Head and Neck Diseases by Alexandros G.Sfakianakis: 02/04/16

Πέμπτη 4 Φεβρουαρίου 2016

Medtech approvals: FDA releases December 2015 PMAs

The Food & Drug Administration today released a list of pre-market approvals granted in December 2015: Summary of PMA Originals & Supplements Approved Originals: 2 Supplements: 81 Summary of PMA Originals Under Review Total Under Review: 58 Total Active: 32 Total On Hold: 26 Summary of PMA Supplements Under Review Total Under Review: 599 Total Active: 423 Total On Hold: 176 Summary of All PMA Submissions Originals: 3 Supplements: 92 Summary of PMA Supplement PMA Approval/Denial Decision Times Number of Approvals: 81 Number of Denials: 0 Average Days Fr Receipt to Decision (Total Time): 163.1 FDA Time: 140.4 Days MFR Time: 22.7 Days PMA Original Approvals APPLICATION NUMBER / DATE of APPROVAL DEVICE TRADE NAME COMPANY NAME CITY, STATE, & ZIP DEVICE DESCRIPTION / IN…

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Neural representation of object-specific attentional priority

Publication date: 1 April 2016
Source:NeuroImage, Volume 129
Author(s): Taosheng Liu
Humans can flexibly select locations, features, or objects in a visual scene for prioritized processing. Although it is relatively straightforward to manipulate location- and feature-based attention, it is difficult to isolate object-based selection. Because objects are always composed of features, studies of object-based selection can often be interpreted as the selection of a combination of locations and features. Here we examined the neural representation of attentional priority in a paradigm that isolated object-based selection. Participants viewed two superimposed gratings that continuously changed their color, orientation, and spatial frequency, such that the gratings traversed the same exact feature values within a trial. Participants were cued at the beginning of each trial to attend to one or the other grating to detect a brief luminance increment, while their brain activity was measured with fMRI. Using multi-voxel pattern analysis, we were able to decode the attended grating in a set of frontoparietal areas, including anterior intraparietal sulcus (IPS), frontal eye field (FEF), and inferior frontal junction (IFJ). Thus, a perceptually varying object can be represented by patterned neural activity in these frontoparietal areas. We suggest that these areas can encode attentional priority for abstract, high-level objects independent of their locations and features.

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Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation

Publication date: 1 April 2016
Source:NeuroImage, Volume 129
Author(s): Dorothee Schoemaker, Claudia Buss, Kevin Head, Curt A. Sandman, Elysia P. Davis, M. Mallar Chakravarty, Serge Gauthier, Jens C. Pruessner
The volumetric quantification of brain structures is of great interest in pediatric populations because it allows the investigation of different factors influencing neurodevelopment. FreeSurfer and FSL both provide frequently used packages for automatic segmentation of brain structures. In this study, we examined the accuracy and consistency of those two automated protocols relative to manual segmentation, commonly considered as the "gold standard" technique, for estimating hippocampus and amygdala volumes in a sample of preadolescent children aged between 6 to 11years. The volumes obtained with FreeSurfer and FSL-FIRST were evaluated and compared with manual segmentations with respect to volume difference, spatial agreement and between- and within-method correlations.Results highlighted a tendency for both automated techniques to overestimate hippocampus and amygdala volumes, in comparison to manual segmentation. This was more pronounced when using FreeSurfer than FSL-FIRST and, for both techniques, the overestimation was more marked for the amygdala than the hippocampus. Pearson correlations support moderate associations between manual tracing and FreeSurfer for hippocampus (right r=0.69, p<0.001; left r=0.77, p<0.001) and amygdala (right r=0.61, p<0.001; left r=0.67, p<0.001) volumes. Correlation coefficients between manual segmentation and FSL-FIRST were statistically significant (right hippocampus r=0.59, p<0.001; left hippocampus r=0.51, p<0.001; right amygdala r=0.35, p<0.001; left amygdala r=0.31, p<0.001) but were significantly weaker, for all investigated structures. When computing intraclass correlation coefficients between manual tracing and automatic segmentation, all comparisons, except for left hippocampus volume estimated with FreeSurfer, failed to reach 0.70. When looking at each method separately, correlations between left and right hemispheric volumes showed strong associations between bilateral hippocampus and bilateral amygdala volumes when assessed using manual segmentation or FreeSurfer. These correlations were significantly weaker when volumes were assessed with FSL-FIRST. Finally, Bland–Altman plots suggest that the difference between manual and automatic segmentation might be influenced by the volume of the structure, because smaller volumes were associated with larger volume differences between techniques.These results demonstrate that, at least in a pediatric population, the agreement between amygdala and hippocampus volumes obtained with automated FSL-FIRST and FreeSurfer protocols and those obtained with manual segmentation is not strong. Visual inspection by an informed individual and, if necessary, manual correction of automated segmentation outputs are important to ensure validity of volumetric results and interpretation of related findings.

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Widespread metachronous carcinoid tumour metastases to the head and neck: a unique presentation

Publication date: Available online 4 February 2016
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): Mohamed Koraitim, Anne V. Spedding, Katy Bradley, Peter A. Brennan
Carcinoid tumours are usually slow-growing, neuroendocrine neoplasms that primarily affect the gastrointestinal tract and bronchial tree. Although relatively rare, isolated, single metastasis to the head and neck has been reported. We present a unique case of 6 metachronous carcinoid metastases to both parotid glands, the left submandibular gland, upper lip, and thyroid, over 3 years. To our knowledge, this widespread presentation in the head and neck has not previously been reported.

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Physiology of haemostasis

Publication date: Available online 4 February 2016
Source:Anaesthesia & Intensive Care Medicine
Author(s): James Sira, Lorna Eyre
Haemostasis is a complex and sophisticated process that requires the interplay of multiple physiological pathways. Cellular and molecular mechanisms interact to seal damaged blood vessels with localized clot formation preventing significant bleeding. Once vascular integrity is restored, clot breakdown occurs and normal haemostasis is reinstated. Thrombohaemorrhagic imbalance may occur in the perioperative period or during critical illness, leading to an increased risk of thrombosis, bleeding or in some instances both. Therefore an understanding of the normal physiological processes is important for the anaesthetist as: (i) it allows us to identify targets for the therapeutic modulation of bleeding and thrombosis; (ii) many commonly encountered medications alter the normal haemostatic pathways and it is important to recognize their effects; and (iii) it enables enhanced understanding of the dynamic tests of haemostasis and clotting.

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The genetic assessment of looked after children: common reasons for referral and recent advances

Looked after children are recognised as generally having greater health needs than their peers. There are numerous potential causes, environmental and genetic, and the aetiology is often multifactorial. Assessments, especially clinical genetic ones, may be limited if the information available is incomplete or not shared. There have been some exciting recent advances in diagnostic genetic testing and more are on the horizon. However, we are currently only able to make a genetic diagnosis in less than half of patients, even when both parents are available for comparative testing. There may, therefore, remain an inevitable degree of residual uncertainty about the genetic contribution to a particular child's problems. There are increasing societal pressures for genetic information to be made available to individuals in general. However, there are significant considerations in carrier/predictive testing in children and we would maintain that looked after children should not be treated differently to other children in this regard, unless there is a compelling 'best interest' justification for so doing. Diagnostic criteria exist for fetal alcohol syndrome and other embryopathies and should be applied. Such should be considered as diagnoses of exclusion, so a child should not be prematurely labelled with these conditions, without fully assessing for the contribution of other factors, genetic or otherwise.

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Regulation of Stem Cell Proliferation and Cell Fate Specification by Wingless/Wnt Signaling Gradients Enriched at Adult Intestinal Compartment Boundaries

journal.pgen.1005822.g001

by Ai Tian, Hassina Benchabane, Zhenghan Wang, Yashi Ahmed

Intestinal stem cell (ISC) self-renewal and proliferation are directed by Wnt/β-catenin signaling in mammals, whereas aberrant Wnt pathway activation in ISCs triggers the development of human colorectal carcinoma. Herein, we have utilized the Drosophila midgut, a powerful model for ISC regulation, to elucidate the mechanisms by which Wingless (Wg)/Wnt regulates intestinal homeostasis and development. We provide evidence that the Wg signaling pathway, activation of which peaks at each of the major compartment boundaries of the adult intestine, has essential functions. Wg pathway activation in the intestinal epithelium is required not only to specify cell fate near compartment boundaries during development, but also to control ISC proliferation within compartments during homeostasis. Further, in contrast with the previous focus on Wg pathway activation within ISCs, we demonstrate that the primary mechanism by which Wg signaling regulates ISC proliferation during homeostasis is non-autonomous. Activation of the Wg pathway in absorptive enterocytes is required to suppress JAK-STAT signaling in neighboring ISCs, and thereby their proliferation. We conclude that Wg signaling gradients have essential roles during homeostasis and development of the adult intestine, non-autonomously controlling stem cell proliferation inside compartments, and autonomously specifying cell fate near compartment boundaries.

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The genetic assessment of looked after children: common reasons for referral and recent advances

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TORS for Obstructive Sleep Apnea–Hypopnea Syndrome

Abstract

Trans oral robotic surgery is currently one of several surgical strategies in managing tongue base obstruction in sleep apnea patients. This article outlines a novel way to treat obstructive sleep apnea lingual obstruction using the da Vinci robotic surgical system. This technique offers significant potential advantages over other established approaches and it should be included in the surgical armamentarium of sleep surgeons. Despite a large body of favorable retrospective data, prospective studies are not currently available in order to evaluate the efficacy of robotic approach to tongue base as stand-alone procedure in treating sleep apnea patients.

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Inter-hemispheric connectivity in the fusiform gyrus supports memory consolidation for faces

Abstract

In this study we investigated how changes of functional connectivity over time accompanies consolidation of face memories. Based on previous research we hypothesised that particularly connectivity changes in networks initially active during face perception and face encoding would be associated with individual recognition memory performance. Resting-state functional connectivity was examined shortly before, shortly after and about forty minutes after incidental learning of faces. Memory performance was assessed in a surprise recognition test shortly after the last resting-state session. Results reveal that memory performance related connectivity between the left fusiform face area and other brain areas gradually changed over the course of the experiment. Specifically, the increase in connectivity with the contralateral fusiform gyrus, the hippocampus, the amygdala and the inferior frontal gyrus correlated with recognition memory performance. Since especially the increase in connectivity in the two final resting-state sessions was associated with memory performance the present results demonstrate that memory formation is not restricted to the incidental learning phase but continues and increases in the following forty minutes. We discuss that particularly the delayed increase in inter-hemisphere connectivity between the left and right fusiform gyrus is an indicator for memory formation and consolidation processes.

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Oncogene swap as a novel mechanism of acquired resistance to EGFR-tyrosine kinase inhibitor in lung cancer

Abstract

Mutant selective epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as rociletinib and AZD9291, are effective for tumors with T790M secondary mutation that become refractory to first-generation EGFR-TKIs. However, acquired resistance to these prospective drugs is anticipated considering the high adaptability of cancer cells and the mechanisms remain largely obscure. Here, CNX-2006 (tool compound of rociletinib) resistant sublines were established by chronic exposure of HCC827EPR cells harboring exon 19 deletion and T790M to CNX-2006. Through the analyses of these resistant subclones, we identified two resistant mechanisms accompanied by MET amplification. One was bypass signaling by MET amplification in addition to T790M, which was inhibited by the combination of CNX-2006 and MET-TKI. Another was loss of amplified EGFR mutant allele including T790M while acquiring MET amplification. Interestingly, MET-TKI alone was able to overcome this resistance, suggesting that oncogenic dependence completely shifted from EGFR to MET. We propose to describe this phenomenon as "oncogene swap". Furthermore, we analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKIs. This possibility should be considered in order to avoid futile inhibition of the original oncogene.

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Symptomatic Versus Asymptomatic Colorectal Cancer:

Publication date: Available online 3 February 2016
Source:Academic Radiology
Author(s): Matthew H. Lee, J. Louis Hinshaw, David H. Kim, Perry J. Pickhardt
Rationale and ObjectivesComputed tomographic colonography (CTC) is a robust tool for evaluating colorectal lesions in both screening and diagnostic settings. The purpose of this study was to assess the relationship between colorectal cancer (CRC) tumor characteristics and patient symptomatology.Materials and MethodsThis is a retrospective analysis of all pathology-confirmed cases of CRC evaluated with CTC at our institution from October 2004 to October 2012. Cases were reviewed to determine tumor size, morphology, and degree of luminal narrowing. An electronic medical record review was performed to delineate specific patient symptomatology and determine depth of invasion.ResultsA total of 55 patients (36 symptomatic and 19 asymptomatic) with a total of 63 CRCs were evaluated by CTC during the study time period. The most common symptoms were gastrointestinal (GI) bleeding/anemia (n = 26), followed by obstructive symptoms (n = 23), and constitutional symptoms (n = 5). Symptomatic cancers were more likely to have annular morphology (n = 30/43, 70% vs. n = 3/20, 15%; odds ratio [OR] = 13.1, P = 0.0003), whereas asymptomatic cancers were more likely to be polypoid (n = 11/20, 55% vs. n = 6/43, 14%, OR = 7.5, P = 0.001). Symptomatic cancers were also larger (46.1 ± 22.4 vs. 38.8 ± 18.4 mm, P = 0.005) and resulted in greater luminal narrowing (8.7 ± 8.5 mm vs. 35.8 ± 18.8 mm, P < 0.0001) with deeper invasion (n = 29/35 [invasion unknown for 8 cases], 83% vs. n = 6/20, 30%, OR = 11.3, P = 0.0003). Invasive cancers were more likely to have annular morphology (66%, 23/25, P = 0.002).ConclusionsThere is an intuitive and predictable relationship between tumor characteristics on CTC and patient symptoms. Annular morphology, tumor size, degree of luminal narrowing, and invasive disease all correlate with the presence of symptoms.

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Comparison of Measured and Estimated CT Organ Doses for Modulated and Fixed Tube Current: A Human Cadaver Study

Publication date: Available online 3 February 2016
Source:Academic Radiology
Author(s): Atul Padole, Ranish Deedar Ali Khawaja, Alexi Otrakji, Da Zhang, Bob Liu, X. George Xu, Mannudeep K. Kalra
Rationale and ObjectivesThe aim of this study was to compare the directly measured and the estimated computed tomography (CT) organ doses obtained from commercial radiation dose-tracking (RDT) software for CT performed with modulated tube current or automatic exposure control (AEC) technique and fixed tube current (mAs).Materials and MethodsWith the institutional review board (IRB) approval, the ionization chambers were surgically implanted in a human cadaver (88 years old, male, 68 kg) in six locations such as liver, stomach, colon, left kidney, small intestine, and urinary bladder. The cadaver was scanned with routine abdomen pelvis protocol on a 128-slice, dual-source multidetector computed tomography (MDCT) scanner using both AEC and fixed mAs. The effective and quality reference mAs of 100, 200, and 300 were used for AEC and fixed mAs, respectively. Scanning was repeated three times for each setting, and measured and estimated organ doses (from RDT software) were recorded (N = 3*3*2 = 18).ResultsMean CTDIvol for AEC and fixed mAs were 4, 8, 13 mGy and 7, 14, 21 mGy, respectively. The most estimated organ doses were significantly greater (P < 0.01) than the measured organ doses for both AEC and fixed mAs. At AEC, the mean estimated organ doses (for six organs) were 14.7 mGy compared to mean measured organ doses of 12.3 mGy. Similarly, at fixed mAs, the mean estimated organ doses (for six organs) were 24 mGy compared to measured organ doses of 22.3 mGy. The differences among the measured and estimated organ doses were higher for AEC technique compared to the fixed mAs for most organs (P < 0.01).ConclusionsThe most CT organ doses estimated from RDT software are greater compared to directly measured organ doses, particularly when AEC technique is used for CT scanning.

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Cerebral vasospasm and delayed cerebral infarctions in 225 patients with non-aneurysmal subarachnoid hemorrhage: the underestimated risk of Fisher 3 blood distribution

Objective

Recent data have shown increasing numbers of non-aneurysmal subarachnoid hemorrhage (NASAH). However, data are limited and often only small series have been published. Our objective was to analyze the rate of cerebral vasospasm (CVS), delayed cerebral infarction (DCI), and their influence on the clinical outcome, especially in patients with diffuse Fisher 3 bleeding pattern NASAH (Fi3).

Methods

Between 1999 and 2014, 225 patients had NASAH. CVS, DCI, and outcome (according to the modified Rankin Scale at 6 months) were analyzed retrospectively. Patients were stratified according to the bleeding type. After univariate analysis a multivariate analysis was performed and NASAH Fi3 was also compared with aneurysmal SAH Fi3.

Results

Patient characteristics and the outcome of perimesencephalic (PM) and non-PM (NPM) SAH were similar. Excluding Fi3, PM and NPM without Fi3 had similar patient characteristics, clinical course, and outcome. In particular, the Fi3 subgroup had a significantly increased risk of CVS, DCI, unfavorable outcome, hydrocephalus, and death. Early hydrocephalus was associated with Fi3 and intraventricular hemorrhage. The multivariate regression model showed the variables elderly patients, Fi3, and early hydrocephalus as independent and significant predictors for an unfavorable outcome. A further comparison of NASAH Fi3 with aneurysmal SAH Fi3 showed similar characteristics, CVS rate, and mortality.

Conclusions

Patients with NASAH without a Fi3 bleeding pattern had a similar excellent outcome to patients with PM-SAH. Patients with Fi3 had a high risk for early hydrocephalus, CVS, DCI, and an unfavorable outcome, similar to patients with aneurysmal SAH. After multivariate analysis, early hydrocephalus, elderly patients, and Fi3 were identified as negative prognostic factors. Therefore, patients with Fi3 are at risk and need careful clinical observation.

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Get 25% Off the Biggerplate New York Mind Map Conference

If you're a MindManager user, then you won't want to miss the Biggerplate Unplugged mind mapping conference in New York City on March 10, 2016.

Join the Biggerplate team and a host of fantastic speakers for a full day dedicated to exploring use cases for mind mapping software, practical tips and tricks, as well as interactive workshops that explore the future of mind mapping. What's more, you can get 25% off admission using the code MINDMANAGER25.

Now in its fourth year, Biggerplate Unplugged is firmly established as the global gathering for mind mappers. This event is your chance to connect with and learn from other mind map users before the conference heads back to Europe in 2017.

Speakers include Larry Wolfe from Boeing, who will share how MindManager is being used within the organization, and how a self-organized user group within Boeing has helped enable peer-to-peer learning and adoption of mind mapping as a working tool. We've also got great presentations from Stephanie Diamond, author of Visual Marketing Revolution, and best-selling author Roger C. Parker. These expert content marketers and authors will be sharing their tips on using mind mapping for planning and executing content marketing plans, as well as exploring the ways that mind maps can help with both reading and writing books.

Education expert Toni Krasnic will also be speaking about the use of mind mapping in schools to help students move from collecting dots to connecting dots, while Dr. Pablo Buitron will be exploring the use of mind maps to help med school students prepare for medical exams.

And be sure to join the interactive workshop sessions where you can share your own experiences and insights as we explore what the future holds for mind mapping software.

Don't miss out, space at Biggerplate Unplugged is limited and the event is just a few weeks away! Grab your seat now using the code MINDMANAGER25 and join the mind mapping user community on March 10 in New York City.

Register today! We hope to see you there.

The post Get 25% Off the Biggerplate New York Mind Map Conference appeared first on via @Mindjet Blogs.

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Yes. Yes but.

Yes. Yes absolutely. Yes but.

Yes I agree with every bit of this argument, and have in fact made it myself, (1986) over (1989) and over (2006) again.1–4 I can even argue that it is worse, yet more damaging than the author says, that knowledge of fetal sex damages pregnancy in some fundamental ways. So yes, yes, yes, it would have been a far better thing had these technologies never been invented.

But. They are. The train has left the station, the ship has sailed, the genie is out of the bottle and the fetus is out of the pregnancy.

That perhaps is one of the reasons this technology is more dangerous than originally thought or even than the author, focusing on the consequences of sex selection itself, can discuss here. A sexed fetus is a named fetus, a baby in all but the birth….

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Risk of acute kidney injury associated with neuroimaging obtained during triage and treatment of patients with acute ischemic stroke symptoms

Background

Combining non-contrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) imaging (referred to as a CT stroke study, CTSS) provides a rapid evaluation of the cerebrovascular axis during acute ischemic stroke. Iodinated contrast-enhanced CT imaging is not without risk, which includes renal injury. If a patient's CTSS identifies vascular pathology, digital subtraction angiography (DSA) is often performed within 24–48 h. Such patients may receive multiple administrations of iodinated contrast material over a short time period.

Objective

We aimed to evaluate the incidence of acute kidney injury (AKI) in patients who underwent a CTSS and DSA for evaluation of acute ischemic symptoms or for stroke intervention within a 48 h period between August 2012 and December 2014.

Methods

We identified 84 patients for inclusion in the analysis. Patients fell into one of two cohorts: AKI, defined as a rise in the serum creatinine level of ≥0.5 mg/dL from baseline, or non-AKI. Clinical parameters included pre- and post-imaging serum creatinine level, time between CTSS and DSA, and type of angiographic procedure (diagnostic vs intervention) performed.

Results

Four patients (4.7%) experienced AKI, one of whom had baseline renal dysfunction (defined as baseline serum creatinine level ≥1.5 mg/dL). The mean difference between baseline and peak creatinine values was found to be significantly greater in patients with AKI than in non-AKI patients (1.65 vs –0.09, respectively; p=0.0008).

Conclusions

This study provides preliminary evidence of the safety and feasibility of obtaining CTSS with additional DSA imaging, whether for diagnosis or intervention, to identify possible acute ischemic stroke.

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Sex, lies and gender

Browne1 (this issue) argues that what may appear to be a benevolent practice—disclosing the sex of a fetus to expecting parents who wish to know—is in fact an epistemically problematic and, as a result, ethically questionable medical practice. Browne worries that not only will the disclosure of fetal sex encourage sex-selective abortions (an issue we will not take up here), but also that it will convey a misleading and pernicious message about the relationship between sex and gender. More specifically, she contends that the practice of disclosure is problematic because (1) it purports to establish the gender of the developing baby based on information about the baby's sex, whereas this is not a warranted inference because while sex is determined by biological factors, gender is determined by social factors and (2) it conflates (biological) sex with (social) gender or encourages such conflation or reduction and thereby promotes 'essentialistic'…

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A bar too high: why we should not bar parents from knowing the sex of their fetus

In her article, 'Why Parents Should Not Be Told the Sex of Their Fetus' Tamara Browne sets herself a challenging task. She argues that, in the interest of fighting gender essentialism, parents ought not to be told the sex of their fetus even when they request it. This is a very high bar for her arguments to hurdle. Many commentators, myself included, have argued that it would be better for parents not to know, and that parents ought not to seek to find out, the sex of their fetus. I have suggested, for example, that parents not be routinely provided with this information, but be required to ask for it, thus shifting the default.1 But it is one thing to claim that parents should voluntarily refrain from finding out, and another to argue that they should be barred from doing so.

There are a number of perspectives from which…

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Modification d’un traitementcontre l’ostéoporose

Publication date: February 2016
Source:Actualités Pharmaceutiques, Volume 55, Issue 553
Author(s): Françoise Couic-Marinier, François Pillon
Une patiente de 67 ans, traitée depuis trois ans par bisphosphonate suite à une fracture du poignet et la découverte d'une ostéoporose pathologique, présente des tassements vertébraux. Une modification de son traitement s'impose.A 67-year-old patient, treated for three years with bisphosphonate following a wrist fracture and the discovery of pathological osteoporosis, is presenting vertebral collapse. A modification of her treatment is required.

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Survey of ankle-brachial pressure index use and its perceived barriers by general practitioners in the UK

Background

Peripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle–brachial pressure index (ABPI) is the recommended diagnostic tool for PAD.

Purpose

We explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice.

Methods

GPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle–brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study.

Results

All respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use.

Conclusions

Targeted training of nursing staff may improve ABPI usage, although a less time-consuming test for PAD may be another option.

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Effects of Hot Chemical Etching and 10-Metacryloxydecyl Dihydrogen Phosphate (MDP) Monomer on the Bond Strength of Zirconia Ceramics to Resin-Based Cements

Abstract

Purpose

The purpose of this in vitro study was to evaluate the hot chemical etching method on the shear bond strength between zirconia and two resin cements.

Materials and Methods

Sixty zirconia specimens (13 × 7.5 × 2.5 mm3) were prepared and treated as follows: (1) airborne-particle abrasion with 50 μm Al2O3 particles; (2) hot chemical etching for 10 minutes; (3) hot chemical etching for 30 minutes. Sixty composite cylinders of 3 mm diameter and height were prepared and bonded to zirconia specimens, which were divided into subgroups A and B. Group A: cemented with conventional resin cement (Variolink II); group B: cemented with 10-metacryloxydecyl dihydrogen phosphate (MDP) monomer containing resin cement (Panavia SA) after the application of surface treatments. Next, the specimens were stored in 37ºC distilled water for 24 hours. Following water storage, shear bond strength test was performed at a 1 mm/min crosshead speed in a universal testing machine. The statistical analyses were performed with one-way ANOVA and post hoc Tukey tests. p < 0.05 was considered statistically significant.

Results

The results from all of the tested groups exhibited lower shear bond strength values than group II-B and higher shear bond strength values than group I-A (p < 0.05).

Conclusion

The use of the hot chemical etching method for 10 minutes increased the shear bond strength of zirconia ceramics to both conventional and resin cements and seems to be an effective method. The MDP monomer-containing resin cement, Panavia SA, improved the resin bonding of zirconia ceramics when combined with airborne-particle abrasion.

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Oncogene swap as a novel mechanism of acquired resistance to EGFR-tyrosine kinase inhibitor in lung cancer

Abstract

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Why parents should not be told the sex of their fetus

A new technique called non-invasive prenatal testing (NIPT) has been developed, which can detect a range of genetic and chromosomal diseases, as well as fetal sex earlier, more easily and more reliably. NIPT, therefore, potentially expands the market for sex determination and sex selective abortion. This paper argues that both practices should be prevented by not including fetal sex in prenatal test reports. This is because there is a discrepancy between what parents are concerned with (gender) and what the prenatal test can provide (sex). The paper first presents arguments, which indicate a difference between sex and gender before presenting parental motivations for sex selection and sex determination to show that parents are not concerned with their child's sex chromosomes, or even their genitalia, but the gender role that their child will espouse. That, however, is not something that a prenatal test can provide. We are thus left with a situation in which what parents are told, and what they think they are being told, are two different things. In other words, as the conflation of sex with gender is implicit in the disclosure of fetal sex, it may be more accurate to refer to it as misinformation. This misinformation promotes sexism via gender essentialism, which is neither in the interests of the future child nor society.

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Fatty Acids and Breast Cancer: Make them on Site or have them Delivered

Abstract

Brisk fatty acid (FA) production by cancer cells is accommodated by the Warburg effect. Most breast and other cancer cell types are addicted to fatty acids (FA), which they require for membrane phospholipid synthesis, signaling purposes, and energy production. Expression of the enzymes required for FA synthesis is closely linked to each of the major classes of signaling molecules that stimulate BC cell proliferation. This review focuses on the regulation of FA synthesis in BC cells, and the impact of FA, or the lack thereof, on the tumor cell phenotype. Given growing awareness of the impact of dietary fat and obesity on BC biology, we will also examine the less-frequently considered notion that, in addition to de novo FA synthesis, the lipolytic uptake of preformed FA may also be an important mechanism of lipid acquisition. Indeed, it appears that cancer cells may exist at different points along a "lipogenic-lipolytic axis", and FA uptake could thwart attempts to exploit the strict requirement for FA focused solely on inhibition of de novo FA synthesis. Strategies for clinically targeting FA metabolism will be discussed, and the current status of the medicinal chemistry in this area will be assessed. This article is protected by copyright. All rights reserved

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Effects of the Addition of Titanium Dioxide and Silaned Silica Nanoparticles on the Mechanical Properties of Maxillofacial Silicones

Abstract

Purpose

Silicone-based elastomeric materials are commonly used to fabricate maxillofacial prostheses. The aim of this study was to evaluate the effect of different types of silica and nanosized titanium dioxide addition on the mechanical properties of two RTV silicone elastomers.

Materials and Methods

A-2000 and A-2006 silicone elastomers were used, and each was divided into four subgroups (n = 5). The first group was the control without additives. Other groups were titanium dioxide, fumed silica, and silaned silica. Each specimen was prepared in compliance with the manufacturer's instructions for the tensile strength, percent elongation, tear resistance, and the hardness tests according to ISO and ASTM standards. A factorial ANOVA with pairwise interaction indicated that the pattern for all four outcomes of the materials was different for A-2000 and A-2006 (p < 0.05). Therefore, the average outcome values for the materials within silicone elastomers were then analyzed by Tukey HSD. For the hardness test results, Kruskal-Wallis and Mann-Whitney U test methods were used. The level of statistical significance was p < 0.05.

Results

There was a statistically significant interaction (p < 0.05) between materials and silicone type for all four tests (tensile strength, tear, hardness, percent elongation). The hydrophobic silica group had significantly higher tensile strength than TiO2 for A-2000. The fumed hydrophilic silica group had significantly higher tensile strength than TiO2 for A-2006. Most of silica specimens had higher tensile strength when compared with the control and TiO2 groups for A-2000 and A-2006 silicones. The TiO2 group had the highest hardness value for A-2000 while the lowest hardness value for A-2006 (p < 0.05). There was no significant difference of tear strength among the type of additives (p > 0.05) for A-2000. The fumed silica and TiO2 groups had significantly higher tear strength than the control group for A-2006. The fumed silica and the hydrophobic silica groups had significantly higher percent elongation than the control group (p < 0.05) for A-2000. The TiO2 group had the lowest percent elongation for A-2006.

Conclusions

Results in this in vitro study may clarify future studies about the effect of different additives on the physical and mechanical properties of maxillofacial elastomers. There is a great interest in the effect of a new-generation hydrophobic silica incorporation into A-2000 silicone as well as the effect of fumed hydrophilic silica incorporation into A-2006 silicone. Future research should be supported with more in vitro trials in different percentages of such additives used in this study.

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Predictors of immune reconstitution inflammatory syndrome associated with Kaposi’s sarcoma: a case report

We present here a case of immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma (KS-IRIS) developed in an AIDS patient two months after initiation of antiretroviral therapy (ART). Baseli…

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Ultrasound Characteristics and Metastatic Papillary Thyroid Carcinoma

This study evaluates the usefulness of preoperative ultrasound characteristics in predicting pathologic extranodal extension in patients with metastatic papillary thyroid carcinoma.

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Destructive Hard Palate Mass

A woman presented with painful swelling along the roof of her mouth and cheek associated with new-onset malocclusion, ipsilateral upper lip numbness, and a submucosal growth on the mesial aspect of the left maxillary alveolus. What is your diagnosis?

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Fellowship Training and Otolaryngology Training Examination Scores

This analysis of an academic otolaryngology residency program examines associations between pursuit of fellowship training and scores on the Otolaryngology Training Examination among residents who completed the 5-year program.

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Surgical treatment pattern and outcomes in epithelial ovarian cancer patients from a cancer institute in Kerala, India

P Georgeena, Anupama Rajanbabu, DK Vijaykumar, K Pavithran, KR Sundaram, KS Deepak and MR Sanal

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Technology Access and Smartphone App Preferences for Medication Adherence in Adolescents and Young Adults With Sickle Cell Disease

Background

Hydroxyurea is the only Food and Drug Administration approved medication for sickle cell disease (SCD) with short- and long-term benefits for both morbidity and mortality. However, hydroxyurea underutilization and adherence remain challenges for patients with SCD. The objectives of this study were to determine access to technology among adolescents and young adults (AYA) with SCD and to identify their preferred technology-based strategies for improving medication adherence.

Procedure

A cross-sectional survey was administered in a variety of clinical settings from October 2014 through May 2015 to AYA (12–22 years) with SCD (all genotypes) followed in a Comprehensive Sickle Cell Program.

Results

Eighty of 107 eligible participants completed the survey for a 75% response rate. Participants (51% female, 94% Black) had a mean age of 15.3 ± 2.8 years. Most participants (75%) were on a daily medication with about half on hydroxyurea. Forgetfulness (67%) was the most common barrier to medication adherence. The majority of participants (85%) owned smartphones and either owned or had access to electronic tablets (83%), laptops (72%), or desktops (70%). Of the proposed smartphone app features, daily medication reminders were ranked first most frequently, followed by education about SCD, adherence text prompts, education about SCD medications, and medication log.

Conclusions

The majority of our AYA with SCD owned smartphones and had access to other electronic devices. Our survey results provided valuable insight into the preferred app features and optimal strategies for developing technology-based interventions, such as a multicomponent app, to increase medication adherence for AYA with SCD or other chronic conditions.

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Spinal Epidural Hematoma Following Cupping Glass treatment in an Infant With Hemophilia A

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A 6 months old infant, diagnosed with a rare mutation causing severe hemophilia A, presented with spinal epidural hematoma. Parents later admitted the infant had glass cupping therapy performed within 2 weeks of the onset of symptoms. The rare mutation, rare bleeding complication, and the eventual course of therapy applied in this case will be discussed in our case report.

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Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy

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Background

Childhood cancer survivors show evidence of diffuse myocardial fibrosis that is related to exercise capacity. The mechanism of reduced exercise tolerance in anthracycline cardiotoxicity remains unclear. We explored the determinants of exercise intolerance by evaluating left ventricular (LV) distensibility and functional reserve.

Methods

Patients (n = 22) and healthy controls (n = 10) underwent two-dimensional echocardiography while supine, upright, and during cycle exercise. LV distensibility was measured as the change in end-diastolic cavity area (EDCA) from supine to the upright position. LV functional reserve was assessed during peak exercise, and measured as the exercise-induced change in systolic circumferential strain rate (SR) and early-diastolic SR (EDSR). The peak rate of oxygen consumption was measured by indirect calorimetry.

Results

Median age of patients was 16 years (range 8–19) and controls 14 years (range 8–19). Median time since anthracycline therapy was 6 years (range 2–16). Peak oxygen consumption was significantly lower in patients compared to controls (35 ml/kg/min [28–60] vs. 45 ml/kg/min [44–53], P = 0.005). Transitioning from the supine position to the upright position caused a similar reduction in LV EDCA, suggesting similar LV distensibility between patients (–22% [–46 to –4]) and controls (–20% [–46 to –3], P = 0.3). However, during exercise, both systolic SR and EDSR reserve were significantly impaired in patients (∆SR: 93% [14–308], ∆EDSR: –4.5% [–88 to 121]) compared to controls (∆SR: 128% [54–230], P = 0.046; ∆EDSR: 74% [22–234], P = 0.02).

Conclusions

Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility.

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MicroRNA-761 is upregulated in hepatocellular carcinoma and regulates tumorigenesis by targeting Mitofusin-2

Abstract

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-related deaths worldwide. The fate of a cell is determined by the balance between the processes of fission and fusion that constantly occur in the mitochondria of cells. We previously showed that overexpression of Mitofusin-2 can induce apoptosis in HCC cells by triggering an influx of Ca²⁺ into the mitochondria from the ER. The function of Mitofusin-2 has been studied extensively, but the mechanism underlying the post-transcriptional regulation of Mitofusin-2 has not been elucidated. In this study, we aimed to identify the mechanism of Mitofusin-2 regulation in HCC. We demonstrated that Mitofusin-2 is a direct target of miR-761, which was found to be upregulated in HCC tissues. Further, a miR-761 inhibitor impairs mitochondrial function by upregulating Mitofusin-2 and effectively repressed tumor growth and metastasis both in vivo and vitro. Our findings provide new insights into the mechanism underlying Mitofusin-2 regulation and the potential role of miR-761 in HCC, making it a potential candidate for use in HCC therapy in the future.

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The Global Enteric Multicenter Study (GEMS) (Clin Infect Dis 2012; 55(S4):doi:10.1093/cid/cis983)

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An Evidence-Based Drug Development Tool for Tuberculosis Regimens: The Hollow Fiber System Model (Clin Infect Dis 2015; 61(S1):doi:10.1093/cid/civ650)

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Dietz et al (Clin Infect Dis 2015;61:1648-54)

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The Meningitis Vaccine Project: The Development, Licensure, Introduction, and Impact of a New Group A Meningococcal ConjugateVaccine for Africa (Clin Infect Dis 2015; 61(S5): doi:10.1093/cid/civ916)

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Reply to Okatch et al

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Reply to Davido and Dinh

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Advances in Tuberculosis Research: A Blueprint for Opportunities (Clin Infect Dis 2015; 61(S3): doi:10.1093/cid/civ623)

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CD4 Cell Counts at Antiretroviral Therapy Initiation in Botswana Have Been Increasing

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Oral Fosfomycin and Prostatitis

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MALDI-TOF Utility in a Region With Low Antibacterial Resistance Rates

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HIV Postexposure Prophylaxis Starter Packs Were Not Designed to Help or Hinder Adherence

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Reply to Zimmer

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Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001.

Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)–infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0.

Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%–9.5%) in 2008–2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones.

Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

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Tooth Discoloration in a Patient With Multidrug-Resistant Tuberculosis

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Continuous Retention and Viral Suppression Provide Further Insights Into the HIV Care Continuum Compared to the Cross-sectional HIV Care Cascade

Background. The human immunodeficiency virus (HIV) care continuum has become an important tool for evaluating HIV care. Current depictions of the care continuum are often cross-sectional and evaluate retention and viral suppression (VS) in a single year, yet the National HIV/AIDS Strategy calls for programs with long-lasting outcomes.

Methods. Retrospective chart review of HIV-infected patients enrolled in a large, urban clinic in 2010 followed longitudinally for 36 months. McNemar comparisons and logistic regression analyses were conducted to evaluate covariate association with continuous retention and VS. Generalized estimating equation log-linear models were used to integrate time into the model.

Results. Among 655 patients (77% male, 83% black, 54% men who have sex with men (MSM), 78% uninsured) continuous retention/VS at 12 months (84%/64%), 24 months (60%/48%), and 36 months (49%/39%) showed significant attrition (P < .0001) over time. Continuous retention was associated with prevalent VS at the end of 36 months (adjusted prevalence ratio 3.12; 95% confidence interval [CI], 2.40, 4.07). 12-month retention for black (84%) and nonblack (85%) patients was equivalent, yet fewer blacks (46%) than nonblacks (63%) achieved 36-month continuous retention due to a significant interaction between race and time (aOR 0.75, 95% CI, .59, .95).

Conclusions. Continuous retention is a critically important measure of long-term success in HIV treatment and the crucial component of successful treatment-as-prevention but is infrequently evaluated. Single cross-sections may overestimate successful retention and virologic outcomes. A longitudinal HIV care continuum provides greater insight into long-term outcomes and exposes disparities not evident with traditional cross-sectional care continua.

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Αρχειοθήκη ιστολογίου

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Η λίστα ιστολογίων μου

Πέμπτη 4 Φεβρουαρίου 2016

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Αρχειοθήκη ιστολογίου