Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults

Purpose:

To examine the long‐term consequences of manganese exposure due to the use of manganese‐enhanced magnetic resonance imaging (MEMRI) in a model of closed head injury, the fluid‐percussion injury (FPI) model.

Materials and Methods:

Two groups of adult male Wistar rats (n = 72) were studied with either MEMRI, whereby rats receive MnCl₂ (100 mg/kg intraperitoneally) 24 hours prior to scanning, or standard MRI (sMRI) with no contrast agent. Rats from both groups underwent FPI or sham injury and were longitudinally assessed for 6 months for neurological toxicity using behavioral tests, EEG recording, and MRI scanning.

Results:

Regardless of whether they received FPI, MEMRI animals showed progressive signs of cerebral toxicity compared with sMRI rats, including significantly reduced weight gain, progressive brain volume decrease, and increased anxiety and depressive‐like behaviors.

Conclusion:

Long‐term structural and functional consequences of using manganese as a contrast agent for MRI can confound experimental outcomes and must be taken into account when designing longitudinal imaging studies using manganese‐enhanced MRI. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

A 3D analysis of fore- and hindlimb motion during overground and ladder walking: Comparison of control and unloaded rats

During locomotion, muscles are controlled by a network of neurones located in the spinal cord and by supraspinal structures. Alterations in that neuromuscular system have a functional impact, in particular on locomotion. The hindlimb unloading (HU) model in rat has been commonly used to generate disuse since it suppresses the hindlimb loading and limits movements. In consequence, it induces plastic mechanisms in the muscle, the spinal cord and the sensorimotor cortex. The aim of this study was to assess the locomotion in HU rats in two conditions: (1) on a runway and (2) in a challenging situation involving the participation of supraspinal structures (ladder walking). For that purpose, the motor pattern has been investigated by means of 3D motion analysis of the right fore- and hindlimbs as well as electromyographic recording of the soleus and tibialis anterior muscles. The 3D motion results show that HU induces a support-dependent alteration of the kinematics: increased duration of step, stance and swing; increased ankle flexion during stance and hyperextension at toe-off; lower protraction during swing. The electromyographic results show that whatever the support, the flexor and extensor burst duration was longer in HU rats. In addition, results show that ladder exacerbates some effects of HU. As ladder walking is a situation which requires precision, it is suggested that the control of hindlimb movement by supraspinal structures is affected in HU rats.     

Cancer du sein en ligne : effets de l’utilisation des technologies de l’information et de la communication

Objectives

We want to know the effects of virtual exchanges places, on psychological adaptation of women patients to cancer pathology, and especially breast cancer.

Autosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late-Onset Phenotypes

Background

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. MPAN typically appears in the first two decades of life and presents with progressive dystonia-parkinsonism, lower motor neuron signs, optic atrophy, and abnormal iron deposits predominantly in the basal ganglia. MPAN, initially considered as a strictly autosomal recessive disease (AR), turned out to be also dominantly inherited (AD).

Objectives

Our aim was to better characterize the clinical, molecular, and functional spectra associated with such dominant pathogenic heterozygous C19orf12 variants.

Methods

We collected clinical, imaging, and molecular information of eight individuals from four AD-MPAN families and obtained brain neuropathology results for one. Functional studies, focused on energy and iron metabolism, were conducted on fibroblasts from AD-MPAN patients, AR-MPAN patients, and controls.

Results

We identified four heterozygous C19orf12 variants in eight AD-MPAN patients. Two of them carrying the familial variant in mosaic displayed an atypical late-onset phenotype. Fibroblasts from AD-MPAN showed more severe alterations of iron storage metabolism and autophagy compared to AR-MPAN cells.

Conclusion

Our data add strong evidence of the realness of AD-MPAN with identification of novel monoallelic C19orf12 variants, including at the mosaic state. This has implications in diagnosis procedures. We also expand the phenotypic spectrum of MPAN to late onset atypical presentations. Finally, we demonstrate for the first time more drastic abnormalities of iron metabolism and autophagy in AD-MPAN than in AR-MPAN. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Dietary management of insulin resistance and the metabolic syndrome

Strategies are being developed to reduce the incidence of diabetes and other associated chronic diseases, including heart disease and many common cancers. Part of the strategy has been to define at-risk groups, especially those with the metabolic syndrome. Perhaps the most readily useable classification is that of National Cholesterol Education Program Adult Treatment Panel III criteria. The ultimate goal has been to increase exercise and reduce body weight. Diets with different macronutrient profiles have been proposed, all of which appear useful if compliance is maintained but may differ somewhat in the spectrum of benefits they confer. Newer drugs have appeared that also may confer benefit metabolically (peroxisome proliferator-activated receptor agonists) or by central mechanisms (cannabinoid antagonists). The changes will likely have to be metabolic and societal and include not only the food industry but also modes of transportation and urban planning.     

Observer variability when evaluating patient movement from electronic portal images of pelvic radiotherapy fields.

BACKGROUND AND PURPOSE: A study has been performed to evaluate inter-observer variability when assessing pelvic patient movement using an electronic portal imaging device (EPID). MATERIALS AND METHODS: Four patient image sets were used with 3-6 portal images per set. The observer group consisted of nine radiographers with 3-18 months clinical EPID experience. The observers outlined bony landmarks on a digital simulator image and used matching software to evaluate field placement errors (FPEs) on each portal image relative to the reference simulator image. Data were evaluated statistically, using a two-component analysis of variance technique, to quantify both the inter-observer variability in evaluating FPEs and inter-fraction variability in patient position relative to the residuals of the analysis. Intra-observer variability was also estimated using four of the observers carrying out three sets of repeat readings. RESULTS: Eight sets of variance data were analysed, based on FPEs in two orthogonal directions for each of the four patient image sets studied. Initial analysis showed that both inter-observer variation and inter-fraction-patient position variation were statistically significant (P<0.05) in seven of the eight cases evaluated. The averaged root-mean-square (RMS) deviation of the observers from the group mean was 1.1 mm, with a maximum deviation of 5.0 mm recorded for an individual observer. After additional training and re-testing of two of the observers who recorded the largest deviations from the group mean, a subsequent analysis showed the inter-observer variability for the group to be significant in only three of the eight cases, with averaged RMS deviation reduced to 0.5 mm, with a maximum deviation of 2.7 mm. The intra-observer variability was 0.5 mm, averaged over the four observers tested. CONCLUSIONS: We have developed a quantitative approach to evaluate inter-observer variability in terms of its statistical significance compared to inter-fraction patient movement. This will assist us in training and assessing observers required to perform this task on a routine basis.