Background. Use of radioactive iodine (RAI) ablation has been reported to vary significantly between studies. We explored variation in RAI ablation care patterns between seven thyroid cancer treatment centers in Canada. Methods. The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe and analyze patterns of care for thyroid cancer. We analyzed data from seven participating centers on RAI ablation in patients diagnosed with well-differentiated (papillary and follicular) thyroid cancer between 2000 and 2010. We compared RAI ablation protocols including indications (based on TNM staging), preparation protocols, and administered dose. We excluded patients with known distant metastases at time of RAI ablation. Results. We included 3072 patients. There were no significant differences in TNM stage over time. RAI use increased in earlier years and then declined. The fraction of patients receiving RAI varied significantly between centers, ranging between 20–85% for T1, 44–100% for T2, 58–100% for T3, and 59–100% for T4. There were significant differences in the RAI doses between centers. Finally, there was major variation in the use of thyroid hormone withdrawal or rhTSH for preparation of RAI ablation. Conclusion. Our study identified significant variation in use of RAI for ablation in patients with well-differentiated thyroid cancer both between Canadian centers and over time.
http://ift.tt/2fHF1Ow
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 29 Νοεμβρίου 2016
Regional Variation across Canadian Centers in Radioiodine Administration for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer Diagnosed in 2000–2010
The role of the otolaryngologist in the evaluation and diagnosis of eosinophilic esophagitis
Objective
To describe the clinical presentation and role of the otolaryngologist in the evaluation of eosinophilic esophagitis (EoE) at a tertiary pediatric hospital.
Study Design
Retrospective review.
Methods
Records from pediatric patients with a diagnosis of EoE from 2003 to 2015 were reviewed. Study variables were analyzed to compare patients presenting to different specialties.
Results
Two hundred and fifty-one patients with EoE were evaluated. The median age at diagnosis was 9.0 years (range 0.8–19.0); 73% were male. Sixty-seven percent of patients initially presented to gastroenterology and 18% to otolaryngology. Time from initial presentation to diagnosis did not differ between the patients presenting to the two specialties (median 2.3 vs. 2.0 months, P = 0.510). Overall, 26% presented with airway symptoms (stridor, chronic cough, croup, or dysphonia). Patients diagnosed by the otolaryngology service were younger (3.4 vs. 10.4 years, P < 0.0001), had a higher incidence of airway symptoms (68% vs. 15%, P < 0.001), and demonstrated fewer gastrointestinal symptoms (86% vs. 100%, P < 0.001).
Conclusion
Patients with EoE frequently present to otolaryngology undiagnosed in the first 5 years of life, making esophagoscopy with biopsy an important adjunct to airway endoscopy in children with refractory aerodigestive symptoms. Otolaryngologists are uniquely poised to facilitate early diagnosis and initiation of therapy for these children, potentially reducing long-term sequelae.
Level of Evidence
4. Laryngoscope, 2016
http://ift.tt/2fPs48E
Paclitaxel inhibits post-traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model
Objectives/Hypothesis
To investigate the efficacy of paclitaxel, a potent microtubule inhibitor with a more favorable therapeutic index as compared with vincristine, in preventing post-traumatic nerve regeneration of the recurrent laryngeal nerve into the posterior cricoarytenoid muscle in a canine laryngeal model.
Study Design
Experimental animal study.
Methods
Forty-nine canine hemilaryngeal specimens were divided into five experimental groups. Under general anesthesia, a tracheostomy, recurrent laryngeal nerve (RLN) transection and repair, and laryngeal adductory pressures (LAP) were measured pre–RLN injury. The approach to the posterior cricoarytenoid (PCA) muscle for neurotoxin injection was transoral or open transcervical, at 0 or 3 months. At 6 months, postinjury LAPs were measured and the animals were sacrificed at 6 months to allow for laryngeal harvesting and analysis.
Results
Paclitaxel demonstrated increased mean laryngeal adductory pressures (70.6%) as compared with saline control (55.5%). The effect of paclitaxel was the same as observed with vincristine at 0 months and with a delayed injection at 3 months. There was no difference between transoral or open injection groups.
Conclusions
PCA muscle injection with paclitaxel resulted in improved strength of laryngeal adduction. This effect was similar to that of vincristine at both 0 and 3 months following nerve injury. A single intramuscular injection of paclitaxel was well tolerated. Additional human studies are needed to determine the degree of clinical benefit of this intervention.
Level of Evidence
NA Laryngoscope, 2016
http://ift.tt/2gw0aN5
Pilot testing of a novel surgical simulator for endoscopic zenker's diverticulotomy
Objectives/Hypothesis
Restrictions on resident work hours and the increasing purview of otolaryngology reduce the efficacy of the traditional surgical training model. With limited case volumes at many institutions and the unique instrumentation of endoscopic Zenker's diverticulotomy (EZD), simulation may be useful to improve training. In this study, a novel surgical simulator for EZD is developed and validated.
Study Design
Simulation model development.
Methods
An EZD model was designed using an intubation trainer and disposable diverticulum inserts. A novel objective structured assessment of technical skill (OSATS) for EZD was developed. Performance of otolaryngology residents on simulations using the OSATS and time to completion were evaluated during an instructional course. Pre- and postencounter surveys were completed. Inter-rater and intrarater reliability were evaluated via blinded video review of resident performance.
Results
Seventeen residents participated (n = 17). Surveys showed confidence improved two points on a five-point scale (P < .001), and 94% agreed that the model would improve resident performance with in vivo EZD. More experienced trainees (postgraduate year [PGY] 3–5, n = 11 vs. PGY 1–2, n = 6) had shorter times to completion (P < .001) and higher assessment scores on initial attempts (P = .006). Both groups showed significant improvements from initial to final attempts on 30-point scales for global rating by 6.2 ± 4.2 (mean ± standard deviation, P < .001). The novel OSATS demonstrated fair live/video reliability (к = 0.40) and inter-rater reliability (к = 0.44), and moderate intrarater reliability (к = 0.60).
Conclusions
Pilot testing of an EZD simulator demonstrated acceptability, content validity, and construct validity. A novel OSATS was developed and evaluated. Further investigation of the impact on operative performance and validation of the OSATS in vivo is needed.
Level of Evidence
NA Laryngoscope, 2016
http://ift.tt/2fPt0to
Contemporary management of carotid blowout syndrome utilizing endovascular techniques
Objectives/Hypothesis
To illustrate complex interdisciplinary decision making and the utility of modern endovascular techniques in the management of patients with carotid blowout syndrome (CBS).
Study Designs
Retrospective chart review.
Methods
Patients treated with endovascular strategies and/or surgical modalities were included. Control of hemorrhage, neurological, and survival outcomes were studied.
Results
Between 2004 and 2014, 33 patients had 38 hemorrhagic events related to head and neck cancer that were managed with endovascular means. Of these, 23 were localized to the external carotid artery (ECA) branches and five localized to the ECA main trunk; nine were related to the common carotid artery (CCA) or internal carotid artery (ICA), and one event was related to the innominate artery. Seven events related to the CCA/ICA or innominate artery were managed with endovascular sacrifice, whereas three cases were managed with a flow-preserving approach (covered stent). Only one patient developed permanent hemiparesis. In two of the three cases where the flow-preserving approach was used, the covered stent eventually became exposed via the overlying soft tissue defect, and definitive management using carotid revascularization or resection was employed to prevent further hemorrhage. In cases of soft tissue necrosis, vascularized tissues were used to cover the great vessels as applicable.
Conclusions
The use of modern endovascular approaches for management of acute CBS yields optimal results and should be employed in a coordinated manner by the head and neck surgeon and the neurointerventionalist.
Level of Evidence
4. Laryngoscope, 2016
http://ift.tt/2gw3GXF
Is nonabsorbable nasal packing after septoplasty essential? A meta-analysis
Objectives
Septoplasty is one of the most frequently performed rhinologic surgeries. Complications include nasal bleeding, pain, headache, septal hematoma, synechia, infection, residual septal deviation, and septal perforation. In this study, we aimed to compare complication rates among patients according to packing method.
Methods
We performed a literature search using PubMed, Embase, and the Cochrane Library through August 2016. Our systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effect models were used to calculate risk differences and risk ratio with 95% confidence intervals (CIs). Cases referred to the nonpacking group included patients treated with transseptal sutures or septal splints. Cases referred to as the packing group included patients treated with nonabsorbable packing such as Merocel or gauze.
Results
Our search included 20 randomized controlled trials (RCTs) with a total of 1,321 subjects in the nonpacking group and 1,247 subjects in the packing group. There were no significant differences between packing methods regarding bleeding, hematoma, perforation, infection, and residual septal deviation. The risk differences of postoperative pain, headache, and postoperative synechia were −0.50 [95% CI: −0.93 to −0.07, P = .02], −0.42 [95% CI: −0.66 to −0.19, P = .0004], and −0.03 [95% CI: −0.06 to −0.01, P = .01], respectively.
Conclusions
Nonabsorbable nasal packing is no more effective than treatments without packing after septoplasty. Septal splints and transseptal sutures reduce postoperative pain, headache, and synechia.
Level of Evidence
NA Laryngoscope, 2016
http://ift.tt/2fPsUCl
A novel thyroid cancer nodal map classification system to facilitate nodal localization and surgical management: The A to D map
Objectives/Hypothesis
To evaluate the effectiveness, reproducibility, and usability of our proposed nodal nomenclature and classification system employed for several years in our high-volume thyroid cancer unit, for the adequate localization and mapping of lymph nodes in thyroid cancer patients with extensive nodal disease.
Study Design
Retrospective review.
Methods
Thirty-three thyroid cancer patients with extensive nodal disease treated from January 2004 to May 2013 were included in our study. Preoperative ultrasound and computed tomography scans of these patients were reanalyzed by blinded radiologists to investigate the feasibility for the assignment of abnormal lymph nodes to compartments defined in our proposed nodal classification system and to identify areas of difficulty in the assignment.
Results
Analysis of nodal localization revealed a discrepancy in compartment agreement between the two radiologists in the assignment of abnormal nodes in nine patients (9/33, 27%). In six patients (6/33, 18%), discrepancy existed in labeling paratracheal and pretracheal nodes. In three patients (3/33, 9%), disagreement arose in the classification of retrocarotid nodes into lateral versus central compartment. A further refinement of the definition of key borderline regions of the pretracheal versus paratracheal and retrocarotid regions of our classification improved the agreement and demonstrated a complete concordance (100%) amongst the reviewing radiologists.
Conclusions
The proposed nodal classification system, derived specifically for differentiated thyroid carcinoma, with readily identifiable anatomic boundaries on imaging and at surgery, facilitates communication among multidisciplinary physicians and aids in creating a uniform and reproducible radiographic nodal map to guide surgical therapy.
Level of Evidence
4 Laryngoscope, 2016
http://ift.tt/2gIhTQT
Treatment of cutaneous larva migrans with a single session of carbon dioxide laser: a study of ten cases in the Philippines
Abstract
Background
Cutaneous larva migrans (CLM) has a detrimental effect on patients' emotional and physical quality of life. Due to local unavailability of gold standard oral treatments for CLM, carbon dioxide laser was attempted. We present a case series where a single session of carbon dioxide laser treatment was associated with cessation of signs and symptoms of CLM.
Aims
The aim of this study was to assess the efficacy of a single session of carbon dioxide laser in the treatment of CLM.
Materials and Methods
Ten cases (eight patients) with CLM were treated with one session of carbon dioxide laser treatment and followed up daily for the first week with photographic documentation and then weekly for the next 3 weeks to complete a 4 week follow-up period.
Results
The first cases in our series, who received one to two passes of fractional CO2 laser, experienced further larval migration for 2–3 days, after which no more progression was noted. For the next seven cases, we increased the number of CO2 laser passes to 3–4, and noted no further larval migration. At the end of the 4-week follow-up period, all CO2 laser-treated areas were completely healed, leaving postinflammatory hyperpigmentation of the serpiginous track.
Conclusion
The results of this case series indicate the efficacy of a single session of CO2 laser in treating CLM. Further studies are required to identify the minimum number of passes required to effectively control CLM.
http://ift.tt/2gHv45q
Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status
http://ift.tt/2gI8XuF
Favorable Swallowing Outcomes following Vagus Nerve Sacrifice for Vagal Schwannoma Resection
Objective
To determine the impact of unilateral vagal sacrifice for vagal schwannoma on postoperative swallowing function.
Study DesignCase series, chart review.
SettingAcademic medical institution.
Subjects and MethodsTen patients underwent vagus nerve sacrifice for vagal schwannoma resection. Archived pathology records dating from 1985 through 2012 at our institution were retrospectively queried for cases of vagal schwannoma with vagus nerve sacrifice. Medical records were abstracted for demographic and disease information as well as cranial nerve and swallowing function. Preoperative and postoperative cranial nerve function, subjective and objective measures of swallowing function, Functional Oral Intake Scale (FOIS) level, and need for vocal fold medialization were variables collected. Data were analyzed with summary statistics.
ResultsThe patients who underwent vagal sacrifice for vagal schwannoma at our institution had a mean age of 42.3 years (median, 44 years; range, 15-63 years) and follow-up of 35.6 months (median, 9 months; range, 1-115 months). Most presented with no preoperative cranial nerve deficit or difficulty swallowing. Immediately postoperatively, 90% had a vagus nerve deficit, but 50% had no subjective difficulty swallowing, and 70% had a FOIS level of 7 at postoperative hospital discharge. Within 1 month after surgery, 70% had normal swallowing function according to a modified barium swallow study. A full diet was tolerated by mouth within an average of 2.7 days (median, 2 days; range, 1-6 days) after surgery in this cohort. Seventy percent required vocal fold medialization postoperatively for incomplete glottic closure.
ConclusionVagal nerve sacrifice during resection of vagal schwannoma can be performed with normal postoperative swallowing function.
http://ift.tt/2gvG3ic
A case of multiple empyema caused by Streptococcus intermedius
Publication date: Available online 29 November 2016
Source:Auris Nasus Larynx
Author(s): Akihito Kaga, Ryuzaburo Higo, Hiroshi Yoshikawa, Naoko Yokoi, Takuo Haruyama, Hiroaki Komatsu, Ayumi Yabe, Takeshi Kusunoki, Katsuhisa Ikeda
We report the case of a patient with multiple empyema present throughout his body, including chronic sinusitis and chronic suppurative otitis media, as well as subsequent epidural empyema, all caused by Streptococcus intermedius. A 38-year-old man presented with chief complaints of headache, left ear discharge, and nasal congestion. Imaging studies revealed pansinusitis, soft tissue signs in the mastoid cells, and otitis media. The patient was treated with meropenem hydrate, 6g/day. While clinical findings indicated improvement of the sinusitis, his headache did not improve. Further examination with contrast computerized tomography (CT) 'a chest radiography' blood cultures were performed, and the patient was diagnosed with multiple empyema (with an epidural empyema, pulmonary suppuration) caused by S. intermedius. Subsequent burr hole drainage was implemented to drain the epidural empyema. Long-term administration was required to treat pulmonary suppuration. While they remain rare, there has been a recent upward trend in the frequency of cases in which a young, previously healthy patient has developed multiple empyema throughout their body despite the absence of complicating diseases that pose an immune deficiency risk, such as diabetes or infection with the human immunodeficiency virus (HIV). In order to properly diagnose and treat patients presenting with multiple empyema infection with S. intermedius should be included in the differential diagnosis.
http://ift.tt/2gHeAdG
The use of the FLACC pain scale in pediatric patients undergoing adenotonsillectomy
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Andrew J. Redmann, Yu Wang, James Furstein, Charles M. Myer, Alessandro de Alarcón
Objectives1) Determine the usage rate of opioid pain medication after adenotonsillectomy (T&A). 2) Review the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain scale for T&A patients 3) Determine the rate of postoperative physician contacts for pain related complaints.MethodsA retrospective case series review was performed on 125 pediatric patients undergoing T&A and subsequent 23-hour postoperative observation at an academic tertiary care center from June–August of 2015. Postoperative pain scores using the FLACC pain scale, the utilization of opioid pain medications, and the number of postoperative contacts for pain were recorded.ResultsAverage age of patients was 5.7 years and 50% were female. 90% of T&A's were performed for adenotonsillar hypertrophy. The post-tonsillectomy hemorrhage rate was 4%. 70 (56%) patients required postoperative opioid pain medication, with (30) 43% of these patients requiring more than one dose. The mean number of opioid doses was 1.64 ± 0.9 and was not related to age, weight or gender. FLACC scores were highly associated (spearman correlation 0.77) with the amount of opioid medication given. Mean FLACC scores decreased over time after T&A. 20% of patients contacted a physician for unsatisfactory pain control postoperatively with 6% requiring emergency department visits and 14% contacting the office via phone call.ConclusionsA significant portion of pediatric patients undergoing T&A require postoperative opioids for pain control. The FLACC scale is a valuable way of quantifying post-operative T&A pain in pediatric patients. Despite routine pain management postoperatively, a significant proportion of patients require contact with a physician postoperatively for pain management.
http://ift.tt/2gDWGLo
No evidence for impaired humoral immunity to pneumococcal proteins in Australian Aboriginal children with otitis media
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Ruth B. Thornton, Lea-Ann S. Kirkham, Karli J. Corscadden, Harvey L. Coates, Shyan Vijayasekaran, Jessica Hillwood, Sophie Toster, Phillipa Edminston, Guicheng Zhang, Anthony Keil, Peter C. Richmond
BackgroundThe Australian Aboriginal population experiences disproportionately high rates of otitis media (OM). Streptococcus pneumoniae is one of the main pathogens responsible for OM and currently no vaccine offering cross strain protection exists. Vaccines consisting of conserved antigens to S. pneumoniae may reduce the burden of OM in high-risk populations; however no data exists examining naturally acquired antibody in Aboriginal children with OM.MethodsSerum and salivary IgA and IgG were measured against the S. pneumoniae antigens PspA1 and 2, CbpA and Ply in a cross sectional study of 183 children, including 36 non-Aboriginal healthy control children and 70 Aboriginal children and 77 non-Aboriginal children undergoing surgery for OM using a multiplex bead assay.ResultsSignificant differences were observed between the 3 groups for serum anti-PspA1 IgA, anti-CbpA and anti-Ply IgG and for all salivary antibodies assessed. Aboriginal children with a history of OM had significantly higher antibody titres than non-Aboriginal healthy children with no history of OM and non-Aboriginal children with a history of OM for several proteins in serum and saliva. Non-Aboriginal children with a history of OM had significantly higher salivary anti-PspA1 IgG than healthy children, while all other titres were comparable between the groups.ConclusionsConserved vaccine candidate proteins from S. pneumoniae induce serum and salivary antibody responses in Aboriginal and non-Aboriginal children with a history of OM. Aboriginal children do not have an impaired antibody response to the antigens measured from S. pneumoniae and they may represent vaccine candidates in Indigenous populations.
http://ift.tt/2gDY94s
IL-9 and Th9 in parasite immunity
Abstract
Interleukin-9 is a cytokine classically related to type 2 immune responses whose cellular identity has been recently reevaluated to identify a new specialized T helper subset called Th9 and an innate source referred as innate lymphoid cell type 2. Over the past years, IL-9 has been associated with allergic responses, tumor immunology, and autoimmunity; however, in this review, we will specifically focus on the role of IL-9 and Th9 cells in the context of parasitic infections. We will summarize and discuss all the evidence relating IL-9 expression and function in parasitic infections with a particular emphasis in helminth infections, an important health issue in developing countries; we will also provide a general description and classification of parasites, the immune response and cellular compartments activated in this context, and its implications and future directions towards a complete understanding of this interesting new T helper subset and its potential therapeutic use.
http://ift.tt/2g3S5P2
A case of multiple empyema caused by Streptococcus intermedius
We report the case of a patient with multiple empyema present throughout his body, including chronic sinusitis and chronic suppurative otitis media, as well as subsequent epidural empyema, all caused by Streptococcus intermedius. A 38-year-old man presented with chief complaints of headache, left ear discharge, and nasal congestion. Imaging studies revealed pansinusitis, soft tissue signs in the mastoid cells, and otitis media. The patient was treated with meropenem hydrate, 6g/day. While clinical findings indicated improvement of the sinusitis, his headache did not improve.
http://ift.tt/2guPD4B
Determination of insertion depth of flexible laryngeal mask airway in pediatric population—A prospective observational study
The purpose of this study was to determine the ideal insertion depth of the flexible laryngeal mask airway (FLMA) by elucidating the relationships between insertion depth and patient's age, body weight, height, and other parameters. We also evaluated an insertion technique that uses the change in intracuff pressure for proper positioning of the FLMA in cases where it is difficult to sense resistance during FLMA insertion.
http://ift.tt/2gDrU5a
Real-Time Genomic Characterization Utilizing Circulating Cell-Free DNA in Patients with Anaplastic Thyroid Carcinoma
http://ift.tt/2g3eTOL
Attention-Deficit/Hyperactivity Disorder in Atopic Dermatitis: An Appraisal of the Current Literature
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
http://ift.tt/2ggOaBA
Prevalence of beta-lactam allergy: a retrospective chart review of drug allergy assessment in a predominantly pediatric population
Research suggests that 90% of patients labeled beta-lactam allergic are able to tolerate penicillins following further assessment. This study aims to define and describe the frequency of true beta-lactam aller...
http://ift.tt/2gG4jyp
Lymphocyte Kv1.3-channels in the pathogenesis of chronic obstructive pulmonary disease: novel therapeutic implications of targeting the channels by commonly used drugs
In patients with chronic obstructive pulmonary disease (COPD), over-activated T-lymphocytes produce pro-inflammatory cytokines and proliferate in situ in the lower airways and pulmonary parenchyma, contributin...
http://ift.tt/2gSMKhp
Presymptomatic diagnosis of Fabry’s disease: a case report
Fabry's disease is a rare X-linked genetic disorder characterized by reduced levels of the α-galactosidase A enzyme. It may present with a cardiac phenotype resembling hypertrophic cardiomyopathy. However, as ...
http://ift.tt/2gFPURB
Asthma heterogeneity and severity
Asthma is a common, chronic inflammatory airways disease characterized by a clinical syndrome of bronchial hyperresponsiveness, inflammation, and reversible airflow obstruction. Individuals with asthma can var...
http://ift.tt/2g2B8EF
Correction to Supporting Information for Biswas et al., E-cadherin junction formation involves an active kinetic nucleation process [SI Correction]
BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction to Supporting Information for "E-cadherin junction formation involves an active kinetic nucleation process," by Kabir H. Biswas, Kevin L. Hartman, Cheng-han Yu, Oliver J. Harrison, Hang Song, Adam W. Smith, William Y. C. Huang, Wan-Chen Lin, Zhenhuan Guo, Anup Padmanabhan, Sergey M. Troyanovsky, Michael L....
http://ift.tt/2gtxUKX
Correction for Coates et al., Wildfire, climate, and invasive grass interactions negatively impact an indicator species by reshaping sagebrush ecosystems [Correction]
ECOLOGY Correction for "Wildfire, climate, and invasive grass interactions negatively impact an indicator species by reshaping sagebrush ecosystems," by Peter S. Coates, Mark A. Ricca, Brian G. Prochazka, Matthew L. Brooks, Kevin E. Doherty, Travis Kroger, Erik J. Blomberg, Christian A. Hagen, and Michael L. Casazza, which appeared in issue...
http://ift.tt/2fNjW8C
Correction for Delgehyr et al., Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability [Correction]
CELL BIOLOGY Correction for "Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability," by Nathalie Delgehyr, Uta Wieland, Hélène Rangone, Xavier Pinson, Guojie Mao, Nikola S. Dzhindzhev, Doris McLean, Maria G. Riparbelli, Salud Llamazares, Giuliano Callaini, Cayetano Gonzalez, and David M. Glover, which appeared in...
http://ift.tt/2gtwbp0
Correction for Sakata et al., Voltage-dependent motion of the catalytic region of voltage-sensing phosphatase monitored by a fluorescent amino acid [Correction]
BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction for "Voltage-dependent motion of the catalytic region of voltage-sensing phosphatase monitored by a fluorescent amino acid," by Souhei Sakata, Yuka Jinno, Akira Kawanabe, and Yasushi Okamura, which appeared in issue 27, July 5, 2016, of Proc Natl Acad Sci USA (113:7521–7526; first published June 21,...
http://ift.tt/2fNpsI6
Arabidopsis thaliana GH3.5 acyl acid amido synthetase mediates metabolic crosstalk in auxin and salicylic acid homeostasis [Plant Biology]
In Arabidopsis thaliana, the acyl acid amido synthetase Gretchen Hagen 3.5 (AtGH3.5) conjugates both indole-3-acetic acid (IAA) and salicylic acid (SA) to modulate auxin and pathogen response pathways. To understand the molecular basis for the activity of AtGH3.5, we determined the X-ray crystal structure of the enzyme in complex with...
http://ift.tt/2fNjaYY
Standing genetic variation in a tissue-specific enhancer underlies selfing-syndrome evolution in Capsella [Plant Biology]
Mating system shifts recurrently drive specific changes in organ dimensions. The shift in mating system from out-breeding to selfing is one of the most frequent evolutionary transitions in flowering plants and is often associated with an organ-specific reduction in flower size. However, the evolutionary paths along which polygenic traits, such...
http://ift.tt/2gtBqoO
Cortical networks involved in visual awareness independent of visual attention [Psychological and Cognitive Sciences]
It is now well established that visual attention, as measured with standard spatial attention tasks, and visual awareness, as measured by report, can be dissociated. It is possible to attend to a stimulus with no reported awareness of the stimulus. We used a behavioral paradigm in which people were aware...
http://ift.tt/2gtzlsW
Trypanosoma brucei metabolite indolepyruvate decreases HIF-1{alpha} and glycolysis in macrophages as a mechanism of innate immune evasion [Immunology and Inflammation]
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be...
http://ift.tt/2fNpArc
Lifestyle chemistries from phones for individual profiling [Chemistry]
Imagine a scenario where personal belongings such as pens, keys, phones, or handbags are found at an investigative site. It is often valuable to the investigative team that is trying to trace back the belongings to an individual to understand their personal habits, even when DNA evidence is also available....
http://ift.tt/2gtAArT
Statistics of natural reverberation enable perceptual separation of sound and space [Psychological and Cognitive Sciences]
In everyday listening, sound reaches our ears directly from a source as well as indirectly via reflections known as reverberation. Reverberation profoundly distorts the sound from a source, yet humans can both identify sound sources and distinguish environments from the resulting sound, via mechanisms that remain unclear. The core computational...
http://ift.tt/2fNnkjz
Unreasonable effectiveness of learning neural networks: From accessible states and robust ensembles to basic algorithmic schemes [Computer Sciences]
In artificial neural networks, learning from data is a computationally demanding task in which a large number of connection weights are iteratively tuned through stochastic-gradient-based heuristic processes over a cost function. It is not well understood how learning occurs in these systems, in particular how they avoid getting trapped in...
http://ift.tt/2fNmEut
Role of nucleotide-binding oligomerization domain 1 (NOD1) and its variants in human cytomegalovirus control in vitro and in vivo [Microbiology]
Induction of nucleotide-binding oligomerization domain 2 (NOD2) and downstream receptor-interacting serine/threonine-protein kinase 2 (RIPK2) by human cytomegalovirus (HCMV) is known to up-regulate antiviral responses and suppress virus replication. We investigated the role of nucleotide-binding oligomerization domain 1 (NOD1), which also signals through RIPK2, in HCMV control. NOD1 activation by Tri-DAP...
http://ift.tt/2fNm544
Tissue-scale, personalized modeling and simulation of prostate cancer growth [Engineering]
Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed "predictive medicine." Prostate cancer (PCa) is a major health problem and an...
http://ift.tt/2fNpIHn
Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma [Immunology and Inflammation]
Melanoma metastases can be categorized by gene expression for the presence of a T-cell–inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer–testis antigens. Therapies are being pursued to trigger...
http://ift.tt/2fNpvUi
Life cycle greenhouse gas emissions and freshwater consumption associated with Bakken tight oil [Sustainability Science]
In recent years, hydraulic fracturing and horizontal drilling have been applied to extract crude oil from tight reservoirs, including the Bakken formation. There is growing interest in understanding the greenhouse gas (GHG) emissions associated with the development of tight oil. We conducted a life cycle assessment of Bakken crude using...
http://ift.tt/2fNjirq
In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway [Immunology and Inflammation]
Cancer progression is associated with the development of antitumor autoantibodies in patients' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan...
http://ift.tt/2fNvit5
The emergence of longevous populations [Social Sciences]
The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life. Here we reveal a fundamental regularity. Two straight lines describe...
http://ift.tt/2fNjnLS
Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter [Neuroscience]
Circadian rhythms are based on endogenous clocks that allow organisms to adjust their physiology and behavior by entrainment to the solar day and, in turn, to select the optimal times for most biological variables. Diverse model systems—including mice, flies, fungi, plants, and bacteria—have provided important insights into the mechanisms of...
http://ift.tt/2fNrVST
Molecular mechanisms of substrate-controlled ring dynamics and substepping in a nucleic acid-dependent hexameric motor [Biochemistry]
Ring-shaped hexameric helicases and translocases support essential DNA-, RNA-, and protein-dependent transactions in all cells and many viruses. How such systems coordinate ATPase activity between multiple subunits to power conformational changes that drive the engagement and movement of client substrates is a fundamental question. Using the Escherichia coli Rho transcription...
http://ift.tt/2gtvwEd
Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression [Genetics]
Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes....
http://ift.tt/2fNr3Oh
Paraneoplastic pityriasis rubra pilaris: case report and literature review
Summary
Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous inflammatory dermatosis. Only a few cases of PRP associated with an underlying malignancy have been documented. We investigated a 59-year-old patient presenting with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the MEDLINE database to find articles reporting on similar associations of PRP with malignancies. We identified 10 studies linking PRP and malignancies, but an association between PRP and cholangiocarcinoma has not yet been reported.
http://ift.tt/2fwIGmP
Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses
Abstract
The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (SπNo or SoNπ, respectively), relative to detection when signal and noise are in identical phase at each ear (SoNo). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: SoNo, SπNo, and SoNπ. BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21–26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the SπNo condition relative to SoNo and SoNπ conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., SoNo amplitude–SπNo amplitude) were significantly predictive of behavioral SπNo BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.
http://ift.tt/2fYJM74
Natural Compounds as Occult Ototoxins? Ginkgo biloba Flavonoids Moderately Damage Lateral Line Hair Cells
Abstract
Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated herbal supplements and suggests that further supplement characterization is warranted.
http://ift.tt/2gcAaIT