Endoscopic versus stereotactic procedure for pineal tumour biopsies: focus on overall efficacy rate.

Endoscopic versus stereotactic procedure for pineal tumour biopsies: focus on overall efficacy rate.

World Neurosurg. 2016 Apr 6;

Authors: Balossier A, Blond S, Reyns N

Abstract
OBJECTIVE: The management of pineal region tumours highly depends on the histological subtypes. Two minimally invasive techniques are available for this issue: endoscopic intraventricular biopsies and stereotactic biopsies. The recent Southampton's and Lille's series are the largest endoscopic and stereotactic series of pineal region tumours reporting both diagnosis rate and accuracy rate, respectively; we elaborated on these results in the light of other recent studies.
METHODS: We compared the Southampton's endoscopic series to the Lille's series reflecting our 25-year experience of stereotactic biopsies, and the metadata of the literature for both approaches, as reported in the Report 2013 of the French-Speaking Society of Neurosurgery on the tumours of the pineal region.
RESULTS: The results of the Southampton's series match the endoscopic literature, in particular regarding the diagnosis rate (81.2%) or the perioperative morbidity (25.0%), and provides rarely-reported accuracy rate (78.6%), giving access to the overall efficacy rate (63.8%). The results of the Lille's series match the stereotactic literature and show better results than endoscopic biopsies concerning the diagnosis rate (98.9%), accuracy rate (100%), resulting overall efficacy rate (98.9%), and perioperative morbidity (6.4%).
CONCLUSION: The Southampton's and Lille's series provide a unique opportunity to compare the overall efficacy rates of endoscopic and stereotactic biopsies, respectively. Until today the stereotactic approach remains safer and more effective for biopsies of pineal region tumours. In order to improve the safety and reliability of endoscopic biopsies, various methods have to be evaluated: alternative burr-hole strategies, use of neuronavigation, and combination of flexible and rigid endoscopes.

PMID: 27060509 [PubMed - as supplied by publisher]

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Second spatial derivative analysis of cortical surface potentials recorded in cat primary auditory cortex using thin film surface arrays: comparisons with multi-unit data.

Second spatial derivative analysis of cortical surface potentials recorded in cat primary auditory cortex using thin film surface arrays: comparisons with multi-unit data.

J Neurosci Methods. 2016 Apr 6;

Authors: Fallon JB, Irving S, Pannu SS, Tooker AC, Wise AK, Shepherd RK, Irvine DR

Abstract
BACKGROUND: Current source density analysis of recordings from penetrating electrode arrays has traditionally been used to examine the layer-specific cortical activation and plastic changes associated with changed afferent input. We report on a related analysis, the second spatial derivative (SSD) of surface local field potentials (LFPs) recorded using custom designed thin-film polyimide substrate arrays.
RESULTS: SSD analysis of tone-evoked LFPs generated from the auditory cortex under the recording array demonstrated a stereotypical single local minimum, often flanked by maxima on both the caudal and rostral sides. In contrast, tone-pips at frequencies not represented in the region under the array, but known (on the basis of normal tonotopic organization) to be represented caudal to the recording array, had a more complex pattern of many sources and sinks.
COMPARISON WITH EXISTING METHODS: Compared to traditional analysis of LFPs, SSD analysis produced a tonotopic map that was more similar to that obtained with multi-unit recordings in a normal-hearing animal. Additionally, the statistically significant decrease in the number of acoustically responsive cortical locations in partially deafened cats following 6 months of cochlear implant use compared to unstimulated cases observed with multi-unit data (p=0.04) was also observed with SSD analysis (p=0.02), but was not apparent using traditional analysis of LFPs (p=0.6).
CONCLUSIONS: SSD analysis of surface LFPs from the thin-film array provides a rapid and robust method for examining the spatial distribution of cortical activity with improved spatial resolution compared to more traditional LFP recordings.

PMID: 27060384 [PubMed - as supplied by publisher]

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Severity and disease control before house dust mite immunotherapy initiation: ANTARES a French observational survey

Allergen immunotherapy (AIT) may be prescribed for patients with allergic rhinitis (AR) induced by house dust mites (HDM) whether asthma is present or not. Current guidelines provide insufficient support for t...

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Alumina-encapsulated vaccine formulation with improved thermostability and immunogenicity

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC02595A, Communication

Hangyu Zhou, Guangchuan Wang, Xiaofeng Li, Yaling Li, Shunya Zhu, Cheng-Feng Qin, Ruikang Tang
Developing vaccine formulations with excellent thermostability and immunogenicity remains a great challenge. By in-situ encapsulating a live-attenuated strain of Human enterovirus 71 (EV71) in alumina, we obtained a robust vaccine...
The content of this RSS Feed (c) The Royal Society of Chemistry

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An expert opinion from the European Society of Hypertension-European Union Geriatric Medicine Society working group on the management of hypertension in very old, frail subjects

Two years after the publication of the 2013 guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC),1 the ESH and the European Union Geriatric Medicine Society have created a common working group to examine the management of hypertensive subjects aged >80 years. The general term hypertension in the elderly is not sufficiently accurate because it mixes younger old patients (60–70 years) with the oldest old. Our group believes that the management of hypertension in individuals aged ≥80 years should be specifically addressed. Although arbitrary, this cutoff value identifies a population that is expanding faster than any other age group with a 50% increase of life expectancy during the past 50 years2,3; furthermore, the incidence and prevalence of comorbidities, frailty, and loss of autonomy greatly increases after the age of 80 years4; finally, although there is limited evidence on the management of hypertension in this age group, the latest clinical studies indicate that in these patients, treatment may not be the same as in patients in the lower age strata. The aim of this Working Group was to discuss more in-depth treatment aspects of hypertensive patients aged ≥80 years or older, with special focus on the difficulties and uncertainties posed by very old frail individuals. We focused, in particular, on the following points of the 2013 ESH/ESC guidelines: Benefits of treatment. Blood pressure (BP) thresholds and targets. The choice of treatment.

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Mortality, hospitalisation, institutionalisation in community-dwelling oldest old: the impact of medication

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Solutions sought for EMS volunteer shortage

BISMARK, N.D. — The future of EMS is the subject of a series of statewide meetings to discuss the challenges of providing EMS, especially in the face of a declining pool of EMS volunteers.

Most of North Dakota's EMS services rely on volunteer emergency responders and a combination of grants and state and local tax dollars to operate, reported the Public News Service.

"As a state, no one has the magic solution, and so we're just looking for different ideas," said Curt Halmrast, president of the North Dakota EMS Association. "The easy fix is just to pay everybody, but there's not the funding there to do it, nor are there the people."

The association is hosting meetings throughout the state and inviting EMS leaders and providers, as well as local and state legislators, hospital administrators and the general public to participate.

The purpose of the meetings to discuss the future of the North Dakota EMS system including the challenges of the decline in the largest subsidy to EMS systems which is volunteer providers, other funding issues, transport reimbursement, pending regulations, training, and the difficulty in transition to EMS integration into the health care system.  

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Paramedics and EMTs celebrated as unsung heroes

WASHINGTON — The American Ambulance Association is honoring 103 "Stars of Life" from 90 communities in 29 states across the country – plus Trinidad & Tobago – for their selfless acts as EMS professionals.

Ceremonies, to be held in Washington, D.C., on Monday and Tuesday will include recognition for these EMS providers: 

• Paramedics who responded to the San Bernardino terrorist attack.
• An Advanced EMT who single-handily provided the initial triage to pedestrians hit by a woman who had driven her car on busy sidewalk along the Las Vegas Strip.      
• An off-duty EMS director of operations who, upon learning no ambulances were available, left her family and responded to a call of an infant who was not breathing. Once on the scene, she performed CPR and intubated the baby before an ambulance was able to arrive. The baby survived.
• A paramedic in Oklahoma who helped resolve a potentially deadly situation involving a friend who had barricaded himself in his house and threatened to kill himself.
• A communications and dispatch technician who, while out grocery shopping, was pressed into duty and performed CPR on an elderly man in cardiac arrest, despite having had recent abdominal surgery and being told not to do any strenuous activity. The man survived.
• A paramedic who responded to a tragic school bus accident in Kentucky where three children died and several were injured.
• A paramedic who helped pull two passengers out of burning car and provided the initial treatment.

Eeach year the American Ambulance Association recognizes the dedication of ambulance services professionals who, day in and day out, serve their communities, often inconspicuously.

"Anytime someone dials 911 there are a number of highly trained professionals who respond and arrive to deliver excellent emergency medical and pre-hospital care," said Mike Hall, AAA president. "EMS professionals are extraordinary men and women who make a difference every day."

Past Stars of Life have included heroic individuals involved with the response to September 11th attacks, Hurricanes Katrina and Sandy, and other disasters. The AAA represents organizations serving more than 75 percent of the U.S. population with emergency and non-emergency care and medical transportation services.

The keynote speaker at this year's luncheon at the National Press Club will be Marc Creswell, operations manager of Air Med Services. He is responsible for the day-to-day operation of 10 helicopters and three fixed wing aircraft. Creswell has been involved in several large-scale rescues, including Hurricane Katrina and the Deepwater Horizon oil spill.

While in Washington, the "Stars" will meet with members of Congress, and key congressional aides to discuss legislative issues critical to all emergency medical service professionals, including ensuring that ambulance service providers receive fair Medicare and Medicaid reimbursement and that EMTs and paramedics at private companies receive the same benefits as provided to public safety officers who are employed by the federal or state and local governments.

Founded in 1979, the American Ambulance Association promotes health care policies that ensure excellence in the ambulance services industry and provides research, education and communications programs to enable its members to effectively address the needs of the communities they serve. 

 

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Comparison of the Effects of Dibutyl and Monobutyl Phthalates on the Steroidogenesis of Rat Immature Leydig Cells

Dibutyl phthalate (DBP) is a widely used synthetic phthalic diester and monobutyl phthalate (MBP) is its main metabolite. DBP can be released into the environment and potentially disrupting mammalian male reproductive endocrine system. However, the potencies of DBP and MBP to inhibit Leydig cell steroidogenesis and their possible mechanisms are not clear. Immature Leydig cells isolated from rats were cultured with 0.05–50 μM DBP or MBP for 3 h in combination with testosterone synthesis regulator or intermediate. The concentrations of 5α-androstanediol and testosterone in the media were measured, and the mRNA levels of the androgen biosynthetic genes were detected by qPCR. The direct actions of DBP or MBP on CYP11A1, CYP17A1, SRD5A1, and AKR1C14 activities were measured. MBP inhibited androgen production by the immature Leydig cell at as low as 50 nM, while 50 μM was required for DBP to suppress its androgen production. MBP mainly downregulated Cyp11a1 and Hsd3b1 expression levels at 50 nM. However, 50 μM DBP downregulated Star, Hsd3b1, and Hsd17b3 expression levels and directly inhibited CYP11A1 and CYP17A1 activities. In conclusion, DBP is metabolized to more potent inhibitor MBP that downregulated the expression levels of some androgen biosynthetic enzymes.

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Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms.

Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms.

Blood. 2016 Apr 8;

Authors: Emadali A, Hoghoughi N, Duley S, Hajmirza A, Verhoeyen E, Cosset FL, Bertrand P, Roumier C, Roggy A, Suchaud-Martin C, Chauvet M, Bertrand S, Hamaidia S, Rousseaux S, Josserand V, Charles J, Templier I, Maeda T, Bruder-Costa J, Chaperot L, Plumas J, Jacob MC, Bonnefoix T, Park S, Gressin R, Tensen CP, Mecucci C, Macintyre E, Leroux D, Brambilla E, Nguyen-Khac F, Luquet I, Penther D, Bastard C, Jardin F, Lefebvre C, Garnache F, Callanan M

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive leukemia for which knowledge on disease mechanisms and effective therapies are currently lacking. Only a handful of recurring genetic mutations have been identified and none are specific to BPDCN. In this study, through molecular cloning in an index case that presented a balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, we identify monoallelic deletion ofNR3C1(5q31), encoding the glucocorticoid receptor (GCR), in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including 10 withNR3C1deletion, did not revealNR3C1point mutations or in/dels. Haploinsufficiency forNR3C1defined a subset of BPDCN with lowered GCR expression and extremely poor overall survival (P = 0.0006). Consistent with a role for GCR in tumor suppression, functional analyses coupled with gene expression profiling (GEP), identified cortico-resistance and loss-of-EZH2 function to be major downstream consequences ofNR3C1deletion in BPDCN. Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion ofNR3C1to a lncRNA gene (lincRNA-3q) that encodes a novel, nuclear, non-coding RNA involved in the regulation of leukemia stem cell programmes and G1/S transition, via E2F. Overexpression oflincRNA-3qwas a consistent feature of malignant cells and could be abrogated by BET protein (bromo and extra-terminal domain) inhibition. Taken together, this work points toNR3C1as a haploinsufficient tumor suppressor in a subset of BPDCN and identifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN.

PMID: 27060168 [PubMed - as supplied by publisher]

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Inflammatory breast cancer in a previously treated case of breast cancer: a diagnostic dilemma for the clinician.

Inflammatory breast cancer in a previously treated case of breast cancer: a diagnostic dilemma for the clinician.

BMJ Case Rep. 2016;2016

Authors: Ravind R, Kumar PV, Prabaharan S

Abstract
Inflammatory breast cancer (IBC) is a relatively rare and aggressive subtype, accounting for nearly 2.5% of all diagnosed breast cancers worldwide. It is usually characterised by an acute onset, rapid clinical progression, poor prognosis and micrometastasis at the time of presentation. Prompt recognition of clinical symptoms and identification of warning signs are vital in diagnosing and appropriately treating a patient with IBC.

PMID: 27060073 [PubMed - as supplied by publisher]

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Paramedic Lorie Burton treats a suspect, after he almost shot her husband

The Ohio paramedic treated and forgave the man who came inches away from killing her husband a day earlier

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Percutaneous dilation tracheostomy by Melker cricothyrotomy set in PICU: retrospective evaluation of a new combined approach.

Percutaneous dilation tracheostomy by Melker cricothyrotomy set in PICU: retrospective evaluation of a new combined approach.

Paediatr Anaesth. 2016 May;26(5):569-71

Authors: Rossetti E, Bianchi R, Germani A, Chiusolo F, Appierto L, Picardo S

PMID: 27059422 [PubMed - in process]

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Practice patterns in endoscopic dacryocystorhinostomy: survey of the American Rhinologic Society.

Practice patterns in endoscopic dacryocystorhinostomy: survey of the American Rhinologic Society.

Int Forum Allergy Rhinol. 2016 Apr 6;

Authors: Chen S, Le CH, Liang J

Abstract
BACKGROUND: The introduction of advanced endoscopic techniques has facilitated significant growth in endoscopic dacryocystorhinostomy (EnDCR). The purpose of this study is to evaluate clinical practice patterns of otolaryngologists performing EnDCR.
METHODS: A 25-item survey was electronically disseminated to the American Rhinologic Society (ARS) membership from November 17, 2014 to December 14, 2014. The target group encompassed 1157 ARS members.
RESULTS: A total of 85 (7.3%) physicians completed the survey. EnDCR was performed by 87% of respondents. The annual average number of EnDCR cases ranged from 1 to 10 in 65% of respondents, 11 to 25 in 15%, 26 to 50 in 6%, and >50 in 1%. A total of 48% of respondents had some to a lot of DCR exposure during training, and 60% had completed a rhinology fellowship. Respondents frequently perform preoperative nasal endoscopy and computed tomography (CT) imaging, but very infrequently perform ophthalmologic workup. Lacrimal stents were used often or always in 80%, with 38% keeping stents in place for 6 to 8 weeks. The mucosal flap preservation technique was used often or always in 40%. Topical antimetabolites were used often or always in only 1%. Ophthalmology was present in most cases to perform lacrimal intubation. Postoperative antibiotics, topical ophthalmic steroids, and oral steroids were prescribed often or always in 62%, 47%, and 23%, respectively. Postoperative endoscopic debridement was performed often or always in 69%. A total of 81% of respondents followed DCR patients for >2 months, with 17% following these patients for >1 year.
CONCLUSION: There is widespread integration of EnDCR procedures into rhinologic clinical practice among respondents. EnDCR practice patterns demonstrate moderate variation. In conjunction with evidence-based medicine, these trends can highlight areas of controversy and help advance patient care.

PMID: 27060784 [PubMed - as supplied by publisher]

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Predictive significance of computed tomography in eosinophilic chronic rhinosinusitis with nasal polyps.

Predictive significance of computed tomography in eosinophilic chronic rhinosinusitis with nasal polyps.

Int Forum Allergy Rhinol. 2016 Apr 5;

Authors: Meng Y, Lou H, Wang C, Zhang L

Abstract
BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP), characterized by eosinophil-predominant inflammation in mucosa, is a subject of much investigation. However, no satisfactory atraumatic clinical parameter has been established to date for prediagnosis of this condition. The aim of this study was therefore to compare the use of computed tomography (CT) scans with other clinical parameters in prediagnosis of eCRSwNP.
METHODS: This was a prospective cohort, single-institution study. Two hundred consecutive CRSwNP patients (123 eCRSwNP and 77 non-eosinophilic CRSwNP [neCRSwNP]) undergoing functional endoscopic sinus surgery in Beijing TongRen Hospital were recruited. Preoperative CT scan, skin-prick test (SPT), and oral fractional exhaled nitric oxide (FENO) measurements were performed in each patient and full blood count with differential analysis under the patients' regular condition was performed within 1 week before surgery. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to assess the predictive value of clinical parameters.
RESULTS: History of surgery, onset of asthma, history of allergy, total Lund-Mackay scores, presence of osteoneogenesis, FENO, and blood eosinophil counts were all significantly higher in the eCRSwNP group, compared to the neCRSwNP group. The ratio of the CT scores for the ethmoid sinus and maxillary sinus (E/M ratio) had the highest predictive value, with an area under the ROC curve (AUC) of 0.938. The cutoff point of >2.59 for E/M ratio demonstrated a sensitivity of 94.2% and a specificity of 89.6% for eCRSwNP.
CONCLUSION: The E/M ratio is a more useful predictor in diagnosis of eCRSwNP compared to the other clinical parameters.

PMID: 27060677 [PubMed - as supplied by publisher]

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A Homozygous Nme7 Mutation is Associated with Situs Inversus Totalis.

A Homozygous Nme7 Mutation is Associated with Situs Inversus Totalis.

Hum Mutat. 2016 Apr 6;

Authors: Reish O, Aspit L, Zouella A, Roth Y, Polak-Charcon S, Baboushkin T, Benyamini L, Scheetz TE, Mussaffi H, Sheffield VC, Parvari R

Abstract
We investigated the cause of situs inversus totalis (SIT) in two siblings from a consanguineous family. Genotyping and whole-exome analysis revealed a homozygous change in NME7, resulting in deletion of an exon causing an in-frame deletion of 34 amino acids located in the 2(nd) NDK domain of the protein, and segregated with the defective lateralization in the family. NME7 is an important developmental gene and NME7 protein is a component of the γ-tubulin ring complex. This mutation is predicted to affect the interaction of NME7 protein with this complex as it deletes the amino acids crucial for the binding. SIT associated with homozygous deletion in our patients is in line with Nme7(-/-) mutant mice phenotypes consisting of congenital hydrocephalus and SIT, indicating a novel human laterality patterning role for NME7. Further cases are required to elaborate the full human phenotype associated with NME7 mutations. This article is protected by copyright. All rights reserved.

PMID: 27060491 [PubMed - as supplied by publisher]

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Short-term effect of short, intensive speech therapy on articulation and resonance in Ugandan patients with cleft (lip and) palate.

Short-term effect of short, intensive speech therapy on articulation and resonance in Ugandan patients with cleft (lip and) palate.

J Commun Disord. 2016 Mar 29;61:71-82

Authors: Luyten A, Bettens K, D'haeseleer E, Hodges A, Galiwango G, Vermeersch H, Van Lierde K

Abstract
OBJECTIVES: The purpose of the current study was to assess the short-term effectiveness of short and intensive speech therapy provided to patients with cleft (lip and) palate (C(L)P) in terms of articulation and resonance.
METHODS: Five Ugandan patients (age: 7.3-19.6 years) with non-syndromic C(L)P received six hours of individualized speech therapy in three to four days. Speech therapy focused on correct phonetic placement and contrasts between oral and nasal airflow and resonance. Speech evaluations performed before and immediately after speech therapy, including perceptual and instrumental assessment techniques, were compared.
RESULTS: Post-therapy, improvement of speech was noted for most of the patients, although to varying degrees. Clinically relevant progress of objective nasalance values and/or articulation was obtained in four patients. Overall, two patients showed normal speech intelligibility, while three patients required additional speech therapy.
CONCLUSION: These preliminary short-term results demonstrate that short and intensive speech therapy can be effective for patients with C(L)P in countries with limited access to speech-language therapy. However, further research is needed on the long-term effectiveness and the advantages of applying this treatment protocol in countries with good access to speech therapy.
LEARNING OUTCOMES: The reader will be able to (1) list the challenges in resource poor-countries to achieve access to speech-language therapy services, (2) describe when the application of speech therapy is appropriate in patients with C(L)P, (3) describe the speech therapy that can be applied to reduce compensatory articulation and resonance disorders in patients with C(L)P, and (4) list the (possible) advantages of short, intensive speech therapy for both resource-poor and developed countries.

PMID: 27060419 [PubMed - as supplied by publisher]

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Characterization of a novel high-dose ovalbumin-induced murine model of allergic sinonasal inflammation.

Characterization of a novel high-dose ovalbumin-induced murine model of allergic sinonasal inflammation.

Int Forum Allergy Rhinol. 2016 Apr 5;

Authors: Mendiola M, Tharakan A, Chen M, Asempa T, Lane AP, Ramanathan M

Abstract
BACKGROUND: Few efficacious topical therapies exist for chronic rhinosinusitis (CRS). The lack of a reproducible mouse model of CRS limits the pilot testing of potential novel anti-inflammatory therapies. Although the ovalbumin-induced mouse model of sinonasal inflammation is commonly used, it is difficult to reproduce and can generate variable histologic results. In this study, we explore a variation of this model in different strains of mice and explore various inflammatory cytokines as reproducible molecular markers of inflammation.
METHODS: Allergic sinonasal inflammation was generated in BALB/c and C57BL/6 mice using intraperitoneal high-dose injections of ovalbumin (Ova; Sigma Chemical Co.) followed by 10 days of high-dose intranasal sensitization. Real-time polymerase chain reaction (RT-PCR) for eotaxin, interleukin 4 (IL-4), and IL-13 were measured from sinonasal mucosa. We also pilot tested a known topical budesonide to characterize the anti-inflammatory response. Histological sections were analyzed for epithelial thickness and eosinophilia.
RESULTS: Both BALB/c and C57BL/6 mice consistently showed increases in T helper 2 (Th2) cytokines after sensitization with high-dose Ova (p < 0.0001) when compared to controls. There were also significant increases in epithelial thickening in Ova-sensitized mice and eosinophilia in both BALB/c and C57BL/6 strains. In addition, topical budesonide significantly reduced anti-inflammatory cytokines, eosinophilia, and epithelial thickness.
CONCLUSION: Our variation of the ovalbumin-induced mouse model of sinonasal inflammation in both BALB/c and C57BL/6 mice provides an efficacious model for testing potential topical anti-inflammatory therapies for CRS. The utilization of sinonasal mucosal Th2 cytokines along with histologic markers provides a consistent and quantifiable marker of inflammation in assessing the efficacy of candidate drugs.

PMID: 27060366 [PubMed - as supplied by publisher]

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Tumor necrosis factor-α regulates interleukin-33 expression through extracellular signal-regulated kinase, p38, and nuclear factor-κB pathways in airway epithelial cells.

Tumor necrosis factor-α regulates interleukin-33 expression through extracellular signal-regulated kinase, p38, and nuclear factor-κB pathways in airway epithelial cells.

Int Forum Allergy Rhinol. 2016 Apr 5;

Authors: Park IH, Park JH, Shin JM, Lee HM

Abstract
BACKGROUND: Interleukin (IL)-33 plays an important role in controlling immune responses in barrier tissues, and is a potent mediator of inflammatory diseases such as asthma, rheumatoid disease, and chronic rhinosinusitis. The aims of the present study were 2-fold: (1) to determine the stimulatory effect of tumor necrosis factor-α (TNF-α) on IL-33 production in nasal epithelial and A549 cells; and (2) to identify downstream pathways that activate IL-33 production.
METHODS: Primary nasal epithelial cells (PNECs) from 5 normal patients were isolated and cultured. To identify which cytokines stimulate IL-33 production, we performed reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. Three mitogen-activated protein kinases (MAPKs) (p38, extracellular signal-regulated kinase [ERK], and c-Jun N-terminal kinase [JNK]) and nuclear factor κB (NF-κB) were evaluated as downstream signaling molecules by RT-PCR, ELISA, Western blot analysis, and luciferase reporter assay.
RESULTS: The IL-33 messenger RNA (mRNA) and protein levels were increased significantly by TNF-α in PNECs and A549 cells. TNF-α stimulated the expression of IL-33 in a dose- and time-dependent manner in A549 cells. PNECs and A549 cells were treated with TNF-α in the presence of specific inhibitors of p38, ERK, JNK, and NF-κB. In both cell types, inhibitors of ERK, p38, and NF-κB reversed TNF-α-induced IL-33 production. In the luciferase reporter assay, NF-κB activity was inhibited not only by an NF-κB inhibitor, but also by ERK and p38 inhibitors.
CONCLUSION: TNF-α stimulated IL-33 expression through ERK, p38, and NFκB pathways in PNECs and A549 cells.

PMID: 27060290 [PubMed - as supplied by publisher]

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FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases.

FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases.

Nucleic Acids Res. 2016 Apr 7;

Authors: Kuchta K, Muszewska A, Knizewski L, Steczkiewicz K, Wyrwicz LS, Pawlowski K, Rychlewski L, Ginalski K

Abstract
FAM46 proteins, encoded in all known animal genomes, belong to the nucleotidyltransferase (NTase) fold superfamily. All four human FAM46 paralogs (FAM46A, FAM46B, FAM46C, FAM46D) are thought to be involved in several diseases, with FAM46C reported as a causal driver of multiple myeloma; however, their exact functions remain unknown. By using a combination of various bioinformatics analyses (e.g. domain architecture, cellular localization) and exhaustive literature and database searches (e.g. expression profiles, protein interactors), we classified FAM46 proteins as active non-canonical poly(A) polymerases, which modify cytosolic and/or nuclear RNA 3' ends. These proteins may thus regulate gene expression and probably play a critical role during cell differentiation. A detailed analysis of sequence and structure diversity of known NTases possessing PAP/OAS1 SBD domain, combined with state-of-the-art comparative modelling, allowed us to identify potential active site residues responsible for catalysis and substrate binding. We also explored the role of single point mutations found in human cancers and propose that FAM46 genes may be involved in the development of other major malignancies including lung, colorectal, hepatocellular, head and neck, urothelial, endometrial and renal papillary carcinomas and melanoma. Identification of these novel enzymes taking part in RNA metabolism in eukaryotes may guide their further functional studies.

PMID: 27060136 [PubMed - as supplied by publisher]

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What vestibular tests to choose in symptomatic patients after a cochlear implant? A systematic review and meta-analysis.

What vestibular tests to choose in symptomatic patients after a cochlear implant? A systematic review and meta-analysis.

Eur Arch Otorhinolaryngol. 2016 Apr 8;

Authors: Abouzayd M, Smith PF, Moreau S, Hitier M

Abstract
Vestibular function after cochlear implantation is difficult to understand, as subjective vestibular symptoms seem uncorrelated with the results of objective tests. Consequently, clinicians may struggle to decide what assessments to perform for a symptomatic patient. We used a systematic review and meta-analysis approach to enlighten this point. After a study inclusion process, results were classified into four different groups for each test in each study: (1) 'true positive' if the test showed impairment from pre-operative to post-operative in symptomatic patients; (2) 'false positive' if the test showed impairment from pre-operative to post-operative in asymptomatic patients; (3) 'true negative' if the test showed no impairment in asymptomatic patients; and (4) 'false negative' if the test showed no impairment in symptomatic patients. From these groups, sensitivities and specificities of each test were calculated in a meta-analysis. After reviewing more than 3000 references, 16 studies were included, representing 957 patients. The meta-analysis revealed a sensitivity of 0.21 (CI 95 % 0.08-0.40) for the caloric tests, of 0.32 (CI 95 % 0.15-0.54) for the cervical vestibular evoked myogenic potentials (c-VEMP), and of 0.5 (CI 95 % 0.07-0.93) for the head impulse tests. The analysis of prevalence revealed that c-VEMPs were the most often impaired, and the HIT the most often conserved. Our review and meta-analysis revealed that no vestibular test is sensitive enough to be recommended as a single test. Ideally, all the five vestibular sensors should be tested. In clinical practice, we suggest a case-to-case strategy according to patient's symptoms and their suspected origin.

PMID: 27059840 [PubMed - as supplied by publisher]

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Concerning: Subtotal facial nerve decompression in preventing further recurrence and promoting facial nerve recovery of severe idiopathic recurrent facial palsy (Wu SH et al., Eur Arch Otorhinolaryngol. 2015;272(11):3295-8. doi:10.1007/s00405-014-2991-9. Epub 2014 Mar 12).

Concerning: Subtotal facial nerve decompression in preventing further recurrence and promoting facial nerve recovery of severe idiopathic recurrent facial palsy (Wu SH et al., Eur Arch Otorhinolaryngol. 2015;272(11):3295-8. doi:10.1007/s00405-014-2991-9. Epub 2014 Mar 12).

Eur Arch Otorhinolaryngol. 2016 Apr 8;

Authors: Wittekindt C, Kroll T

PMID: 27059838 [PubMed - as supplied by publisher]

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Vibratory stimulus reduces in vitro biofilm formation on tracheoesophageal voice prostheses.

Vibratory stimulus reduces in vitro biofilm formation on tracheoesophageal voice prostheses.

Laryngoscope. 2016 Apr 5;

Authors: Wannemuehler TJ, Lobo BC, Johnson JD, Deig CR, Ting JY, Gregory RL

Abstract
OBJECTIVES/HYPOTHESIS: Demonstrate that biofilm formation will be reduced on tracheoesophageal prostheses when vibratory stimulus is applied, compared to controls receiving no vibratory stimulus, in a dynamic in vitro model of biofilm accumulation simulating the interface across the tracheoesophageal puncture site.
STUDY DESIGN: Prospective, randomized, controlled, crossover in university laboratory.
METHODS: Ex vivo tracheoesophageal prostheses were obtained from university-affiliated speech language pathologists at Indiana University School of Medicine, Indianapolis. Prostheses demonstrating physical integrity and an absence of gross biofilm accumulation were utilized. Sixteen prostheses were cleansed and sterilized prior to random placement by length in two modified Robbins devices arranged in parallel. Each device was seeded with a polymicrobial oral flora on day 1 and received basal artificial salivary flow continuously with three growth medium meals daily. One device was randomly selected for vibratory stimulus, and 2 minutes of vibration was applied to each prosthesis before and after meals for 5 days. The prostheses were explanted and sonicated, and the biofilm cultured for enumeration. This process was repeated after study arm crossover.
RESULTS: Tracheoesophageal prostheses in the dynamic model receiving vibratory stimulus demonstrated reduced gross biofilm accumulation and a significant biofilm colony forming unit per milliliter reduction of 5.56-fold compared to nonvibratory controls (P < 0.001). Significant reductions were observed within length subgroups.
CONCLUSION: Application of vibratory stimulus around meal times significantly reduces biofilm accumulation on tracheoesophageal prostheses in a dynamic in vitro model. Further research using this vibratory stimulus method in vivo will be required to determine if reduced biofilm accumulation correlates with longer device lifespan.
LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.

PMID: 27059830 [PubMed - as supplied by publisher]

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Reply to "In reference to What Is the Optimal Perioperative Management of Antiplatelet Therapy?"

Reply to "In reference to What Is the Optimal Perioperative Management of Antiplatelet Therapy?"

Laryngoscope. 2016 Apr 5;

Authors: Shah RR, Lalwani AK

PMID: 27059712 [PubMed - as supplied by publisher]

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Controlled-Potential Electromechanical Reshaping of Cartilage.

Controlled-Potential Electromechanical Reshaping of Cartilage.

Angew Chem Int Ed Engl. 2016 Apr 5;

Authors: Hunter BM, Kallick J, Kissel J, Herzig M, Manuel C, Protsenko D, Wong BJ, Hill MG

Abstract
An alternative to conventional "cut-and-sew" cartilage surgery, electromechanical reshaping (EMR) is a molecular-based modality in which an array of needle electrodes is inserted into cartilage held under mechanical deformation by a jig. Brief (ca. 2 min) application of an electrochemical potential at the water-oxidation limit results in permanent reshaping of the specimen. Highly sulfated glycosaminoglycans within the cartilage matrix provide structural rigidity to the tissue through extensive ionic-bonding networks; this matrix is highly permselective for cations. Our studies indicate that EMR results from electrochemical generation of localized, low-pH gradients within the tissue: fixed negative charges in the proteoglycan matrix are protonated, resulting in chemically induced stress relaxation of the tissue. Re-equilibration to physiological pH restores the fixed negative charges, and yields remodeled cartilage that retains a new shape approximated by the geometry of the reshaping jig.

PMID: 27059655 [PubMed - as supplied by publisher]

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Transorbital endoscopic assisted management of intraorbital lesions: lessons learned from our first 9 cases.

Transorbital endoscopic assisted management of intraorbital lesions: lessons learned from our first 9 cases.

Rhinology. 2016 Apr 9;

Authors: Dallan I, Castelnuovo P, Turri-Zanoni M, Fiacchini G, Locatelli D, Battaglia P, Sellari-Franceschini S

Abstract
BACKGROUND: The management of intraorbital lesions is challenging and it is strongly dependent to their nature, position and biological behaviour. Traditionally, the superior and lateral compartments of the orbit are addressed via lateral orbitotomy or transcranial approaches. Herein we present our preliminary experience in the management of selected supero-lateral intraorbital lesion through an endoscopic-assisted superior-eyelid approach.
METHODOLOGY: All cases of intraorbital lesion treated in two Italian tertiary care referral centres using a superior eyelid endoscopic-assisted transorbital approach were retrospectively reviewed.
RESULTS: Nine patients have been analysed. The aim of surgery was diagnostic in 5 cases and curative in the remaining 4 patients. Significant tissue biopsy was obtained in all the five diagnostic procedures. Complete resection was obtained in 3/4 lesions. No major intra- or postoperative complications have been observed. Mean surgical time was 68 minutes. Mean hospitalization time was 4.4 days. All patients were satisfied about the surgical procedure, as emerged by the post-operative counselling. At present, the mean follow-up time is 18 months, ranging from 11 to 25 months.
CONCLUSIONS: Our preliminary results are promising with successful functional and cosmetic outcomes and reduced morbidity for the patient. This approach should be considered as an option for selected intraorbital lesions.

PMID: 27059408 [PubMed - as supplied by publisher]

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Drug-induced sleep endoscopy in children with Prader-Willi syndrome.

Drug-induced sleep endoscopy in children with Prader-Willi syndrome.

Sleep Breath. 2016 Apr 8;

Authors: Lan MC, Hsu YB, Lan MY, Chiu TJ, Huang TT, Wong SB, Chen YC, Tsai LP

Abstract
PURPOSE: Review drug-induced sleep endoscopy (DISE) findings in children with Prader-Willi syndrome (PWS) and correlate the patterns of airway collapse with apnea-hypopnea index (AHI) and body mass index (BMI).
METHODS: A total of nine children with PWS underwent DISE. DISE findings were recorded using the VOTE classification system. The relationship between different patterns of airway collapse with AHI and BMI was analyzed.
RESULTS: The majority of children with PWS were found to have multilevel obstruction (six out of nine children, 66.6 %). The velum was the most common site of obstruction (nine out of nine children, 100 %). All of the patients had positional obstructive sleep apnea (OSA). Patients with partial or complete anterior-posterior tongue base collapse were associated with a significantly higher AHI (P = 0.016) compared to patients with no anterior-posterior tongue base collapse. Apart from tongue base collapse, no other patterns of airway collapse showed a consistent association with AHI in our results. No patterns of airway collapse showed a significant association with BMI in our study.
CONCLUSIONS: In our study, partial or complete anterior-posterior tongue base collapse was associated with higher AHI values in children with PWS. Therefore, careful attention should be addressed to the management of tongue base collapse. Positional therapy could be a potential treatment for patients with PWS since it may alleviate the severity of tongue base collapse.

PMID: 27059377 [PubMed - as supplied by publisher]

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Expanded endoscopic endonasal surgery for advanced stage juvenile angiofibromas: a retrospective multi-center study.

Expanded endoscopic endonasal surgery for advanced stage juvenile angiofibromas: a retrospective multi-center study.

Rhinology. 2016 Apr 9;

Authors: Langdon C, Herman P, Verillaud B, Carrau RL, Prevedello D, Nicolai P, Schreiber A, Padoan G, Castelnuovo P, Bernal-Sprekelsen M

Abstract
OBJECTIVES: Endoscopic resection has become an established surgical option for most juvenile nasopharyngeal angiofibromas (JNA). However, surgical management of JNA with intracranial extension remains challenging. This retrospective multicenter study reviews a series of patients with advanced stage JNA treated via endonasal/endoscopic approach.
METHODS: The experience of five academic tertiary or quaternary care ORL-HNS Departments were included. Medical records of all patients operated for JNA staged as Radkowski stage IIIA or IIIB were reviewed. Main outcome measures included intraoperative blood loss, length of hospital stay, complication rate, and rate of persistence or recurrence.
RESULTS: A total of 74 male patients with stages IIIA and IIIB were included. The mean age was 16.4 years and preoperative embolization was performed in 71 patients. The mean blood loss in 45 patients for whom the data was available was 1279.7 ml. The more anatomic subsites were involved, the higher the risk was of intraoperative bleeding. The mean follow-up for 54 out of 73 patients was 37.9 months. Patients with residual disease are significantly linked to involvement of combined (anterior-lateral and posterior) anatomic subsites and to a higher number of affected subsites. At last follow-up, all patients were asymptomatic and those with residual tissue displayed no imaging signs of growth.
CONCLUSIONS: This retrospective multicenter study supports the notion that expanded endonasal endoscopic approaches for advance staged JNA are a feasible option associated with good long-term results.

PMID: 27059153 [PubMed - as supplied by publisher]

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Biomechanical assessment of fixation methods for segmental mandible reconstruction with fibula in the polyurethane model.

Biomechanical assessment of fixation methods for segmental mandible reconstruction with fibula in the polyurethane model.

Microsurgery. 2016 Apr 5;

Authors: Fontana SC, Smith RB, Nazir N, Andrews BT

Abstract
BACKGROUND: A variety of plating techniques are employed by microsurgeons to provide rigid fixation for vascularized bone constructs of the mandible. The aim of this study was to biomechanically compare three commonly utilized plating techniques for rigid fixation of fibula bone flaps in reconstructing lateral segmental mandibular defects.
MATERIALS AND METHODS: Polyurethane mandibles with 3-cm segmental defects were reconstructed using polyurethane fibula models. Three fixation techniques were compared (n = 5 models per group): Group 1 used two 2.0-mm miniplates at each osteotomy site, Group 2 used a single 2.3-mm plate, and Group 3 used a single 2.7-mm plate. Biomechanical testing of maximum force and displacement at failure for each plating technique was assessed and statistical comparison performed.
RESULTS: The average displacement for Group 1 was 14.08 ± 1.42 mm, Group 2 was 5.79 ± 0.89 mm, and Group 3 was 6.03 ± 1.59 mm. Group 1 had significantly greater (P < 0.05) displacement when compared with Group 2 and 3. Analysis of variance demonstrated the three groups varied significantly in mean displacement (0 < 0.01). The average force before failure for Group 1 was 616.4 ± 33.83N, Group 2 was 737.8 ± 72.57N, and Group 3 was 681.0 ± 67.98N. Group 2 withstood significantly greater force than Group 1 (P < 0.05), and withstood greater force than Group 3, although the difference was not significant. Analysis of variance showed the three groups varied significantly in mean force at failure (P < 0.05).
CONCLUSION: Reconstruction using a single 2.3-mm plate provided the best rigid fixation for lateral segmental defects of the mandible. © 2016 Wiley Periodicals, Inc. Microsurgery, 2016.

PMID: 27059150 [PubMed - as supplied by publisher]

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Real-life study showing better control of allergic rhinitis by immunotherapy than regular pharmacotherapy.

Real-life study showing better control of allergic rhinitis by immunotherapy than regular pharmacotherapy.

Rhinology. 2016 Apr 9;

Authors: Droessaert V, Timmermans M, Dekimpe E, Seys S, Ceuppens JJ, Fokkens WJ, Hellings PW

Abstract
BACKGROUND: Treatment for allergic rhinitis (AR) aims at reducing the burden of allergic inflammation, either by suppression of the nasal inflammation with pharmacotherapy or by inducing tolerance via immunotherapy (IT). At present, we lack information on the comparison between the degree of symptom control in AR patients treated with IT and those on pharmacotherapy.
AIMS: An observational study was conducted evaluating the degree of symptom control, the total and individual nasal symptom severity and current medication use at 3 years after starting either pharmacotherapy or subcutaneous immunotherapy (SCIT) for AR.
METHODS: A total number of 800 patients diagnosed with AR between October 2007 and February 2010 at the Ear, Nose and Throat Unit and Allergology Clinical Department of the University Hospitals of KU Leuven, Belgium, were included. Among these patients, 120 had been started on IT at the time of their initial visit, and 680 were prescribed guideline-based pharmacotherapy. In 2013, patients were sent a questionnaire asking for the current severity of nasal symptoms using a visual analogue scale (VAS) score, duration of nasal symptoms and presence or absence of abnormal sleep, impairment of daily activities, sport, leisure, impaired functioning at work/school, troublesome symptoms, and current medication use. A VAS score for total nasal symptoms (TNS) was used to distinguish between controlled and uncontrolled AR.
RESULTS: An overall response rate of 54%. At 3 years after the initiation of the treatment, the IT group showed lower VAS scores for TNS than the pharmacotherapy group, with lower percentages of patients having a VAS score of equal or higher than 5. The IT group consisted of more patients with mild AR than the pharmacotherapy group despite the higher percentage of polysensitization at the onset of treatment in the IT group. 18% of the IT patients met the criteria of persistent AR whereas this was 51% amongst non-IT patients. Interestingly, 70% of IT patients did not use any medical treatment for AR anymore, whereas 61% of pharmacotherapy patients were still on medical treatment.
CONCLUSIONS: This observational study demonstrates that IT is associated with higher control of AR, reduced symptom severity and reduced medication use at 3 years after the onset of treatment. Therefore, this real-life study reinforces the clinical value of immunotherapy in allergic rhinitis.

PMID: 27059095 [PubMed - as supplied by publisher]

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Neurological involvement in hereditary hemorrhagic telangiectasia.

Neurological involvement in hereditary hemorrhagic telangiectasia.

J Neuroradiol. 2016 Apr 5;

Authors: Labeyrie PE, Courthéoux P, Babin E, Bergot E, Touzé E, Pelage JP

Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by epistaxis, telangiectases, and multi-organ vascular dysplasia. Head and neck localizations of HHT are recurrent, frequent associated with serious complications. The aim of this study was to describe the clinical and imaging patterns of neurological involvement in HHT and to discuss the role of interventional radiology in the management of HHT patients. Based on a multidisciplinary experience of twenty years at our center, we report here the different aspects of neurological involvement of HHT. Depending on the genetic type of the disease, vascular abnormalities may affect different organs. The knowledge of neurological involvement according to specific localization of HHT makes detection easier. As cerebral or spinal arteriovenous fistula may be present in patients with epistaxis or pulmonary arteriovenous malformations (PAVMs), radiologists should be able to detect high-risk lesions and prevent related complications. Finally, we review indications and techniques of embolization for hemorrhagic lesions and emphasize that endovascular therapies are very effective and safe in experienced hands. Head and neck imaging is commonly used for the diagnosis of HHT. Imaging plays also a key role for patient evaluation before treatment as pluridisciplinary management is needed.

PMID: 27059009 [PubMed - as supplied by publisher]

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Kimura Disease of the Breast - A Previously Undescribed Entity.

Kimura Disease of the Breast - A Previously Undescribed Entity.

Breast J. 2016 Apr 5;

Authors: Kakkar A, Gupta RK, Khanna P, Balasundaram P, Ray R, Shukla NK

Abstract
Kimura disease (KD) is a rare chronic inflammatory disorder of unknown etiology, primarily seen in young Asian males. The disease is characterized by a triad of painless subcutaneous masses in the head and neck region, blood and tissue eosinophilia, and elevated serum immunoglobulin E levels. We report an unusual case of a 40-year-old woman found to have KD of the breast which presented clinically as carcinoma, leading to a diagnostic dilemma. To the best of our knowledge, this is the first case of KD in the breast to be documented in the literature. The patient also had scabies, which may have provided the stimulus for hypersensitivity, which is considered to be the pathogenetic mechanism responsible for development of KD.

PMID: 27058987 [PubMed - as supplied by publisher]

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Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.

Related Articles

Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.

Nat Commun. 2015;6:7353

Authors: Cai L, Ye Y, Jiang Q, Chen Y, Lyu X, Li J, Wang S, Liu T, Cai H, Yao K, Li JL, Li X

Abstract
Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC.

PMID: 26135619 [PubMed - indexed for MEDLINE]

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A natural food sweetener with anti-pancreatic cancer properties

A natural food sweetener with anti-pancreatic cancer properties

Oncogenesis 5, e217 (April 2016). doi:10.1038/oncsis.2016.28

Authors: C Liu, L-H Dai, D-Q Dou, L-Q Ma & Y-X Sun

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Assessing the validity of subjective reports in the auditory streaming paradigm

While subjective reports provide a direct measure of perception, their validity is not self-evident. Here, the authors tested three possible biasing effects on perceptual reports in the auditory streaming paradigm: errors due to imperfect understanding of the instructions, voluntary perceptual biasing, and susceptibility to implicit expectations. (1) Analysis of the responses to catch trials separately promoting each of the possible percepts allowed the authors to exclude participants who likely have not fully understood the instructions. (2) Explicit biasing instructions led to markedly different behavior than the conventional neutral-instruction condition, suggesting that listeners did not voluntarily bias their perception in a systematic way under the neutral instructions. Comparison with a random response condition further supported this conclusion. (3) No significant relationship was found between social desirability, a scale-based measure of susceptibility to implicit social expectations, and any of the perceptual measures extracted from the subjective reports. This suggests that listeners did not significantly bias their perceptual reports due to possible implicit expectations present in the experimental context. In sum, these results suggest that valid perceptual data can be obtained from subjective reports in the auditory streaming paradigm.

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Computationally efficient method for estimation of angle of arrival with non-uniform reconfigurable receiver arrays

The main focus of this paper is the design and formulation of a computationally efficient approach to the estimation of the angle of arrival with non-uniform reconfigurable receiver arrays. Subsequent to demodulation and matched filtering, the main signal processing task is a double-integration operation. The simplicity of this algorithm enables the implementation of the estimation procedure with simple operational amplifier (op-amp) circuits for real-time realization. This technique does not require uniform and structured array configurations, and is most effective for the estimation of angle of arrival with dynamically reconfigurable receiver arrays.

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The role of continuous low-frequency harmonicity cues for interrupted speech perception in bimodal hearing

Low-frequency acoustic cues have been shown to enhance speech perception by cochlear-implant users, particularly when target speech occurs in a competing background. The present study examined the extent to which a continuous representation of low-frequency harmonicity cues contributes to bimodal benefit in simulated bimodal listeners. Experiment 1 examined the benefit of restoring a continuous temporal envelope to the low-frequency ear while the vocoder ear received a temporally interrupted stimulus. Experiment 2 examined the effect of providing continuous harmonicity cues in the low-frequency ear as compared to restoring a continuous temporal envelope in the vocoder ear. Findings indicate that bimodal benefit for temporally interrupted speech increases when continuity is restored to either or both ears. The primary benefit appears to stem from the continuous temporal envelope in the low-frequency region providing additional phonetic cues related to manner and F1 frequency; a secondary contribution is provided by low-frequency harmonicity cues when a continuous representation of the temporal envelope is present in the low-frequency, or both ears. The continuous temporal envelope and harmonicity cues of low-frequency speech are thought to support bimodal benefit by facilitating identification of word and syllable boundaries, and by restoring partial phonetic cues that occur during gaps in the temporally interrupted stimulus.

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Predictions of middle-ear and passive cochlear mechanics using a finite element model of the pediatric ear

A finite element (FE)model was developed based on histological sections of a temporal bone of a 4-year-old child to simulate middle-ear and cochlear function in ears with normal hearing and otitis media. This pediatric model of the normal ear, consisting of an ear canal, middle ear, and spiral cochlea, was first validated with published energy absorbance (EA) measurements in young children with normal ears. The model was used to simulate EA in an ear with middle-ear effusion, whose results were compared to clinical EA measurements. The spiral cochlea component of the model was constructed under the assumption that the mechanics were passive. The FEmodel predicted middle-ear transfer functions between the ear canal and cochlea. Effects of ear structure and mechanical properties of soft tissues were compared in model predictions for the pediatric and adult ears. EA responses are predicted to differ between adult and pediatric ears due to differences in the stiffness and damping of soft tissues within the ear, and any residual geometrical differences between the adult ear and pediatric ear at age 4 years. The results have significance for predicting effects of otitis media in children.

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Is aerobic workload positively related to ambulatory blood pressure?: a cross-sectional field study among cleaners

Cardiovascular disease is prevalent among workers with high levels of occupational physical activity. The increased risk may be due to a high relative aerobic workload, possibly leading to increased blood pressure. However, studies investigating the relation between relative aerobic workload and ambulatory blood pressure (ABP) are lacking. The aim was to explore the relationship between objectively measured relative aerobic workload and ABP. A total of 116 cleaners aged 18-65 years were included after informed consent was obtained. A portable device (Spacelabs 90217) was mounted for 24-h measurements of ABP, and an Actiheart was mounted for 24-h heart rate measurements to calculate relative aerobic workload as percentage of relative heart rate reserve. A repeated-measure multi-adjusted mixed model was applied for analysis. A fully adjusted mixed model of measurements throughout the day showed significant positive relations (p < 0.001): a 1 % increase in mean relative aerobic workload was associated with an increase of 0.42 +/- A 0.05 mmHg (95 % CI 0.32-0.52 mmHg) in systolic ABP and 0.30 +/- A 0.04 mmHg (95 % CI 0.22-0.38 mmHg) in diastolic ABP. Correlations between relative aerobic workload and ABP were significant. Because workers may have an elevated relative aerobic workload for several hours each working day, this relationship may elucidate a mechanism behind the increased risk for cardiovascular disease among workers exposed to high levels of occupational physical activity.

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Respiratory muscle endurance, oxygen saturation index in vastus lateralis and performance during heavy exercise

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Factors associated with low back pain before pubertal peak growth

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Sagittal whole-body postural balance: the missing link between sagittal spinopelvic alignment and coronal plane trunk asymmetry?

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Fysiologie van Duchenne musculaire dystrofie: invloed van calcium in de spiercel

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Identifying profiles of actual and perceived motor competence among adolescents: associations with motivation, physical activity, and sports participation

The present study identified adolescents' motor competence (MC)-based profiles (e.g., high actual and low perceived MC), and accordingly investigated differences in motivation for physical education (PE), physical activity (PA) levels, and sports participation between profiles by using regression analyses. Actual MC was measured with the Körperkoordinationstest für Kinder. Adolescents (n = 215; 66.0% boys; mean age = 13.64 ± .58 years) completed validated questionnaires to assess perceived MC, motivation for PE, PA-levels, and sports participation. Actual and perceived MC were only moderately correlated and cluster analyses identified four groups. Two groups of overestimators (low - overestimation, average - overestimation) were identified (51%), who particularly displayed better motivation for PE when compared to their peers who accurately estimated themselves (low - accurate, average - accurate). Moreover, adolescents with low actual MC, but high perceived MC were significantly more active than adolescents with low actual MC who accurately estimated themselves. Results pointed in the same direction for organised sports participation. Underestimators were not found in the current sample, which is positive as underestimation might negatively influence adolescents' motivation to achieve and persist in PA and sports. In conclusion, results emphasise that developing perceived MC, especially among adolescents with low levels of actual MC, seems crucial to stimulate motivation for PE, and engagement in PA and sports.

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P53- and mevalonate pathway-driven malignancies require Arf6 for metastasis and drug resistance

Drug resistance, metastasis, and a mesenchymal transcriptional program are central features of aggressive breast tumors. The GTPase Arf6, often overexpressed in tumors, is critical to promote epithelial–mesenchymal transition and invasiveness. The metabolic mevalonate pathway (MVP) is associated with tumor invasiveness and known to prenylate proteins, but which prenylated proteins are critical for MVP-driven cancers is unknown. We show here that MVP requires the Arf6-dependent mesenchymal program. The MVP enzyme geranylgeranyl transferase II (GGT-II) and its substrate Rab11b are critical for Arf6 trafficking to the plasma membrane, where it is activated by receptor tyrosine kinases. Consistently, mutant p53, which is known to support tumorigenesis via MVP, promotes Arf6 activation via GGT-II and Rab11b. Inhibition of MVP and GGT-II blocked invasion and metastasis and reduced cancer cell resistance against chemotherapy agents, but only in cells overexpressing Arf6 and components of the mesenchymal program. Overexpression of Arf6 and mesenchymal proteins as well as enhanced MVP activity correlated with poor patient survival. These results provide insights into the molecular basis of MVP-driven malignancy.

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Doa1 targets ubiquitinated substrates for mitochondria-associated degradation

Mitochondria-associated degradation (MAD) mediated by the Cdc48 complex and proteasome degrades ubiquitinated mitochondrial outer-membrane proteins. MAD is critical for mitochondrial proteostasis, but it remains poorly characterized. We identified several mitochondrial Cdc48 substrates and developed a genetic screen assay to uncover regulators of the Cdc48-dependent MAD pathway. Surprisingly, we identified Doa1, a substrate-processing factor of Cdc48 that inhibits the degradation of some Cdc48 substrates, as a critical mediator of the turnover of mitochondrial Cdc48 substrates. Deletion of DOA1 causes the accumulation and mislocalization of substrates on mitochondria. Profiling of Cdc48 cofactors shows that Doa1 and Cdc48^-Ufd1-Npl4 form a functional complex mediating MAD. Biochemically, Doa1 interacts with ubiquitinated substrates and facilitates substrate recruitment to the Cdc48^-Ufd1-Npl4 complex. Functionally, Doa1 is critical for cell survival under mitochondrial oxidative stress, but not ER stress, conditions. Collectively, our results demonstrate the essential role of the Doa1–Cdc48^-Ufd1-Npl4 complex in mitochondrial proteostasis and suggest that Doa1 plays dual roles on the Cdc48 complex.

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Sigma1 receptors inhibit store-operated Ca2+ entry by attenuating coupling of STIM1 to Orai1

Sigma1 receptors (1Rs) are expressed widely; they bind diverse ligands, including psychotropic drugs and steroids, regulate many ion channels, and are implicated in cancer and addiction. It is not known how 1Rs exert such varied effects. We demonstrate that 1Rs inhibit store-operated Ca²⁺ entry (SOCE), a major Ca²⁺ influx pathway, and reduce the Ca²⁺ content of the intracellular stores. SOCE was inhibited by expression of 1R or an agonist of 1R and enhanced by loss of 1R or an antagonist. Within the endoplasmic reticulum (ER), 1R associated with STIM1, the ER Ca²⁺ sensor that regulates SOCE. This interaction was modulated by 1R ligands. After depletion of Ca²⁺ stores, 1R accompanied STIM1 to ER–plasma membrane (PM) junctions where STIM1 stimulated opening of the Ca²⁺ channel, Orai1. The association of STIM1 with 1R slowed the recruitment of STIM1 to ER–PM junctions and reduced binding of STIM1 to PM Orai1. We conclude that 1R attenuates STIM1 coupling to Orai1 and thereby inhibits SOCE.

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Kindlin-2 directly binds actin and regulates integrin outside-in signaling

Reduced levels of kindlin-2 (K2) in endothelial cells derived from K2^+/– mice or C2C12 myoblastoid cells treated with K2 siRNA showed disorganization of their actin cytoskeleton and decreased spreading. These marked changes led us to examine direct binding between K2 and actin. Purified K2 interacts with F-actin in cosedimentation and surface plasmon resonance analyses and induces actin aggregation. We further find that the F0 domain of K2 binds actin. A mutation, LK⁴⁷/AA, within a predicted actin binding site (ABS) of F0 diminishes its interaction with actin by approximately fivefold. Wild-type K2 and K2 bearing the LK⁴⁷/AA mutation were equivalent in their ability to coactivate integrin αIIbβ3 in a CHO cell system when coexpressed with talin. However, K2-LK⁴⁷/AA exhibited a diminished ability to support cell spreading and actin organization compared with wild-type K2. The presence of an ABS in F0 of K2 that influences outside-in signaling across integrins establishes a new foundation for considering how kindlins might regulate cellular responses.

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Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate phosphoinositides

Endoplasmic reticulum–plasma membrane (ER–PM) contact sites play an integral role in cellular processes such as excitation–contraction coupling and store-operated calcium entry (SOCE). Another ER–PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER–PM junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P₂. Activation of G protein–coupled receptors that deplete PM PI(4,5)P₂ disrupts E-Syt2–mediated ER–PM junctions, reducing Sac1's access to the PM and permitting PM PI(4)P and PI(4,5)P₂ to recover. Conversely, depletion of ER luminal calcium and subsequent activation of SOCE increases the amount of Sac1 in contact with the PM, depleting PM PI(4)P. Thus, the dynamic presence of Sac1 at ER–PM contact sites allows it to act as a cellular sensor and controller of PM phosphoinositides, thereby influencing many PM processes.

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Metalloproteinase MT1-MMP islets act as memory devices for podosome reemergence

Podosomes are dynamic cell adhesions that are also sites of extracellular matrix degradation, through recruitment of matrix-lytic enzymes, particularly of matrix metalloproteinases. Using total internal reflection fluorescence microscopy, we show that the membrane-bound metalloproteinase MT1-MMP is enriched not only at podosomes but also at distinct "islets" embedded in the plasma membrane of primary human macrophages. MT1-MMP islets become apparent upon podosome dissolution and persist beyond podosome lifetime. Importantly, the majority of MT1-MMP islets are reused as sites of podosome reemergence. siRNA-mediated knockdown and recomplementation analyses show that islet formation is based on the cytoplasmic tail of MT1-MMP and its ability to bind the subcortical actin cytoskeleton. Collectively, our data reveal a previously unrecognized phase in the podosome life cycle and identify a structural function of MT1-MMP that is independent of its proteolytic activity. MT1-MMP islets thus act as cellular memory devices that enable efficient and localized reformation of podosomes, ensuring coordinated matrix degradation and invasion.

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