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Background and purpose: Centers for training in autonomic nervous system (ANS) disorders are not widely available and the recent coronavirus 2019 pandemic temporarily reduced training opportunities in autonomic medicine across European countries. Here we evaluated the current state of education, clinical skills and postgraduate educational preferences on ANS disorders of European neurology residents and consultants. Methods: A 23‐item questionnaire was developed and distributed online amongst European neurology residents and consultants via mailing lists of the European Academy of Neurology. The questions assessed demographics, current training opportunities and learning preferences in ANS disorders. Six multiple‐choice questions were used to self‐evaluate knowledge of ANS disorders. Results: In all, 285 individuals answered the survey (60% female, mostly 25–34 years of age). All respondents considered clinical autonomic skills necessary for good clinical neurological practice, and 92% would like to increase their ANS knowledge. Female respondents and those who trained in Southern/Eastern/Greater Europe more frequently judged ANS skills important for clinical practice than male respondents (p = 0.012) and respondents from Northern/Western Europe (p = 0.011). Female and younger respondents felt less confident in managing ANS disorders (p = 0.001 and p < 0.001, respectively). Respondents below 45 years of age (p < 0.001) and those with lower confidence in managing ANS disorders (p = 0.004) were more likely to recommend that ANS education is embedded in the residency curriculum. Conclusions: Most European neurology residents and consultants reported a need for more autonomic education, with additional gender, age and regional differences. These findings underscore the importance of increasing the educational content on autonomic medicine in European medical and postgraduate curricula. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recognized treatment for medication‐refractory dystonia. Problems in executive functions and social cognition can be part of dystonia phenotypes. The impact of pallidal DBS on cognition appears limited, but not all cognitive domains have been investigated yet. In the present study, we compare cognition before and after GPi DBS. Seventeen patients with dystonia of various aetiology completed pre‐ and post‐DBS assessment (mean age 51 years; range 20–70 years). Neuropsychological assessment covered intelligence, verbal memory, attention and processing speed, executive functioning, social cognition, language and a depression questionnaire. Pre‐DBS scores were compared with a healthy control group matched for age, gender and education, or with normative data. Patients were of average intelligence but performed significantly poorer than healthy peers on tests for planning and for information processing speed. Otherwise, they were cognitively unimpaired, including social cognition. DBS did not change the baseline neuropsychological scores. We confirmed previous reports of executive dysfunctions in adult dystonia patients with no significant influence of DBS on cognitive functioning in these patients. Pre‐DBS neuropsychological assessments appear useful as they support clinicians in counselling their patients. Decisions about post‐DBS neuropsychological evaluations should be made on a case‐by‐case basis. [ABSTRACT FROM AUTHOR]

Background and purpose: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. Methods: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI‐DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut‐off scores. Inter‐rater reliability was evaluated by Cohen's kappa coefficient. Results: This study included 59 patients. CI‐DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI‐)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI‐DCI 0.89 (95% confidence interval [CI] 0.79–0.99), DCI 0.68 (95% CI 0.50–0.87) and functional outcome 0.74 (95% CI 0.57–0.91). Cohen's kappa between the two raters was moderate to substantial (0.57–0.63). Conclusions: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI‐)DCI and unfavorable outcome. [ABSTRACT FROM AUTHOR]

The highly lipophilic outer barrier of mycobacteria, such as M. tuberculosis and M. leprae, is key to their virulence and intrinsic antibiotic resistance. Various components of this mycomembrane interact with the host immune system but many of these interactions remain ill‐understood. This review covers several chemical syntheses of one of these components, mycobacterial phenolic glycolipids (PGLs), and outlines the interaction of these PGLs with the human immune system, as established using these well‐defined pure compounds. [ABSTRACT FROM AUTHOR]

Background and purpose: Aneurysm wall enhancement (AWE) of intracranial aneurysms on magnetic resonance imaging has been described in previous studies as a surrogate marker of instability. With this study, an updated literature overview and summary risk estimates of the association between AWE and different specific outcomes (i.e., rupture, growth or symptomatic presentation) for both cross‐sectional and longitudinal studies are provided. Methods: The PRISMA guideline was followed and a search was performed of PubMed and Embase to 1 January 2021 for studies that reported on AWE and aneurysm instability. In cross‐sectional studies, AWE was compared between patients with stable and unstable aneurysms. In longitudinal studies, AWE of stable aneurysms was assessed at baseline after which patients were followed longitudinally. Risk ratios were calculated for longitudinal studies, prevalence ratios for cross‐sectional studies and then the ratios were pooled in a random‐effects meta‐analysis. Also, the performance of AWE to differentiate between stable and unstable aneurysms was evaluated. Results: Twelve studies were included with a total of 1761 aneurysms. In cross‐sectional studies, AWE was positively associated with rupture (prevalence ratio 11.47, 95% confidence interval [CI] 4.05–32.46) and growth or symptomatic presentation (prevalence ratio 4.62, 95% CI 2.85–7.49). Longitudinal studies demonstrated a positive association between AWE and growth or rupture (risk ratio 8.00, 95% CI 2.14–29.88). Assessment of the performance of AWE showed high sensitivities, mixed specificities, low positive predictive values and high negative predictive values. Conclusions: Although AWE is positively associated with aneurysm instability, current evidence mostly supports the use of its absence as a surrogate marker of aneurysm stability. [ABSTRACT FROM AUTHOR]

Introduction: In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. Methods: In this retrospective cohort study, we searched video‐EEG databases for individuals with focal seizures and IA (asystole ≥ 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting ≤3 s before syncope onset, or after syncope began, could not have been the dominant cause. Results: We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5–32] vs. 5 [range: 3–9] s; p <.001) and those with the patient seated vs. supine (79% vs. 46%; p =.049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. Conclusions: In IA, cardioinhibition played an important role in most seizure‐induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA. [ABSTRACT FROM AUTHOR]

Objective: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). Methods: Inclusion criteria for VVS were a history of VVS and tilt‐induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head‐up tilt to when BP reached one‐half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations. Results: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19–98 sec) than in VVS (median 1571 sec, IQR 1381–1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%. Interpretation: These new hemodynamic criteria reliably differentiate cOH from VVS. [ABSTRACT FROM AUTHOR]

Background and purpose: The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was built to harmonize the treatment decision making on unruptured intracranial aneurysms. Therefore, it may also function as a predictor of aneurysm progression. In this study, we aimed to assess the validity of the UIATS model to identify aneurysms at risk of growth or rupture during follow‐up. Methods: We calculated the UIATS for a consecutive series of conservatively treated unruptured intracranial aneurysms, included in our prospectively kept neurovascular database. Computed tomography angiography and/or magnetic resonance angiography imaging at baseline and during follow‐up was analyzed to detect aneurysm growth. We defined rupture as a cerebrospinal fluid or computed tomography–proven subarachnoid hemorrhage. We calculated the area under the receiver operator curve, sensitivity, and specificity, to determine the performance of the UIATS model. Results: We included 214 consecutive patients with 277 unruptured intracranial aneurysms. Aneurysms were followed for a median period of 1.3 years (range 0.3–11.7 years). During follow‐up, 17 aneurysms enlarged (6.1%), and two aneurysms ruptured (0.7%). The UIATS model showed a sensitivity of 80% and a specificity of 44%. The area under the receiver operator curve was 0.62 (95% confidence interval 0.46–0.79). Conclusions: Our observational study involving consecutive patients with an unruptured intracranial aneurysm showed poor performance of the UIATS model to predict aneurysm growth or rupture during follow‐up. [ABSTRACT FROM AUTHOR]

Summary: Ossification of the ungular cartilages of the equine foot has been well documented. There is growing evidence to suggest that extensively ossified cartilages (≥grade 4) can be associated with injury, pain and lameness. The objectives of this study were to describe the locations and extent of new bone on the proximal and distal phalanges and to determine the frequency of occurrence related to the ossification grade of the ungular cartilages. It was hypothesised that new bone formation would be seen more commonly in horses with grades ≥4 ossification than those with ossification of grade ≤3. Data were collected from 929 sets of images from individual limbs of 589 horses. Logistic regression modelling was used to indicate predictor variables that were significant. In 15.4% of limbs, there was grade 4 or 5 ossification of one or both ungular cartilages. New bone formation was seen on the palmaromedial and palmarolateral aspects of the diaphyseal and distal metaphyseal regions of the proximal phalanx in 28.7% of limbs. New bone formation was seen on the dorsal, dorsomedial and dorsolateral aspects of the distal phalanx, midway between proximal and distal in 7.2% of limbs. New bone formation was seen more commonly on the proximal phalanx (P≤0.002) and the distal phalanx (P≤0.042) in feet with grade ≥4 ossification of the ungular cartilages than in feet with ossification grade ≤3. Thoroughbred (odds ratio [OR] 0.398) and Warmblood (OR 0.522) breeds had a lower risk of new bone formation on the proximal phalanx compared with other breeds. Increasing age was a risk factor for new bone formation on the proximal phalanx (OR 1.092) but was associated with reduced risk of new bone on the distal phalanx. New bone formation on the proximal and distal phalanges may contribute to pain and lameness. [ABSTRACT FROM AUTHOR]

Summary: Identification of low‐grade lameness is challenging. A whole horse ridden ethogram has been developed, describing 24 behavioural markers. Previous work indicated that the presence of ≥8 behavioural markers was likely to reflect musculoskeletal pain. The objectives of this repeated measures study were to compare the results of application of the ridden‐horse ethogram by trained and untrained assessors to horses before and after musculoskeletal pain had been substantially improved using diagnostic analgesia, and to assess the repeatability of the ethogram application among untrained assessors, and to compare their performance with a trained assessor. All horses underwent a comprehensive lameness investigation. Anonymised video recordings of 21 lame horses, ridden by professional riders in trot and canter before and after diagnostic analgesia had abolished lameness, were reviewed in a random order by a trained assessor and 10 untrained assessors. For each horse the duration of the recordings before and after diagnostic analgesia was time matched. The most frequent lameness grade was 2/8 (range 1–4). For the trained assessor, the number of behaviours exhibited by lame horses before diagnostic analgesia ranged from 3–12/24 (median 10; mean 8.9). After lameness and overall performance had been substantially improved using diagnostic analgesia, the number of behaviours ranged from 0–6/24 (median 3; mean 3.0). The decrease in behaviour scores for all assessors after diagnostic analgesia was highly significant (Z = 20,147, P<0.0001). Agreement between the trained assessor and untrained assessors was moderate before diagnostic analgesia and non‐existent after analgesia (Fleiss Kappa 0.49, 0 respectively), when individual behaviours were assessed. The main limitation was that horses were anonymised, but it was impossible to blind their identity, so bias is possible. It was concluded that despite limitations in the agreement between untrained observers and the trained assessor, the ethogram is a potentially valuable tool for determining the presence of musculoskeletal pain and may be useful for longitudinal monitoring of improvement in lameness. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of two manoeuvres at the end of gynaecological laparoscopy on postoperative pain. Design: Randomised controlled trial. Setting: One teaching and one university hospital in the Netherlands. Sample: Women aged between 18 and 65 years, with American Society of Anaesthesiologists (ASA) classification I–II, scheduled for an elective laparoscopic procedure for a benign gynaecological indication. Methods: Women were randomly allocated to two groups. In the intervention group, carbon dioxide was removed from the abdomen by a combination treatment of intraperitoneal warm saline and performing a pulmonary recruitment manoeuvre. In the control group, carbon dioxide was removed with gentle abdominal pressure. Main outcome measures: Frequency and intensity of post‐laparoscopic shoulder pain and pain in the upper abdomen at 8, 24, and 48 hours after surgery. Results: A total of 200 women participated, with 100 in each group. No difference was observed in the occurrence of post‐laparoscopic shoulder pain during the first 48 hours after surgery between the intervention group (46%) and the control group (55%). The incidence of abdominal pain was not significantly different between the two groups. The mean visual analogue scale (VAS) scores of participants who reported shoulder pain were not statistically different between the groups. The mean VAS score for abdominal pain at 8 hours after surgery was significantly lower in the intervention group compared with the control group (3.2 versus 4.2, P = 0.02). No difference in pain medication between the groups was observed, nor was there any difference in nausea or vomiting. Conclusions: Combined intervention of intraperitoneal saline and the pulmonary recruitment manoeuvre does not lower post‐laparoscopic shoulder pain. Funding: This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors. Tweetable abstract: PRM with intraperitoneal saline does not influence the incidence and intensity of post‐laparoscopic shoulder pain. [ABSTRACT FROM AUTHOR]

Introduction: Despite the importance of a biopsychosocial approach in chronic pain, many physiotherapists still adhere to a biomedical framework.1 To facilitate the adoption of a biopsychosocial view, more insight into barriers and facilitators for using this approach is required. The aim for this study is to map these barriers and facilitators. Methods: A scoping review was performed.2 Eligible studies present data on barriers and facilitators, chronic pain, primary care physiotherapy and a biopsychosocial perspective. Extracted data on barriers and facilitators was discussed and sub grouped in themes following a qualitative content analysis approach, using the Theoretical Domains Framework3 and a micro-meso-macro layout to organise and map the different themes. Results: Twenty-three studies were included. Although analyses are ongoing preliminary results show that on a micro-level barriers and facilitators concern the therapist (knowledge, skills, attitudes, confidence, role clarity, patient perception, etc.), the patient (expectations, etc.) and the patient-therapist relationship. On a meso-level barriers relating to the environmental context (time, treatment-fee, etc.) were identified. Discussion: It appears that a level of saturation was reached, suggesting a complete picture of known barriers and facilitators. There is, however, a large variety in used terminology and unclarity of what a biopsychosocial model entails. The presented overview can be used to inform professionals, researchers and policy-makers when designing strategies for implementation. Process evaluation: The focus in the search strategy was on studies mentioning the biopsychosocial model. This might have resulted in missing studies that implicitly adopted this approach. [ABSTRACT FROM AUTHOR]

Introduction: Despite the importance of a biopsychosocial approach in chronic pain, many physiotherapists still adhere to a biomedical framework. Designing a teaching program that supports obtaining adequate competencies in the participant's context is challenging.1 This study describes the development of a program for learning primary care physiotherapists to use the biopsychosocial model in chronic pain. Methods: Participatory Action Research methodology, including experts in chronic pain, education and co-design as well as the target audience, was used. Information gathered from literature and curricula of EFIC and IASP was combined with interviews and focusgroups with stakeholders. Co-design methods structured by several design-sprints were used to create, iterate and pilot-test choices of content, and design-and educational solutions.2 Data were summarized in a Plan of Requirements. Results: Based on the Plan of Requirements a three-month program was developed containing three days of face-to-face learning, online learning and facilitated learning in the workspace.3 The program challenges participants to move out of their comfort zone, with room for active personal learning and respect for the dynamic nature of skills needed for working with chronic pain. Discussion: The use of a broad range of stakeholders strengthens the consistency, content and validity of the program. Co-design as a method for development is, though rich, difficult to replicate and present in a transparent manner. Next a feasibility study is needed to evaluate the program. Process evaluation: Because of COVID the design-process had to take place online hindering the interaction. However, it also facilitated the possibility for stakeholders to join for a brief consultation. [ABSTRACT FROM AUTHOR]

Background The term 'cluster-tic syndrome' is used for the rare ipsilateral co-occurrence of attacks of cluster headache and trigeminal neuralgia. Medical treatment should combine treatment for cluster headache and trigeminal neuralgia, but is very often unsatisfactory. Case Here, we describe a 41-year-old woman diagnosed with cluster-tic syndrome who underwent microvascular decompression of the trigeminal nerve, primarily aimed at the 'trigeminal neuralgia' part of her pain syndrome. After venous decompression of the trigeminal nerve both a decrease in trigeminal neuralgia and cluster headache attacks was seen. However, the headache did not disappear completely. Furthermore, she reported a decrease in pain intensity of the remaining cluster headache attacks. Discussion This case description suggests that venous vascular decompression in cluster-tic syndrome can be remarkably effective, both for trigeminal neuralgia and cluster headache. [ABSTRACT FROM AUTHOR]

Introduction: The presence of a Tinel sign in leg nerves has been proposed as a criterion for decompressive surgery in polyneuropathy. We investigated the diagnostic yield of the Tinel sign for nerve entrapment and for distal symmetrical peripheral neuropathy (DSPN).Methods: We prospectively tested for the Tinel sign at 3 sites of possible nerve entrapment per leg in 91 patients. Entrapment was defined using nerve conduction data. We also investigated whether the number of sites at which the Tinel sign was present identified patients with DSPN.Results: Sensitivity of the Tinel sign for nerve entrapment was low (29%, 44%, and 17%) for the 3 sites, and specificity was moderate (86%, 75%, and 81%). In the subgroup with DSPN, sensitivity was extremely low (0%, 20%, and 8%), and specificity was moderate (91%, 79%, and 73%). The number of sites with a Tinel sign did not identify patients with DSPN.Conclusion: The Tinel sign does not reliably indicate nerve entrapment or DSPN. Muscle Nerve 54: 25-30, 2016. [ABSTRACT FROM AUTHOR]

Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness: Consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN). For neurologists that should not be difficult, as the recommendations make it very clear that history taking, the neurologists' preferred diagnostic tool, is at the heart of the VVS and TLOC diagnosis. [Extracted from the article]

Context Drug resistance is a serious threat to human health, food security and the livelihood of livestock farmers. As vets and farmers routinely calculate drug volumes from weight estimates based on visual inspection of cows, an associated risk of underdosing may contribute to the build up of resistance. This study investigated administrator-induced error in the delivery of optimal doses of drugs to dairy cattle. Main conclusion Dairy cows were much heavier than observers thought. Vets were highly likely to underestimate the weight of ≥650 kg animals and dairy farmers underestimated the weight of cows significantly more than vets. Approach Seventeen cattle vets (median experience 10 years) and 18 dairy farmers (median experience 22 years) were asked to estimate the weight of seven cows (actual weights 580 kg, 624 kg, 638 kg, 694 kg, 728 kg, 740 kg and 808 kg). The weight of the 638 kg cow was then revealed and the observers were asked to rescore the other six cows. Logistic regression (on the probability of underestimating weight) and multiple linear regression (on the difference between estimated and measured weight) were carried out using the covariates 'vet or farmer', 'actual cow weight', 'knowing the weight of one of the cows' and 'years of experience of the observer'. Results Of the veterinary observations made, 64.7 per cent were underestimations of the weight of cows (mean underestimation 63 kg, maximum 248 kg), whereas 80.9 per cent of farmer observations were underestimations (mean underestimate 97 kg, maximum 233 kg). The likelihood and degree of underestimation increased significantly with the weight of the cow observed. Accuracy of weight estimation increased significantly after the weight of one animal was revealed. Farmers were 2.34 times more likely to underestimate weight than vets. Observer experience did not appear to have an effect on weight estimation accuracy. Interpretation The probability of non-weighed dairy cows receiving too low a drug dose is high and, in heavier animals, the degree of underdosing may be substantial. The degree to which this contributes to the development of drug resistance needs further investigation. Significance of findings Farmers administer the vast majority of drug doses and currently employed weight estimation methodology may contribute to the development of drug resistance. Practicable improvements on current methods need to be developed and training needs to be provided. [ABSTRACT FROM AUTHOR]

Due to the development of anthelmintic resistance, there have been calls for more sustainable nematode control practices. Two important concepts were introduced to study and promote the sustainable use of anthelmintics: targeted treatments (TT), where the whole flock/herd is treated based on knowledge of the risk, or parameters that quantify the severity of infection; and targeted selective treatments (TST), where only individual animals within the grazing group are treated. The aim of the TT and TST approaches is to effectively control nematode-induced production impacts while preserving anthelmintic efficacy by maintaining a pool of untreated parasites in refugia. Here, we provide an overview of recent studies that assess the use of TT/TST against gastrointestinal nematodes in ruminants and investigate the economic consequences, feasibility and knowledge gaps associated with TST. We conclude that TT/TST approaches are ready to be used and provide practical benefits today. However, a major shift in mentality will be required to make these approaches common practice in parasite control. [ABSTRACT FROM AUTHOR]

Aim Sensory function is assumed to recover almost completely in obstetric brachial plexus lesion (OBPL), and is reported to recover much better than motor function. However, there is no obvious physiological reason why this should be so. Any persistent problems with sensory innervation might contribute to disability, therefore we aimed to assess sensory dysfunction in adults resulting from OBPL. Method Adults with conservatively treated OBPL ( n=17; 12 females, five males; median age 38y; lesion levels: C5-C6, n=7; C5-C7, n=7; C5-C8, n=2; C5-Th1, n=1) and 19 healthy comparison persons (10 females, nine males; median age 23y) were investigated. Sensory function was measured using Semmes-Weinstein monofilaments, two-point discrimination, object recognition, and a locognosia test. Results Scores of the Semmes-Weinstein monofilaments and two-point discrimination, but not object recognition or locognosia, were significantly worse in those with OBPL than in those without OBPL. Interpretation There may be systematic abnormalities in sensory function in adults with conservatively treated OBPL. The existence of these impairments and their contribution to functional impairment needs to be acknowledged. [ABSTRACT FROM AUTHOR]

A faecal egg count reduction test, using composite samples, was developed in order to assess the efficacy of the flukicide, triclabendazole (TCBZ) on commercial sheep farms in England and Wales. First, a comparison between individual counts and composite counts was conducted using sheep on two farms with different levels of infection. Faecal samples were collected from 50 sheep on each farm at the time of TCBZ treatment and 21 days later. The results showed that a composite fluke egg count (CFEC) was as sensitive as using individual samples, and the test was subsequently validated on an additional 18 sheep farms. The pre-and post-treatment CFECs using five composite samples were subjected to bootstrap analysis. The variance in fluke egg counts of composite samples was high, but analyses indicated that 20 individual samples analysed as two composites was as sensitive as using five composites. The two-composite assay was evaluated on another five farms. On seven out of 25 farms sampled, egg counts either did not decrease significantly or increased following treatment, suggesting TCBZ resistance on these farms. This assay represents a practical field test that can be used in the first instance to evaluate the efficacy of TCBZ on sheep farms where resistance is suspected. [ABSTRACT FROM AUTHOR]

Aim Treatment decisions in obstetric brachial plexus lesions are often based on clinical paralysis of elbow flexion at 3 months of age, when electromyography (EMG) is misleading because motor unit potentials (MUPs) occur in clinically paralytic muscles. We investigated whether EMG at 1 week or 1 month identifies infants with flexion paralysis at 3 months, allowing early referral. Method Forty-eight infants (27 females, 21 males) were prospectively studied. The presence or absence of flexion paralysis at around 1 week (median 9d; range 5-17d), 1 month (median 31d; range 24-53d), and 3 months of age (median 87d; range 77-106d) was noted for clinical (shoulder external rotation, elbow flexion, extension, and supination) and EMG parameters (denervation activity, MUPs and polyphasic MUPs in the deltoid, biceps, and triceps muscles). Results At 1 month, the absence of biceps MUPs had a sensitivity of 95% for later flexion paralysis, and absence of deltoid MUPs had a sensitivity of 100% for flexion paralysis; the false-positive rates for the same findings were 21% and 33% respectively. EMG at 3 months was highly misleading as MUPs were seen in 19 of 20 clinically paralytic biceps muscles. Interpretation EMG at 1 month can identify severe cases of flexion paralysis for early referral EMG of the biceps at 3 months is highly misleading; the discrepancy between the EMG and clinical testing may be due to abnormal axonal branching and aberrant central motor control. [ABSTRACT FROM AUTHOR]

The sustained attention to response task comprises withholding key presses to one in nine of 225 target stimuli; it proved to be a sensitive measure of vigilance in a small group of narcoleptics. We studied sustained attention to response task results in 96 patients from a tertiary narcolepsy referral centre. Diagnoses according to ICSD-2 criteria were narcolepsy with ( n = 42) and without cataplexy ( n = 5), idiopathic hypersomnia without long sleep time ( n = 37), and obstructive sleep apnoea syndrome ( n = 12). The sustained attention to response task was administered prior to each of five multiple sleep latency test sessions. Analysis concerned error rates, mean reaction time, reaction time variability and post-error slowing, as well as the correlation of sustained attention to response task results with mean latency of the multiple sleep latency test and possible time of day influences. Median sustained attention to response task error scores ranged from 8.4 to 11.1, and mean reaction times from 332 to 366 ms. Sustained attention to response task error score and mean reaction time did not differ significantly between patient groups. Sustained attention to response task error score did not correlate with multiple sleep latency test sleep latency. Reaction time was more variable as the error score was higher. Sustained attention to response task error score was highest for the first session. We conclude that a high sustained attention to response task error rate reflects vigilance impairment in excessive daytime sleepiness irrespective of its cause. The sustained attention to response task and the multiple sleep latency test reflect different aspects of sleep/wakefulness and are complementary. [ABSTRACT FROM AUTHOR]

Dommering CJ, Garvelink MM, Moll AC, van Dijk J, Imhof SM, Meijers-Heijboer H, Henneman L. Reproductive behavior of individuals with increased risk of having a child with retinoblastoma. To investigate reproductive behavior of individuals at increased risk of having a child with retinoblastoma (Rb), we conducted a cross-sectional questionnaire survey among 118 counselees visiting the Clinical Genetics Department of the National Rb Center in the Netherlands. The recurrence risk for counselees ranged from <1% to 50%. The response rate was 69%. Of 43 respondents considering having children after becoming aware of their increased risk, Rb influenced reproductive behavior for 25 (58%), of whom 14 had a recurrence risk <3%. Twenty of these 25 decided against having more children and 5 used prenatal diagnosis. Eighteen of the 43 respondents did not use any of the alternative reproductive options and had children (or more children), although half indicated having had doubts about their decisions. Multiple logistic regression showed that only perceived risk (p = 0.003) was significantly associated with Rb influencing reproductive behavior. Of 17 respondents planning children (or more children), 11 (65%) considered using one of the alternative reproductive options. We conclude that reproductive behavior is greatly influenced by Rb and that perceived risk, not objective risk, is the most important factor of influence. It is important to offer individuals at increased risk continued access to genetic counseling, even when this risk is small. [ABSTRACT FROM AUTHOR]

Summary The month of birth has been proposed as a risk factor for narcolepsy, suggesting a harmful influence during early development. Several authors have described an excess of births in March in those developing narcolepsy later. Analysis methods in published studies varied, but no study corrected completely for possible changes in seasonal birth pattern over time in the appropriate population. The present study describes changes in seasonal birth pattern of the entire Dutch population over a 79-year span and compared the monthly birth pattern of Dutch narcoleptics with the population data. Month and year of birth were noted for 307 patients with non-familial narcolepsy with cataplexy, born in the Netherlands between 1923 and 2001. The numbers of live births per month and per year from the entire Dutch population for the same period were used to calculate a virtual data set of expected births per month with exactly the number of cataplexy cases, but with the birth pattern of the Dutch population. Observed and expected numbers per month were compared using the chi-square test. In the 1970s the peak of births shifted from spring to autumn, confirming the need to correct for changing seasonal patterns. There was no significant difference between observed and expected birth numbers per month. An effect of birth month on the occurrence of narcolepsy with cataplexy was not found in a study of 307 cases after adjusting for changing birth patterns in the general population. [ABSTRACT FROM AUTHOR]

Background: The P3 event-related potential (ERP) is presumably partly generated by the basal ganglia. Because degeneration of these brain structures starts many years before clinical disease onset in Huntington's disease (HD), studying the interplay between P3 characteristics and basal ganglia volumes in 'premanifest' carriers might lead to new insights into the disease process. Methods: Fourteen premanifest HD mutation carriers and twelve non-mutation carriers underwent clinical, MRI and P3-ERP investigations. The P3 was measured during the Sustained Attention to Response Task. Results: P3 amplitude and latency did not differ between groups. In carriers, longer P3 latency during Go-trials was strongly associated with smaller caudate, putamen and globus pallidus volumes (r values up to )0.827, P ≤ 0.001). Conclusion: The exceptionally strong relations of P3 latency with basal ganglia volumes in carriers suggest that the P3 may provide a marker for disease progression in HD. [ABSTRACT FROM AUTHOR]

The article presents information on a study which described a systematic approach for the design of ultraviolet (UV) reactors that makes use of computational fluid dynamics (CFD) modeling. Variables considered include placing mirrros, determining the lamp size and placing reactors in series. Criterion considered were disinfection performance, oxidation performance and energy consumption. It explores the potential in energy reduction for existing UV reactors as well as new reactor designs.

Background: Charcot–Marie–Tooth disease type 1A (CMT1A) is known as a demyelinating hereditary neuropathy. Secondary axonal dysfunction is the most important determinant of disease severity. In adult patients, clinical progression may be because of further axonal deterioration as was shown with compound muscle action potential (CMAP) amplitude reductions over time. The motor unit number estimation (MUNE) technique may be more accurate to determine the number of axons as it is not disturbed by the effect of reinnervation. The purpose of this study was to investigate the number and size of motor units in relation to age in patients and controls. Methods: In a cross-sectional design, we assessed arm and hand strength and performed electrophysiological examinations, including CMAP amplitudes and MUNE of the thenar muscles using high-density surface EMG in 69 adult patients with CMT1A and 55 age-matched healthy controls. Results: In patients, lower CMAP amplitudes and MUNE values were related to hand weakness. The CMAP amplitude and MUNE value of the thenar muscles were significantly lower in patients than in controls. CMAP amplitudes declined with age in controls, but not in patients. MUNE values declined with age in both patients and controls. Conclusions: The age-dependent decrease in the number of motor units was not significantly different between patients with CMT1A and controls, indicating that loss of motor units in adult patients is limited. [ABSTRACT FROM AUTHOR]

Background and purpose: Although autonomic function tests have revealed abnormalities of the autonomic nervous system in Huntington’s disease (HD), autonomic symptoms and their association with other symptoms and signs of HD have not yet been assessed in large groups of patients or pre-manifest mutation carriers. Therefore, we aimed at delineating the characteristics and correlates of autonomic symptoms in HD. Methods: Using the scales for outcomes in Parkinson’s disease-autonomic symptoms (SCOPA-AUT) and Beck Depression Inventory questionnaires, autonomic symptoms and depressed mood were assessed in 63 patients with HD, 21 pre-manifest mutation carriers, and 85 controls. The Unified Huntington’s Disease Rating Scale was used to assess other HD symptoms and signs. Results: Relative to controls, patients with HD experienced significantly more gastrointestinal, urinary, cardiovascular and, in men, sexual problems. The most prevalent symptoms were swallowing difficulties, erection and ejaculation problems, dysphagia, sialorrhea, early abdominal fullness, straining for defecation, fecal and urinary incontinence, urgency, incomplete bladder emptying, and light-headedness whilst standing. Pre-manifest mutation carriers experienced significantly more swallowing difficulties and light-headedness on standing up compared with controls. In patients with HD, autonomic symptoms were associated with a greater degree of functional disability, more severe depression, and antidepressant drugs use. However, depression was the only independent predictor of autonomic dysfunction. Conclusions: Autonomic symptoms are highly prevalent in patients with HD and may even precede the onset of motor signs. Moreover, autonomic dysfunction is related to functional disability and depression in HD. [ABSTRACT FROM AUTHOR]

Malaria during pregnancy is associated with maternal and fetal morbidity and mortality. In order to minimize the burden, sulfadoxine–pyrimethamine (SP) is widely used in Africa as an intermittent preventive treatment of malaria in pregnancy (IPTp). However, only limited data are available on the pharmacokinetics of sulfadoxine and pyrimethamine during pregnancy. We conducted a prospective, self-matched, multicenter study of 98 pregnant women in four African countries in order to determine the effects of pregnancy on SP pharmacokinetics. After adjusting for the effects of potential confounders, blood concentrations (associated with therapeutic efficacy) of pyrimethamine were higher (geometric mean ratio (GMR) 1.33; 95% confidence interval (CI) 1.18–1.51; P < 0.001) and those of sulfadoxine were lower (GMR 0.91; 95% CI 0.84–0.98; P = 0.013) on day 7 after SP administration during pregnancy than after the postpartum period. SP pharmacokinetic parameters differed significantly among the study sites. Given the inconsistency of changes in pharmacokinetic parameters between sulfadoxine and pyrimethamine as well as among the study sites, it is not possible to recommend any dose adjustment to prolong the therapeutic life span of the fixed dose combination of SP for IPTp on the basis of our study findings. [ABSTRACT FROM AUTHOR]

Objective: To assess coping strategies of long-term retinoblastoma (RB) survivors and explore determinants of behavioural functioning, including medical, socio-demographic and coping variables. Methods: This population-based cross-sectional study included 117 RB survivors (12–35 years), registered in the Dutch national RB register. Survivors were asked to fill in coping, social support and behavioural questionnaires, and situational characteristics were obtained from medical archives and from an interview. Prevalence rates of coping strategies were computed based on self-reports. One-sample t-tests were applied to analyse differences in the use of coping strategies compared with healthy reference samples. Multiple regression analyses were performed to identify various determinants for behavioural problems within the RB sample. Results: RB survivors differed from their healthy reference group in one coping style, i.e. they showed significantly less emotion-oriented coping behaviour. Adolescents who came from a single-parent family and/or experienced lower social support and used more emotion-oriented coping reported more total problem behaviour. More internalizing problems were reported for adolescents who experienced less social support and less acceptance of the disease. For adults, more life events, emotion-oriented coping and lower social support explained more total problem behaviour, especially internalizing problems. Conclusion: RB survivors showed less emotion-oriented coping behaviour compared with the reference group. Behavioural problems are best determined by emotion-oriented coping, social support, life events other than RB and acceptance of the disease, and not by medical variables. Therefore, these variables should be taken into consideration during interventions for this group. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Early identification of deaf-blindness is essential to ensure appropriate management. Previous studies indicate that deaf-blindness is often missed. We aim to discover the extent to which deaf-blindness in people with intellectual disability (ID) is undiagnosed. Method A survey was made of the 253 residents of an institute offering residential and occupational facilities for people with IDs. Data are included for the 224 individuals who were able to complete both auditory and visual assessments. Otoacoustic emissions were used to screen for hearing impairment; those who did not pass were assessed by behavioural audiometry. Visual acuity was assessed with one of the following: EH-Optotypes, LH-Optotypes, Teller Acuity Cards, Cardiff Acuity Cards or the Stycar Ball Vision Test. Results Prior to the study hearing impairment had been diagnosed in 12.5% of the 224 subjects, and visual impairment in 17%. Upon completion of the study these figures rose to 46% and 38.4% respectively. Deaf-blindness was diagnosed in 3.6% of the subjects before, and in 21.4% after, the study. Most (87.5%) of the deaf-blind individuals had profound ID. Conclusion Deaf-blindness is most often not identified either by standard medical screening or by care staff. Individuals with this disability, however, require provision of special kinds of care. Four categories of deaf-blindness are proposed, according to the severity of sensory impairment in each modality. The tests used in this study are non-invasive and are appropriate for individuals with ID and children. Early and periodic screening for visual and hearing impairment in individuals with ID is recommended. [ABSTRACT FROM AUTHOR]

Introduction: Some studies reported an increased incidence of premature ventricular complexes (PVCs) during triggered myocardial contrast echocardiography (MCE) using high-intensity ultrasound destruction. Whether PVCs are also induced by real time MCE using low emission power, is unknown. The aim of the study was to assess the occurrence of arrhythmias during real time adenosine MCE in healthy volunteers and patients with stable coronary artery disease (CAD). Methods: Fifty healthy volunteers and 26 patients with stable CAD underwent real time MCE using Sonovue and power pulse inversion (ATL 5000) at rest and during adenosine stress. The occurrence of premature atrial complexes (PAC) and PVCs was analyzed before and during MCE using ECG-tracings from videotapes. Results: In healthy subjects, the occurrence of PVCs at baseline (0.04 ± 0.23 PVCs/min) was similar at rest (0.04 ± 0.23 PVCs/min, P = NS), and adenosine stress (0.03 ± 0.14, P = NS). In CAD patients, the occurrence of PVCs at baseline was 0.30 ± 0.76 PVC/min, compared to 0.29 ± 0.74 at rest (P = NS), and 0.34 ± 0.74 during adenosine stress (P = NS). The number of subjects demonstrating PVCs did not increase during MCE. The occurrence of PACs during MCE was not increased compared to baseline. Conclusion: Real time MCE using low emission power does not increase the occurrence of premature complexes in healthy volunteers or CAD patients. [ABSTRACT FROM AUTHOR]

3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert–Eaton myasthenic syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, double-dummy, double-blind, randomized, crossover study in nine patients with LEMS.Clinical Pharmacology & Therapeutics (2009); 86, 1, 44–48 doi:10.1038/clpt.2009.35 [ABSTRACT FROM AUTHOR]

Objective: To assess behavioural problems in retinoblastoma (RB) survivors. Methods: This population-based cross-sectional study included 148 RB survivors (8–35 years), registered in the Dutch national RB register. Survivors and parents were asked to fill in behavioural questionnaires. Prevalence rates were computed, based on both self-reports and proxy reports. One-sample T-tests were applied to analyse differences compared with healthy reference samples. Multiple regression analyses were performed to identify predictors for behavioural problems within the RB sample. Results: Between-group differences varied across informants and across age groups. Parents reported significantly elevated total problem behaviour in 30% of their offspring (aged 8–17 years); this against 9% in adolescents (12–17 years) and 12% in adults (18–35 years) based on self-report. Parental reports showed significantly elevated rates of (1) internalising problems in boys and (2) somatic complaints in both girls and boys. Self-reports indicate significantly lowered levels of (1) externalising problems in adolescent and adult women and (2) thought problems in female adolescents and in adult men. Especially survivors who suffered hereditary RB, who had undergone more intensive treatment, and who came from a single-parent family were identified to be at most behavioural risk. Conclusion: Perception of severity and the nature of behavioural problems seem to differ between beholder, and to vary between age groups, if not between life stages. Health professionals should be aware that especially those who are confronted with hereditary RB and who subsequently undergo intensive treatment, and who grow up in broken families, run the risk of developing behavioural difficulties. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and purpose: Multiple sclerosis (MS) is a chronic disease that is difficult to predict and to cope with. Mastery refers to the extent to which patients see themselves as being in control of the forces that affect their lives. It may play an important role in perceived health status and well-being. The purpose of this study was to clarify whether mastery is associated with functional disability and perceived health status in MS patients and how such an association might function. Methods: Two hundred and three MS patients completed the Short-Form-36 Health Survey as well as the Pearlin–Schooler Mastery Scale. Functional disability was assessed using the Kurtzke Expanded Disability Status Scale. Hierarchical multiple linear regression analyses were performed on the data from two MS age groups: <45 and ≥45 years of age. Results: Functional disability was negatively associated with perceived physical health status in both age groups and with perceived mental health status in younger age group. Mastery was positively associated with perceived health status in older age group. Discussion: The findings confirm that mastery might be helpful for older MS patients. Education strategies for MS patients aimed at personal empowerment for the maintaining of physical and mental well-being may be important. [ABSTRACT FROM AUTHOR]

The radiologist is likely to be the first medical practitioner on the scene for contrast reactions, anaphylaxis and other common medical emergencies that occur in radiology departments and stand-alone practices. Until 2007, the Royal Australian and New Zealand College of Radiologists (RANZCR) did not provide resuscitation training as a CPD service for fellows, and the need for such a service has not been gauged. In 2007, the authors ran the first RANZCR large-group resuscitation refresher training workshop at the Melbourne 2007 annual scientific meeting. The workshop maximized audience participation and knowledge transfer in a constrained time, disseminated guidelines, and collected feedback on the need for further resuscitation training for radiologists. Of the 100 feedback forms, 82 were returned. All the 82 responses wanted the workshop repeated at future annual scientific meetings, and 71 wanted RANZCR to provide hands-on refresher training. Sixty-six responders indicated when they had their most recent resuscitation training: six in the past 12 months, 25 in the past 3 years and 35 longer than 3 years. Sixty-nine responded on availability of resuscitation training at their workplace: 33 indicated ‘Yes’ and 36 ‘No’. There is a definite need to provide resuscitation training for radiologists in Australia. At the end of this article, we reproduce the currently applicable guidelines as a service to our readers. [ABSTRACT FROM AUTHOR]

The occurrence of pesticides in drinking water sources is of concern for drinking water production companies as well as for the end users. However, it is still unclear which pesticides are removed, and to what extent, in widely used treatment methods such as coagulation–flocculation. Pesticides possibly interact with colloidal particles by adsorption on the flocs during coagulation–flocculation. In this study, removal of four pesticides (aldrin, dieldrin, atrazine, bentazon) was observed during jar test experiments in distilled and surface water (Dijle river, Belgium), using aluminium sulphate as a coagulant in different amounts ranging from no coagulant to high doses (300 mg/L). Without aiming at an accurate description of the removal process, the purpose of this study was to evaluate how much of the pesticides can be removed by changing the concentration, the dosage, the water matrix and the properties of the pesticides. The results show that the removal is usually low. The efficiency was worse when the matrix was distilled water than for Dijle river water, which is consistent with the idea that the removal of micropollutants only occurs through adsorption on the available organic material, and not on inorganic coagulants. Sorption on the natural material available in the Dijle river water seemed to be the main mechanism controlling the removal of micropollutants with coagulation/flocculation, rather than the amount of coagulant added. The hydrophobicity of the compounds was found to be a major factor in determining the removal efficiency with coagulation–flocculation; the most hydrophobic compound had the highest removal efficiency. Nevertheless, the removal was below 50% under all the tested circumstances. The results of this study prove that pesticide removal in conventional water treatment plants depends on physico-chemical interactions, but is insufficient even with extreme doses of alum. [ABSTRACT FROM AUTHOR]

The article presents a model for trace organic solute rejection in high-pressure membranes such as nanofiltration and reverse osmosis. Uncharged organic solute rejection values are determined, as well as sigmoidal rejection curves for solutes with varying levels of hydrophobicity. The basis for the model is described, noting its similarity to a log-normal pore size distribution model. A model of charged organic solute rejection is also presented, which is based on uncharged pollutant rejection and charge concentration polarization. Issues related to the adaptation of the model in a full-scale environment are discussed, noting that the full-scale model uses convection-diffusion principles to pass organic solutes through the membranes and balance mass in the system.

Background and purpose: Fatigue is frequent and important in the lives of Parkinson’s disease (PD) patients. It is multidimensional, with physical and mental aspects. The aim of our study was to explore the impact of fatigue on quality of life (QoL) for PD patients. Methods: The sample consisted of 175 PD patients from Eastern Slovakia (52% males, mean age 68.2 ± 9.2, mean disease duration 7.4 ± 6.7). The Multidimensional Fatigue Inventory (five dimensions), the Parkinson’s Disease Quality of Life Questionnaire (eight dimensions) and the Unified Parkinson’s Disease Rating Scale were used. Demographic data were obtained in a structured interview. Fisher’s exact test, t-test, and multiple linear regression analysis were used. Results: Different aspects of fatigue selectively explained different domains of QoL – physical dimensions of fatigue were connected with Mobility and Activities of daily living; mental fatigue dimensions affected Cognition, Emotional well-being, Communication and Activities of daily living; general fatigue was related to Bodily discomfort. The explained variances varied from 5% (Social support) to 65% (Activities of daily living). Conclusion: Fatigue combined with worse functional status appears to be a significant contributor to poor quality of life. Its multidimensional construct can be used to develop strategies for improving specific aspects of fatigue to improve QoL for PD patients. [ABSTRACT FROM AUTHOR]

Question: What is the contribution of a rise in groundwater level to vegetation restoration of degraded peat meadows compared to abandonment only? Location: Abandoned peat meadows in the central part of The Netherlands. Methods: Comparison of species composition and species abundance of vegetation and seed banks of reference and rewetted peat meadows, using plant trait and seed bank analysis. Results: Vegetation of rewetted meadows shared on average only 27% of their species with the reference meadow, while this was 50% on average for species in the seed bank. Rewetted meadows had a lower total number of species and a lower number of wet grassland and fen species present in the vegetation, but had higher species richness per m2, although evenness was not affected. Rewetting increased the dominance of species of fertile and near neutral habitats, but did not result in an increase of species of wet or waterlogged habitats. Rewetted meadows were dominated by species relying mainly on vegetative reproduction and species with a low average seed longevity compared to the reference meadow. Conclusion: Rewetting was not effective as a restoration measure to increase plant species diversity or the number of wet grassland and fen species in the vegetation. If no additional restoration management is applied, the seed bank will be depleted of seeds of species of wet grassland or fen habitats, further reducing the chances of successful vegetation restoration. [ABSTRACT FROM AUTHOR]

Auditory startle reflexes can accelerate simple voluntary reaction times (StartReact effect). To investigate the role of startle reflexes on more complex motor behaviour we formulated two questions: (1) can auditory startle reflexes shorten choice reaction times?; (2) is the StartReact effect differentially modulated when startling auditory stimuli are delivered ipsilaterally or contralaterally to an imperative ‘go’ signal? We instructed 16 healthy subjects to rotate their head as rapidly as possible to the left or to right in response to a guiding visual imperative stimulus (IS), in both a simple and choice reaction protocol. Startling acoustic stimuli (113 dB) were delivered simultaneously with the IS (from either the same or opposite side) to induce the StartReact effect. We recorded kinematics of head rotations and electromyographic responses. The StartReact effect was present during choice reaction tasks (56 ms onset reduction; P < 0.001). The presentation side of the startling stimulus (left/right) did not influence the effect in choice reaction tasks. We observed a directional effect in simple reaction tasks, but this probably occurred due to a flooring effect of reaction times. Onsets of EMG responses in neck muscles were not influenced by the direction of the acoustic startling stimulus. Startling acoustic stimuli decrease reaction times not only in simple but also in choice reaction time tasks, suggesting that startle reflexes can accelerate adequate human motor responses. The absence of a clear directional sensitivity of reaction times to startling acoustic stimuli suggests that the acceleration is not highly specific, but seems to provide a global preparatory effect upon which further tailored action can be undertaken more quickly. [ABSTRACT FROM AUTHOR]

The ataxic mouse rolling Nagoya (RN) carries a missense mutation in the Cacna1a gene, encoding the pore-forming subunit of neuronal Cav2.1 (P/Q-type) Ca2+ channels. Besides being the predominant type of Cav channel in the cerebellum, Cav2.1 channels mediate acetylcholine (ACh) release at the peripheral neuromuscular junction (NMJ). Therefore, Cav2.1 dysfunction induced by the RN mutation may disturb ACh release at the NMJ. The dysfunction may resemble the situation in Lambert–Eaton myasthenic syndrome (LEMS), in which autoantibodies target Cav2.1 channels at NMJs, inducing severely reduced ACh release and resulting in muscle weakness. We tested neuromuscular function of RN mice and characterized transmitter release properties at their NMJs in diaphragm, soleus and flexor digitorum brevis muscles. Clinical muscle weakness and fatigue were demonstrated using repetitive nerve-stimulation electromyography, grip strength testing and an inverted grid hanging test. Muscle contraction experiments showed a compromised safety factor of neuromuscular transmission. In ex vivo electrophysiological experiments we found severely impaired ACh release. Compared to wild-type, RN NMJs had 50–75% lower nerve stimulation-evoked transmitter release, explaining the observed muscle weakness. Surprisingly, the reduction in evoked release was accompanied by an ∼ 3-fold increase in spontaneous ACh release. This synaptic phenotype suggests a complex effect of the RN mutation on different functional Cav2.1 channel parameters, presumably with a positive shift in activation potential as a prevailing feature. Taken together, our studies indicate that the gait abnormality of RN mice is due to a combination of ataxia and muscle weakness and that RN models aspects of the NMJ dysfunction in LEMS. [ABSTRACT FROM AUTHOR]