Molecular correlates of muscle spindle and Golgi tendon organ afferents.

Proprioceptive feedback mainly derives from groups Ia and II muscle spindle (MS) afferents and group Ib Golgi tendon organ (GTO) afferents, but the molecular correlates of these three afferent subtypes remain unknown. We performed single cell RNA sequencing of genetically identified adult proprioceptors and uncovered five molecularly distinct neuronal clusters. Validation of cluster-specific transcripts in dorsal root ganglia and skeletal muscle demonstrates that two of these clusters correspond to group Ia MS afferents and group Ib GTO afferent proprioceptors, respectively, and suggest that the remaining clusters could represent group II MS afferents. Lineage analysis between proprioceptor transcriptomes at different developmental stages provides evidence that proprioceptor subtype identities emerge late in development. Together, our data provide comprehensive molecular signatures for groups Ia and II MS afferents and group Ib GTO afferents, enabling genetic interrogation of the role of individual proprioceptor subtypes in regulating motor output.

Effect of tear supplements on signs, symptoms and inflammatory markers in dry eye.

PURPOSE: Three tear supplements were compared for their effects on the signs, symptoms and inflammatory status of subjects with dry eye disease. Assessments were made before and after both 2 and 4 weeks of treatment. METHODS: In this masked, randomized, 3-way crossover trial, eighteen dry eye subjects were recruited. At each visit, symptoms, tear evaporation rate, stability and osmolarity were measured and tear samples were analyzed for 7 inflammatory markers, using multiplex immunoassays. The 3 treatments included carboxymethylcellulose-glycerine-castor oil (CGC), carboxymethylcellulose (CMC) and hydroxypropyl guar (HPG). The CGC and HPG drops are emulsified lipids; CGC also contains osmoprotectants. The CMC drop is a standard aqueous polymeric supplement. RESULTS: Significant improvements were seen in symptoms (OSDI) and tear stability (NITBUT) with all 3 treatments at 4 weeks. At 4 weeks post-CGC, 6 out of 7 biomarkers demonstrated a >25% reduction (in 40% of subjects). The same reduction (>25%) was seen in 10% of the subjects for CMC and in none of the subjects for HPG. No significantly different change to either evaporation rate or tear osmolarity was found following any of the three treatments. CONCLUSIONS: In this study, the CGC treatment resulted in the greatest reduction in ocular biomarkers of inflammation, while all 3 treatments reduced symptoms and improved tear stability. These results indicate that subject-perceived symptomatic improvements are not necessarily associated with a reduction in objective measures of inflammation.

Lynx1 supports neuronal health in the mouse dorsal striatum during aging: an ultrastructural investigation.

Nicotinic acetylcholine receptors have been shown to participate in neuroprotection in the aging brain. Lynx protein modulators dampen the activity of the cholinergic system through direct interaction with nicotinic receptors. Although lynx1 null mutant mice exhibit augmented learning and plasticity, they also exhibit macroscopic vacuolation in the dorsal striatum as they age, detectable at the optical microscope level. Despite the relevance of the lynx1 gene to brain function, little is known about the cellular ultrastructure of these age-related changes. In this study, we assessed degeneration in the dorsal striatum in 1-, 3-, 7-, and 13-month-old mice, using optical and transmission electron microscopy. We observed a loss of nerve fibers, a breakdown in nerve fiber bundles, and a loss of neuronal nuclei in the 13-month-old lynx1 null striatum. At higher magnification, these nerve fibers displayed intracellular vacuoles and disordered myelin sheaths. Few or none of these morphological alterations were present in younger lynx1 null mutant mice or in heterozygous lynx1 null mutant mice at any age. These data indicate that neuronal health can be maintained by titrating lynx1 dosage and that the lynx1 gene may participate in a trade-off between neuroprotection and augmented learning.

Dendritic cells and HNSCC: a potential treatment option? (Review).

Patient survival in head and neck squamous cell cancer (HNSCC) has not changed significantly in many years, despite progress in surgical, radiotherapy and chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer treatment, aims to prompt or assist the body's immune system to combat the disease itself. A number of strategies exist including the use of dendritic cells, natural antigen presenting cells capable of stimulating an anti-tumor immune response. Encouraging work has been performed using these cells as vaccines against a number of tumors especially melanoma. Work with head and neck cancer is also encouraging, but less advanced. Dendritic cell presence in head and neck squamous cell cancers is associated with an improved prognosis, however due to immunosuppression, the exact mechanism of which remains poorly understood, these cells do not function efficiently. This prevents the stimulation of an effective anti-tumor immune response by the patient and allows tumor growth to continue. This review summarises the current level of understanding of dendritic cells and their relationship with HNSCC. It briefly summarises work with dendritic cells and other cancers where relevant to HNSCC; dendritic cells and head and neck cancer; the possible causes of dendritic cell impairment; the techniques used to restore their function and the methods used to prime the dendritic cells prior to their use as vaccines for the stimulation of an anti-tumor response.

Effect of hyperopic photorefractive keratectomy on corneal sensitivity: a longitudinal study.

PURPOSE: To investigate corneal sensitivity after photorefractive keratectomy (PRK) for low hyperopia, as measured with a non-invasive stimulus. METHODS: Two experimental groups were recruited: a control group of 17 patients (mean age 61.65 years) who underwent no treatment, and a PRK group of 11 patients (mean age 58.64 years) who underwent one of three attempted hyperopic corrections: +2.00 D (two patients), +3.00 D (four patients), +4.00 D (five patients). Corneal sensitivity was assessed centrally and peripherally, at temporal, medial, and inferior locations, approximately 1 mm from the limbus, using the Non-Contact Corneal Aesthesiometer (NCCA). Measurements were taken at each location for the control group and at preoperative, and postoperative weeks 1 and 2, 1, 3, and 6 months for the PRK group. RESULTS: Comparison of control and PRK groups (preoperative sensation threshold) (t-test): central P=.715, temporal P=.719, medial P=.943, inferior P= .920. Comparison of longitudinal changes in PRK group (one-way ANOVA): central P=.612, temporal P=.997, medial P=.981, inferior P=.993. CONCLUSIONS: Using the Non-Contact Corneal Aesthesiometer, no significant difference was found between the control and PRK groups for preoperative sensation thresholds, and no significant change in corneal sensitivity was found between any of the test time periods at any of the four corneal test locations for the PRK group.