X-ray crystallographic structure of a novel enantiopure chiral isothiourea with potential applications in enantioselective synthesis.

The synthesis of a chiral isothiourea, namely, (4aR,8aR)-3-phenyl-4a,5,6,7,8,8a-hexahydrobenzo[4,5]imidazo[2,1-b]thiazol-9-ium bromide, C15H17N2S+·Br-, with potential organocatalytic and anti-inflammatory activity is reported. The preparation of the heterocycle of interest was carried out in two high-yielding steps. The hydrobromide salt of the isothiourea of interest provided suitable crystals for X-ray diffraction analysis, the results of which are reported. Salient observations from this analysis are the near perpendicular arrangement of the phenyl ring and the mean plane of the heterocycle. This conformational characteristic may be relevant with regard the stereoselectivity induced by the chiral isothiourea in asymmetric reactions. Furthermore, evidence was found for the existence of an S...Br- halogen bond.

Evidence of movement variability patterns during a repetitive pointing task until exhaustion.

Human movement is characterized by its variability: the same task is never performed twice in exactly the same way. This variability is believed to play a functional role in movement performance and adaptability, as well as in preventing musculoskeletal damage. This article focuses on the time-evolution of movement variability throughout a repetitive pointing task until exhaustion. The kinematics of 13 subjects performing the pointing task is analyzed. Principal Component Analysis of joint angles identifies joint coordinations for each pointing cycle, and cycle-by-cycle comparison highlights movement variability. Non-supervised clustering reveals that subjects adopt successive coordination patterns at an intra-individual level. Inter-individual variability is characterized by the number and type of such patterns: from 3 to 5 patterns, mobilizing the trunk, the shoulder and the upper limbs differently. Movement variability exists even in a seemingly basic and constrained task. It appears in the very early stages of fatigue onset, and may correspond to adaptative coordination responses throughout task performance. This observation should encourage workstation designers to better account for movement variability in order to preserve operators' health and safety.

Intrinsic movement variability at work. How long is the path from motor control to design engineering?

For several years, increasing numbers of studies have highlighted the existence of movement variability. Before that, it was neglected in movement analysis and it is still almost completely ignored in workstation design. This article reviews motor control theories and factors influencing movement execution, and indicates how intrinsic movement variability is part of task completion. These background clarifications should help ergonomists and workstation designers to gain a better understanding of these concepts, which can then be used to improve design tools. We also question which techniques--kinematics, kinetics or muscular activity--and descriptors are most appropriate for describing intrinsic movement variability and for integration into design tools. By this way, simulations generated by designers for workstation design should be closer to the real movements performed by workers. This review emphasises the complexity of identifying, describing and processing intrinsic movement variability in occupational activities.

Using a mammalian cell cycle simulation to interpret differential kinase inhibition in anti-tumour pharmaceutical development.

Systems biology needs to show practical relevance to commercial biological challenges such as those of pharmaceutical development. The aim of this work is to design and validate some applications in anti-cancer therapeutic development. The test system was a group of novel cyclin-dependent kinase (CDK) inhibitors synthesised by Cyclacel Ltd. The measured in vitro IC50s of each compound were used as input data to a proprietary cell cycle model developed by Physiomics plc. The model was able to predict over three orders of magnitude the cytotoxicity of each compound without model adaptation to specific cancer cell types. This pattern matched the experimentally determined data. One class of compounds was predicted to cause an increase of the cell cycle length with a non-linear dose-response curve. Further work will use apoptosis and DNA replication simulations to look at overall cell effects.

The effect of inositol supplements on the psoriasis of patients taking lithium: a randomized, placebo-controlled trial.

BACKGROUND: Lithium carbonate is the most widely used long-term treatment for bipolar affective disorders, but its ability to trigger and exacerbate psoriasis can become a major problem in patients for whom lithium is the only treatment option. Inositol depletion underlies the action of lithium in bipolar affective disorders and there are good theoretical reasons why the use of inositol supplements might be expected to help this group of patients. OBJECTIVES: To determine whether inositol supplements improve the psoriasis of patients on lithium therapy. METHODS: Fifteen patients with psoriasis, who were taking lithium, took part in a randomized, double-blind, placebo-controlled, crossover clinical trial comparing the effect of inositol supplements with those of a placebo (lactose). Changes in the severity of their psoriasis were measured by Psoriasis Area and Severity Index scores recorded before and after the different courses of treatment. The effect of inositol supplements on the psoriasis of 11 patients who were not taking lithium was evaluated in the same way. RESULTS: The inositol supplements had a significantly beneficial effect on the psoriasis of patients taking lithium. No such effect was detected on the psoriasis of patients not on lithium. CONCLUSIONS: The use of inositol supplements is worth considering for patients with intractable psoriasis who need to continue to take lithium for bipolar affective disorders.

Osler and the skin.

William Osler was the greatest physician of his time. Specialists reading his textbooks agreed that in their own specialities he was accurate and illuminating. His grasp of dermatology was particularly striking and skin changes are prominent in five of the syndromes named after him and in at least 100 of his papers. This paper describes how his early training in dermatology under Tilbury Fox in London and Hebra in Vienna combined with his unusual personal qualities to enable him to make massive contributions to a wide variety of dermatological topics. These include smallpox, cutaneous tuberculosis, nail growth, leprosy, scleroderma, pigmentation and purpuric eruptions as well as the more obvious hereditary haemorrhagic telangiectasia, angio-neurotic oedema and Osler's nodes.

Some observations on the direction of scratch marks.

This study consists of two parts. In the first we recorded 1696 scratch marks seen on 69 pruritic patients. The scratch marks followed a consistent pattern on the skin, which was independent of the cause of the itching. The most striking feature was a longitudinal alignment on the limbs. Next we tried to relate our findings to experimental work that suggests that itching is extinguished most effectively by counterstimuli applied within the same dermatomal segment. If this is the case, sufferers from itchy skin diseases might be expected to scratch itchy points on their skin using strokes directed along dermatomal lines, thereby gaining maximal relief. We used the data obtained during the first part of our study to test this possibility. Fifty-one percent of the scratch marks analyzed ran at an angle of less than 20 degrees to the nearest interdermatomal line (significantly higher than the 22.5% expected by chance). However the tendency for scratch marks to run along dermatomal lines was confined to the limbs. In addition, the preferred scratch directions of a group of nonitchy subjects, not driven by the need to alleviate actual itching, coincided closely with the pattern of scratch marks seen on the itchy patients. The direction of scratch marks may therefore be determined as much by mechanical factors affecting the ease of scratching as by the distribution of dermatomes.

How should we define itching?

The standard definition of itching (as "an unpleasant sensation that provokes the desire to scratch") takes no account of recent advances in knowledge about itch physiology. Always imprecise, this definition is also out-of-date. Its defects are discussed in this article, and some modifications are proposed.

HTLV-I associated sicca syndrome in Guadeloupe: lack of relation with a peculiar encoding sequence of surface envelope glycoprotein.

We previously reported a strikingly high prevalence of ocular diseases in HTLV-I infected patients in Guadeloupe (Caribbean basin). We sequenced the surface envelope encoding region of 7 HTLV-I proviruses from guadeloupean patients (5 with sicca syndrome, 2 with TSP/HAM). No relation between sequence and disease was observed. These 7 sequences are the first described from Guadeloupe.

Third molar surgery--a preliminary report on aspects affecting quality of life in the early postoperative period.

The issue of quality of life has largely been neglected within oral surgical practice. A questionnaire was designed to assess the effect of third molar surgery on a number of measures of health care outcome within the first postoperative week, that appeared not to have been previously addressed. These included level of physical discomfort, oral and vocal function, patients' perception of their appearance and social interaction. Patients were asked to complete the questionnaire one day following surgery and again 7 days after surgery. For each question they recorded the answer best describing how they felt, on a 4-point scale. Twenty-nine paired returns were received, for which the results for day 1 and day 7 were summated and compared. A two sample t-test revealed a small but significant improvement in the patients' perception of their quality of life over that time period. When a subset of 11 questions relating to physical wellbeing were analysed using the Wilcoxon Signed Rank Test, a significant improvement in only two of the 11 parameters (ability to masticate and perception of appearance) was found. These results show that within the first postoperative week some patients can experience a deterioration in their quality of life, that extends beyond the traditionally recognized side effects and which shows little improvement in the first postoperative week. It has been stated that patients have a right to know if their lifestyles are to be compromised by the effects of their treatment. We suggest that consideration be given to including reference at the preoperative assessment to some of these outcomes.