Reduced vitamin D levels in painful diabetic peripheral neuropathy.

AIM: Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls. METHODS: Forty-five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during the summer months, July to September. RESULTS: After adjusting for age, BMI, activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25-hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01). CONCLUSIONS: We have demonstrated a significant difference in 25-hydroxyvitamin D levels in well-characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.

An ergonomics action research demonstration: integrating human factors into assembly design processes.

In action research (AR), the researcher participates 'in' the actions in an organisation, while simultaneously reflecting 'on' the actions to promote learning for both the organisation and the researchers. This paper demonstrates a longitudinal AR collaboration with an electronics manufacturing firm where the goal was to improve the organisation's ability to integrate human factors (HF) proactively into their design processes. During the three-year collaboration, all meetings, workshops, interviews and reflections were digitally recorded and qualitatively analysed to inform new 'actions'. By the end of the collaboration, HF tools with targets and sign-off by the HF specialist were integrated into several stages of the design process, and engineers were held accountable for meeting the HF targets. We conclude that the AR approach combined with targeting multiple initiatives at different stages of the design process helped the organisation find ways to integrate HF into their processes in a sustainable way. PRACTITIONER SUMMARY: Researchers acted as a catalyst to help integrate HF into the engineering design process in a sustainable way. This paper demonstrates how an AR approach can help achieve HF integration, the benefits of using a reflective stance and one method for reporting an AR study.

Modified conventional gait model vs. Six degrees of freedom model: A comparison of lower limb kinematics and associated error.

BACKGROUND: The conventional gait model (CGM) is commonly utilised within clinical motion analysis but has a number of inherent limitations. To overcome some of these limitations modifications have been made to the CGM and six-degrees of freedom models (6DoF) have been developed. RESEARCH QUESTION: How comparable are lower limb kinematics calculated using modified CGM and 6DoF models and what is the error associated with the output of each model during walking? METHODS: Ten healthy males attended two gait analysis sessions, in which they walked at a self-selected pace, while a 10-camera motion capture system recorded lower limb kinematics. Hip, knee and ankle joint kinematics in all three anatomical planes were calculated using a modified CGM, with medial anatomical markers and a three-dimensional foot added, and 6DoF. Mean absolute differences were calculated on a point-by-point basis over the walking gait cycle and interpreted relative to a 5° threshold to explore the comparability of model outputs. The standard error of the measurement (SEM) was also calculated on a point-by-point basis over the walking gait cycle for each model. RESULTS: Mean absolute differences above 5° were reported between the two model outputs in 58-86% of the walking gait cycle at the knee in the frontal plane, and over the entire walking gait cycle at the hip and knee in the transverse plane. SEM was typically larger for the modified CGM compared to the 6DoF, with the highest SEM values reported at the knee in the frontal plane, and the hip and the knee in the transverse plane. SIGNIFICANCE: Caution should be taken when looking to compare findings between studies utilising modified CGM and 6DoF outside of the sagittal plane, especially at the hip and knee. The reduced SEM associated with the 6DoF suggests this modelling approach may be preferable.

Soccer fatigue, sprinting and hamstring injury risk.

The aim of this study was to investigate the effect of a multi-directional soccer-specific fatigue protocol on sprinting kinematics in relation to hamstring injury risk. Nine semi-professional soccer players (Mean +/- SD: Age: 21.3 +/- 2.9 year; Height 185.0 +/- 8.7 cm; Body Mass 81.6 +/- 6.7 kg) completed the SAFT(90); a multi-directional, intermittent 90 min exercise protocol representative of soccer match-play. The 10m sprint times and three-dimensional kinematic data were recorded using a high-speed motion capture system (Qualisys Track Manager) every 15 min during the SAFT(90). A significant time dependent increase was observed in sprint time during the SAFT(90) (P<0.01) with a corresponding significant decrease in stride length (P<0.01). Analysis of the kinematic sprint data revealed significantly reduced combined maximal hip flexion and knee extension angle, indicating reduced hamstring length, between pre-exercise and half-time (P<0.01) and pre-exercise and full-time (P<0.05). These findings revealed that the SAFT(90) produced time dependent impairments in sprinting performance and kinematics of technique which may result from shorter hamstring muscle length. Alterations in sprinting technique may have implications for the increased predisposition to hamstring strain injury during the latter stages of soccer match-play.

Soccer half-time strategy influences thermoregulation and endurance performance.

AIM: In the first 15 min of the second half in professional soccer, there is a reduction of high intensity distance covered and a high incidence of injuries sustained, possibly due to a reduction in body temperature during the half-time (HT). The aim of this study was to investigate the effect of active and passive re-warm-up strategies on cardiovascular (heart rate, HR) and thermoregulatory stress, and second-half soccer-specific endurance performance (SSEP). METHODS: Seven professional players performed two intermittent field tests of 16.5 min duration, with a 15 min HT. On separate, randomised occasions, 4 trials were completed during which different HT strategies were undertaken between minutes 7 and 14 of the HT interval. Two passive trials were completed: rest control trial (CON), or players were immersed to the gluteal fold in a hot bath (approximately 40 degrees C-passive heating, PH); in the active trials, players performed at 70% maximum HR, either steady-state non-specific active heating (cycling, NSAH) or intermittent soccer-specific active heating (sprinting repeatedly, SSAH). HR and core temperature (Tc) were measured every 5 min, and body weight was recorded pre and post each trial. RESULTS: Active re-warm-up strategies maintained SSEP in the second period with respect to CON (P<0.01), whereas PH did not reduce the decrement in performance (P>0.05). Active heating strategies increased HR during HT in comparison to CON, whereas PH did not. During the HT period in the CON trial, T(c) decreased by 0.97+/-0.29 degrees C, PH and SSAH trials did not attenuate this decrease (P>0.01), whereas NSAH increased T(c) in respect to CON (P<0.01). These differences in HR and T(c) between re-warm-up strategies during HT were not apparent at the end of the trials. CONCLUSION: Active re-warm-up strategies during HT attenuated the decrement in second-half SSEP that was observed during passive trials.

The Use of Silgel STC-SE, a Topical Silicone Gel for the Treatment and Reduction of Hypertrophic and Keloid Scars.

BACKGROUND: A single-center study assessing the efficacy of Nagor's Silgel STC-SE silicone gel to reduce the appearance of hypertrophic and keloid scars. METHODS: A 16-week controlled study of 36 patients with hypertrophic or keloid scars. The subjects were divided between 2 cohorts: one assessing recently healed scars (<6 mo) and other assessing older scars (6 mo to 2 y). The efficacy of Silgel STC-SE on the scar was evaluated by skin hydration, skin moisture evaporation, skin elasticity, basic scar measurements, subjective patient questionnaire data, and image analysis. All subjects had data collected at baseline and weeks 1, 4, 8, 12, and 16. Photographs were taken for image analysis at baseline, week 8, and week 16. Statistical analysis was conducted on all data. RESULTS: Twenty-nine patients completed the study (27 presented with hypertrophic scars and 2 with keloid scars), and 90% reported a marked improvement in their scar appearance. Patient questionnaire data showed great satisfaction with the product. Image analysis showed visual improvement with a statistically significant reduction of the "red" color of scars. Overall, scar dimensions were significantly reduced. There was a significant decrease from baseline levels in average scar length. Skin elasticity, skin hydration, and skin moisture evaporation did not change significantly from baseline. CONCLUSIONS: The results of this study indicate that Silgel STC-SE is an effective treatment in reducing the appearance and red color of hypertrophic scars up to 2 years old. Further study is required to draw significant conclusion in regard to the treatment of keloid scars.

Best practice in primary care pathology: review 1.

This first best practice review examines four series of common primary care questions in laboratory medicine, namely: (i) measurement and monitoring of cholesterol and of liver and muscle enzymes in patients in the context of lipid lowering drugs, (ii) diagnosis and monitoring of vitamin B12/folate deficiency, (iii) investigation and monitoring of paraprotein bands in blood, and (iv) management of Helicobacter pylori infection. The review is presented in a question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.

A hierarchical model of factors influencing a battery of agility tests.

AIM: The aim of this study was to investigate the hierarchical contributions of anthropometry, strength and cognition to a battery of prescriptive and reactive agility tests. METHODS: Nineteen participants (mean±S.D.; age:22.1±1.9 years; height: 182.9±5.5 cm; body mass: 77±4.9 kg) completed four agility tests: a prescriptive linear sprint, a prescriptive change-of-direction sprint, a reactive change-of-direction sprint, and a reactive linear deceleration test. Anthropometric variables included body fat percentage and thigh girth. Strength was quantified as the peak eccentric hamstring torque at 180, 300, and 60°·s-1. Mean reaction time and accuracy in the Stroop word-colour Test was used to assess perceptual and decision making factors. RESULTS: There was little evidence of intertest correlation with the strongest relationship observed between 10 m sprint and t-test performance (r2=0.49, P<0.01). Anthropometric measures were not strong predictors of agility, accounting for a maximum 23% (P=0.12) in the prescriptive change-of-direction test. Cognitive measures had a stronger correlation with the reactive (rather than prescriptive) agility tests, with a maximum 33% (P=0.04) of variance accounted for in the reactive change-of-direction test. Eccentric hamstring strength accounted for 62% (P=0.01) of the variance in the prescriptive change-of-direction test. Hierarchical ordering of the agility tests revealed that eccentric hamstring strength was the primary predictor in 3 of the 4 tests, with cognitive accuracy the next most common predictor. CONCLUSION: There is little evidence of inter-test correlation across a battery of agility tests. Eccentric hamstring strength and decision making accuracy are the most common predictors of agility performance.

Nucleic acids. 16. Orally active derivatives of ara-cytidine.

Water-soluble derivatives of ara-cytidine (cytarabine, Cytosar) were prepared and tested for antitumor, immunosuppressive, and antiarthritic activities in animals after oral administration. The compounds tested included the 5'-palmitate, 5'-benzoate, and 5'-adamantoate esters of ara-cytidine, made water soluble by use of their hydrochloride salts of peptidyl derivatives, and two basic 5' esters (5'-nicotinoate and 5'-quinuclidinate) as their hydrochloride salts. Five of the compounds had antitumor activity superior to that found with ara-cytidine itself after oral administration in the L1210 leukemic mouse assay. One of these, 5'-adamantoyl-ara-cytidine hydrochloride, had antitumor activity after oral administration approaching that achieved with parenterally administered ara-cytidine.

2'-O-aminopropyl ribonucleotides: a zwitterionic modification that enhances the exonuclease resistance and biological activity of antisense oligonucleotides.

Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine (APC), 2'-O-(aminopropyl)-guanosine (APG), and 2'-O-(aminopropyl)uridine (APU) have been prepared in high yield from the ribonucleoside, protected, and incorporated into an oligonucleotide using conventional phosphoramidite chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the sugar pucker of the nucleoside but does not form a tight ion pair with the proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using NMR. As predicted from the modeling results, the sugar pucker of the APU moiety is shifted toward a C3'-endo geometry. In addition, the primary amine rotates freely and is not bound electrostatically to any phosphate group, as evidenced by the different sign of the NOE between sugar proton resonances and the signals from the propylamine chain. Incorporation of aminopropyl nucleoside residues into point-substituted and fully modified oligomers does not decrease the affinity for complementary RNA compared to 2'-O-alkyl substituents of the same length. However, two APU residues placed at the 3'-terminus of an oligomer gives a 100-fold increase in resistance to exonuclease degradation, which is greater than observed for phosphorothioate oligomers. These structural and biophysical characteristics make the 2'-O-aminopropyl group a leading choice for incorporation into antisense therapeutics. A 20-mer phosphorothioate oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted against C-raf mRNA has been transfected into cells via electroporation. This oligonucleotide has 5-10-fold greater activity than the control phosphorothioate for reducing the abundance of C-raf mRNA and protein.

Detection of oligonucleotide-ligand complexes by ESI-MS (DOLCE-MS) as a component of high throughput screening.

With the advent of combinatorial chemistry and high throughput screening, a major bottleneck in the pharmaceutical industry has changed from quickly finding active compounds to limiting them to a manageable number for proper follow-up. With hundreds to thousands of active compounds identified by a multitude of biological screens, there need to be rapid and unambiguous methods for eliminating false positive, toxic, or otherwise difficult compounds from further scrutiny. We have used electrospray ionization mass spectrometry as a rapid screening method to identify compounds from viral screens that yield a positive assay response by interaction with DNA rather than inhibiting the target enzyme. Both the sample preparation and data acquisition have been automated, allowing the screening of all hits from relevant biological screens (up to 1,000/week). The assay was validated using several known DNA intercalators and minor groove binders. These "standards" and many but not all of our "active compounds" were shown to form noncovalent complexes with a variety of different DNA:DNA and DNA:RNA duplexes.

Suicidal destruction of Helicobacter pylori: metabolic consequence of intracellular accumulation of ammonia.

The role of pH, citrate buffer, and urea were investigated in the suicidal destruction of Helicobacter pylori, with particular reference to the organism's urea and ammonia metabolism. The median five minute survival of H pylori in the presence of 50 mmol/l urea in 0.2 M citrate buffer at pH 6.0 was only 14%, compared with 53% in the same solution at pH 7.0. The median amount of ammonium released into the incubating solution over five minutes was lower at pH 6.0 (9 mumol) than at pH 7.0 (18 mumol) despite similar uptake of urea. The median five minute survival of H pylori in 0.2 M citrate buffer, pH 6.0, decreased from 89% to 14% when the urea concentration was increased from 1 mmol/l to 50 mmol/l. Likewise, the recovery in the incubating solution of ammonia resulting from the hydrolysis of urea fell from 27% to 3% when the initial urea concentration was increased from 1 mmol/l to 50 mmol/l. Survival of H pylori in the presence of 30 mmol/l urea at pH 6.0 was compared in 0.2 M citrate, acetate, and phosphate buffers. The median five minute survival was less in the citrate buffer, at 29%, than in either the acetate buffer 80% or the phosphate buffer 100%. The percentage recovery of ammonia was similar in the three buffers. These findings indicate that the suicidal destruction of the bacterium may be explained by intracellular accumulation of ammonia due to production in excess of the rate of excretion.

Harnessing of urease activity of Helicobacter pylori to induce self-destruction of the bacterium.

Eradication of Helicobacter pylori with currently available antibacterial agents is unsatisfactory due to the risk of side-effects and the emergence of resistance. The organism rapidly dies in vitro in the presence of urea at pH 6. When incubated in citrate buffer (pH 6) plus urea (10 mM) the five minute survival was 26% compared with 96% without urea and the survival progressively decreased with increasing urea concentrations, being only 9% in 50 mM urea. The bactericidal effect depended on pH as the organism survived in citrate buffer (pH 7) plus urea (50 mM). The death of the organism at pH 6 in the presence of urea was prevented by the addition of the competitive urease inhibitor hydroxyurea. These findings indicate that destruction of the organism is mediated by its exceptionally high urease activity. Harnessing this enzyme to induce self-destruction could provide a new approach to eradicating this common infection.

Characterization of oligonucleotide metabolism in vivo via liquid chromatography/electrospray tandem mass spectrometry with a quadrupole ion trap mass spectrometer.

The pattern of nuclease degradation observed for an antisense phosphorothioate oligonucleotide in pig kidney was determined using liquid chromatography/electrospray mass spectrometry (LC/ESI-MS) and LC/ESI-MS/MS with a quadrupole ion trap mass spectrometer. Metabolites were separated by length using reversed-phase high-performance liquid chromatography with aqueous hexafluoropropan-2-ol-triethylamine and a methanol gradient. The individual masses of metabolites in each LC peak were determined via deconvolution and converted into potential nucleotide compositions. The nucleotide composition was used to locate metabolites within the known oligomer sequence. The identity of metabolites was confirmed using on-line LC/MS/MS to generate fragment ions suitable for sequence verification. A limited number of shorter oligonucleotide fragments were observed, suggesting that metabolism in vivo may be sequence dependent.

A comparative study of the numbers of bacteria present in enteral feeds prepared and administered in hospital and the home.

Levels and types of bacterial contamination were compared in enteral feeds prepared and administered in hospital or in the home. Samples of feed administered to children suffering from cystic fibrosis were collected for microbiological analysis immediately after preparation, immediately prior to use (unless administered after preparation) and at the end of feeding. No bacteria were detected in 51 (70%) of the 73 feeds sampled on the hospital ward, and in most of the remaining feeds viable counts were less than 10(1) colony-forming units (cfu) ml-1. However, only four (18%) of the feeds sampled in the home were free from bacterial growth and the remaining 18 feeds contained from 10(1) to more than 10(6) cfu ml-1. Bacteria isolated from feeds sampled both in hospital and the home, included Staphylococcus spp., Bacillus spp., viridans and faecal streptococci, Klebsiella spp. and Enterobacter spp. Enterobacter cloacae was isolated from 11 of the 73 hospital feeds and four of the 22 home feeds. Staphylococcus aureus was isolated from five of the home feeds but from none of the hospital feeds. The higher incidence and numbers of bacteria found in home enteral feeds indicate that further, more detailed studies need to be carried out to find the sources and routes of this contamination and devise methods to minimize the problem.

A prospective study of the development of coronary heart disease in a group of 1202 middle-aged men.

A prospective study of the development of coronary heart disease (CHD) in men aged 45--54 was conducted in six group practices in Belfast, Northern Ireland Of the 1343 men examined once by clinical, electrocardiographic, biochemical and anthropometric methods, 1202 free from CHD entered the prospective study. All 1202 men were followed for at least five years and the average annual incidence of CHD during this period was estimated as 1.73% (104 men developed). Of the 28 measurements made at initial examination, four--S-T depression, total lifetime tobacco consumption, diastolic blood pressure, and height (significant on classical linear discriminant function analysis)--were investigated in more detail. Using multidimensional contingency table methods, the probability of developing CHD was found to depend, in rand order of importance, on S-T depression, total lifetime tobacco consumption, and diastolic blood pressure. The risk of development was maximal (0.3732, four times the 'random' risk) in men with S-T depression, greater than average total lifetime tobacco consumption, and a diastolic pressure of 100 mm Hg or more.

Issues of accountability in the assessment of practice.

The nature of nursing work makes the Code of Professional Conduct's moral and professional emphasis appropriate. However this is to the detriment of practitioners' moral, professional and contractual accountability towards learners. Practitioners may fail to make the paradigmatic shift necessary for them to be accountable for the teaching, supervision and assessment of learners. This is a direct consequence of the paucity of assessor preparation and the utilization of assessors with limited professional experience. They have been invested with an authority of which they are unaware and for which they are unprepared.

Basic life support skill acquisition and retention in student nurses undertaking a pre-registration diploma in higher education/nursing course.

Many studies have investigated the ability of health care professionals to provide competent Basic Life Support (BLS) and all results indicate that the majority of staff fail to demonstrate competence. However, it has not yet been shown whether this poor performance is due to deterioration of skill or the nonacquisition of the skill during BLS training. This study seeks to identify aspects of BLS acquisition and retention by student nurses during their three years of training. The two issues under consideration are the effect of teacher-student ratio and the effect of regular practice on BLS performance. This paper provides a review of the methodology and the initial findings.

The effects of multidirectional soccer-specific fatigue on markers of hamstring injury risk.

The purpose of this work was to investigate the effect of multidirectional soccer-specific fatigue on hamstring muscle strength and angle of peak torque. Sixteen male semi-professional soccer players (mean+/-S.D.: age: 21.3+/-2.9 years; height 185.0+/-8.7 cm; body mass 81.6+/-6.7 kg) completed the SAFT(90), a multidirectional, intermittent 90-min exercise protocol based on data from English Championship soccer matches. Prior to exercise (t(0)), at half-time (t(45)) and post-exercise (t(105)), subjects performed three maximal dominant limb isokinetic contractions (Biodex, System 3) at 120 degrees s(-1) through a 90 degrees range for concentric and eccentric knee flexors and concentric knee extensors. Analysis of variance revealed significant time dependant reductions in gravity corrected eccentric hamstring peak torque, and consequently in the functional hamstring:quadriceps ratio (P<0.01). Eccentric hamstring peak torque decreased significantly during each half (t(0): 272.0+/-43.2; t(45): 240.4+/-43.3; t(105): 226.3+/-45.7 Nm). The functional hamstring:quadriceps ratio also decreased significantly during each half (t(0): 116.6+/-21.2; t(45): 107.1+/-17.6; t(105): 98.8+/-20.3%). There were no significant changes in concentric hamstring or quadriceps peak torque observed during SAFT(90) (P>0.05). Data analysis also revealed significant differences for Angle of Peak Torque for eccentric hamstrings (P<0.05) which was significantly higher at the end of each half (t(45): 37+/-15; t(105): 38+/-18 degrees ) than the pre-exercise value (t(0): 28+/-12 degrees ). There was a time dependant decrease in peak eccentric hamstring torque and in the functional strength ratio which may have implications for the increased predisposition to hamstring strain injury during the latter stages of match-play.