The level of agreement between the numerical rating scale and visual analogue scale for assessing pain intensity in adults with chronic pain.

The numerical rating scale and visual analogue scale are used to quantify pain intensity. However, it has not yet been explored whether these scores are interchangeable in adults with chronic pain. Data from the prospective multicentre cross-sectional INTERVAL study were used to evaluate the one-dimensionality and agreement between numerical rating scale scores and visual analogue scale scores in adults with chronic pain. Pain intensity scores using the numerical rating scale and visual analogue scale were provided by 366 patients with chronic pain for current, average, minimal and maximal pain. To evaluate whether pain intensity scales are completed in accordance with each other, the proportion of patients who satisfied the following condition was calculated: minimal pain intensity ≤ maximal pain intensity. A factor analysis confirmed the one-dimensionality of the pain measures. A significant difference was found between numerical rating scale and visual analogue scale scores for average, current, minimum and maximum pain. Intra-class correlation coefficient estimates ranged from 0.739 to 0.858 and all measures failed to show sufficient and acceptable agreement at the 95% level. The strength of agreement between pain severity categories was classified as 'moderate' for average and minimal pain and 'substantial' for current and maximal pain. The proportion of patients who scored minimal pain ≤ maximal pain was 97.5% for the numerical rating scale and 89.5% for the visual analogue scale. This study failed to show an acceptable agreement between the numerical rating scale and visual analogue scale when pain intensity was rated by adults with chronic pain, despite showing both scales measure the same information.

Human echolocators adjust loudness and number of clicks for detection of reflectors at various azimuth angles.

In bats it has been shown that they adjust their emissions to situational demands. Here we report similar findings for human echolocation. We asked eight blind expert echolocators to detect reflectors positioned at various azimuth angles. The same 17.5 cm diameter circular reflector placed at 100 cm distance at 0°, 45° or 90° with respect to straight ahead was detected with 100% accuracy, but performance dropped to approximately 80% when it was placed at 135° (i.e. somewhat behind) and to chance levels (50%) when placed at 180° (i.e. right behind). This can be explained based on poorer target ensonification owing to the beam pattern of human mouth clicks. Importantly, analyses of sound recordings show that echolocators increased loudness and numbers of clicks for reflectors at farther angles. Echolocators were able to reliably detect reflectors when level differences between echo and emission were as low as -27 dB, which is much lower than expected based on previous work. Increasing intensity and numbers of clicks improves signal-to-noise ratio and in this way compensates for weaker target reflections. Our results are, to our knowledge, the first to show that human echolocation experts adjust their emissions to improve sensory sampling. An implication from our findings is that human echolocators accumulate information from multiple samples.

Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative cohort study to explore the influence of patient-reported outcomes on therapy decisions.

PURPOSE: Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. METHODS: In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. RESULTS: Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. CONCLUSIONS: Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.

Relationship between neovascularization and clinical severity in Achilles tendinopathy in 556 paired measurements.

Neovascularization is frequently observed in tendinopathy. Previous studies have focused on the role of neovascularization in Achilles tendinopathy, but have been conducted in small series. It is still unclear whether the degree of neovascularization is related to severity of symptoms. The purpose was to study the relationship between ultrasonographic neovascularization and clinical severity in patients with Achilles tendinopathy. In this prospective cohort study, data on 127 patients (141 tendons) were assembled from databases of three clinical trials. All patients followed an eccentric exercise program. The Öhberg neovascularization score (0-4+) and Victorian Institute of Sports Assessment-Achilles (VISA-A) score (split into domains: pain, function and activity) were collected during baseline and follow-up. The relationship between neovascularization and VISA-A score was calculated. At baseline, 107 tendons (76%) showed some degree of neovascularization. In 556 coupled measurements, neovascularization was weakly related to the VISA-A score [Exp (B) 1.017, 95% confidence interval (CI), 1.007-1.026]. No significant relationship was found between neovascularization and the pain domain (P = 0.277) and the activity domain (P = 0.283), but there was between neovascularization and the function domain of the VISA-A score [Exp (B) = 1.067, 95% CI 1.018-1.119]. In conclusion, neovascularization in Achilles tendinopathy is weakly related to clinical severity, mainly based on the function domain of the VISA-A score.

Sarcopenic obesity is associated with adverse clinical outcome after cardiac surgery.

BACKGROUND & AIMS: Both undernutrition - low fat free mass (FFM) - and obesity - high fat mass (FM) - have been associated with adverse outcome in cardiac surgical patients. However, whether there is an additional effect on outcome of these risk factors present at the same time, that is sarcopenic obesity (SO), is unknown. Furthermore, the association between SO and muscle function is unidentified. METHODS AND RESULTS: In 325 cardiac surgical patients, we prospectively analysed the association between preoperative FFM and FM, measured by bioelectrical impedance spectroscopy, and postoperative adverse outcomes, and their correlation with muscle function - handgrip strength (HGS). SO was associated with postoperative infections (28.2% vs. 5.3%, adj. odds ratio (OR): 7.9; 95% confidence interval (CI): 1.2-54.1; p=0.04). Further, a low FFM index (FFMI; kgm(-2)) was associated with postoperative infections (18.5% vs. 4.7%, adj. OR: 6.6; 95% CI: 1.7-25.2; p=0.01) while a high FM index (FMI; kgm(-2)) was not. Both components of SO, FFMI and FMI, correlated with HGS (FFMI: r=0.570; p<0.001, FMI: r=-0.263; p<0.001). CONCLUSION: SO is associated with an increased occurrence of adverse outcome after cardiac surgery. Our results suggest an additional risk of a low FFMI and high FMI present at the same time. Furthermore, SO is characterised by less muscle function. We advocate determining body composition in cardiac surgical patients to classify and treat undernourished patients, in particular those who are also obese.

The JUMPFOOD study: additional effect of hydrolyzed collagen and vitamin C to exercise treatment for patellar tendinopathy (jumper's knee) in athletes-study protocol for a double-blind randomized controlled trial.

BACKGROUND: Patellar tendinopathy (PT) is a common problem in jumping athletes. Management can be challenging and treatment outcome is not always successful. In combination with tendon loading exercises, hydrolyzed collagen/vitamin C supplementation appears to have a promising effect on the recovery of tendinopathy. The aim of this study is to evaluate whether the use of oral supplementation of hydrolyzed collagen and vitamin C in combination with progressive tendon loading exercises (PTLE) is superior to PTLE and placebo on VISA-P score (which rates pain, function, sports participation) after 24 weeks for athletes with PT. METHODS: The JUMPFOOD study is a double-blinded, two-armed randomized controlled trial, in which the effectiveness of oral supplementation of hydrolyzed collagen/vitamin C combined with PTLE compared to PTLE with placebo on pain and recovery of function in athletes with PT will be investigated. Seventy-six athletes aged 16-40 years, with symptoms of PT for at least 12 weeks, who play sports at least once a week will be included. All participants will receive education, advice with regard to load management and a PTLE program according to the Dutch guidelines for anterior knee pain. In addition, the intervention group will receive daily 10 g hydrolyzed collagen and 40 mg vitamin C supplementation for 24 weeks whereas the control group receives 10 g maltodextrin placebo supplementation. Measurements will take place at baseline and at 12 and 24 weeks' follow-up. Primary outcome is the VISA-P score, which evaluates pain, function, and sports participation. For secondary outcome measures, data with regard to pain during functional tests, flexibility measurements, blood withdrawals, imaging characteristics of the tendon, and health questionnaires will be collected. During the follow-up period, participants will register sports participation, amount of training and tendon load, pain during sports, co-medication, and side-effects in a digital weekly diary. DISCUSSION: The JUMPFOOD study is the first large RCT to study the effectiveness of hydrolyzed collagen/vitamin C supplementation in combination with the PTLE program in athletes with patellar tendinopathy. If supplementation of collagen/vitamin C appears to be effective, this treatment can be implemented in daily sports medicine practice to improve the treatment outcome of patients with PT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05407194. Registered on 7 June 2022.

Pathoanatomy of cerebellar degeneration in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3).

The cerebellum is one of the well-known targets of the pathological processes underlying spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Despite its pivotal role for the clinical pictures of these polyglutamine ataxias, no pathoanatomical studies of serial tissue sections through the cerebellum have been performed in SCA2 and SCA3 so far. Detailed pathoanatomical data are an important prerequisite for the identification of the initial events of the underlying disease processes of SCA2 and SCA3 and the reconstruction of its spread through the brain. In the present study, we performed a pathoanatomical investigation of serial thick tissue sections through the cerebellum of clinically diagnosed and genetically confirmed SCA2 and SCA3 patients. This study demonstrates that the cerebellar Purkinje cell layer and all four deep cerebellar nuclei consistently undergo considerable neuronal loss in SCA2 and SCA3. These cerebellar findings contribute substantially to the pathogenesis of clinical symptoms (i.e., dysarthria, intention tremor, oculomotor dysfunctions) of SCA2 and SCA3 patients and may facilitate the identification of the initial pathological alterations of the pathological processes of SCA2 and SCA3 and reconstruction of its spread through the brain.

Seed storage at elevated partial pressure of oxygen, a fast method for analysing seed ageing under dry conditions.

BACKGROUND AND AIMS: Despite differences in physiology between dry and relative moist seeds, seed ageing tests most often use a temperature and seed moisture level that are higher than during dry storage used in commercial practice and gene banks. This study aimed to test whether seed ageing under dry conditions can be accelerated by storing under high-pressure oxygen. methods: Dry barley (Hordeum vulgare), cabbage (Brassica oleracea), lettuce (Lactuca sativa) and soybean (Glycine max) seeds were stored between 2 and 7 weeks in steel tanks under 18 MPa partial pressure of oxygen. Storage under high-pressure nitrogen gas or under ambient air pressure served as controls. The method was compared with storage at 45 °C after equilibration at 85 % relative humidity and long-term storage at the laboratory bench. Germination behaviour, seedling morphology and tocopherol levels were assessed. KEY RESULTS: The ageing of the dry seeds was indeed accelerated by storing under high-pressure oxygen. The morphological ageing symptoms of the stored seeds resembled those observed after ageing under long-term dry storage conditions. Barley appeared more tolerant of this storage treatment compared with lettuce and soybean. Less-mature harvested cabbage seeds were more sensitive, as was the case for primed compared with non-primed lettuce seeds. Under high-pressure oxygen storage the tocopherol levels of dry seeds decreased, in a linear way with the decline in seed germination, but remained unchanged in seeds deteriorated during storage at 45 °C after equilibration at 85 % RH. CONCLUSIONS: Seed storage under high-pressure oxygen offers a novel and relatively fast method to study the physiology and biochemistry of seed ageing at different seed moisture levels and temperatures, including those that are representative of the dry storage conditions as used in gene banks and commercial practice.

A 5-year follow-up study of Alfredson's heel-drop exercise programme in chronic midportion Achilles tendinopathy.

BACKGROUND: Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy. Although short-term studies show significant improvement, little is known of the long-term (>3 years) results. AIM: To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson's heel-drop exercise programme. STUDY DESIGN: Part of a 5-year follow-up of a previously conducted randomised controlled trial. Methods 58 patients (70 tendons) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson. At baseline and at 5-year follow-up, the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire score, pain status, alternative treatments received and ultrasonographic neovascularisation score were recorded. RESULTS: In 46 patients (58 tendons), the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years (p<0.001) and from the 1-year to 5-year follow-up from 75.0 to 83.4 (p<0.01). 39.7% of the patients were completely pain-free at follow-up and 48.3% had received one or more alternative treatments. The sagittal tendon thickness decreased from 8.05 mm (SD 2.1) at baseline to 7.50 mm (SD 1.6) at the 5-year follow-up (p=0.051). CONCLUSION: At 5-year follow-up, a significant increase of VISA-A score can be expected. After the 3-month Alfredson's heel-drop exercise programme, almost half of the patients had received other therapies. Although improvement of symptoms can be expected at long term, mild pain may remain.

Prevalence of radiological signs of femoroacetabular impingement in patients presenting with long-standing adductor-related groin pain.

OBJECTIVE: A decreased range of motion (ROM) of the hip joint is known to predispose to athletic groin injury. Femoroacetabular impingement (FAI) of the hip leads to a reduced ROM. This study examined the prevalence of radiological signs of FAI in patients presenting with long-standing adductor-related groin pain (LSARGP). DESIGN: Prospective case series. SETTING: Outpatient Sports Medicine Department. PATIENTS: 34 athletes with LSARGP defined as pain on palpation of the proximal insertion of adductor muscle and a painful, resisted adduction test. ASSESSMENT: A clinician blinded to the results of the radiological assessment performed a physical examination: iliopsoas length, hip ROM and anterior hip impingement test. Anteroposterior pelvic radiographs were examined by a second blinded clinician for the presence of: pistol grip deformity, centrum-collum-diaphyseal angle, femoral head neck ratio, coxa profunda, protrusio acetabuli, lateral centre edge angle, acetabular index and cross-over sign. RESULTS: The prevalence of radiological signs of FAI was 94% (64/68). The mean number of radiological signs in hips with LSARGP was 1.84 (range 0-4, SD 1.05) and 1.96 (range 0-5, SD 1.12) in asymptomatic groins (p=0.95). The anterior hip impingement test was positive in nine cases. There was no relationship with the number of radiological signs (p=0.95). There was no correlation between hip ROM and the number of radiological signs (p=0.37). CONCLUSION: Radiological signs of FAI are frequently observed in patients presenting with LSARGP. Clinicians should be aware of this fact and the possible lack of correlation when assessing athletes with groin pain.

No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy.

OBJECTIVE: To assess whether a platelet-rich plasma (PRP) injection leads to an enhanced tendon structure and neovascularisation, measured with ultrasonographic techniques, in chronic midportion Achilles tendinopathy. DESIGN: Double-blind, randomised, placebo-controlled clinical trial. SETTING: Sports medical department of The Hague medical centre. PATIENTS: 54 patients with chronic midportion Achilles tendinopathy were included. INTERVENTIONS: Patients were randomised to eccentric exercise therapy with either a PRP injection (PRP group) or a saline injection (placebo group). MAIN OUTCOME MEASUREMENTS: Tendon structure was evaluated by ultrasonographic tissue characterisation, a novel technique which quantifies tendon structure into four echo-types: echo-types I+II represent organised tendon bundles, whereas echo-types III+IV represent a disorganised tendon structure. Colour Doppler ultrasonography was used to measure the degree of neovascularisation. Follow-up was at 6, 12 and 24 weeks. RESULTS: A significant improvement in echo-types I+II was found after 24 weeks within both the PRP group (n=27) and the placebo group (n=27), but there was no significant between-group difference (95% CI -1.6 to 7.8, p=0.169). After 6 weeks, the neovascularisation score increased within the PRP group (p=0.001) and the placebo group (p=0.002), but there was no significant between-group difference in change in neovascularisation score at any point in time. CONCLUSION: Injecting PRP for the treatment of chronic midportion Achilles tendinopathy does not contribute to an increased tendon structure or alter the degree of neovascularisation, compared with placebo. FUNDING: Biomet Biologics LLC, Warsaw, Indiana.

Incidence of midportion Achilles tendinopathy in the general population.

BACKGROUND: Achilles tendon disorders, like Achilles tendinopathy, are very common among athletes. In the general population, however, knowledge about the incidence of Achilles tendinopathy is lacking. Design Cross-sectional study. METHODS: In a cohort of 57.725 persons registered in primary care, the number of patients visiting the general practitioner (GP) with diagnosis of mid-portion Achilles tendon problems was counted using computerised registration networks of GPs in 2009. Subsequently, the authors assessed associations of these rates with demographic characteristics. RESULTS: The incidence rate of Achilles tendinopathy is 1.85 per 1,000 Dutch GP registered patients. In the adult population (21-60 years), the incidence rate is 2.35 per 1,000. In 35% of the cases, a relationship with sports activity was recorded. CONCLUSION: This is the first report on incidence rates of mid-portion Achilles tendinopathy in general practice. With an incidence of 1.85 per 1,000 registered persons, Achilles tendinopathy is frequently seen by GPs. The actual incidence might even be higher due to study limitations. More research on the frequency of this injury is required.

Potential contribution of the wastewater sector to energy supply.

The biological treatment of wastewater could yield high energy fuels such as methane and alcohols, however most conventional treatment systems do not recover this energy potential. with a simple model of the energy yields of various wastewater treatment technologies it is possible to demonstrate how minor shifts in technology selection can lead the industry from being identified as predominantly energy intensive, to being recognised as a source of energy resources. The future potential energy yield is estimated by applying energy yield factors to alternative use scenarios of the same wastewater loads. The method for identifying the energy potential of wastewater was demonstrated for the New Zealand wastewater sector, but can equally be applied to other countries or regions. The model suggests that by using technologies that maximise the recovery of energy from wastewater, the potential energy yield from this sector would be substantially increased (six fold for New Zealand).

Automated procedure for candidate compound selection in GC-MS metabolomics based on prediction of Kovats retention index.

MOTIVATION: Matching both the retention index (RI) and the mass spectrum of an unknown compound against a mass spectral reference library provides strong evidence for a correct identification of that compound. Data on retention indices are, however, available for only a small fraction of the compounds in such libraries. We propose a quantitative structure-RI model that enables the ranking and filtering of putative identifications of compounds for which the predicted RI falls outside a predefined window. RESULTS: We constructed multiple linear regression and support vector regression (SVR) models using a set of descriptors obtained with a genetic algorithm as variable selection method. The SVR model is a significant improvement over previous models built for structurally diverse compounds as it covers a large range (360-4100) of RI values and gives better prediction of isomer compounds. The hit list reduction varied from 41% to 60% and depended on the size of the original hit list. Large hit lists were reduced to a greater extend compared with small hit lists. AVAILABILITY: http://appliedbioinformatics.wur.nl/GC-MS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Autologous growth factor injections in chronic tendinopathy: a systematic review.

Chronic degenerative tendinopathies are frequent and difficult to treat. Tendon healing and regeneration may be improved by injecting autologous growth factors obtained from the patient's blood. Autologous growth factors can be injected with autologous whole blood or platelet-rich plasma (PRP). Electronic databases were searched for prospective clinical trials on treatment with autologous growth factors of patients with chronic tendinopathy. Chronic tendinopathy in this study included wrist extensors, flexors, plantar fasciopathy and patellar tendinopathy. Studies examining the treatment of other tendinopathies were not identified. The Physiotherapy Evidence Database score was used to examine the methodological quality of the assessment, and a qualitative analysis was performed with the levels of evidence. There are many proposed treatment options for chronic tendinopathy. Treatments in the form of injections with autologous whole blood or PRP are increasingly used in clinical practice. There are high expectations of these regenerative injections, and there is a clear need for effective conservative therapies. All studies showed that injections of autologous growth factors (whole blood and PRP) in patients with chronic tendinopathy had a significant impact on improving pain and/or function over time. However, only three studies using autologous whole blood had a high methodological quality assessment, and none of them showed any benefit of an autologous growth factor injection when compared with a control group. At present, there is strong evidence that the use of injections with autologous whole blood should not be recommended. There were no high-quality studies found on PRP treatment. There is limited evidence to support the use of injections with PRP in the management of chronic tendinopathy. There is growing interest in the working mechanisms of autologous growth factors. The amount and mixture of growth factors produced using different cell separating systems are largely unknown and it is also uncertain whether platelet activation prior to injection is necessary. These variables should be taken into account when starting clinical studies. A good experimental model for studying tendinopathy would be helpful for basic research. Future clinical studies using a proper control group, randomization, blinding and validated disease-specific outcome measures for pain and function are needed.

One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy.

OBJECTIVE: The study examined whether the addition of a night splint to eccentric exercises is beneficial for functional outcome in chronic midportion Achilles tendinopathy. DESIGN: One-year follow-up of a randomised controlled single blinded clinical trial. SETTING: Sports medicine department in a general hospital. PATIENTS: 58 patients (70 tendons) were included. INTERVENTIONS: All patients completed a 12-week heavy load eccentric training programme. One group received a night splint in addition to eccentric exercises. MAIN OUTCOME MEASUREMENTS: Outcome scores were: Victorian Institute of Sport Assessment-Achilles (VISAA) score, subjective patient satisfaction and neovascularisation score measured with power Doppler ultrasonography (PDU). RESULTS: For both groups the VISA-A score increased significantly (from 50 to 76 (p<0.01) in the eccentric group and from 49 to 78 (p<0.01) in the night splint group). No significant differences in the VISA-A score were found between the groups from baseline to one year (p = 0.32). The presence of neovessels at baseline did not predict a change in the VISA-A score after one year in the whole group (p = 0.71). CONCLUSION: Eccentric exercises with or without a night splint improved functional outcome at one year follow-up. At follow-up there was no significant difference in clinical outcome when a night splint was used in addition to an eccentric exercise programme. Between 3 months and one year follow-up, a continuing increase in the VISA-A score was found. Assessment of the neovascularisation score with PDU at baseline has no prognostic value on long-term clinical outcome.

Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach.

OBJECTIVE: To assess whether three-dimensional imaging of the Achilles tendon by ultrasonographic tissue characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. DESIGN: Case-control study. SETTING: Sports Medical Department of the Hague Medical Centre. PATIENTS: Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The "matched" control group consisted of 26 asymptomatic tendons. INTERVENTIONS: Symptomatic and asymptomatic tendons were scanned using the UTC procedure. One researcher performed the ultrasonographic data collection. These blinded data were randomised, and outcome measures were determined by two independent observers. MAIN OUTCOME MEASUREMENTS: The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echo patterns, qua intensity and distribution over contiguous transverse images. This three-dimensional stability was related to tendon structure in previous studies. UTC categorises four different echotypes that represent (I) highly stable; (II) medium stable; (III) highly variable and (IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated, and the maximum tendon thickness was measured. Finally, the inter-observer reliability of UTC was determined. RESULTS: Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% vs 76.6%, p<0.001), thus less three-dimensional stability of the echo pattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p<0.001). The Intraclass Correlation Coefficient (ICC) for the interobserver reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. CONCLUSION: UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such, UTC might be useful to monitor treatment protocols.

Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites.

AIMS: Spinocerebellar ataxia type 6 (SCA6) is a late onset autosomal dominantly inherited ataxic disorder, which belongs to the group of CAG repeat, or polyglutamine, diseases. Although, it has long been regarded as a 'pure' cerebellar disease, recent clinical studies have demonstrated disease signs challenging the view that neurodegeneration in SCA6 is confined to the well-known lesions in the cerebellum and inferior olive. METHODS: We performed a systematic pathoanatomical study throughout the brains of three clinically diagnosed and genetically confirmed SCA6 patients. RESULTS: This study confirmed that brain damage in SCA6 goes beyond the known brain predilection sites. In all of the SCA6 patients studied loss of cerebellar Purkinje cells and absence of morphologically intact layer V giant Betz pyramidal cells in the primary motor cortex, as well as widespread degeneration of brainstem nuclei was present. Additional damage to the deep cerebellar nuclei was observed in two of three SCA6 patients. CONCLUSIONS: In view of the known functional role of affected central nervous grey components it is likely that their degeneration at least in part is responsible for the occurrence of a variety of SCA6 disease symptoms.

Start of induction of labour with oxytocin in the morning or in the evening. A randomised controlled trial.

OBJECTIVE: The objective of this study was to compare outcomes of induced labour with intravenous oxytocin with a start in the evening versus in the morning. DESIGN: Randomised controlled trial. SETTING: Labour wards of three hospitals in Amsterdam, the Netherlands. PARTICIPANTS: Women with an indication for induction of labour with intravenous oxytocin. METHODS: Included women were randomized to either the evening group with a start of induction of labour at 21:00 hours, or the morning group with a start at 07:00 hours. MAIN OUTCOME MEASURES: Primary outcome was duration of labour. Secondary outcomes were instrumental delivery rate, adverse neonatal outcome defined as an Apgar score below 7 after 5 minutes, number and indications of paediatric consults and neonatal admissions, duration of second stage, number of intrapartum infections and necessity of pain relief. RESULTS: We randomised 371 women. Mean duration of labour was not significantly different (primiparae: morning 12 hours and 8 minutes versus evening 11 hours and 22 minutes, P value 0.29; multiparae: morning 7 hours and 34 minutes versus evening 7 hours and 46 minutes, P value 0.70). There were no significant differences in instrumental deliveries rates, number of infections or patient satisfaction. Unexpectedly, neonatal outcome was better in women induced in the evening. CONCLUSION: Induction of labour with intravenous oxytocin in the evening is equally effective as induction in the morning.

Identification of a novel PEX14 mutation in Zellweger syndrome.

BACKGROUND: Peroxisome biogenesis disorders are a clinically and genetically heterogeneous group of very severe autosomal recessive disorders caused by impaired peroxisome biogenesis. The prototype of this group of disorders is the cerebro-hepato-renal syndrome of Zellweger. METHODS AND RESULTS: Here we report a patient with Zellweger syndrome, who presented at the age of 3 months with icterus, dystrophy, axial hypotonia, facial dysmorphy, posterior embryotoxon, and hepatomegaly. Abnormal findings of metabolic screening tests included hyperbilirubinaemia, hypoketotic dicarboxylic aciduria, increased C(26:0) and decreased C(22:0) plasma levels, and strongly reduced plasmalogen concentrations. In fibroblasts, both peroxisomal alpha- and beta-oxidation were impaired. Liver histology revealed bile duct paucity, cholestasis, arterial hyperplasia, very small branches of the vena portae, and parenchymatic destruction. Immunocytochemical analysis of cultured fibroblasts demonstrated that the cells contain peroxisomal remnants lacking apparent matrix protein content and PEX14, a central membrane component of the peroxisomal matrix protein import machinery. Transfection of fibroblasts with a plasmid coding for wild-type PEX14 restored peroxisomal matrix protein import, indicating that the primary genetic defect affecting the patient is indeed linked to PEX14. Mutational analysis of this gene revealed a genomic deletion leading to the deletion of exon 3 from the coding DNA (c.85-?_170+?del) and a concomitant change of the reading frame (p.[Ile29_Lys56del;Gly57GlyfsX2]). CONCLUSIONS: This report represents the second PEX14-deficiency associated with Zellweger syndrome and the first documentation of a PEX14-deficient patient with detailed clinical follow-up and biochemical, morphological, and radiological data.