An in vitro model of nociceptors in human trigeminal nerves

Background: The oro-facial region is densely innervated by the trigeminal nerve, which when stimulated can induce noxious pain sensation and contribute to neurogenic inflammation in local tissues. Recent research on the expression of specialised ion channels on the trigeminal nerve has highlighted the need to undertake more extensive studies on ion channel expression/functionality with the aim of elucidating their role in pain sensations. A major family of such ion channels is the transient receptor potential (TRP) channels which are activated by a wide variety of thermal, mechanical or chemical stimuli and merit investigation as possible druggable targets for future analgesics. <br/>Objective: Study of TRP channel expression and regulation in oro-facial tissues is hindered by the fact that the cell bodies of neurons innervating these tissues are located in the trigeminal ganglion. Using dental pulp stem cells differentiated towards peripheral neuronal equivalents (PNEs), we sought to determine TRP channel expression, functionality and potential modulation by cytokines in this novel model. <br/>Method: Dental pulp stem cells (DPSCs) were grown on substrate-coated tissue culture plates and differentiated towards a neuronal phenotype using neuronal induction media. Quantitative polymerase chain reaction (qPCR) was performed on PNEs +/-cytokine treatment. Ion channel functionality was investigated using whole cell patch clamping. <br/>Result: qPCR analysis showed that PNEs expressed the TRP channels TRPA1, TRPV1, TRPV4 and TRPM8. TRPA1 was the most abundantly expressed TRP channel studied whereas TRPM8 was lowly expressed. TRP channel expression was shown to be regulated by treatment with inflammatory cytokines. Patch clamp studies using specific agonists and antagonists for TRPA1 and TRPV1 showed these channels were functional. <br/>Conclusion: PNEs differentiated from DPSCs provide a suitable model for TRP channel expression, regulation, and sensistisation in oro-facial tissues. This human neuronal model has potential for use in pre-clinical studies of novel analgesics.<br/>

Age, gender, biometry, refractive error, and the anterior chamber angle among Alaskan Eskimos.

BACKGROUND: <br/><br/>The prevalence of angle-closure glaucoma (ACG) is greater for Eskimos/Inuit than it is for any other ethnic group in the world. Although it has been suggested that this prevalence may be due to a population tendency toward shallower anterior chamber angles, available evidence for other populations such as Chinese with high rates of ACG has not consistently demonstrated such a tendency.<br/><br/>METHODS: <br/><br/>A reticule, slit-lamp, and standard Goldmann one-mirror goniolens were used to make measurements in the anterior chamber (AC) angle according to a previously reported protocol for biometric gonioscopy (BG) (Ophthalmology 1999;106:2161-7). Measurements were made in all four quadrants of one eye among 133 phakic Alaskan Eskimos aged 40 years and older. Automatic refraction, dilated examination of the anterior segment and optic nerve, and A-scan measurements of AC depth, lens thickness, and axial length were also carried out for all subjects.<br/><br/>RESULTS: <br/><br/>Both central and peripheral AC measurements for the Eskimo subjects were significantly lower than those previously reported by us for Chinese, blacks, and whites under the identical protocol. Eskimos also seemed to have somewhat more hyperopia. There were no differences in biometric measurements between men and women in this Eskimo population. Angle measurements by BG seemed to decline more rapidly over life among Eskimos and Chinese than blacks or whites. Although there was a significant apparent decrease in AC depth, increase in lens thickness, and increase in hyperopia with age among Eskimos, all of these trends seemed to reverse in the seventh decade and beyond.<br/><br/>CONCLUSIONS: <br/><br/>Eskimos do seem to have shallower ACs than do other racial groups. Measurements of the AC angle seem to decline more rapidly over life among Eskimos than among blacks or whites, a phenomenon also observed by us among Chinese, another group with high ACG prevalence. This apparent more rapid decline may be due to a cohort effect with higher prevalence of myopia and resulting wider angles among younger Eskimos and Chinese.<br/>

Traffic gap judgment in people with significant peripheral field loss.

PURPOSE: Subjects with significant peripheral field loss (PFL) self report difficulty in street crossing. In this study, we compared the traffic gap judgment ability of fully sighted and PFL subjects to determine whether accuracy in identifying crossable gaps was adversely affected because of field loss. Moreover, we explored the contribution of visual and nonvisual factors to traffic gap judgment ability. METHODS: Eight subjects with significant PFL as a result of advanced retinitis pigmentosa or glaucoma with binocular visual field &lt;20 degrees and five age-matched normals (NV) were recruited. All subjects were required to judge when they perceived it was safe to cross at a 2-way 4-lane street while they stood on the curb. Eye movements were recorded by an eye tracker as the subjects performed the decision task. Movies of the eye-on-scene were made offline and fixation patterns were classified into either relevant or irrelevant. Subjects' street-crossing behavior, habitual approach to street crossing, and perceived difficulties were assessed. RESULTS: Compared with normal vision (NV) subjects, the PFL subjects identified 12% fewer crossable gaps while making 23% more errors by identifying a gap as crossable when it was too short (p &lt; 0.05). The differences in traffic gap judgment ability of the PFL subjects might be explained by the significantly smaller fixation area (p = 0.006) and fewer fixations distributed to the relevant tasks (p = 0.001). The subjects' habitual approach to street crossing and perceived difficulties in street crossing (r &gt; 0.60) were significantly correlated with traffic gap judgment performance. CONCLUSIONS: As a consequence of significant field loss, limited visual information about the traffic environment can be acquired, resulting in significantly reduced performance in judging safe crossable gaps. This poor traffic gap judgment ability in the PFL subjects raises important concerns for their safety when attempting to cross the street.

Heritability of peripheral refraction in Chinese children and adolescents: the Guangzhou Twin Eye study.

PURPOSE: <br/><br/>To estimate the heritability of peripheral refraction in Chinese children and adolescents.<br/><br/>METHODS: <br/><br/>The authors examined 72 monozygotic (MZ) twins and 48 dizygotic (DZ) twins aged 8 to 20 years from a population-based twin registry. Temporal and nasal peripheral refraction, each 40° from the visual axis, and axial refraction were measured using an autorefractor. Relative peripheral refractive error (RPRE) was defined as the peripheral refraction minus the axial refraction. Heritability was assessed by structural equation modeling after adjustment for age and sex.<br/><br/>RESULTS: <br/><br/>The mean and SD of temporal refraction (T(40)), nasal refraction (N(40)), RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were -0.27 ± 2.0 D, 0.36 ± 2.19 D, 1.18 ± 1.39 D, 1.80 ± 1.69 D, and -0.62 ± 1.58 D, respectively. The intraclass correlations for T(40) refraction, N(40) refraction, RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were 0.87, 0.83, 0.65, 0.74, and 0.58 for MZ pairs and 0.49, 0.42, 0.30, 0.41, and 0.32 for DZ pairs, respectively. A model with additive genetic and unique environmental effects was the most parsimonious, with heritability values estimated as 0.84, 0.76, 0.63, 0.70, and 0.55, respectively, for the peripheral refractive parameters.<br/><br/>CONCLUSIONS: <br/><br/>Additive genetic effects appear to explain most of the variance in peripheral refraction and relative peripheral refraction when adjusting for the effects of axial refraction.<br/>

Rocking behaviour of multi-block columns subjected to pulse-type ground motion accelerations

Ancient columns, made with a variety of materials such as marble, granite, stone or masonry are an important part of the<br/>European cultural heritage. In particular columns of ancient temples in Greece and Sicily which support only the architrave are<br/>characterized by small axial load values. This feature together with the slenderness typical of these structural members clearly<br/>highlights as the evaluation of the rocking behaviour is a key aspect of their safety assessment and maintenance. It has to be noted<br/>that the rocking response of rectangular cross-sectional columns modelled as monolithic rigid elements, has been widely investigated<br/>since the first theoretical study carried out by Housner (1963). However, the assumption of monolithic member, although being<br/>widely used and accepted for practical engineering applications, is not valid for more complex systems such as multi-block columns<br/>made of stacked stone blocks, with or without mortar beds. In these cases, in fact, a correct analysis of the system should consider<br/>rocking and sliding phenomena between the individual blocks of the structure. Due to the high non-linearity of the problem, the<br/>evaluation of the dynamic behaviour of multi-block columns has been mostly studied in the literature using a numerical approach<br/>such as the Discrete Element Method (DEM). This paper presents an introductory study about a proposed analytical-numerical<br/>approach for analysing the rocking behaviour of multi-block columns subjected to a sine-pulse type ground motion. Based on the<br/>approach proposed by Spanos (2001) for a system made of two rigid blocks, the Eulero-Lagrange method to obtain the motion<br/>equations of the system is discussed and numerical applications are performed with case studies reported in the literature and with a<br/>real acceleration record. The rocking response of single block and multi-block columns is compared and considerations are made<br/>about the overturning conditions and on the effect of forcing function’s frequency.<br/>.