Background HIV/AIDS is a major health burden worldwide. India bears the third highest HIV-patients load globally. In the Darjeeling district, HIV-prevalence is >1% with very little known about the profile of HIV-lymphadenopathy. The aim of this study was to identify the different causes of peripheral lymphadenopathy among HIV–infected patients in this region, correlate them with CD4+ T-cell counts and formulate some common clinico-haematological parameters as potential predictors of CD4+ T-cell count. Methods In the present study, 76 cases were evaluated. Fine Needle Aspiration Cytology (FNAC) was performed as an out-patient procedure in the Department of Pathology. Smears were stained routinely with Haematoxylin-Eosin and Leishman stains. ZN stains were done when indicated by the cytological findings. Immediate CD4+ T-cell count was obtained by referring the patients to the Anti-retroviral therapy centre. Results Cytological diagnoses included tuberculosis (82.9%), reactive hyperplasia (6.6%), nonspecific granulomatous lesions (3.9%), non-Hodgkin lymphoma (2.6%), histoplasmosis (2.6%) and simultaneous filariasis with toxoplasmosis (1.3%). Statistically, the opportunistic infections and lymphomas significantly concurred with a CD4+ T-cell count <350/μl. Likewise, the number of enlarged lymph nodes and absolute lymphocyte count (ALC) were found to be useful predictors of CD4+ T-cell counts. Conclusions Lymph node cytology in HIV-infected patients is essential to identify opportunistic infections from neoplastic lesions and; to enable therapeutic strategies. Correlation of lesions with mean CD4+ T-cell count predicts personal immunity, stage of disease and disease activity. Furthermore, enlarged lymph node numbers and ALC can be surrogate markers of CD4+ T-cell count for monitoring the severity of the immune suppression in under-resourced countries like India. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc. Read More » Cytohistology of papillary carcinoid and emerging concept of pulmonary neuroendocrine neoplasms This timely review starts by reporting the clinical, cytologic and histologic features of a morphologic variant of pulmonary carcinoid tumor forming exclusively of papillae. This growth pattern is so rare that it was not included in 2014 WHO classification of pulmonary neuroendocrine neoplasms. The current concept is reviewed, and example of spindle cell carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma are illustrated with fine needle aspiration cytology, surgical and clinical follow-up. Finally, the new findings in cell biology and molecular biology that led to the emerging concept that carcinoids and high-grade neuroendocrine lung carcinomas are separate biological entities are reviewed and summarized in a tumorigenic module. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc. Read More » Temporal characteristics of Punjabi word-medial singletons and geminates Many studies have investigated the temporal characteristics of the word-medial singletons and geminates in Indo-Aryan languages. However, little is known about the acoustic cues distinguishing between the word-medial singletons and geminates of Punjabi. The present study examines the temporal characteristics of Punjabi word-medial singleton and geminate stops in a C1V1C2V2 template. The results from five Punjabi speakers showed that, unlike previous studies of Indo-Aryan languages, the durations of C2 and V2 are the most important acoustic correlates of singleton and geminate stops in Punjabi. These findings therefore point towards the cross-linguistic differences in the acoustic correlates of singletons and geminates. Read More » Arctic underwater noise transients from sea ice deformation: Characteristics, annual time series, and forcing in Beaufort Sea A 13-month time series of Arctic Ocean noise from the marginal ice zone of the Eastern Beaufort Sea is analyzed to detect under-ice acoustic transients isolated from ambient noise with a dedicated algorithm. Noise transients due to ice cracking, fracturing, shearing, and ridging are sorted out into three categories: broadband impulses, frequency modulated (FM) tones, and high-frequency broadband noise. Their temporal and acoustic characteristics over the 8-month ice covered period, from November 2005 to mid-June 2006, are presented and their generation mechanisms are discussed. Correlations analyses showed that the occurrence of these ice transients responded to large-scale ice motion and deformation rates forced by meteorological events, often leading to opening of large-scale leads at main discontinuities in the ice cover. Such a sequence, resulting in the opening of a large lead, hundreds by tens of kilometers in size, along the margin of landfast ice and multiyear ice plume in the Beaufort-Chukchi seas is detailed. These ice transients largely contribute to the soundscape properties of the Arctic Ocean, for both its ambient and total noise components. Some FM tonal transients can be confounded with marine mammal songs, especially when they are repeated, with periods similar to wind generated waves. Read More » Description and clustering of echolocation signals of Commerson's dolphins (Cephalorhynchus commersonii) in Bahía San Julián, Argentina Commerson's dolphins (Cephalorhynchus commersonii) inhabit coastal waters of Southern South America and Kerguelen Islands. Limited information exists about the acoustic repertoire of this species in the wild. Here, echolocation signals from free-ranging Commerson's dolphins were recorded in Bahía San Julián, Argentina. Signal parameters were calculated and a cluster analysis was made on 3180 regular clicks. Three clusters were obtained based on peak frequency (129, 137, and 173 kHz) and 3 dB bandwidth (8, 6, and 5 kHz). The 428 buzz clicks were analyzed separately. They consisted of clicks emitted with a median inter-click interval of 3.5 ms, peak frequency at 131 kHz, 3 dB bandwidth of 9 kHz, 10 dB bandwidth of 18 kHz, and duration of 56 μs. Buzz clicks were significantly shorter and with a lower peak frequency and a broader bandwidth than most of the regular clicks. This study provided the first description of different echolocation signals, including on- and off-axis signals, recorded from Commerson's dolphins in the wild, most likely as a result of animals at several distances and orientations to the recording device. This information could be useful while doing passive acoustic monitoring. Read More » A real-time articulatory visual feedback approach with target presentation for second language pronunciation learning Articulatory information can support learning or remediating pronunciation of a second language (L2). This paper describes an electromagnetic articulometer-based visual-feedback approach using an articulatory target presented in real-time to facilitate L2 pronunciation learning. This approach trains learners to adjust articulatory positions to match targets for a L2 vowel estimated from productions of vowels that overlap in both L1 and L2. Training of Japanese learners for the American English vowel /æ/ that included visual training improved its pronunciation regardless of whether audio training was also included. Articulatory visual feedback is shown to be an effective method for facilitating L2 pronunciation learning. Read More » University of Toronto Press cooperates with De Gruyter. Partnership for electronic content Read More » Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology BACKGROUND Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). METHODS The study consisted of consecutive fine-needle aspiration biopsy (FNAB) cases collected between January 1, 2013 and June 30, 2014 from 5 academic institutions. Demographic information, cytology diagnoses, and surgical pathology follow-up were recorded. The ROM was calculated with and without NI-FVPTC and was presented as a range: all cases (ie, overall risk of malignancy [OROM]) versus those with surgical follow-up only. RESULTS The FNAB cohort consisted of 6943 thyroid nodules representing 5179 women and 1409 men with an average age of 54 years (range, 9-94 years). The combined average ROM and OROM for the diagnostic categories of TBSRTC were as follows: nondiagnostic, 4.4% to 25.3%; benign, 0.9% to 9.3%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12.1% to 31.2%; follicular neoplasm (FN), 21.8% to 33.2%; suspicious for malignancy (SM), 62.1% to 82.6%; and malignant, 75.9% to 99.1%. The impact of reclassifying NI-FVPTC on the ROM and OROM was most pronounced and statistically significant in the 3 indeterminate categories: the AUS/FLUS category had a decrease of 5.2% to 13.6%, the FN category had a decrease of 9.9% to 15.1%, and the SM category had a decrease of 17.6% to 23.4% (P < .05), whereas the benign and malignant categories had decreases of 0.3% to 3.5% and 2.5% to 3.3%, respectfully. The trend of the effect on the ROM and OROM was similar for all 5 institutions. CONCLUSIONS The results from this multi-institutional cohort indicate that the reclassification of NI-FVPTC will have a significant impact on the ROM for the 3 indeterminate categories of TBSRTC. Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society. Read More » The clinical performance of primary HPV screening, primary HPV screening plus cytology cotesting, and cytology alone at a tertiary care hospital BACKGROUND Algorithms for primary human papillomavirus (HPV) screening, primary HPV screening plus cytology cotesting, and cytology alone were evaluated previously in large cohort trials for cervical cancer detection, although the quality of cytology in those studies was controversial. To investigate whether these 3 algorithms would be applicable in routine practice at a tertiary care hospital, the authors compared their clinical performance. In addition, the prevalence of HPV genotypes was determined. METHODS Cervical cytology samples (n = 1000) were tested using liquid-based cytology (LBC), a nucleic acid hybridization assay, real-time polymerase chain reaction analysis, and direct HPV DNA sequencing. The clinical performance of the 3 algorithms was compared among women in different age groups (age range, 17-86 years; median age, 44.7 years). RESULTS For cervical intraepithelial neoplasia grade 2 or worse (CIN 2+), the sensitivity of primary HPV screening alone, cotesting, and LBC alone was 71.7%, 72.5%, and 63.8%, respectively; whereas the specificity was 87.5%, 96.5%, and 97.4%, respectively. Cotesting and LBC alone had slightly higher positive predictive values for CIN 2 + (97.8% and 98.9%, respectively) than primary HPV screening alone (91%), whereas primary HPV screening alone and cotesting demonstrated higher negative predictive values (63.6% and 62.5%, respectively) than LBC alone (43.2%). High-risk HPV types were detected in 24.3% of individuals. The most common type was HPV type 16 (HPV-16) followed by multiple HPV infections and HPV-58, HPV-52, HPV-31, HPV-35, HPV-51, HPV-39, HPV-56, HPV-33, HPV-18, HPV-59, and HPV-45. CONCLUSIONS Primary HPV screening alone in a tertiary care hospital demonstrated a performance that was equivalent to that of cotesting for CIN 2+, irrespective of patient age. With regard to the distribution of HPV genotypes, the nonavalent HPV vaccine would prevent approximately 60% of high-risk HPV. Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society. Read More » Blatt AJ, Kennedy R, Luff R, Austin RM, Rabin DS. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathology 2015. doi:10.1002/cncy.21544. Read More » Long-Term Evaluation of Eyebrow Soft Tissue Expansion in Thyroid Eye Disease. Purpose: To evaluate the long-term transformation of lateral eyebrow soft tissue in a group of patients with known thyroid eye disease. Methods: A retrospective review of all patients with a known diagnosis of thyroid eye disease with clinical photos available from both their initial diagnosis visit and at least 7 years following their initial visit was performed. Age at diagnosis, sex, disease activity, previous orbital, and eyelid surgery were noted, as was history of treatment with radioactive iodine, steroids, and external beam radiation. The area between the upper eyebrow and upper eyelid crease was evaluated in standardized photographs by a panel of 4 expert, independent, masked observers utilizing a previously published visual grading key. Results: One hundred and four patients met inclusion criteria. Fifteen participants were male and 89 were female. The mean patient age was 50.6 years (+/-1.21 years), and the mean follow up duration was 10.0 years (+/-0.23 years). The mean initial photo grade (1.24) was significantly higher than the mean follow up photo grade (1.00; p 0.05). Conclusions: Expansion of eyebrow soft tissue may improve over time in patients with thyroid eye disease. This change was not affected by age, sex, disease activity, surgery, or medical therapy. (C) 2015 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved. Read More » The role of CTSK in oral and maxillofacial disorders Abstract Cathepsin K (CTSK) was thought to be a collagenase, specifically expressed by osteoclasts and played an important role in bone resorption. However, more and more research found that CTSK was expressed in more extensive cells, tissues and organs. It may not only participate in regulating human physiological activity, but also be closely related to a variety of disease. In this review, we highlight the relationship between CTSK and oral and maxillofacial disorders on the following three aspects: oral and maxillofacial abnormities in pycnodysostosis patients caused by CTSK mutations, oral and maxillofacial abnormities in Ctsk-/- mice and the role of CTSK in oral and maxillofacial diseases, including periodontitis, peri-implantitis, tooth movement, oral and maxillofacial tumor, root resorption and peri-apical disease. This article is protected by copyright. All rights reserved. Read More » Fibrin-targeted echogenic liposomes for localized ablation of thrombi with histotripsy pulses Deep vein thrombosis is a debilitating condition that can result in pulmonary embolism, or post-thrombotic syndrome. Clot lysis can be initiated with histotripsy, a novel form of therapeutic ultrasound that uses the mechanical action of microbubble clouds to ablate tissue. Thrombolytic-loaded echogenic liposomes (t-ELIP) have fibrin targeting capabilities and also entrain gas microbubbles that act as cavitation nuclei. We hypothesize that t-ELIP can nucleate microbubble cloud formation near the clot, providing targeted ablation. Highly retracted porcine whole blood clots were exposed to either histotripsy pulses alone, or histotripsy pulses and t-ELIP between peak negative pressures of 7.5 MPa and 20 MPa. Thrombolytic efficacy was assessed via clot mass before and after treatment. Microbubble cloud activity was monitored with passive cavitation imaging (PCI) during histotripsy exposure. For a given pressure, no significant differences were observed in the thrombolytic efficacy with or without t-ELIP. The dimensions of the bubble cloud, assessed on the PCIs, were significantly reduced in the presence of t-ELIP (p ablation of thrombi resistant to thrombolytic drugs. Read More » Acousto-optic investigation of acoustic anisotropy in paratellurite crystals Propagation velocity and attenuation coefficient of acoustics waves in paratellurite crystals were measured by Bragg diffraction of light in the frequency range of 0.4–1.6 GHz. These results were used for calculation of real and imaginary components of the complex tensor of elastic constants. The analysis of the anisotropy of attenuation was carried out for the acoustic waves of different polarization propagating in the crystallographic planes, which are orthogonal to symmetry axes of second and forth order. The strongest anisotropy of acoustic attenuation and phase velocity is observed for the transverse acoustic waves propagating in the plane (1-10). It is shown that the attenuation reduces the integral efficiency of diffraction in several times in the acousto-optic deflector in which is used an oblique cut of paratellurite and the transverse acoustic wave propagating at an angle of 6 degrees to the [110] axis in the plane (1-10). Read More » Influence of source motion, wind, and temperature profiles on the effective impedance of an absorptive surface This paper presents a theoretical study of the sound field due to a moving source placed above an absorptive surface in a stratified medium in the presence of wind and sound speed profiles. The current analysis starts with the general equations for an isentropic inviscid flow field. A monopole source is assumed to be traveling parallel to the absorptive surface at a constant speed. The standard Lorentz transform can be applied and the Fourier decomposition can be used to express the sound field in an integral form that is amenable to further mathematical treatments. Either the fast field computation or the method of steepest descent can be used to evaluate the integral. A two-dimensional formulation was considered initially, but it can subsequently be extended to three-dimensional flow fields. The effect of source motion, wind, and temperature profiles on the acoustic properties of the absorptive surfaces have been explored. Read More » Evaluating acoustic measurements of creaky voice: A Vietnamese case study It has been proposed that there are two broad categories of creaky voice (CV), laryngealized and aperiodic. Moreover, several subdivisions have been proposed for both categories (Keating & Garellek, 2015), and various combinations of acoustic properties have been associated with each. It remains unclear, however, how to determine which type of CV a language has and which acoustic measurements to rely on. We address this problem with two rising tones in Vietnamese differing in phonation. All of the phonation measurements we tested with ANOVA were statistically significant (p analysis be applied to the various measurements to determine the extent to which each one contributes to classifying creaky vs. modal vowels; and this, in turn, can inform us about the nature of the CV in the language. Specifically in Vietnameses, we found that HNR yields the strongest classification result (84%); the others were closer to chance (58–68%). We can thus conclude that the CV used in Vietnamese is the aperiodic type, as evidenced by the role of irregular F0 as opposed to the other phonation properties. Read More » Acoustic and sediment data in the southern New England Bight This study provides a review of the acoustic and ocean bottom sediment data collected during the Shelf Break Primer experiment conducted in 1996. The location of the experiment was in the southern New England Continental Shelf called the "New England Mud Patch." The mud patch is a 13,000 square kilometer area covered by fine-grained sediment. Previous surveys in this area have estimated the thickness of this fine grained sediment deposit to be as much as 13 m. This layer of sediment rests on a reflector that is geomorphically similar to and continuous with the Holocene transgressive sand sheet, which is exposed on the shelf to the west of this area. This fine-grained sediment layer, which is oriented in an east-west direction seaward of the 55–65 m isobath, contains more than 30% silt and clay. During the Primer experiment, broadband acoustic sources were deployed in the western side of the "mud patch" along and across the continental shelf. The acoustic data collected on a vertical line array will be analyzed. Sediment data from gravity cores from the area will also be presented. [Work sponsored by Office of Naval Research, code 322 OA.] Read More » The acoustics of perceived creaky voice in American English We compared auditory impressions of creaky voice in English to acoustic measures identified as correlates of contrastive voice qualities in other languages (e.g., Khmer, Chong, Zapotec, Gujarati, Hmong, Trique, and Yi). Sixteen trained linguistics undergraduates listened to the IP-final word 'bows' produced five times each by five American English speakers reading the Rainbow Passage, and gave a rating from 0 (no creak) to 5 (very creaky). Results show that stronger auditory impressions of creak are significantly correlated with lower f0, lower cepstral peak prominence (CPP), lower harmonics-to-noise ratios (HNR), and higher subharmonics-to-harmonics ratio (SHR). This suggests that listeners perceive greater creakiness as the voice becomes lower pitched, less periodic, and more audibly interspersed with subharmonic frequencies (i.e., diplophonia). Notably, none of the spectral amplitude measures proposed as acoustic correlates of glottal configurations for creaky voice in other languages (e.g., lower H1-H2 for smaller open quotient, lower H1-A1 for smaller posterior aperture, lower H1-A3 for more abrupt closure, etc.) was significantly correlated with these judgments in any expected direction. Taken together, these results suggest that while listeners consistently use pitch and periodicity as cues to creak, speakers might be varying in their articulatory strategies to achieve those acoustic effects. Read More » High throughput acoustic and optical characterization of microbubbles for optimized contrast ultrasound imaging Echogenic particles, such as microbubbles and volatile liquid micro-/nanodroplets, have shown considerable potential in a variety of clinical diagnostic and therapeutic applications. The accurate prediction of their response to ultrasound excitation is however extremely challenging, and this has hindered the optimization of techniques such as quantitative ultrasound imaging and targeted drug delivery. Existing characterization techniques, such as ultra-high speed microscopy, provide important insights, but suffer from a number of limitations; most significantly difficulty in obtaining large data sets suitable for statistical analysis and the need to physically constrain the particles, thereby altering their dynamics. Here, a microfluidic system is presented that overcomes these challenges to enable the measurement of single echogenic particle response to ultrasound excitation with a throughput of 20 samples/second and an uncertainty below 7% in the measurements. Demonstration of optimized contrast ultrasound imaging is shown based on the characterization of over 100,000 individual SonoVue® bubbles. Read More » Insights into mechanisms of sonothrombolysis using high speed imaging Thrombotic arterial occlusion is the major cause of acute cardiovascular syndromes such as stroke and myocardial infarction. Exposing the thrombus to microbubbles in the presence of ultrasound facilitates thrombus disruption, and is thus a potentially powerful therapeutic strategy for thromboembolic diseases. However, optimization of "sonothrombolysis" is constrained by a lack of understanding of underlying mechanisms for blood clot disruption in response to ultrasound-induced microbubble vibrations. We tested the hypothesis that inertial cavitation induces mechanical clot disruption by optically characterizing lipid microbubble interactions with thrombus + ultrasound using an ultra-high speed microscopy imaging system capable of imaging at MHz frame rates. A microscope/acoustic stage was used to hold an experimentally created thrombus and microbubbles, which were insonified (1 MHz) during synchronized high speed imaging. Large amplitude microbubble oscillations in response to an inertial cavitation regime caused thrombus deformation and pitting. These data implicate a direct mechanical effect of oscillating microbubbles on mediating clot disruption. Read More » Modeling, designing, and testing low frequency impact isolation solutions for building structures with fitness centers above grade There is a trend for fitness centers to find a quick, inexpensive occupancy and ideal location in a vacant office or retail space, often above grade. The tenants sharing the building structure are then subjected to sudden airborne noise and structureborne vibration from the impact energy generated by heavy weights being dropped onto the floor. Because of this trend there is a need to analyze the large, low frequency, shock generated energies that travel through the structure. This paper will discuss the process of designing an experimental floor assembly and apparatus to test weight drops, developing a modeling program to simulate weight drops using three degrees of freedom, which can be tailored to varying isolation solutions, and the means of physically testing the results. Read More » Infrasonic wind noise reduction comparison for wind fences and porous domes This paper reports on an investigation directly comparing the measured wind noise and detected acoustic signals for two types of co-located infrasonic wind noise reduction barriers. The first type is a set of cylindrically shaped wind fence enclosures and the second type is a set of 2.0 m diameter semi-porous fabric domes. The fence configurations included variations to the height, width, and number of filtering layers. Forty and fifty-five percent porosities were used for each of these configurations. Wind Noise reductions for the domes and the 5 m diameter fence are comparable at low wavenumbers, while the reductions for the 5 m fence is better at high wavenumbers. The porous domes and the 6 m high wind fence achieve comparable maximum reduction levels; however, the 6 m high fence mitigates noise for a broader wavenumber range. The 10 m diameter fence achieves the best reduction levels overall, while the porous domes are better at mid-range wavenumbers. Additional filtering layers improve all reductions and show the greatest improvement for the fences and the higher porosity dome. Read More » Acoustic calibration in mass production While calibrations in high volume settings are bound by the same laws of nature that govern laboratory grade measurements, the laws of economics bring their own set of challenges to the bench. This presentation will explore the art and science of making efficient acoustic measurements in small air-filled tanks using mostly COTS equipment. Read More » Design, characterization, and performance of a dual aperture, focused ultrasound system for microbubble-mediated, non-thermal ablation in rat brain Submegahertz ultrasound (US) with microbubbles (µB) can ablate brain tissue: a low amplitude (ablation. Single element transducers at transcranial frequencies have broad axial profiles compared to the size of targets in small animals. Thus, we sought a system to ablate millimeter volumes in normal and tumorous rat brain non-thermally using US and µB. The system consisted of two transducers oriented at 120°, driven at different frequencies (F = 837 kHz, ΔF = 30 Hz) to reduce the depth-of-field by 78%. To monitor cavitation, a passive detector (650 kHz) was confocally aligned with the therapy field. Targets were registered stereotactically. µB injections (100, 200, and 400 µl/kg) with 5-minute sonications proceeded at acoustic pressures relative to the in vivo cavitation threshold (0.3–0.6 MPa) determined a priori. Following MRI and sacrifice (1 h, 4 days, 10 days), tissue was fixed and stained. At 1 h, small lesions (tissue removal histologically after four days. Persistent, strong (>5 dB) inharmonic energy indicated formation of large ablation volumes along the US path. Low level (cavitation indicated incomplete ablation. Results and mechanisms, especially with respect to ischemic stroke, will be discussed. Read More » Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): An update Background: Continuous exposure of intracranial arterial occlusions to pulsed wave ultrasound enhances tissue plasminogen induced recanalization. Our hypothesis is that sonothrombolysis can improve functional outcomes of stroke patients receiving tPA therapy. Methods: The primary objective is to evaluate the efficacy of a novel transcranial ultrasound device and systemic tPA (Target) compared to systemic tPA alone (Controls) in subjects with acute ischemic stroke and NIHSS scores 10 or greater. This is a randomized (1:1), placebo-controlled, multi-site, phase 3 clinical trial to evaluate the efficacy and safety of a novel ultrasound device, as an adjunctive therapy to tPA treatment in subjects with acute ischemic stroke: total projected enrollment 824 patients with interim analyses at ⅓ and ⅔ of enrollment. Current Status: CLOTBUST-ER had active enrollment at approximately 70 sites in 14 countries worldwide. DSMB recommended to stop the trial after second interim analysis. Functional outcomes are still being assessed via modified Rankin Scores at 90 days and the primary endpoint will be analyzed using ordinal shift statistical analysis. Final results will be presented at ISC 2016. Conclusions: CLOTBUST-ER is the first phase three multinational randomized blinded clinical trial of sonothrombolysis for treatment of acute ischemic stroke. ClinicalTrials.gov Trial Registry ID: NCT01098981. Read More » The soundscape of worship Soundscape theory provides insights into the architectural acoustic design of religious buildings that demonstrate how acoustical issues can be integrated within worship spaces of the 21st century. Eliade (1959) conceives of worship spaces as a sacred enclosure where communication with the God is made. The spaces must have a door to the world above, by which the God can descend to earth and man can symbolically ascend to heaven. Sometimes this is manifest as one confronts his or her God alone, in silence; sometimes, it is manifest in the joyous singing and praying or sad wailing of the entire community joined in corporate celebration or solemnity during momentous events. If one pays careful attention to the group involved with the design of a facility, they can tailor the architectural, acoustical, and electronic systems design to provide a unique acoustical identity that expresses the individual aspirations of the particular church. The technical tools for measurement and assessment of existing conditions, modeling of proposed changes, and simulating the anticipated results so evaluations can be made while the design is still in a computer are readily available to allow consultants to develop acoustical aspects of worship spaces that are unique for each project. Read More » Microscale interactions between ultrasound stimulated microbubbles and the fibrin networks of clots While the concept of microbubble mediated sonothrombolysis is now well established, a detailed mechanistic understanding of this process remains both elusive as well as necessary in order to facilitate the development of improved exposure methods. As lytic effects may ultimately arise from microscale bubble-clot interactions, we have employed high-speed microscopy and two-photon microscopy to examine these interactions first in (transparent, fluorescently tagged) fibrin clots, and then in blood clots. Bubble "population" studies in fibrin clots show the prominent role of primary and secondary radiation forces: bubbles are first directed toward the clot boundary, where their concentrations increase and interactions such as clustering and coalescence occur frequently. A subset of bubbles penetrate into the clots, disrupting the fibrin network structure along their paths. Once initiated, the resulting tunnels act in subsequent exposures as conduits for bubbles to enter and access deeper points within the clot. Using optical tweezers, individual bubble experiments reveal that bubble entry into the clots, along with the accompanying network damage and fluid uptake, are a function of the network pore size, bubble size, and the exposure scheme. With blood clots, the erosion surface evolves in a complex manner, involving the ejection of erythrocytes and the development and progression of a cell depleted fibrin network zone. The characteristics of the erosion front are highly dependent on exposure conditions. Read More » Ocean acoustic tomography: Past, present, and maybe future This talk will describe some of the origins of what became known as ocean acoustic tomography, and how it has evolved in the intervening years. Some published mis-conceptions about its beginnings are somewhat interesting. The possibilities of its having a more central role in the determining the evolution of the ocean in future climate raise fascinating technical problems that probably have equally fascinating solutions. Read More » Ultrasound-enhanced thrombolysis: Mechanistic observations Ultrasound and microbubbles have been widely demonstrated to accelerate the breakdown of blood clots, but the mechanisms of treatment require further investigation. In particular, there is a need to clarify the effect on the fibrin matrix—the insoluble polymer mesh that determines a clot's integrity and mechanical properties. The objective of this in vitro study was to observe in real-time the mechanisms of microbubble-enhanced sonothrombolysis at the microscale. Fluorescently labeled porcine plasma clots were prepared on a glass coverslip and exposed to different types of microbubbles with or without the fibrinolytic agent recombinant tissue plasminogen activator. A 1 mm thick piezoelectric element was coupled with the glass substrate and driven at the resonant frequency of the system (1.9 MHz), with a duty cycle of 5% and a 0.1 Hz pulse repetition frequency. The acoustic field within the clot was characterized using a fiber optic hydrophone. Changes in the fiber network were monitored for 30 min by confocal microscopy. Read More » Detailing vowel development in infancy using cortical auditory evoked potentials and multidimensional scaling The present study used an efficient measure of perceptual sensitivity to map perception across the British English vowel space for 80 monolingual English infants (4–5, 8–9, and 10–11 months old). Auditory evoked potentials were measured for spectral changes between concatenated vowels, which, for infants, typically evokes a positivity about 150–200 ms after each spectral change. These were measured for 28 pairs of seven monophthongal vowels (/i/, /ɪ/, /ɛ/, /a/, /ɑ/, /ɔ/, /u/) that were presented in a random concatenated sequence with changes every 300–400 ms. ERPs were averaged across epochs following each spectral change, with the magnitude of the response for each vowel pair used as similarity measure for multidimensional scaling. The 4–5 month old infants had two-dimensional perceptual maps that closely matched the F1 and F2 acoustic differences between vowels. In contrast, the older infant response was less related to acoustic differences and they had selectively larger responses for neighbors around the vowel quadrilateral (e.g., /i/-/ɪ/); suggesting a shift to a more phonologically driven processing. These results provide a more detailed picture of phonetic development than has been shown before, and demonstrate an efficient procedure to map speech processing in infancy. Read More » Adults' perceptual voicing boundaries of 2-year-olds' citation form speech One way that speakers distinguish between phonemic categories is through voicing, frequently measured using voice onset time (VOT). Much perceptual research on voicing identification and discrimination has used synthetic speech stimuli varying in VOT. Results from adult listeners typically show stable crossover regions in the 20–35 ms range. Subsequent work, however, reveals that listeners' VOT boundaries vary with speech rate; further, an extensive history of research into vowel perception indicates that listeners normalize across vocal tract sizes. These considerations lead to the possibility that adult voicing boundaries may differ between the speech of adults vs. children, since children have slower speech rates and smaller vocal tracts. The present study obtained adult discrimination data for natural productions of bilabial and alveolar cognate pairs produced by 2–3-year-old monolingual, English-speaking children. Randomized stimuli were presented twice to 20 listeners resulting in 4,000 rated stimuli per category. The findings show 50% crossover points for VOT values at 28 ms for bilabials and 32 ms for alveolar phonemes. Such outcomes are consistent with past work based on adult data and suggest that mature listeners do not use substantially different perceptual criteria for judging voicing in children's speech. Declaration of Interest Statement The authors have no financial or nonfinancial disclosures to report. Read More » Design and renovation of worship spaces at Fourth Presbyterian Church in Chicago Fourth Presbyterian Church is among Chicago's most iconic buildings. Designed by Ralph Adams Cram, it was dedicated in 1914. Threshold Acoustics worked alongside Gensler on a 5-story addition to the Fourth Church facilities that provided needed worship and program space in celebration of their centennial. The Genevieve and Wayne Gratz Center was included as a case study for the publication "Worship Spaces Acoustics: Three Decades of Design." It houses the 350-seat Buchanan Chapel, which is used as overflow for holiday services, intimate worship services, Children's Chapel, music performances, and weddings. Threshold Acoustics is currently working with Fourth Church on the restoration of their historic Skinner Organ in the sanctuary. An acoustic study of the sanctuary was completed to evaluate and determine the current challenges the organ faces to carry sound to all locations within the Nave. The renovations to the organ and chamber are underway and are to be finished by December 2015 for holiday services. This paper will describe Threshold's acoustic design for the Gratz Center and Sanctuary. Read More » Using the Retrograde Internal Mammary System for Stacked Perforator Flap Breast Reconstruction: 71 Breast Reconstructions in 53 Consecutive Patients. Background: Abdominal tissue is the preferred donor source for autologous breast reconstruction, but in select patients with inadequate tissue, additional volume must be recruited to achieve optimal outcomes. Stacked flaps are an effective approach in these cases, but can be limited by the need for adequate recipient vessels. This study reports outcomes for the use of the retrograde internal mammary system for stacked flap breast reconstruction in a large number of consecutive patients. Methods: Fifty-three patients underwent stacked autologous tissue breast reconstruction with a total of 142 free flaps. Thirty patients underwent unilateral stacked DIEP reconstruction, 5 had unilateral stacked PAP reconstruction, 1 had bilateral stacked DIEP/SGAP reconstruction, and 17 underwent bilateral stacked DIEP/PAP reconstruction. In all cases the antegrade and retrograde internal mammary vessels were used for anastomoses. In situ manometry studies were also conducted comparing the retrograde internal mammary (RIM) arteries in 10 patients to the corresponding systemic pressures. Results: There were 3 total flap losses (97.9 percent flap survival rate), 2 partial flap losses, 4 re-explorations for venous congestion, and 3 patients had operable fat necrosis. The mean weight of the stacked flaps for each reconstructed breast was 622.8 grams. The RIM mean arterial pressures (MAP) were on average 76.6 percent of the systemic MAP. Conclusion: The results demonstrate that the RIM system is capable of independently supporting free tissue transfer. These vessels provide for convenient dissection and improved efficiency of these cases with successful post-surgical outcomes. (C)2015American Society of Plastic Surgeons Read More » Global Aesthetics Consensus Group: Botulinum Toxin Type A - Evidence-Based Review, Emerging Concepts, and Consensus Recommendations for Aesthetic Use, Including Updates on Complications. Background: Botulinum toxin type A injection remains the leading nonsurgical cosmetic procedure worldwide, with a high rate of efficacy and patient satisfaction. Methods: A multinational, multidisciplinary group of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group (GACG) to develop updated consensus recommendations with a worldwide perspective for botulinum toxin and hyaluronic acid fillers. This publication, on botulinum toxin Type A, considers advances in facial analysis, injection techniques, and avoidance and management of complications. Results: Use of botulinum toxin has evolved from the upper face to also encompass the lower face, neck, and midface. The GACG emphasizes an integrative, diagnostic approach. Injection dosage and placement are based on analysis of target muscles in the context of adjacent ones and associated soft and hard tissues. The indication for selecting botulinum toxin as a primary intervention is that excessive muscular contraction is the primary etiology of the facial disharmony to be addressed. GACG recommendations demonstrate a paradigm shift toward neuromodulation rather than paralysis, including lower dosing of the upper face and more frequent combination treatment with hyaluronic acid fillers, and intracutaneous injection where indicated to limit depth and degree of action. Conclusions: Accumulating clinical evidence and experience with botulinum toxin have led to refinements in treatment planning and implementation. The GACG's advocacy of an etiology-driven, patient-tailored approach enables achievement of optimal efficacy and safety in patient populations that are rapidly diversifying with respect to ethnicity, gender, and age. (C)2015American Society of Plastic Surgeons Read More » Management of Stenosing Flexor Tenosynovitis: Maximizing Non-Operative Success without Increasing Morbidity. BACKGROUND: Traditional non-operative management of stenosing tenosynovitis is limited to 1 long-acting corticosteroid injection, followed by surgery in the case of failure. Recently, non-operative strategies have been extended to include 2-3 injections despite the absence of large prospective studies supporting this practice. METHODS: A prospective study was performed of all patients presenting with stenosing tenosynovitis to a single surgeon (RSR) over a 22-year period. Patients with potentially confounding comorbidities were excluded. All digits received 1-3 injections of triamcinolone acetonide+local anesthetic into the tendon sheath. Data were analyzed by digit. RESULTS: Five hundred seventy-one digits (401 patients) were included. Digits that were symptomatic for 3 months (OR 2.6, 95% CI 1.67-4.0, p5 months (OR 9.4, 95% CI 3.0-29.7, p1 corticosteroid injection, as 2nd and 3rd doses increase the overall remission rate without increasing morbidity. (C)2015American Society of Plastic Surgeons Read More » Transplantation of a LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft Tissue Defects: The In-Vitro Development of Polarized Hair Bearing Skin. Background: The LGR6 expressing epithelial stem cell (LGR6+ ESC), within the follicular bulge, is capable of producing all cellular lineages and concomitant structures of the skin and interfollicular epidermis, including keratinocytes, sebaceous gland and hair follicle. Literature has shown that full thickness wounds, devoid of the stem cell niche, can subsequently be reconstructed with functional skin elements following migration of the LGR6+ ESC into the wound bed. Here, we employ a variety of LGR6+ ESC-seeded scaffolds to determine therapeutic potential in immediate reconstruction of full-thickness wounds with polarized functional hair-bearing skin. Methods: Isolated LGR6+GFP ESCs were seeded on a spectrum of acellular matrices and monitored in both in vitro and in vivo environments. These studies were used to determine the ability of the LGR6+GFP ESC population to maintain viability, proliferation and migration processes as well as wound healing and nascent hair follicle development. Results: Wound beds containing LGR6+GFP ESCs seeded scaffolding showed significantly augmented rates of healing, epithelialization and hair growth when compared to controls. Gene and proteomic expression studies indicate that LGR6+GFP ESC seeded matrices up-regulate wingless-type MMTV integration site family (WNT), epidermal growth factor (EGF) and angiogenesis pathways. Finally, the addition of ADSc containing SVF to LGR6+GFP ESC-seeded scaffolding, induces polarity cellular populations, while further augmenting pro-angiogenic analytes. Conclusions: LGR6+GFP ESCs are able to undergo proliferation, differentiation and migration on simple collagen-based scaffolding while augmenting in vivo epithelialization, hair growth and angiogenesis within wound beds. The addition of SVF to LGR6+GFP ESC-seeded scaffolding induces an early form of tissue polarization, providing for the first time, a clinically applicable stem cell based construct for the repair of full thickness wounds and hair regeneration. (C)2015American Society of Plastic Surgeons Read More » Long Term Results and refinement of Turkish delight technique for primary and secondary rhinoplasty: 25 years of experience. Background: All grafts present the potential problem of late visibility, distortion, and (occasionally) absorption. To overcome these problems and obtain a smoother surface, in 1989, the author initiated the use of finely diced cartilage wrapped in Surgicel(R). It is well known that the resolution of edema at the end of one-year post operatively is approximately 90-95%. Complete resolution continues until the end of four years post operatively. However, it is important to understand what happens beyond four years, and how the nose changes as the face ages. Methods: The author presents his experience of the last 25 years on 9,398 primary and secondary rhinoplasty patients treated using his personal approach, the Turkish delight. Patients of a post-operative range of four to 25 years were selected. Results: Using the Turkish Delight type of cartilage graft (diced cartilage wrapped in Surgicel(R)), The technique has been free of late show complications often experienced in other types of tip grafts. Evolution of advanced results from four years to 25 years shows very satisfactory results with an acceptable low complication rate. Conclusions: This technique is safe, reliable, effective, simple, and easily applicable by plastic surgeons at all levels of experience. Early and long-term results from one year to 25 years are very satisfactory. The overall complication rate is very low compared to other techniques. In addition, there is no late show as sometimes seen with other types of cartilage grafts such as crushed, oval, or rectangular grafts. (C)2015American Society of Plastic Surgeons Read More »