Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1

The molecular mechanisms influencing muscle atrophy in humans are poorly understood. Atrogin-1 and MuRF1, two ubiquitin E3-ligases, mediate rodent and cell muscle atrophy and are suggested to be regulated by an Akt/Forkhead (FKHR) signaling pathway. Here we investigated the expression of atrogin-1, MuRF1, and the activity of Akt and its catabolic (FKHR and FKHRL1) and anabolic (p70s6k and GSK-3β) targets in human skeletal muscle atrophy. The muscle atrophy model used was amyotrophic lateral sclerosis (ALS). All measurements were performed in biopsies from 22 ALS patients and 16 healthy controls as well as in G93A ALS mice. ALS patients had a significant increase in atrogin-1 mRNA and protein content, which was associated with a decrease in Akt activity. There was no difference in the mRNA and protein content of FKHR, FKHRL1, p70s6k, and GSK-3β. Similar observations were made in the G93A ALS mice. Human skeletal muscle atrophy, as seen in the ALS model, is associated with an increase in atrogin-1 and a decrease in Akt. The transcriptional regulation of human atrogin-1 may be controlled by an Akt-mediated transcription factor other than FKHR or via another signaling pathway.

Properties of slow- and fast-twitch muscle fibres in a mouse model of amyotrophic lateral sclerosis

This investigation was undertaken to determine if there are altered histological, pathological and contractile properties in presymptomatic or endstage diseased muscle fibres from representative slow-twitch and fast-twitch muscles of SOD1 G93A mice in comparison to wildtype mice. In presymptomatic SOD1 G93A mice, there was no detectable peripheral dysfunction, providing evidence that muscle pathology is secondary to motor neuronal dysfunction. At disease endstage however, single muscle fibre contractile analysis demonstrated that fast-twitch muscle fibres and neuromuscular junctions are preferentially affected by amyotrophic lateral sclerosis-induced denervation, being unable to produce the same levels of force when activated by calcium as muscle fibres from their age-matched controls. The levels of transgenic SOD1 expression, aggregation state and activity were also examined in these muscles but there no was no preference for muscle fibre type. Hence, there is no simple correlation between SOD1 protein expression/activity, and muscle fibre type vulnerability in SOD1 G93A mice.

Lateral positioning for critically ill adult patients

We aim to assess the effect of the lateral position compared to other body positions on patient outcomes (mortality, morbidity and clinical adverse events during and following positioning) in critically ill adult patients. We will examine the single use of the lateral position (that is on the right or left side) and repeat use of the lateral position(s) in a positioning schedule (that is lateral positioning). We plan to undertake subgroup analysis for primary disease and condition, severity of illness, the presence of assisted ventilation and angle of lateral rotation.

Living with amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) : decision-making about 'ongoing change and adaptation

Aims and objectives. To present a model that explicates the dimensions of change and adaptation as revealed by people who are diagnosed and live with amyotrophic lateral sclerosis/motor neurone disease.

Background. Most research about amyotrophic lateral sclerosis/motor neurone disease is medically focused on cause and cure for the illness. Although psychological studies have sought to understand the illness experience through questionnaires, little is known about the experience of living with amyotrophic lateral sclerosis/motor neurone disease as described by people with the disease.

Design. A grounded theory method of simultaneous data collection and constant comparative analysis was chosen for the conduct of this study.

Methods. Data collection involved in-depth interviews, electronic correspondence, field notes, as well as stories, prose, songs and photographs important to participants. QSR NVivo 2® software was used to manage the data and modelling used to illustrate concepts.

Findings. Participants used a cyclic, decision-making pattern about 'ongoing change and adaptation' as they lived with the disease. This pattern formed the basis of the model that is presented in this paper.

Conclusion. The lives of people living with amyotrophic lateral sclerosis/motor neurone disease revolve around the need to make decisions about how to live with the disease progression and their deteriorating abilities. Life decisions were negotiated by participants to maintain a sense of self and well-being in the face of change.

Relevance to clinical practice. The 'ongoing change and adaptation' model is a framework that can guide practitioners to understand the decision-making processes of people living with amyotrophic lateral sclerosis/motor neurone disease. Such understanding will enhance caring and promote models of care that are person-centred. The model may also have relevance for people with other life limiting diseases and their care.

Influence of posture on the range of axial rotation and coupled lateral flexion of the thoracic spine

Objective
This study examines the influence of posture on the range of axial rotation of the thorax and the range and direction of the coupled lateral flexion.

Methods
The ranges of mid thoracic axial rotation and coupled lateral flexion were measured in 52 asymptomatic subjects (aged 18-43 years) using an optical motion analysis system. To examine the influence of posture on primary and coupled motion, we initiated axial rotation from a neutral sitting posture and from end-range thoracic flexion and extension.

Results
There was a significant decrease in the range of thoracic rotation in flexion compared with the neutral and extended postures (P < .001). The mean range of coupled lateral flexion was 8.9% of the axial rotation range in the neutral posture and increased to 14.3% and 23.2% in the extended and flexed postures, respectively. Patterns of coupled motion varied between subjects, but an ipsilateral pattern was more common in the flexed posture, whereas a contralateral pattern was more common in the neutral and extended postures.

Conclusions
The ranges and patterns of coupled motion of the thorax appear to be strongly influenced by the posture from which the movement is initiated. This has important implications in relation to the interpretation of clinical tests of thoracic motion and in consideration of mechanisms of development of thoracic pain disorders.

The bipolar depression rating scale (BDRS) : its development, validation and utility

Objectives: Unipolar and bipolar depression differ neurobiologically and in clinical presentation. Existing depression rating instruments, used in bipolar depression, fail to capture the necessary phenomenological nuances, as they are based on and skewed towards the characteristics of unipolar depression. Both clinically and in research there is a growing need for a new observer-rated scale that is specifically designed to assess bipolar depression.

Methods: An instrument reflecting the characteristics of bipolar depression was drafted by the authors, and administered to 122 participants aged 18–65 (44 males and 78 females) with a diagnosis of DSM-IV bipolar disorder, who were currently experiencing symptoms of depression. The Bipolar Depression Rating Scale (BDRS) was administered together with the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).

Results: The BDRS has strong internal consistency (Cronbach's alpha = 0.917), and robust correlation coefficients with the MADRS (r = 0.906) and HAM-D (r = 0.744), and the mixed subscale correlated with the YMRS (r = 0.757). Exploratory factor analysis showed a three-factor solution gave the best account of the data. These factors corresponded to depression (somatic), depression (psychological) and mixed symptom clusters.

Conclusions: This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales.

Scale matters : the need for a Bipolar Depression Rating Scale (BDRS)

Objective: To briefly review the clinical and biological distinctions between unipolar and bipolar depression critiquing in particular currently available depression rating scales and discuss the need for a new observer-rated scale tailored to bipolar depression.

Method: Relevant literature pertaining to the symptomatic differences between bipolar disorder and unipolar disorder as well as their measurement using existing assessment scales was identified by computerized searches and reviews of scientific journals known to the authors.

Results: Bipolar depression is distinct from unipolar depression in terms of phenomenology and clinical characteristics. These distinguishing features can be used to identify bipolarity in patients that present with recurrent depressive episodes. This is important because current self-report and observer-rated scales are optimized for unipolar depression, and hence limited in their ability to accurately assess bipolar depression.

Conclusion: The development of a specific bipolar depression rating scale will improve the assessment of bipolar depression in both research and clinical settings and assist the development of better treatments and interventions.

Can sand slugs in rivers deliver conservation benefits? The biodiversity value of tributary junction plug wetlands in the Glenelg River, Australia

Restoration works are carried out to alleviate human impacts and improve habitats within ecosystems. However, human impacts may also create new (anthropogenic) habitat for species to exploit.A dilemma arises when proposed restoration works would remove anthropogenic habitat and the assemblages it supports. Sediment input into the Glenelg River has formed tributary junction plug wetlands at confluences. Sand slug removal is proposed as part of river rehabilitation, but would also drain plug wetlands. We sampled four plug wetland, four river run and three river pool sites to determine whether plug wetlands influence water quality and add to the biodiversity of macroinvertebrates in the Glenelg River.Water quality and macroinvertebrate diversity were similar in plug wetlands, river runs and river pools.Assemblages were distinct among all sites, regardless of type, so there was no characteristic ‘plug-wetland fauna’. Therefore, although removal of plug wetlands would not cause a dramatic loss of invertebrate biodiversity, it would destroy anthropogenic habitat that supports a similar range of species to natural habitats in a river subject to multiple degrading processes. Gains from rehabilitation should be weighed against the value of anthropogenic habitat and the extent of similar habitat lost elsewhere in the ecosystem.

Lateral strength of zero bond masonry walls subjected to wind loads

Masonry walls are usually laid with the individual masonry units along a course overlapping units in the course below. Commonly, the perpend joints in the course occur above the mid-points of the units below to form a ‘half-bond’ or above a third point to form a ‘third-bond’. The amount of this overlap has a profound influence on the strength of a wall supported on three or four sides, where lateral pressures from wind cause combined vertical and horizontal flexure. Where masonry units are laid with mortar joints, the torsional shear bond resistance between the mortar and overlapping units largely determines the horizontal flexural strength. If there is zero bond strength between units, then the horizontal flexural strength is derived from the frictional resistance to torsion on the overlapping bed-faces of the units. This thesis reports a theoretical and experimental investigation into the frictional properties of overlapping units when subjected to combinations of vertical and horizontal moments and vertical axial compression. These basic properties were used to develop a theory to predict the lateral strength of walls supported on two, three or four sides. A plastic theory of behaviour was confirmed by experiment. The theory was then used to determine maximum unbraced panel sizes for particular boundary conditions. Design charts were developed to determine temporary bracing requirements for panels during construction.

A novel bipolar time-spread echo hiding based watermarking method for stereo audio signals

In this paper, a novel bipolar time-spread (TS) echo hiding based watermarking method is proposed for stereo audio signals, to overcome the low robustness problem in the traditional TS echo hiding method. At the embedding, echo signals with opposite polarities are added to both channels of the host audio signal. This improves the imperceptibility of the watermarking scheme, since added watermarks have similar effects in both channels. Then decoding part is developed, in order to improve the robustness of the watermarking scheme against common attacks. Since these novel embedding and decoding methods utilize the advantage of two channels in stereo audio signals, it significantly reduces the interference of host signal at watermark extraction which is the main reason for error detection in the traditional TS echo hiding based watermarking under closed-loop attack. The effectiveness of the proposed watermarking scheme is theoretically analyzed and verified by simulations under common attacks. The proposed echo hiding method outperforms conventional TS echo hiding based watermarking when their perceptual qualities are similar.

Obesity is associated with previous suicide attempts in bipolar disorder

Objective: There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder.

Methods: Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese.

Results: Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03) as likely to have a history of suicide attempt(s).

Conclusion: Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.

Diet quality in bipolar disorder in a population-based sample of women

Background : Recent epidemiological evidence has indicated a role for diet quality in unipolar depressive illness. This study examined the association between diet quality and bipolar disorder (BD) in an epidemiological cohort of randomly selected, population-based women aged 20–93 years.

Methods : An a priori diet quality score was derived from food frequency questionnaire data, a factor analysis identified habitual dietary patterns and glycemic load was assessed. Mental health was assessed using the SCID-I/NP.

Results : BD was identified in 23 women and there were 691 participants with no history of psychopathology. Compared to those with no psychopathology, those with BD had a higher glycemic load (p = 0.06) and higher scores on a ‘western’ dietary factor (p = 0.03) and the ‘modern’ dietary factor (p = 0.02). For each standard deviation increase in a ‘western’ and ‘modern’ dietary pattern and glycemic load, the odds ratios for BD were increased (‘western’ OR = 1.88, 95% CI 1.33–2.65; ‘modern’ OR = 1.72, 95% CI 1.14–2.39; GL OR = 1.56, 95% CI 1.13–2.14). Conversely, a ‘traditional’ dietary pattern was associated with reduced odds for BD (OR = 0.53 95% CI 0.32–0.89) after adjustments for overall energy intake.

Limitations : The small sample size did not allow for multivariate analyses and the cross-sectional study design precludes any determinations regarding the direction of the relationships between diet quality and BD.

Conclusion : These data are largely concordant with results from dietary studies in unipolar depression. However, clinical recommendations cannot be made until the direction of the relationship between diet quality and BD is determined. Longitudinal studies are warranted.