The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Conductance heterogeneities induced by multistability in the dynamics of coupled cardiac gap junctions.

In this paper, we study the propagation of the cardiac action potential in a one-dimensional fiber, where cells are electrically coupled through gap junctions (GJs). We consider gap junctional gate dynamics that depend on the intercellular potential. We find that different GJs in the tissue can end up in two different states: a low conducting state and a high conducting state. We first present evidence of the dynamical multistability that occurs by setting specific parameters of the GJ dynamics. Subsequently, we explain how the multistability is a direct consequence of the GJ stability problem by reducing the dynamical system's dimensions. The conductance dispersion usually occurs on a large time scale, i.e., thousands of heartbeats. The full cardiac model simulations are computationally demanding, and we derive a simplified model that allows for a reduction in the computational cost of four orders of magnitude. This simplified model reproduces nearly quantitatively the results provided by the original full model. We explain the discrepancies between the two models due to the simplified model's lack of spatial correlations. This simplified model provides a valuable tool to explore cardiac dynamics over very long time scales. That is highly relevant in studying diseases that develop on a large time scale compared to the basic heartbeat. As in the brain, plasticity and tissue remodeling are crucial parameters in determining the action potential wave propagation's stability.

Psychosocial interventions for children and adolescents after man-made and natural disasters: a meta-analysis and systematic review.

Children and adolescents are a vulnerable group to develop post-traumatic stress symptoms after natural or man-made disasters. In the light of increasing numbers of refugees under the age of 18 years worldwide, there is a significant need for effective treatments. This meta-analytic review investigates specific psychosocial treatments for children and adolescents after man-made and natural disasters. In a systematic literature search using MEDLINE, EMBASE and PsycINFO, as well as hand-searching existing reviews and contacting professional associations, 36 studies were identified. Random- and mixed-effects models were applied to test for average effect sizes and moderating variables. Overall, treatments showed high effect sizes in pre-post comparisons (Hedges' g = 1.34) and medium effect sizes as compared with control conditions (Hedges' g = 0.43). Treatments investigated by at least two studies were cognitive-behavioural therapy (CBT), eye movement desensitization and reprocessing (EMDR), narrative exposure therapy for children (KIDNET) and classroom-based interventions, which showed similar effect sizes. However, studies were very heterogenic with regard to their outcomes. Effects were moderated by type of profession (higher level of training leading to higher effect sizes). A number of effective psychosocial treatments for child and adolescent survivors of disasters exist. CBT, EMDR, KIDNET and classroom-based interventions can be equally recommended. Although disasters require immediate reactions and improvisation, future studies with larger sample sizes and rigorous methodology are needed.

Factors predicting deviation from an enhanced recovery programme and delayed discharge after laparoscopic colorectal surgery.

AIM: The study aimed to identify factors that predict postoperative deviation from an enhanced recovery programme (ERP) and/or delayed discharge following colorectal surgery. METHOD: Data were prospectively collected from all patients undergoing elective laparoscopic colorectal resection between January 2006 and December 2009. They included Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) variables, body mass index (BMI), sex, preoperative serum albumin, pathology, conversion from a laparoscopic to an open approach and postoperative length of hospital stay. RESULTS: There were 176 patients (90 women) of mean age 68 years. Fifteen (9%) operations were converted from laparoscopic to open. The remainder were completed laparoscopically. Fifty-five (31%) deviated from the ERP, with most failing multiple elements. The most common reason was failure to mobilize, which often occurred in conjunction with paralytic ileus or analgesic failure. Factors independently predicting ERP deviation on multivariate analysis were pathology and intra-operative complications. The median length of stay was 5 days. Sixty-four (36%) patients had a prolonged length of stay that was predicted by age, number of procedures and ERP deviation. CONCLUSION: Pathology and intra-operative complications are independent predictors of ERP deviation. Prolonged length of stay can be predicted by age, multiple procedures and ERP deviation. Failure to mobilize should be considered as a red flag sign prompting further investigation following colorectal resection.

Extreme wave excitation from localized phase-shift perturbations.

The modulation instability is a focusing mechanism responsible for the formation of strong wave localizations not only on the water surface, but also in a variety of nonlinear dispersive media. Such dynamics is initiated from the injection of sidebands, which translate into an amplitude modulation of the wave field. The nonlinear stage of unstable wave evolution can be described by exact solutions of the nonlinear Schrödinger equation (NLSE). In that case, the amplitude modulation of such coherent extreme wave structures is connected to a particular phase-shift seed in the carrier wave. In this Letter, we show that phase-shift localization applied to the background, excluding any amplitude modulation excitation, can indeed trigger extreme events. Such rogue waves can be for instance generated by considering the parametrization of fundamental breathers, and thus by seeding only the local phase-shift information to the regular carrier wave. Our wave tank experiments show an excellent agreement with the expected NLSE hydrodynamics and confirm that even though delayed in their evolution, breather-type extreme waves can be generated from a purely regular wave train. Such a focusing mechanism awaits experimental confirmation in other nonlinear media, such optics, plasma, and Bose-Einstein condensates.

Detecting peripheral motor nervous system involvement in chronic spinal cord injury using two novel methods: MScanFit MUNE and muscle velocity recovery cycles.

OBJECTIVE: To examine the peripheral nervous system (PNS) in spinal cord injured (SCI) patients using two novel methods: (1) MScanFit MUNE; a motor unit number estimation method detecting motor unit loss and (2) muscle velocity recovery cycles (MVRCs) measuring muscle membrane properties which has previously shown depolarization of the muscle membrane in denervated muscles. METHODS: Thirty chronic SCI patients (lesion above Th10) and twenty-five gender -and age matched healthy controls (HC) were examined. MScanFit was recorded from peroneal nerve to anterior tibial muscle (TA) and tibial nerve to abductor hallucis muscle after excluding localized mononeuropathies. MVRCs were recorded from TA. RESULTS: Nerve conduction studies showed mononeuropathy in 8 patients (27%) (sciatic (2), -or peroneal nerve (6)). SCI patients had in average reduced motor unit number compared with HC and prolonged muscle refractory period and reduced supernormality. SIGNIFICANCE: A high prevalence of nerve lesion and a diffuse affection of the PNS following SCI are highly relevant findings that should be accounted for when planning neurorehabilitation for persons living with SCI.

Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth.

The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.

The interstellar carbon budget and the role of carbon in dust and large molecules.

Published data on stellar composition show that carbon in the sun is substantially more abundant than in other stars. A carbon abundance of 225 carbon atoms per 10(6) hydrogen atoms is representative of galactic stars, whereas published values for the sun range from 350 to 470 carbon atoms per 10(6) hydrogen atoms. Other elements are also present in enhanced quantities in the solar system, consistent with suggestions that a supernova event was closely associated with the formation of the solar system. The overabundance of carbon in the solar system has many important implications, including new constraints on nucleosynthesis models for supernovae and substantial modification of the so-called "cosmic" composition normally adopted in discussions of galactic and interstellar abundances. A reduction in the galactic carbon budget, as suggested by the stellar composition data, strongly constrains the quantity of carbon that is available for the formation of interstellar dust, and some dust models now appear implausible because they require more carbon than is available.

Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial.

OBJECTIVE: Antimycotics effectively treat sporadic and recurrent vulvovaginal candidiasis (RVVC). Classic homeopathy (CH) is also used to treat this condition. We compared the efficacy of CH and itraconazole in reducing the frequency of RVVC episodes. DESIGN: Single-centre, prospective, randomised trial. SAMPLE: One hundred-and-fifty patients with a history of RVVC and an acute episode of VVC. METHODS: Women were randomised into 3 groups: itraconazole with lactobacilli (group 1), itraconazole without lactobacilli (group 2) and CH (group 3). Itraconazole treatment of acute infection was followed by a 6-month maintenance regimen with monthly single-day itraconazole (200 mg bid). Women in group 1 were given additional vaginal lactobacilli for 6 days per month throughout the maintenance regimen Thereafter, patients were followed without treatment for 6 months. CH treatment was performed for 12 months. RESULTS: Women in groups 1 and 2 reached a culture-free status significantly earlier than women in group 3 (log-rank test; P < 0.0001). Specifically, before the start of the maintenance regimen, 44 of 49 women (89.8%) in group 1 and 40 of 47 women (85%) in group 2 were free of Candida detectable by culture, 22 of 46 (47%) women in group 3 reached a culture-free status after the first visit, but had a recurrence significantly earlier compared with women in groups 1 and 2 (log-rank test; P = 0.002). After 12 months, 19 of 25 (76%) women in group 1, 18 of 23 (78%) women in group 2 and 9 of 23 (39%) women in group 3 were free of culture-detectable Candida. Assessment of RVVC-associated complaints by VAS score showed that women in group 3 had a significantly higher level of discomfort (36.8, 25.1 and 27.7 respectively; P < 0.001) and were significantly less satisfied (59.2, 68.2 and 71.7 respectively; P < 0.001) than patients in groups 1 and 2. CONCLUSIONS: Monthly cycle-dependent itraconazole is more effective than CH in the treatment of RVVC. Lactobacilli do not confer an added benefit.

Muscle velocity recovery cycles in neurogenic muscles.

OBJECTIVE: To examine muscle membrane properties in neurogenic muscles using Muscle Velocity Recovery Cycles (MVRCs). METHODS: Forty-seven patients referred to Nerve Conduction Studies (NCS) and Electromyography (EMG) for peroneal nerve entrapment neuropathy were prospectively included. The patients were categorized as peroneal nerve entrapment neuropathy across knee (n = 22), L5-radiculapathy (n = 10), normal NCS/EMG (n = 9) and other disorders (n = 6) using NCS/EMG and neuroimaging results. Strength in anterior tibial muscle was measured by Medical Council Scale (MRC) and disease duration was recorded. In addition to conventional NCS/EMG, all subjects were examined with MVRCs in anterior tibial muscle. This provided parameters of muscle relative refractory period (MRRP) and early supernormality (ESN) and late supernormality (LSN). The results were compared with 29 age-matched healthy control subjects. RESULTS: MRRP was prolonged and ESN and LSN were reduced in neurogenic muscles. MRRP, ESN and LSN correlated to MRC and incidence of spontaneous activity but not to motor unit potential parameters or disease duration. CONCLUSIONS: MVRC changes provide in vivo evidence of depolarization in intact human muscle fibres that could underlie reduced muscle excitability and hence weakness in neurogenic muscles. SIGNIFICANCE: MVRCs appear to be a useful technique for revealing disease mechanism in a broad range of neuromuscular diseases.

MScanFit motor unit number estimation (MScan) and muscle velocity recovery cycle recordings in amyotrophic lateral sclerosis patients.

OBJECTIVE: Motor Unit Number Estimation (MUNE) methods, such as the recently developed MScanFit MUNE (MScan), may be valuable in tracking motor unit loss in ALS. Muscle Velocity Recovery Cycles (MVRCs) provide information about muscle membrane properties and can reveal disease-related changes. This study was undertaken to test the applicability of MScan to the anterior tibial muscle (TA) and to test whether the MVRCs could improve understanding of ALS pathophysiology. METHODS: Twenty-six ALS patients and 25 healthy controls were evaluated by quantitative electromyography, nerve conduction study and the two novel methods: MScan and MVRC; all in the TA and peroneal nerve. RESULTS: The estimated number of motor units for ALS patients (Median: 45, interquartile range: 28.5-76.5) was significantly lower than for the controls (117, 96.0-121.0) (P = 2.19 × 10-7). Unit size was increased only when amplitudes were expressed as percentage of CMAP. Of MVRC measurements, only relative refractory period was significantly abnormal in patients. CONCLUSION: MScanFit MUNE gives a sensitive and quantitative measure of loss of TA motor units in ALS. Muscle fiber membrane properties are mostly unaffected, despite substantial denervation, presumably due to collateral reinnervation. SIGNIFICANCE: MScan is suitable for detecting motor unit loss in TA. MVRCs do not provide new insights in ALS.

Quantification of DTI in the Pediatric Spinal Cord: Application to Clinical Evaluation in a Healthy Patient Population.

BACKGROUND AND PURPOSE: The purpose of the study is to characterize diffusion tensor imaging indices in the developing spinal cord, evaluating differences based on age and cord region. Describing the progression of DTI indices in the pediatric cord increases our understanding of spinal cord development. MATERIALS AND METHODS: A retrospective analysis was performed on DTI acquired in 121 pediatric patients (mean, 8.6 years; range, 0.3-18.0 years) at Monroe Carell Jr. Children's Hospital at Vanderbilt from 2017 to 2018. Diffusion-weighted images (15 directions; b = 750 s/mm2; slice thickness, 5 mm; in-plane resolution, 1.0 × 1.0 mm2) were acquired on a 3T scanner in the cervicothoracic and/or thoracolumbar cord. Manual whole-cord segmentation was performed. Images were masked and further segmented into cervical, upper thoracic, thoracolumbar, and conus regions. Analyses of covariance were performed for each DTI-derived index to investigate how age affects diffusion across cord regions, and 95% confidence intervals were calculated across age for each derived index and region. Post hoc testing was performed to analyze regional differences. RESULTS: Analyses of covariance revealed significant correlations of age with axial diffusivity, mean diffusivity, and fractional anisotropy (all, P < .001). There were also significant differences among cord regions for axial diffusivity, radial diffusivity, mean diffusivity, and fractional anisotropy (all, P < .001). CONCLUSIONS: This research demonstrates that diffusion evolves in the pediatric spinal cord during development, dependent on both cord region and the diffusion index of interest. Future research could investigate how diffusion may be affected by common pediatric spinal pathologies.

The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis.

OBJECTIVE: To evaluate the efficacy of additional topical Lactobacillus casei rhamnosus (Lcr35) subsequent to antibiotic treatment of bacterial vaginosis (BV) to restore the normal vaginal flora. STUDY DESIGN: Single-centre, randomised, observerblinded study. SETTING: Population-based study in Vienna over 1 year. SAMPLE: 190 women were enrolled in the study. METHODS: Women with Nugent scores between 7 and 10 on initial vaginal swab were randomised to the one of two groups. All women were treated with standard antibiotic therapy for 7 days. Only women in the intervention group received vaginal capsules containing 10(9) colony-forming units of live Lcr35 for 7 days after antibiotic treatment. Final vaginal swabs for Nugent scoring were taken 4 weeks after the last administration of the study medication. MAIN OUTCOME MEASURES: The primary efficacy variable was a change in the Nugent score between the baseline and the end of the study of at least 5 grades in each individual woman. RESULTS: Sixty-nine of the 83 women (83%) in the intervention group and 31 of the 88 women (35%) in the control group showed a reduction of the Nugent score by at least 5 grades. The difference in the number of women with improvement was highly significant (P < 0.001). The median difference in Nugent scores between initial and final swabs was 6.61 in the intervention group and 4.13 in the control group (P < 0.001). CONCLUSION: Our data show that the restoration of the vaginal flora after antibiotic treatment of BV can be significantly enhanced by exogenously applied lactobacilli.

Evaluation of OMNIgene®â€¢SPUTUM reagent for mycobacterial culture.

SETTING: National Mycobacterium Reference Laboratory, Borstel, Germany. OBJECTIVE: To evaluate the effectiveness of OMNIgene®â€¢SPUTUM (OM-S) reagent in comparison with a method using N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) with regard to mycobacterial recovery and contamination of broth and solid cultures. DESIGN: Sputum samples from patients with tuberculosis and other respiratory diseases underwent decontamination with NALC-NaOH-based (MycoDDR™) or OM-S reagent. The decontamination procedure was assigned by block randomisation. Samples were inoculated on Löwenstein-Jensen, Stonebrink and MGIT™ (Mycobacterial Growth Indicator Tubes). Mycobacterial recovery from samples spiked with Mycobacterium tuberculosis following decontamination was determined. RESULTS: Eighty-five samples were randomised to NALC-NaOH and 84 to OM-S reagent. Mycobacterial recovery was significantly lower for samples processed with OM-S reagent compared with the NALC-NaOH method across all media types. Culture contamination was lower with NALC-NaOH reagent on solid media (9.4-12.9% vs. 28.6-29.8%). Growth was not observed in MGIT among samples spiked with 10 600-16 800 colony-forming units of M. tuberculosis following decontamination with OM-S reagent. CONCLUSION: Low mycobacterial recovery, especially in MGIT, observed in the present study suggests that OM-S reagent might not be compatible with the MGIT system. More extensive field evaluations of the OM-S reagent are warranted to demonstrate a significant benefit over currently used methods.

The utility of motor unit number estimation methods versus quantitative motor unit potential analysis in diagnosis of ALS.

OBJECTIVE: To compare the diagnostic utility of motor unit number estimation (MUNE) methods to motor unit potential (MUP) analysis in amyotrophic lateral sclerosis (ALS). METHODS: Twenty-five patients (1 definite, 11 probable, 9 possible ALS and 4 progressive muscular atrophy) and 22 healthy controls were prospectively included. Quantitative MUP analysis and three MUNE methods; Multiple Point Stimulation MUNE (MPS), Motor Unit Number Index (MUNIX) and MScanFit MUNE (MScan) were done in abductor pollicis brevis muscle. The sensitivities were compared by McNemar chi-square test. MUNE, MUP and revised ALS Functional Rating Scale (ALSFRS-R) parameters were correlated by regression analysis. RESULTS: The sensitivities of MPS (76%) and MScan (68%) were higher than MUP duration (36%) and amplitude (40%) in detecting motor unit loss (p < 0.05). MUNE methods increased the categorical probability from possible to probable ALS in 4 patients (16%). There was only significant correlation between ALSFRS-R and MScan (r = 0.443, p = 0.027) among the electrophysiological tests. MUNE methods did not correlate to MUP parameters. CONCLUSIONS: MUNE methods are more sensitive in showing abnormality than MUP analysis. SIGNIFICANCE: MUNE methods, in particular MScan, may have the potential to be implemented in the clinical practice for diagnosis and follow-up of neuromuscular disorders particularly ALS.

A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter.

In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score /= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.

Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer.

Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.

Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons.

Altered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.

Formation of compact myelin is required for maturation of the axonal cytoskeleton.

Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.