Overview of the Management of Cough: CHEST Guideline and Expert Panel Report

This overview will demonstrate that cough is a common and potentially expensive health-care problem. Improvement in the quality of care of those with cough has been the focus of study for a variety of disciplines in medicine. The purpose of the Cough Guideline and Expert Panel is to synthesize current knowledge in a form that will aid clinical decision-making for the diagnosis and management of cough across disciplines and also identify gaps in knowledge and treatment options.

Different frequencies of acupuncture for treatment for chronic low back pain: an-assessor blinded pilot randomised controlled trial.

OBJECTIVES:
To examine the feasibility of a main RCT to compare the effectiveness of two frequencies (2 versus 5 times/week) of acupuncture treatment for chronic low back pain (LBP).
METHODS:
Participants (n=30) with chronic LBP were randomised into two groups to receive 10 acupuncture treatments: Low Frequency Group, 2 times/week for five weeks (n=15); High Frequency Group, 5 times/week for two weeks (n=15). The following outcomes were measured blindly at baseline, 2 weeks, 5 weeks, 3 months and 1 year: pain on a VAS, functional disability using the RMDQ, quality of life using the Measure Yourself Medical Outcome Profile (MYMOP-2), psychological impact with the Coping Strategies Questionnaire (CSQ) and Pain Locus of Control (PLC) questionnaire. Two objective outcomes, the Shuttle Walk Test (SWT) and Lateral Trunk Flexibility (LTF), were also measured.
RESULTS:
The compliance rate was 100% for each group. Some of the measurements were shown to be sensitive (VAS, RMDQ, MYMOP-2 Wellbeing). 66-330 participants would be required for a fully powered non-inferiority trial. The groups were balanced at baseline for LBP and demographic characteristics. There were no significant differences between the groups in terms of any of the outcomes, at each follow-up time point. It was notable however that the clinically important improvement in terms of pain, functional disability, quality of life, and SWT in both groups was achieved within the first two weeks, which was maintained at one year follow-up.
CONCLUSIONS:
It is feasible to conduct a main RCT, to compare different frequencies of acupuncture for LBP, using sensitive measurements. Also the trend for early clinically important improvement within a minimum of four measurements is worthy of further study.

Optimisation of a two-liquid component pre-filled acrylic bone cement system: A design of experiments approach to optimise cement final properties

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery—acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery.

Antibiotic and anti-inflammatory therapies for cystic fibrosis

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.

Extent and mechanism of phase separation during the extrusion of calcium phosphate pastes

The aim of this study was to increase understanding of the mechanism and dominant drivers influencing phase separation during ram extrusion of calcium phosphate (CaP) paste for orthopaedic applications. The liquid content of extrudate was determined, and the flow of liquid and powder phases within the syringe barrel during extrusion were observed, subject to various extrusion parameters. Increasing the initial liquid-to-powder mass ratio, LPR, (0.4-0.45), plunger rate (5-20 mm/min), and tapering the barrel exit (45°-90°) significantly reduced the extent of phase separation. Phase separation values ranged from (6.22 ± 0.69 to 18.94 ± 0.69 %). However altering needle geometry had no significant effect on phase separation. From powder tracing and liquid content determination, static zones of powder and a non-uniform liquid distribution was observed within the barrel. Measurements of extrudate and paste LPR within the barrel indicated that extrudate LPR remained constant during extrusion, while LPR of paste within the barrel decreased steadily. These observations indicate the mechanism of phase separation was located within the syringe barrel. Therefore phase separation can be attributed to either; (1) the liquid being forced downstream by an increase in pore pressure as a result of powder consolidation due to the pressure exerted by the plunger or (2) the liquid being drawn from paste within the barrel, due to suction, driven by dilation of the solids matrix at the barrel exit. Differentiating between these two mechanisms is difficult; however results obtained suggest that suction is the dominant phase separation mechanism occurring during extrusion of CaP paste.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Osteogenic cell response to 3-D hydroxyapatite scaffolds developed via replication of natural marine sponges

Bone tissue engineering may provide an alternative to autograft, however scaffold optimisation is required to maximize bone ingrowth. In designing scaffolds, pore architecture is important and there is evidence that cells prefer a degree of non-uniformity. The aim of this study was to compare scaffolds derived from a natural porous marine sponge (Spongia agaricina) with unique architecture to those derived from a synthetic polyurethane foam. Hydroxyapatite scaffolds of 1 cm3 were prepared via ceramic infiltration of a marine sponge and a polyurethane (PU) foam. Human foetal osteoblasts (hFOB) were seeded at 1x105 cells/scaffold for up to 14 days. Cytotoxicity, cell number, morphology and differentiation were investigated. PU-derived scaffolds had 84-91% porosity and 99.99% pore interconnectivity. In comparison marine sponge-derived scaffolds had 56-61% porosity and 99.9% pore interconnectivity. hFOB studies showed that a greater number of cells were found on marine sponge-derived scaffolds at than on the PU scaffold but there was no significant difference in cell differentiation. X-ray diffraction (XRD) and inductively coupled plasma mass spectrometry (ICP-MS) showed that Si ions were released from the marine-derived scaffold. In summary, three dimensional porous constructs have been manufactured that support cell attachment, proliferation and differentiation but significantly more cells were seen on marine-derived scaffolds. This could be due both to the chemistry and pore architecture of the scaffolds with an additional biological stimulus from presence of Si ions. Further in vivo tests in orthotopic models are required but this marine-derived scaffold shows promise for applications in bone tissue engineering.

Wavelet entropy of Doppler ultrasound blood velocity flow waveforms distinguishes nitric oxide-modulated states

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis. The ability of this method to track the effects of pharmacologic modulation of vascular function on Doppler blood velocity waveforms was assessed. Waveforms were captured from ophthalmic arteries of 10 healthy subjects at baseline, after the administration of glyceryl trinitrate (GTN) and after two doses of N(G)-nitro-L-arginine-methyl ester (L-NAME) to produce vasodilation and vasoconstriction, respectively. Wavelet entropy had a tendency to decrease from baseline in response to GTN, but significantly increased after the administration of L-NAME (mean: 1.60 ± 0.07 after 0.25 mg/kg and 1.72 ± 0.13 after 0.5 mg/kg vs. 1.50 ± 0.10 at baseline, p < 0.05). Relative wavelet entropy had a spectral distribution from increasing doses of L-NAME comparable to baseline, 0.07 ± 0.04 and 0.08 ± 0.03, respectively, whereas GTN had the most dissimilar spectral distribution compared with baseline (0.17 ± 0.08, p = 0.002). Wavelet entropy can detect subtle changes in Doppler blood velocity waveform structure in response to nitric-oxide-mediated changes in arteriolar smooth muscle tone.

Estudo de síntese e reactividade de novos derivados do tipo corrol

A presente dissertação contempla estudos de reactividade na periferia e no interior do macrociclo corrólico, nomeadamente do 5,10,15- tris(pentafluorofenil)corrol. Nesses estudos foram estabelecidas novas rotas de síntese para a preparação de novos derivados tetrapirrólicos do tipo corrol, alguns deles com potencial aplicação medicinal. Na primeira parte, foi estudado o comportamento de 5,10,15- tris(pentafluorofenil)corrol como componente 2ʌ em reacções de cicloadição de Diels-Alder com hidrocarbonetos aromáticos policíclicos, designadamente antraceno, tetraceno, nafto[2,3-a]pireno e pentaceno. Estas reacções foram efectuadas em aquecimento clássico e com radiação de microondas. Desses estudos concluiu-se que todos os hidrocarbonetos aromáticos considerados, à excepção do nafto[2,3-a]pireno, reagem segundo reacções de Diels-Alder, mas apenas com o pentaceno se obtêm aductos provenientes de reacções de cicloadição [4+4]. Os resultados obtidos em algumas destas reacções levaram a um estudo aprofundado sobre a estabilidade do macrociclo considerado. Este estudo foi efectuado sob condições térmicas, sob a acção da luz e na presença de um agente promotor de radicais. Desses estudos concluiu-se que apenas com aquecimento clássico é possível obter o dímero com o anel ciclooctatetraeno ligado pelas posições C-2, C-2’ e C-18, C-18’ e o dímero assimétrico ligado pelas posições C-2 e C-3’. Na presença de luz ou na presença de agente promotor de radicais obtém-se o dímero simétrico ligado pelas posições C-3 e C-3’. O estudo do mecanismo da reacção de dimerização na presença de luz levou ainda à síntese de um corrol mono-iodado. Foi ainda analisado o comportamento de 5,10,15-tris(pentafluorofenil)corrol e de 5,10,15-tris(pentafluorofenil)corrolatogálio(III)(piridina) na presença de iletos de azometino. Destes estudos resultou o desenvolvimento de novas rotas de síntese para a obtenção de novos derivados do tipo amina e do tipo éter. Na terceira parte, descrevem-se estudos de complexação do 5,10,15- tris(pentafluorofenil)corrol com diferentes sais metálicos por espectrometria de massa. Foram usados como fontes de ionização o Electrospray e o LSIMS. Os resultados obtidos comprovaram que os metalocorróis obtidos na fonte são idênticos aos metalocorróis sintetizados. Na quarta parte deste trabalho foram sintetizados novos conjugados corrolciclodextrina por meio de reacções de substituição nucleófila. A actividade fotodinâmica destes derivados foi avaliada numa linha celular cancerígena. A estrutura dos compostos sintetizados foi estabelecida recorrendo a diversas técnicas espectroscópicas actuais, principalmente espectroscopia de Ressonância Magnética Nuclear (RMN de 1H, 13C e 19F, DEPT, COSY, HSQC, HMBC e NOESY), espectrometria de massa em LSIMS, ESI e MALDI e ainda recorrendo a espectrofotometria de Ultravioleta-Visível (UV-vis).