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Background: Multimodal research combining biomarkers of intracortical activity and cortical damage could shed light on pathophysiological and adaptive neural processes related to the clinical severity of neurological conditions such as multiple sclerosis (MS)., Objective: Among people with relapsing-remitting and progressive forms of MS, we assessed the extent to which transcranial magnetic stimulation (TMS)-based biomarkers of excitatory and inhibitory cortical activity are related to cortical damage and clinical impairment., Methods: Participants included 18 healthy individuals and 36 people with MS who had a relapsing-remitting or progressive clinical course. Using TMS, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and cortical silent period (CSP) were obtained. Cortical volume and cortical magnetization transfer ratio (MTR) were quantified. Disability was assessed with Multiple Sclerosis Functional Composite (MSFC)., Results: Lower mean MTR within the cerebral cortex correlated with shorter CSP among MS participants with a progressive, but not a relapsing-remitting, clinical course. Within the cortical hand knob region targeted with TMS, lower MTR was correlated with lower SICI only among individuals with relapsing-remitting MS. Longer CSP, higher ICF, lower cortical MTR, and sex were all independent significant predictors of poor upper extremity motor performance, while only cortical MTR was a significant independent predictor of total MSFC score among people with MS., Conclusions: Cortical damage and cortical activity (both inhibitory and excitatory) may contribute to the severity of motor disability experienced by people with MS. When interpreting TMS-based outcomes, cortical integrity, clinical course, and symptom type should be considered., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The impact of inhibitory cortical activity on motor impairment of people with relapsing-remitting multiple sclerosis (RRMS) has not been fully elucidated despite its relevance to neurorehabilitation. The present study assessed the extent to which transcranial magnetic stimulation (TMS)-based metrics of intracortical inhibition are related to motor disability and brain damage., Methods: Participants included forty-three persons with RRMS in the remitting phase and twenty-nine healthy controls. We stimulated the dominant hemisphere and recorded from the dominant hand to assess short-interval intracortical inhibition (SICI) and cortical silent period (CSP) duration. Disability was evaluated with the Multiple Sclerosis Functional Composite (MSFC). Regional cortical thickness and lesion volume were measured., Results: RRMS participants with dominant upper limb dexterity impairments had prolonged CSP, but equivalent SICI, compared to participants with preserved function. CSP was not related to walking or cognitive performance. Higher normalized lesion volume correlated with longer CSP duration. When adjusting for normalized lesion volume, longer CSP significantly predicted worse dominant upper extremity impairment., Conclusions: High intracortical inhibition possibly contributes to (or prevents remission from) motor impairment. Lesions may be associated with intracortical inhibition shifts., Significance: CSP duration and lesion burden should be considered when developing interventions aiming to mitigate motor impairment., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Anthropogenic mercury (Hg) air emissions for the eight Great Lakes states in 1999-2000 were evaluated by analyzing three inventories. The US Environmental Protection Agency (EPA) National Emissions Inventory (NEI) had the most complete coverage for all states, and total Hg emissions ranged from 4226 lb in Minnesota to 15,828 lb in Pennsylvania. Coal-fired electric utilities accounted for 52.7% of the region's Hg emissions, varying from 20.2% of the total in New York to 67.5% in Ohio. Other important contributors to regional emissions included municipal waste combustion (5.6%), mercury-cell chlor-alkali plants and hazardous-waste incinerators (4% each), stationary internal combustion engines (ICEs) (3.5%), industrial, commercial, and institutional (ICI) boilers (3.3%), and lime manufacturing (3.0%). Although medical waste incineration accounted for just over 1% of regional emissions using the original classifications, the inclusion of health care facilities that may have been inappropriately identified with other sectors would increase the sector to 4.5% of regional emissions (and decrease the stationary ICE sector to 1.4% of the regional total). There were substantial differences for some sectors between the NEI and the Great Lakes Regional Air Toxics Emissions Inventory (GLEI), as well as unexplained differences within inventories between states (particularly for the cement, lime, and asphalt industries, and for lamp breakage). Toxics Release Inventory data for 2000 mainly covered electric utilities, and differences from the NEI were significant for several states. An independent assessment indicates the possibility of underestimated Hg emissions by about twofold for ICI boilers, although data for the sector (in particular concerning fuel oil emissions) are highly uncertain. Limited data indicate the likelihood of significant underestimates of electric arc furnace mercury emissions in the NEI and GLEI inventories. Several measures are here identified for improving the reliability of the inventories, both for modeling of atmospheric transport and deposition modeling and for tracking progress in Hg reduction initiatives.

Individuals with incomplete spinal cord injuries (SCI) retain varying degrees of voluntary motor control. The complexity of the motor control system and the nature of the recording biophysics have inhibited efforts to develop objective measures of voluntary motor control. This paper proposes the definition and use of a voluntary response index (VRI) calculated from quantitative analysis of surface electromyographic (sEMG) data recorded during defined voluntary movement as a sensitive measure of voluntary motor control in such individuals. The VRI is comprised of two numeric values, one derived from the total muscle activity recorded for the voluntary motor task (magnitude), and the other from the sEMG distribution across the recorded muscles (similarity index (SI)). Calculated as a vector, the distribution of sEMG from the test subject is compared to the average vector calculated from sEMG recordings of the same motor task from 10 neurologically intact subjects in a protocol called brain motor control assessment (BMCA). To evaluate the stability of the VRI, a group of five healthy subjects were individually compared to the prototype, average healthy-subject vectors for all of the maneuvers. To evaluate the sensitivity of this method, the VRI was obtained from two SCI subjects participating in other research studies. One was undergoing supported treadmill ambulation training, and the other a controlled withdrawal of anti-spasticity medications. The supported treadmill training patient's VRI, calculated from pre- and post-training BMCA recordings, reflected the qualitative changes in sEMG patterns and functional improvement of motor control. The VRI of the patient followed by serial BMCA during medication withdrawal also reflected changes in the motor control as a result of changes in anti-spasticity medication. To validate this index for clinical use, serial studies using larger numbers of subjects with compromised motor control should be performed.

Type I oculocutaneous albinism is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes because of deficient activity of tyrosinase (EC 1.14.18.1). Type I oculocutaneous albinism is caused by mutations in the tyrosinase structural gene, TYR; however, no large TYR gene deletions have been identified previously in humans. Here we report a patient with type IB oculocutaneous albinism who is a compound heterozygote for TYR allele containing a mutation that is likely to affect pre-RNA splicing and a paternally inherited allele in which the TYR gene is completely deleted, the first such allele described to date. Aside from the albinism in the proband, his phenotype and that of his normally pigmented father is otherwise normal, suggesting that this TYR deletion does not involve other functionally important contiguous genes.

Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cellular receptor transmembrane tyrosine kinase for mast/stem cell growth factor. Here we describe two novel KIT mutations associated with human piebaldism. These amino acid substitutions, located in the most highly conserved sections of the KIT kinase domain, would be expected to dominant-negatively inhibit KIT-dependent signal transduction, resulting in aberrant melanocyte proliferation or migration during embryologic development.