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.

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.

Surgical treatment of lateral clavicle fractures associated with complete coracoclavicular ligament disruption: clinico-radiological outcomes of acromioclavicular joint sparing and spanning implants

Distal clavicle fracture associated with complete coracoclavicular ligament disruption represents an unstable injury, and osteosynthesis is recommended. This study was performed (1) to retrospectively analyse the clinico-radiological outcomes of two internal fixation techniques, and (2) to identify and analyse radiographic fracture patterns of fracture that are associated with this injury. Conclusions: Internal fixation of this fracture pattern is associated with a high union rate and favorable clinical outcomes with both techniques. A combination of distal radius plate and ligament reconstruction device resulted in stable fixation and significantly lower reoperation rates, and should be used when fracture geometry permits (Types 1 and 2).

Lateral positioning for critically ill adult patients: a systematic review

A systematic review was undertaken to evaluate the effect of lateral positioning compared to other body positions on morbidity, mortality, and clinical adverse events for critically ill patients. Twenty three studies met the criteria. Hypoxaemia was not consistently reported. No clinical practice recommendations could be drawn from the included studies due to methodological shortcomings.