Exercise-induced laryngeal obstruction: natural history and effect of surgical treatment

The current follow-up study concerning the supraglottic type of exercise-induced laryngeal obstruction (EILO) was performed to reveal the natural history of supraglottic EILO and compare the symptoms, as well as the laryngeal function in conservatively versus surgically treated patients. A questionnaire-based survey was conducted 2–5 years after EILO was diagnosed by a continuous laryngoscopy exercise (CLE) test in 94 patients with a predominantly supraglottic obstruction. Seventy-one patients had been treated conservatively and 23 with laser supraglottoplasty. The questionnaire response rate was 70 and 100% in conservatively treated (CT) and surgically treated (ST) patients, respectively. A second CLE test was performed in 14 CT and 19 ST patients. A visual analogue scale on symptom severity indicated improvements in both the groups, i.e. mean values (± standard deviations) declined from 73 (20) to 53 (26) (P < 0.001) in the CT group and from 87 (26) to 25 (27) (P < 0.001) in the ST group. At follow-up, ST patients reported lower scores regarding current level of complaints, and higher ability to perform exercise, as well as to push themselves physically, all compared to CT patients (P < 0.001). CLE scores were normalized in 3 of 14 (21%) CT and 16 of 19 (84%) ST patients (Z = −3.6; P < 0.001). In conclusion, symptoms of EILO diagnosed in adolescents generally decreased during 2–5 years follow-up period but even more after the surgical treatment. Patients with supraglottic EILO may benefit from supraglottoplasty both as to laryngeal function and symptom relief

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Regeneration of Cryoinjury Induced Necrotic Heart Lesions in Zebrafish Is Associated with Epicardial Activation and Cardiomyocyte Proliferation

In mammals, myocardial cell death due to infarction results in scar formation and little regenerative response. In contrast, zebrafish have a high capacity to regenerate the heart after surgical resection of myocardial tissue. However, whether zebrafish can also regenerate lesions caused by cell death has not been tested. Here, we present a simple method for induction of necrotic lesions in the adult zebrafish heart based on cryoinjury. Despite widespread tissue death and loss of cardiomyocytes caused by these lesions, zebrafish display a robust regenerative response, which results in substantial clearing of the necrotic tissue and little scar formation. The cellular mechanisms underlying regeneration appear to be similar to those activated in response to ventricular resection. In particular, the epicardium activates a developmental gene program, proliferates and covers the lesion. Concomitantly, mature uninjured cardiomyocytes become proliferative and invade the lesion. Our injury model will be a useful tool to study the molecular mechanisms of natural heart regeneration in response to necrotic cell death

Pretreatment organ function in patients with advanced head and neck cancer: clinical outcome measures and patients' views

<p>Abstract</p> <p>Background</p> <p>Aim of this study is to thoroughly assess pretreatment organ function in advanced head and neck cancer through various clinical outcome measures and patients' views.</p> <p>Methods</p> <p>A comprehensive, multidimensional assessment was used, that included quality of life, swallowing, mouth opening, and weight changes. Fifty-five patients with stage III-IV disease were entered in this study prior to organ preserving (chemoradiation) treatment.</p> <p>Results</p> <p>All patients showed pretreatment abnormalities or problems, identified by one or more of the outcome measures. Most frequent problems concerned swallowing, pain, and weight loss. Interestingly, clinical outcome measures and patients' perception did no always concur. E.g. videofluoroscopy identified aspiration and laryngeal penetration in 18% of the patients, whereas only 7 patients (13%) perceived this as problematic; only 2 out of 7 patients with objective trismus actually perceived trismus.</p> <p>Conclusion</p> <p>The assessment identified several problems already pre-treatment, in this patient population. A thorough assessment of both clinical measures and patients' views appears to be necessary to gain insight in all (perceived) pre-existing functional and quality of life problems.</p

Sales promotions and channel coordination

Consumer sales promotions are usually the result of the decisions of two marketing channel parties, the manufacturer and the retailer. In making these decisions, each party normally follows its own interest: i.e. maximizes its own profit. Unfortunately, this results in a suboptimal outcome for the channel as a whole. Independent profit maximization by channel parties leads to a lack of channel coordination with the implication of leaving money on the table. This may well contribute to the notoriously low profitability of sales promotions. This paper first shows analytically why the suboptimality occurs, and then presents an empirical demonstration, using a unique dataset from an Efficient Consumer Response (ECR) project; ECR is a movement in which parties work together to optimize the distribution channel). In this dataset, actual profit is only a small fraction of potential profit, implying that there is a large degree of suboptimality. It is important that (1) channel parties are aware of this suboptimality; and (2) that they have tools to deal with it. Solutions to the channel coordination problem should ensure that the goals of the individual channel parties are aligned with the goals of the channel as a whole. The paper proposes one particular agreement for this purpose, called proportional discount sharing. Application to the ECR data shows a win-win result for both the manufacturer and the retailer. Recognition of the channel coordination problem by the manufacturer and the retailer is the necessary starting point for agreeing on a way of solving it in a win-win fashion

Revised Lithostratigraphy of the Sonsela Member (Chinle Formation, Upper Triassic) in the Southern Part of Petrified Forest National Park, Arizona

BACKGROUND: Recent revisions to the Sonsela Member of the Chinle Formation in Petrified Forest National Park have presented a three-part lithostratigraphic model based on unconventional correlations of sandstone beds. As a vertebrate faunal transition is recorded within this stratigraphic interval, these correlations, and the purported existence of a depositional hiatus (the Tr-4 unconformity) at about the same level, must be carefully re-examined. METHODOLOGY/PRINCIPAL FINDINGS: Our investigations demonstrate the neglected necessity of walking out contacts and mapping when constructing lithostratigraphic models, and providing UTM coordinates and labeled photographs for all measured sections. We correct correlation errors within the Sonsela Member, demonstrate that there are multiple Flattops One sandstones, all of which are higher than the traditional Sonsela sandstone bed, that the Sonsela sandstone bed and Rainbow Forest Bed are equivalent, that the Rainbow Forest Bed is higher than the sandstones at the base of Blue Mesa and Agate Mesa, that strata formerly assigned to the Jim Camp Wash beds occur at two stratigraphic levels, and that there are multiple persistent silcrete horizons within the Sonsela Member. CONCLUSIONS/SIGNIFICANCE: We present a revised five-part model for the Sonsela Member. The units from lowest to highest are: the Camp Butte beds, Lot's Wife beds, Jasper Forest bed (the Sonsela sandstone)/Rainbow Forest Bed, Jim Camp Wash beds, and Martha's Butte beds (including the Flattops One sandstones). Although there are numerous degradational/aggradational cycles within the Chinle Formation, a single unconformable horizon within or at the base of the Sonsela Member that can be traced across the entire western United States (the "Tr-4 unconformity") probably does not exist. The shift from relatively humid and poorly-drained to arid and well-drained climatic conditions began during deposition of the Sonsela Member (low in the Jim Camp Wash beds), well after the Carnian-Norian transition

Identification of Attractive Drug Targets in Neglected-Disease Pathogens Using an In Silico Approach

In cell-based drug development, researchers attempt to create drugs that kill a pathogen without necessarily understanding the details of how the drugs work. In contrast, target-based drug development entails the search for compounds that act on a specific intracellular target—often a protein known or suspected to be required for survival of the pathogen. The latter approach to drug development has been facilitated greatly by the sequencing of many pathogen genomes and the incorporation of genome data into user-friendly databases. The present paper shows how the database TDRtargets.org can identify proteins that might be considered good drug targets for diseases such as African sleeping sickness, Chagas disease, parasitic worm infections, tuberculosis, and malaria. These proteins may score highly in searches of the database because they are dissimilar to human proteins, are structurally similar to other “druggable” proteins, have functions that are easy to measure, and/or fulfill other criteria. Researchers can use the lists of high-scoring proteins as a basis for deciding which potential drug targets to pursue experimentally

Are we there yet? Australian road safety targets and road traffic crash fatalities

Background: Road safety targets are widely used and provide a basis for evaluating progress in road safety outcomes against a quantified goal. In Australia, a reduction in fatalities from road traffic crashes (RTCs) is a public policy objective: a national target of no more than 5.6 fatalities per 100,000 population by 2010 was set in 2001. The purpose of this paper is to examine the progress Australia and its states and territories have made in reducing RTC fatalities, and to estimate when the 2010 target may be reached by the jurisdictions. Methods. Following a descriptive analysis, univariate time-series models estimate past trends in fatality rates over recent decades. Data for differing time periods are analysed and different trend specifications estimated. Preferred models were selected on the basis of statistical criteria and the period covered by the data. The results of preferred regressions are used to determine out-of-sample forecasts of when the national target may be attained by the jurisdictions. Though there are limitations with the time series approach used, inadequate data precluded the estimation of a full causal/structural model. Results: Statistically significant reductions in fatality rates since 1971 were found for all jurisdictions with the national rate decreasing on average, 3% per year since 1992. However the gains have varied across time and space, with percent changes in fatality rates ranging from an 8% increase in New South Wales 1972-1981 to a 46% decrease in Queensland 1982-1991. Based on an estimate of past trends, it is possible that the target set for 2010 may not be reached nationally, until 2016. Unsurprisingly, the analysis indicated a range of outcomes for the respective state/territory jurisdictions though these results should be interpreted with caution due to different assumptions and length of data. Conclusions: Results indicate that while Australia has been successful over recent decades in reducing RTC mortality, an important gap between aspirations and achievements remains. Moreover, unless there are fairly radical ("trend-breaking") changes in the factors that affect the incidence of RTC fatalities, deaths from RTCs are likely to remain above the national target in some areas of Australia, for years to come

Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult

Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R01AR60361, R01AR061988, P41EB002520). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ART was supported by a National Science Foundation Graduate Fellowship