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Multiple sclerosis is a demyelinating disorder of the central nervous system (CNS), in which an immune attack directed against myelin constituents causes myelin destruction and death of oligodendrocytes, the myelin-producing cells. Here, the efficacy of nerve growth factor (NGF), a growth factor for neurons and oligodendrocytes, in promoting myelin repair was evaluated using the demyelinating model of experimental allergic encephalomyelitis (EAE) in the common marmoset. Surprisingly, we found that NGF delayed the onset of clinical EAE and, pathologically, prevented the full development of EAE lesions. We demonstrate by immunocytochemistry that NGF exerts its antiinflammatory effect by downregulating the production of interferon gamma by T cells infiltrating the CNS, and upregulating the production of interleukin 10 by glial cells in both inflammatory lesions of EAE and normal-appearing CNS white matter. Thus, NGF, currently under investigation in human clinical trials as a neuronal trophic factor, may be an attractive candidate for therapy of autoimmune demyelinating disorders.

Objective: High resolution detection of genomic copy number abnormalities in a single cell is relevant to preimplantation genetic diagnosis and potentially to noninvasive prenatal diagnosis. Our objective is to develop a reliable array comparative genomic hybridization (CGH) platform to detect genomic imbalances as small as ~1Mb ina single cell.Methods: We empirically optimized the conditions for oligonucleotide-based array CGH using single cells from multiple lymphoblastoid cell lines with known copy number abnormalities. To improve resolution, we designed custom arrays with high density probes covering clinically relevant genomic regions.Results: The detection of megabase-sized copy number variations (CNVs) in a single cell was influenced by the number of probes clustered in the interrogated region. Using our custom array, we reproducibly detected multiple chromosome abnormalities including trisomy 21, a 1.2Mb Williams syndrome deletion, and a 1.3Mb CMT1A duplication. Replicate analyses yielded consistent results.Conclusion: Aneuploidy and genomic imbalances with CNVs as small as 1.2Mb in a single cell are detectable by array CGH using arrays with high-density coverage in the targeted regions. This approach has the potential to be applied for preimplantation genetic diagnosis to detect aneuploidy and common microdeletion/duplication syndromes and for noninvasive prenatal diagnosis if single fetal cells can be isolated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Oligonucleotide-based array comparative genomic hybridization (array CGH) is an established method for detecting chromosomal abnormalities. Here, we explored the feasibility of using DNA extracted from uncultured amniocytes in amniotic fluid for array CGH on an oligonucleotide array platform. METHODS: Fifteen fetuses from 14 ongoing pregnancies were studied by array CGH on targeted oligonucleotide arrays with DNA isolated from direct amniotic fluid using a modified DNA extraction protocol. RESULTS: High-quality array CGH results were obtained for 13 samples with suboptimal but interpretable results in only 2 samples due to limited DNA amounts. Array CGH using whole genome amplification (WGA) of DNA for the two cases with limited DNA was successful, and results were consistent with those from unamplified DNA. For another five samples, the results of array CGH with amplified DNA matched those with unamplified DNA. Chromosome analysis was performed for 14 cases and was consistent with array CGH results. CONCLUSION: This study demonstrates the feasibility of prenatal genetic diagnosis using oligonucleotide array CGH analysis for direct analysis of amniocytes without culturing cells. The use of oligonucleotide arrays increases the sensitivity and accuracy of detection over previous bacterial artificial chromosome (BAC)-based arrays. Furthermore, the direct analysis allows for rapid array CGH results and shorter reporting time. [ABSTRACT FROM AUTHOR]

Cortical processing of auditory information can be affected by interspecies differences as well as brain states. Here we compare multifeature spectro-temporal receptive fields (STRFs) and associated input/output functions or nonlinearities (NLs) of neurons in primary auditory cortex (AC) of four mammalian species. Single-unit recordings were performed in awake animals (female squirrel monkeys, female, and male mice) and anesthetized animals (female squirrel monkeys, rats, and cats). Neuronal responses were modeled as consisting of two STRFs and their associated NLs. The NLs for the STRF with the highest information content show a broad distribution between linear and quadratic forms. In awake animals, we find a higher percentage of quadratic-like NLs as opposed to more linear NLs in anesthetized animals. Moderate sex differences of the shape of NLs were observed between male and female unanesthetized mice. This indicates that the core AC possesses a rich variety of potential computations, particularly in awake animals, suggesting that multiple computational algorithms are at play to enable the auditory system's robust recognition of auditory events., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: To investigate axial elongation (AE) and changes in relative peripheral refraction (RPR) in anisomyopic children undergoing orthokeratology (ortho-k)., Methods: Bilateral anisomyopic children, 7-12 years of age, were treated with ortho-k. Axial length (AL) and RPR, from 30° nasal (N30°) to 30° temporal (T30°), were measured at baseline and every 6 months over the study period. AE, changes in RPR and changes in the interocular AL difference were determined over time., Results: Twenty-six of the 33 subjects completed the 2-year study. The AE of the higher myopic (HM) eyes (at least 1.50 D more myopia than the other eye) (0.26 ± 0.29 mm) was significantly smaller than for the less myopic (LM) eyes (0.50 ± 0.27 mm; p = 0.003), leading to a reduction in the interocular difference in AL (p = 0.001). Baseline RPR measurements in the HM eyes were relatively more hyperopic at T30°, N20° and N30° (p ≤ 0.02) and greater myopic shifts were observed at T20° (p < 0.001), T30° (p < 0.001), N20° (p = 0.02) and N30° (p = 0.01) after lens wear. After 2 years of ortho-k lens wear, temporal-nasal asymmetry increased significantly, being more myopic at the temporal locations in both eyes (p < 0.001), while AE was associated with the change in RPR at N20° (β = 0.134, p = 0.01). The interocular difference in AE was also positively associated with the interocular difference in RPR change at N30° (β = 0.111, p = 0.02)., Conclusions: Ortho-k slowed AE in bilateral anisomyopia, with slower growth in the HM eyes leading to a reduction in interocular AL differences. After ortho-k, RPR changed from hyperopia to myopia, with greater changes induced in the HM eyes, and slower AE was associated with a more myopic shift in RPR, especially in the nasal field of both eyes., (© 2024 College of Optometrists.)

Introduction: Impaired laryngopharyngeal sensation has been implicated in obstructive sleep apnea (OSA) and may play an important pathophysiological role. We evaluated sensory function in OSA by examining the laryngeal adductor reflex (LAR) response rate and temporal profile to tactile stimulation., Methods: Laryngeal sensation testing was performed in awake adults with and without diagnosed OSA by stimulating the medial aryepiglottic fold or arytenoid using 30-mm 5-0 and 4-0 nylon Cheung-Bearelly monofilaments. Video analysis by two independent reviewers evaluated for the presence of the LAR in response to satisfactory stimuli and LAR latency to vocal fold adduction., Results: Twenty-six OSA and 12 control subjects were tested with 270 satisfactory stimuli. The mean full LAR response rate to 4-0 stimulation was 38.3% in OSA vs 86.9% in control subjects (p <0.001) and to 5-0 stimulation was 27% in OSA vs 63.9% in control subjects (p  <0.001). The mean LAR latency to vocal fold closure in OSA was 123.7 ms (SD 35.8) vs 156.4 ms (SD 44.3) in control (p = 0.04) subjects. OSA LAR latency was positively correlated with the apnea-hypopnea index (r = 0.30; p = 0.008)., Conclusion: The OSA group exhibited reduced LAR response rates and shortened LAR latency, where latency was correlated with disease severity. Laryngeal hyposensitivity was affirmed and changes to LAR sensorimotor temporal dynamics were revealed. These pathophysiological alterations to the LAR may be accounted for by decreased somatosensory receptor sensitivity, increased sympathetic tone, and reorganized brain stem function in OSA., Level of Evidence: 3 Laryngoscope, 134:3856-3861, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To evaluate the safety of orthokeratology contact lens wear in slowing the axial elongation of the eye in myopic children., Methods: Safety data from three prospective studies, which evaluated the use of orthokeratology for slowing myopia progression in children in comparison to a parallel control group of single-vision spectacle lens wearers over a 2-year period, were pooled together for analysis. The primary and secondary safety endpoints are the comparisons of adverse events and slit-lamp findings grades ≥ 2 between orthokeratology and control groups, respectively., Results: Collectively, data from 125 orthokeratology and 118 control subjects were analyzed in this study. Of these, 101 (81 %) and 88 (75 %) orthokeratology and control subjects completed the 2-year follow-up period, respectively. Nineteen orthokeratology subjects experienced 28 adverse events, of which 6 were significant, whereas just one adverse event was found in the control group; this difference was statistically significant (p < 0.001). Most adverse events found in the orthokeratology group were corneal in nature, primarily corneal abrasion/staining, accounting for around 40 % of all adverse events. Of the 28 adverse events, only 18 (3 significant) are likely to be contact lens-related, leading to incidence rates of total and device-related adverse events per 100 patient years of lens wear (95 % confidence intervals) of 13.1 (9.2-18.2) and 8.4 (5.4-10.7), respectively. No significant differences were found between groups in the total number of silt-lamps findings with grades ≥ 2 (p > 0.05)., Conclusion: Around 13% of eyes wearing overnight orthokeratology contact lenses are likely to experience an adverse event over one year of lens wear, with this figure being lower when considering device-related adverse events alone. No serious adverse events were found, with most being non-significant. These results inform eye care practitioners on the safety of orthokeratology lenses when prescribed for slowing myopia progression to myopic children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacinto Santodomingo-Rubido is a full-time employee of Menicon Co., Ltd. The authors alone are responsible for the content and writing of the paper. Menicon Co., Ltd funded the publication costs of this study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To evaluate the efficacy of orthokeratology contact lens wear in slowing the axial elongation of the eye in myopic children., Methods: Data from three prospective studies, which evaluated the use of orthokeratology for slowing myopia progression in children in comparison to a parallel control group of distance, single-vision spectacle lens wearers over a 2-year period, were pooled together for analysis., Results: Collectively, data from 125 orthokeratology and 118 control subjects were analyzed in this study. Of these, 101 (81 %) and 88 (75 %) orthokeratology and control subjects completed the 2-year follow-up period, respectively. Statistically significant differences in the change in axial length from baseline were found over time, between groups and for the time*group interaction (all p < 0.001), indicating that the rate of increase in axial length over time was significantly lower in the orthokeratology versus the control group. The lower axial elongation of the orthokeratology versus the control group was statistically significant at all time points (all p < 0.001), with significant differences being also present between each of the different pairs of time points (all p < 0.001). The interactions of group with age, gender, mean spherical refractive error and ethnicity at baseline were not significant (p > 0.05). The change in axial length at the 2-year visit in comparison to baseline for the orthokeratology and control groups were 0.41 ± 0.25 and 0.65 ± 0.30 mm, respectively, thus providing a treatment effect following 2-years of lens wear of 0.24 mm (95 % confidence intervals: 0.15 to 0.34 mm). About 40 % and 25 % of the orthokeratology subjects experienced remarkably low and high levels of myopia progression, respectively (2-years axial elongation: ≤0.30 mm and >0.59 mm, respectively)., Conclusions: Orthokeratology lens wear slows the axial elongation of the eye in comparison to spectacle lens wear in myopic children. The use of these lenses for slowing myopia progression appears to be very effective and not effective at all in 40% and 25% of orthokeratology lens wearers, respectively., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacinto Santodomingo-Rubido is a full-time employee of Menicon Co., Ltd. The authors alone are responsible for the content and writing of the paper. Menicon Co., Ltd funded the publication costs of this study., (Copyright © 2024. Published by Elsevier Ltd.)