The effects of diet and sex in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no known cure. Approximately 90% of ALS cases are sporadic, suggesting there are multiple contributing factors that influence the disease risk, onset, and progression. Diet and sex are two factors that have been reported to alter ALS risk, onset and progression in humans and in animal models, providing potential modifiers of disease. Several epidemiological studies have identified diets that positively affect ALS patients, including various high-calorie fat or sugar-based diets, while animal models have been developed to test how these diets are working on a molecular level. These diets may offset the metabolic alterations that occur in ALS, such as hypermetabolism, lowered body mass index(BMI), and hyperlipidemia. Sex-dependent differences have also come forth from large-scale epidemiological studies as well as mouse-model studies. In addition, sex hormones have been shown to affect disease risk or progression. Herein, studies on the effects of diet and sex on ALS risk, onset, and progression will be reviewed. Understanding these diet- and sex-dependent outcomes may lead to optimized patient-specific therapies for ALS.

Competencies on environmental health and pedagogical approaches in the nursing curriculum: A systematic review of the literature.

It has been suggested that climate change is the biggest threat to public health for the 21st Century; increased demand on health services will impact on already overstretched resources and systems will need to be able to respond. However limited attention is given to climate change and sustainability in nursing education; there is no clear guidance on curricula content for nurses or recommendations regarding the skills and competencies that will be required. Literature published in Dutch, English, German, and Spanish was searched and 32 papers met the inclusion criteria for the review. Results suggests that holistic/systems thinking is relevant to healthcare so bringing a 'sustainability lens' to nursing curricula could be seen as being consistent with wider determinants of health. The literature review has identified the educational approaches necessary to provide a broad based curriculum and a cross-disciplinary approach. The findings suggest that topics such as the use of resources, food, health promotion, globalism, disease management, and the environmental impact of delivering healthcare, if embedded in nursing education could support the nursing profession's response for this new and important aspect of healthcare.

Microplastics in personal care products: Exploring perceptions of environmentalists, beauticians and students.

Microplastics enter the environment as a result of larger plastic items breaking down ('secondary') and from particles originally manufactured at that size ('primary'). Personal care products are an important contributor of secondary microplastics (typically referred to as 'microbeads'), for example in toothpaste, facial scrubs and soaps. Consumers play an important role in influencing the demand for these products and therefore any associated environmental consequences. Hence we need to understand public perceptions in order to help reduce emissions of microplastics. This study explored awareness of plastic microbeads in personal care products in three groups: environmental activists, trainee beauticians and university students in South West England. Focus groups were run, where participants were shown the quantity of microbeads found in individual high-street personal care products. Qualitative analysis showed that while the environmentalists were originally aware of the issue, it lacked visibility and immediacy for the beauticians and students. Yet when shown the amount of plastic in a range of familiar everyday personal care products, all participants expressed considerable surprise and concern at the quantities and potential impact. Regardless of any perceived level of harm in the environment, the consensus was that their use was unnatural and unnecessary. This research could inform future communications with the public and industry as well as policy initiatives to phase out the use of microbeads.

Exploring attitudes and knowledge of climate change and sustainability in a dental practice: A feasibility study into resource management.

Objective To understand the attitudes and behaviour of staff in dental practice towards adopting a reduce, reuse, recycle approach to resource management.Design A qualitative interview study.Setting The site for the study was a mixed NHS/private dental practice in North Devon.Subjects All disciplines from one dental practice.Methods (1) A practice scoping exercise - provided context and identified an interview sample. (2) Qualitative interviews with practice staff - explored knowledge and attitudes about sustainability and identified opportunities and limitations for the sustainable management of resources.Results The main issue raised by staff was the amount of waste generated. There was a strong desire to implement changes, but deep concerns were expressed about the impact of challenging current guidance on infection control.Conclusions Primary care dentistry provides both surgical and non-surgical care to more than half the UK population. Therefore, lessons learned from general dental practice can encourage positive change. More research is needed across dental practice in order to generalise these findings.

What's in a bin: A case study of dental clinical waste composition and potential greenhouse gas emission savings.

BACKGROUND: Dental practices have a unique position as dental staff use a high number of dental materials and instruments on a daily basis. It is unclear how dentists' and dental care professionals' choices and behaviours around selecting and using materials impact on the amount of unnecessary waste production. Although there are a number of articles exploring the quality and quantity of waste in dental practices, there are no studies on organisational strategies to decrease unnecessary waste. There is no clear economic analysis of the impact on associated cost to dental practices which consequently can affect the access of dental care for disadvantaged groups. METHODS: This study used an audit approach to explore the potential for sustainability in dental practice by measuring the nature and quantity of dental clinical waste, and assessing the feasibility of measuring the financial costs and potential carbon savings in the management of dental clinical waste. CONCLUSIONS: The data from our study would appear to support the view that it is possible to reduce carbon emissions and increase profitability. Successful implementation of an environmentally sustainable approach to waste management will be dependent on the practicalities involved and the financial incentives for adopting such practices.

Can a sustainability and health scenario provide a realistic challenge to student nurses and provoke changes in practice? An evaluation of a training intervention.

Climate change and limited natural resources will impact on the sustainable supply and disposal of materials used in health care. Healthcare students need opportunities to reflect on the ecological footprint of health services to mitigate against negative effects on service delivery. In order to raise awareness of these issues, there is a need for evidence-based teaching tools which are relevant and meaningful to nursing practice. An evidence-based sustainability skills teaching session was delivered to 293 nursing students from child and adult health disciplines. Following the sessions, evaluation sheets were distributed to the participants, of which 290 responded. The majority of nurses valued both the delivery and the content of the training and some were motivated to complete further study. The evaluation provided valuable information on how to deliver sustainability education and important insights into where more information and support was needed in order to change practice. Embedding sustainability teaching in skill sessions appears to be a realistic way of informing and motivating learners to consider current and best practice. Following training, further evaluation of practice-based behaviour is needed.

Does labelling a rare cancer diagnosis 'good' affect the patient's experience of treatment and recovery?

Doctors sometimes tell patients with rare but highly treatable cancers that they have 'good' cancer which some patients have found unhelpful, but this has been little explored. The aim of this study was to explore how patients reacted to being told they had a 'good' cancer. Qualitative interviews were carried out with 25 people with rare but prognostically favourable cancers who had received treatment at two hospitals within a cancer network. Results showed that despite good treatment outcomes, patients are still very shocked to hear the word cancer and react in similar ways to those with other forms of cancer. The potential effects of treatment should be recognised as having a detrimental effect on patient well-being whatever the prognosis. We should therefore avoid using 'good' and 'cancer' in the same sentence. In addition, the impact on all family members should not be underestimated. The data can be used to improve clinical practice and improve support for people affected by cancer.

Intrinsic nanostructure in Zr2-xFe4Si16-y(x = 0.81, y = 6.06).

We present a study of the crystal structure and physical properties of single crystals of a new Fe-based ternary compound, Zr2-xFe4Si16-y(x = 0.81, y = 6.06). Zr1.19Fe4Si9.94 is a layered compound, where stoichiometric ß-FeSi2-derived slabs are separated by Zr-Si planes with substantial numbers of vacancies. High resolution transmission electron microscopy (HRTEM) experiments show that these Zr-Si layers consist of 3.5 nm domains where the Zr and Si vacancies are ordered within a supercell sixteen times the volume of the stoichiometric cell. Within these domains, the occupancies of the Zr and Si sites obey symmetry rules that permit only certain compositions, none of which by themselves reproduce the average composition found in x-ray diffraction experiments. Magnetic susceptibility and magnetization measurements reveal a small but appreciable number of magnetic moments that remain freely fluctuating to 1.8 K, while neutron diffraction confirms the absence of bulk magnetic order with a moment of 0.2µB or larger down to 1.5 K. Electrical resistivity measurements find that Zr1.19Fe4Si9.94 is metallic, and the modest value of the Sommerfeld coefficient of the specific heat γ = C/T suggests that quasi-particle masses are not particularly strongly enhanced. The onset of superconductivity at Tc ≃ 6 K results in a partial resistive transition and a small Meissner signal, although a bulk-like transition is found in the specific heat. Sharp peaks in the ac susceptibility signal the interplay of the normal skin depth and the London penetration depth, typical of a system in which nano-sized superconducting grains are separated by a non-superconducting host. Ultra low field differential magnetic susceptibility measurements reveal the presence of a surprisingly large number of trace magnetic and superconducting phases, suggesting that the Zr-Fe-Si ternary system could be a potentially rich source of new bulk superconductors.

The use of descriptive words and metaphor in patient and carer experience of palliative day care: secondary analysis of a qualitative study.

BACKGROUND: An independent evaluation of changes to the delivery of Palliative Day Services was carried out during 2006-2007 using interviews with service users. The analysis found that the words and metaphors employed by users of services emphasized their emotional response to the changes, and helped to explain their depth of feeling about their experiences, warranting further investigation. AIM: To conduct a secondary analysis on interview data collected for the Day Services Evaluation Study in order to understand how patients and their carers use descriptive words and metaphor when talking about their experiences of palliative day services. METHODS: Interview transcripts from 40 patients and 8 carers were subjected to secondary thematic analysis. These were read individually and coded where metaphor or descriptive words had been used to emphasize the effect of the illness and the experiences of the Day Services. FINDINGS: Examples of the metaphorical expressions and words used described the service as a 'secure rock in a changing world'; transition was felt as 'sadness', a 'betrayal', with feelings that the changes were 'bitter and twisted;' and left 'a black hole'. Post transition the mood had changed to acceptance 'When life throws lemons at you, you make lemonade'. CONCLUSIONS: The metaphors and descriptive words used act as what we describe as 'emotional intensifiers' which provide a measure of the impact of the effect of illness, the effect of the day services on users and carers and the intensity of feeling during the time of transition.

Vibration-assisted electron tunneling in C140 transistors.

We measure electron tunneling in transistors made from C(140), a molecule with a mass-spring-mass geometry chosen as a model system to study electron-vibration coupling. We observe vibration-assisted tunneling at an energy corresponding to the stretching mode of C(140). Molecular modeling provides explanations for why this mode couples more strongly to electron tunneling than to the other internal modes of the molecule. We make comparisons between the observed tunneling rates and those expected from the Franck-Condon model.

Argus: a new instrument for the measurement of the stratospheric dynamical tracers, N2O and CH4.

We describe here a new instrument for the simultaneous, in situ measurement of the stratospheric tracer molecules, nitrous oxide (N2O) and methane (CH4). Argus is unique in its small size making it well suited for limited payload atmospheric research platforms. Argus employs second harmonic spectroscopy using tunable lead-salt diode lasers emitting in the mid-infrared. We first explain the Argus design philosophy followed by detailed descriptions of the instrument's optical, mechanical, and thermal sub-systems. Argus employs an in-flight calibration system providing real time calibrations and tightly constrained uncertainty estimates of the returned data. Data analysis is carried out using non-linear least-squares model fits to the acquired second harmonic spectra. A sampling of Argus data acquired on a recent stratospheric research campaign in the Arctic winter is presented.

Captopril suppression versus salt loading in confirming primary aldosteronism.

This prospective study was designed to compare the captopril suppression test with the salt-loading approach to confirm the diagnosis of primary aldosteronism. A total of 49 patients were referred with a presumed diagnosis of primary aldosteronism. The captopril test was performed in the morning with patients in the seated position after overnight fasting. Blood samples for plasma aldosterone were obtained before captopril administration (25 mg PO) and again 2 hours later. Patients were then subjected to a high salt diet (300 mmol sodium per day for 3 days). On the third day, urinary sodium (24 hours) was measured, and plasma aldosterone levels were measured at 8:00 AM (recumbent) and at noon (standing). Of the 49 patients, 44 had nonsuppressible aldosterone concentrations with all the clinical characteristics of primary aldosteronism: 22 patients had surgically confirmed unique adenoma, and 22 patients had presumed bilateral hyperplasia. There was a significant correlation between plasma aldosterone values of salt-loaded patients (mean of 8:00 AM and noon results) and the values 2 hours after captopril administration (r=0.8, P<0.01). Plasma aldosterone cumulative distribution curves in primary aldosteronism patients (adenoma and hyperplasia) were not significantly different between the 2 suppression tests. Our results showed that the captopril suppression test is as effective as sodium loading in confirming the diagnosis of primary aldosteronism.

Gap detection for similar and dissimilar gap markers.

Detection thresholds for temporal gaps between markers of dissimilar frequency are usually elevated with respect to thresholds for gaps between markers of similar frequency. Because gaps between markers of dissimilar frequency represent both a spectrally based perceptual discontinuity as well as a temporal discontinuity, it is not clear what factors underlie the threshold elevation. This study sought to examine the effects of perceptual dissimilarities on gap detection. The first experiment measured gap detection for configurations of narrow-band gap markers comprised of pure tones, frequency-modulated tones, and amplitude-modulated tones. The results showed that gap thresholds for frequency-disparate pure-tone markers were elevated with respect to isofrequency tonal markers, but that perceptual discontinuities between markers restricted to the same frequency region did not uniformly elevate threshold. The second experiment measured gap detection for configurations of markers where the leading and trailing markers could differ along the dimensions of bandwidth, duration, and pitch. The results showed that, in most cases, gap detection deteriorated when the bandwidth of the two markers differed, even when the spectral content of the narrower-band marker was completely subsumed by the spectral content of the wider-band marker. This finding suggests that gap detection is sensitive to spectral dissimilarity between markers in addition to spectral discontinuity. The effects of marker duration depended on the marker bandwidth. Pitch differences across spectrally similar markers had no effect.

A comparison of threshold estimation methods in children 6-11 years of age.

Estimating detection threshold for auditory stimuli in children can be problematic because of lapses in attention and the time limits usually imposed by scheduling restrictions or fatigue. Data reported here were collected to compare the stability of threshold estimation procedures in testing children ages 6 to 11 in a three-alternative, forced-choice paradigm. Stimuli consisted of a 1-kHz tonal signal and a Gaussian noise masker, bandpass filtered between 500-2,000 Hz and presented at 25-dB spectrum level. The signal was either presented for 400 ms in the presence of a continuous masker (simultaneous masking) or for 10 ms just prior to a 400-ms masker (backward masking). For each masking paradigm the 79% correct threshold was assessed via each of three procedures: 3-down, 1-up adaptive staircase (Levitt), maximum likelihood estimation (MLE), and method of constant stimuli. Percent correct was measured at the end of the study for a signal 10 dB above the previously determined threshold in order to estimate the most appropriate psychometric function asymptote for fitting data collected via the method of constant stimuli. Both the MLE and Levitt procedures produced equally stable threshold estimates for both conditions and age groups. This was the case despite considerable variability in backward-masking thresholds.

Gap duration discrimination in listeners with cochlear hearing loss: effects of gap and marker duration, frequency separation, and mode of presentation.

This study examined the effects of cochlear hearing loss on gap duration discrimination (GDD), with particular interest in whether cochlear hearing loss results in increased difficulty for across-channel temporal judgments. The hypothesis being tested was that listeners with cochlear loss would perform as well as normal-hearing listeners for all within-channel conditions but would exhibit relatively greater performance deficits in the across-channel conditions. A subsidiary aim was to determine whether, in normal-hearing listeners, the across-channel effects previously observed for minimal-duration standard gaps also existed for relatively long standard gaps. Two experiments were undertaken, one dealing with monaural conditions and one dealing with dichotic conditions. The monaural results indicated that across-frequency GDD was poorer than isofrequency GDD, even for the longer gap durations of 35 and 250 ms examined here. However, the results showed no effect of hearing loss on GDD. Rather, GDD appeared to be sensitive to listener age, with younger listeners showing better performance in both within-channel and across-channel conditions. In addition, both within-channel and across-channel performance was sensitive to the duration of the leading gap marker. Finally, the pattern of dichotic "across-ear" performance was similar, but not equivalent, to that of monaural across-frequency performance.

Chronic nitric oxide inhibition aggravates hypertension in erythropoietin-treated renal failure rats.

Alterations in nitric oxide (NO) and endothelin-1 (ET-1) production have recently been reported in erythropoietin (r-HuEPO)-induced hypertension in renal failure rats. The present study was designed to evaluate the effect of NO synthase inhibition with the L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure (BP) and ET-1 production in control and in uremic rats treated or not treated with r-HuEPO. Renal failure was induced by a two-stage 5/6 nephrectomy. Control and uremic rats were studied separately and subdivided into four groups: vehicle, r-HuEPO, L-NAME + vehicle and L-NAME + r-HuEPO. L-NAME (100 mg/kg/day), r-HuEPO (100 U/kg, subcutaneously, three times per week), the vehicle or both were administered during 4 weeks in control rats and during 2 weeks in uremic rats. Systolic BP was recorded before and after the onset of treatment at weeks 2 and 4 in control rats and at weeks 1 and 2 in uremic rats. Hematocrit, serum creatinine, plasma, blood vessel (thoracic aorta and mesenteric artery bed) and renal cortex immunoreactive (ir) ET-1 concentrations were measured at the end of the protocol. L-NAME enhanced BP in control and uremic rats and the increase was significantly higher in uremic rats under r-HuEPO therapy (222 +/- 7 mmHg vs 198 +/- 6 mmHg, p<0.05). L-NAME induced an increase in thoracic aorta ir-ET-1 concentrations in control and uremic rats. In contrast, ir-ET-1 concentrations were unchanged in the mesenteric arterial bed and the renal cortex of control and uremic animals. R-HuEPO increased thoracic aorta ir-ET-1 contents in L-NAME treated control and uremic rats. These results underline the important role of NO release in opposing the action of vasopressors on blood vessel tone which appears more important in uremic rats treated with r-HuEPO. L-NAME treatment increased large vessel, but not small resistance artery ir-ET-1 concentrations, suggesting differential regulation of ET-1 production in different vascular beds under chronic NO synthase inhibition.

Renal and vascular effects of chronic nitric oxide synthase inhibition: involvement of endothelin 1 and angiotensin II.

Endothelin 1 (ET-1) is a potent vasoconstrictor implicated in the control of blood pressure and renal function. Its effects can be modulated by nitric oxide (NO), which inhibits ET-1 production and action. Recently, we reported that ET-1 production can also be modulated by angiotensin II (AngII) in vivo. To investigate the interactions between NO, ET-1, and AngII in hypertension and renal dysfunction, we assessed immunoreactive ET-1 (ir-ET-1) concentration in plasma and urine as well as in vascular and renal tissues of rats with chronic inhibition of NO synthesis, in the presence and the absence of the AngII type 1 receptor antagonist losartan. Normal (protocols A and B) and uninephrectomized rats (protocol C) received the L-arginine analog N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, 0.05% (protocol A) or 0.1% (protocols B and C), with or without losartan (20 mg x kg(-1) x day(-1)). After 6 weeks, systolic blood pressure was significantly increased in L-NAME rats compared with the controls (p < 0.01), while serum creatinine and urea, creatinine clearance, and proteinuria were similar to control values. However, ir-ET-1 concentration in plasma and in the thoracic aorta was augmented in animals receiving 0.1% L-NAME (1 < 0.01), while it was unchanged in the mesenteric arterial bed, preglomerular arteries, and glomeruli. In contrast, ir-ET-1 concentration was decreased in the renal papilla (p < 0.05) as well as in the urine of L-NAME rats (p < 0.01). Treatment with losartan significantly attenuated the rise in systolic blood pressure induced by L-NAME (p < 0.01). Losartan also normalized the increased ir-ET-1 concentration in plasma and in the thoracic aorta, but had no effect on tissues with normal or reduced ir-ET-1 levels. These results indicate that chronic inhibition of NO synthase with L-NAME induces hypertension without renal dysfunction. Increased ET-1 production in some blood vessels and elevated circulating ET-1 concentration may contribute to the maintenance of high blood pressure. The reduction of systolic blood pressure by losartan supports a role for AngII in the pathogenesis of this form of hypertension, which may be due, at least in part, to the modulation of ET-1 production.

Nonpeptide endothelin receptor antagonists attenuate the pressor effect of diaspirin-crosslinked hemoglobin in rat.

Endothelin 1 (ET-1) is a potent vasoactive and mitogenic peptide that is thought to participate in the hemodynamic effects elicited by drugs that block the biosynthesis and release of endothelium-derived nitric oxide (NO), such as NO synthase inhibitors. Using the nonpeptide endothelin receptor antagonists bosentan and LU-135252, we tested the hypothesis that endothelins contribute to the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a hemoglobin-based oxygen carrier, whose pressor activity in mammals is attributed primarily to a scavenging action towards NO. The NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME), ET-1, and noradrenaline (NA) were used as reference drugs. Bosentan markedly reduced the pressor effects elicited by DCLHb, L-NAME, and ET-1, but not those evoked by NA. LU-135252 attenuated the pressor effect elicited by DCLHb and ET-1, but not that produced by L-NAME or NA. The decreases in heart rate associated with the pressor effect of DCLHb and L-NAME were reduced by LU-135252, whereas only those elicited by DCLHb were attenuated by bosentan. In contrast with bosentan, LU-135252 caused a decrease in the baseline blood pressure and heart rate. These results suggest that endothelins may participate in the pressor activity of DCLHb. They suggest also that nonpeptide endothelin receptor antagonists such as bosentan or LU-135252 may be useful to counteract endothelin-mediated undesirable hemodynamic effects of drugs that inhibit the activity of the NO system.

Critical residues influence the affinity and selectivity of alpha-conotoxin MI for nicotinic acetylcholine receptors.

The mammalian skeletal muscle acetylcholine receptor contains two nonequivalent acetylcholine binding sites, one each at the alpha/delta and alpha/gamma subunit interfaces. Alpha-Conotoxin MI, a 14-amino acid competitive antagonist, binds at both interfaces but has approximately 10(4) higher affinity for the alpha/delta site. We performed an "alanine walk" to identify the residues in alpha-MI that contribute to this selective interaction with the alpha/delta site. Electrophysiological measurements with Xenopus oocytes expressing normal receptors or receptors lacking either the gamma or delta subunit were made to assay toxin-receptor interaction. Alanine substitutions in most amino acid positions had only modest effects on toxin potency at either binding site. However, substitutions in two positions, proline-6 and tyrosine-12, dramatically reduced toxin potency at the high-affinity alpha/delta site while having comparatively little effect on low-affinity alpha/gamma binding. When tyrosine-12 was replaced by alanine, the toxin's selectivity for the high-affinity site (relative to that for the low-affinity site) was reduced from 45,000- to 30-fold. A series of additional amino acid substitutions in this position showed that increasing side chain size/hydrophobicity increases toxin potency at the alpha/delta site without affecting alpha/gamma binding. In contrast, when tyrosine-12 is diiodinated, toxin binding is nearly irreversible at the alpha/delta site but also increases by approximately 500-fold at the alpha/gamma site. The effects of position 12 substitutions are accounted for almost entirely by changes in the rate of toxin dissociation from the high-affinity alpha/delta binding site.