Rare occult macular dystrophy with a pathogenic variant in the RP1L1 gene in a patient of Swiss descent

Purpose: We report a first case of bilateral occult macular dystrophy (OMD) with a c.133C>T (p.Arg45Trp) pathogenic variant in the retinitis pigmentosa 1-like 1 (RP1L1) gene in a patient of Caucasian Swiss decent. Observations: A 34-year-old man presented with decreased visual acuity known since childhood. Fundus examination of both eyes revealed no pathology other than mildly increased granularity of the foveal retinal pigment epithelium. The full-field electroretinogram (ffERG) presented with normal findings while the multifocal electroretinogram (mfERG) showed severely reduced amplitudes of the foveal response. Optical coherence tomography (OCT) showed foveal outer retinal atrophy. Fundus autofluorescence (FAF) imaging demonstrated near-normal findings with minimal mottling at the posterior pole. The genetic analysis revealed a heterozygous pathogenic variant (c.133C>T, p.Arg45Trp) in the RP1L1 gene. Conclusion and importance: Our present case suggests that OMD shows a wide range of clinical presentations with a variety of ophthalmological findings, age of disease onset, visual acuity, and genetic diversity

ESTUDIO PRELIMINAR ETNOBOTÁNICO, FITOQUÍMICO, DE LA ACTIVIDAD CITOTÓXICA Y ANTIMICROBIANA DE CUPHEA AEQUIPETALA CAV. (LYTHRACEAE)

The leaves and stems of the Mexican herbCuphea aequipetala Cav. have been usedempirically to treat bruises, diarrhea, stomach ailments and goiters; for postpartum orhip baths; to disinfect wounds; to lower thefever associated with measles and smallpox;for tumors and skin wounds of difficult cicatrization; and to counter hair fall. In this workwe showed the presence of alkaloids, flavonoids and glycosides in the methanolicand ethyl acetate extracts of the plant; glucosides were also found in the hexanic extract, whereas sesquiterpene lactones wereonly found in the methanolic fraction, whichshowed small cytotoxic activity against cervix carcinoma cells (UISO-SQC1). The otherextracts did not show cytotoxic activityagainst nasopharingeal (KB) and colon cancer cells (HCT-15, coladcar).The antimicrobial assays did not exhibit significant inhibition against bacteria and yeastcultures compared to common antibiotics.The results showed positive biological ac- tivity, but we cannot make definitive conclusions about their pharmacological activity without expanding these assays to coverspecimens obtained from different localitiesin the country.Cuphea aequipetala es una especiemexicana, de forma herbácea, cuyas hojas ytallos han sido empleados empíricamenteen el tratamiento de golpes, diarreas,padecimientos estomacales, paperas, ba-ños posparto; para lavar lesiones, disminuirla fiebre en sarampión, viruela y otrasenfermedades, en tumores y heridascutáneas de difícil cicatrización y contra lacaída del cabello. En este estudio, sedemostró la presencia de: alcaloides,flavonoides y glucósidos en las fraccionesmetanólica y de acetato de etilo. Losglicósidos también se encontraron en lafracción hexánica, mientras que las lactonassesquiterpénicas sólo fueron encontradasen la porción metabólica, la que mostró ligeraacción citotóxica sobre la línea celular de cáncer de cérvix [cuello uterino] (UISOSQC1). Los demás extractos no mostraronninguna actividad citotóxica, sobre laslíneas: carcinoma nasofaríngeo (KB) y decolon (HCT-15 Coladcar). Las pruebasde eficacia antimicrobiana no exhibieroninhibición significativa en cultivos debacilos, cocos y levaduras. Los resultadospreliminares indican actividad biológicapositiva, por lo que se recomienda continuarestos estudios con material proveniente dediferentes localidades

Relation of Pupil Size and retinal diseases

Purpose: The aim of this study was to evaluate differences in pupil size of subjects with diabetes mellitus, age-related macular degeneration and retinal vein occlusion at different illumination levels with a novel pupilometer. Methods: The pupil size of study participants was measured with an infrared-video pupillometer (PupilX, Albomed) at 5 different illumination levels (0, 0.5, 4, 32 and 250 lux). Measurements were performed by the same investigator. 90 images were executed during a measurement period of 3 seconds. Results: This cross-sectional study analysed 484 eyes of 242 patients with diabetes mellitus (DM), age-related macular degeneration (AMD) and retinal vein occlusion (RVO); mean age 73.8 ± 12 years, range 45-92 years. A healthy control group had 342 eyes, mean age 61.4 ± 12.5 years, range 40-87 years. There was a statistically significant smaller pupil size at the DM-group in comparison to AMD, RVO and control group at all illumination levels, except 250 lux (p=0.041, Kruskal Wallis test). There was no statistically significant difference in pupil size of RVO and AMD in comparison to the control group. Conclusion: This study provides comparative data for pupil size at different retinal diseases at different illumination conditions measured with PupilX. Pupil size in diabetic patients was significantly smaller at scotopic and mesopic illuminance conditions. Therefore we confirm using pupillometry as a noninvasive and simple tool for additive detection of autonomic dysfunction in diabetes mellitus

Tetrode recording of local neuronal ensembles provides insight into coding mechanisms of short-term memory in macaque prefrontal cortex

As most cortical neurons are broadly tuned to various stimulus parameters, it is inevitable that individual neurons participate in the representation of more than one visual object. Vice versa, accurate representations of individual objects for example in short-term memory that can support reliable decisions require the participation of large neuronal populations. To provide evidence in favor of population codes, we have recently analyzed simultaneously recorded multi- and single-unit signals derived from arrays of single-ended microelectrodes (Waizel et al., SfN 2007). Multi-contact electrodes like tetrodes (tts) which have a real 3D-structure provide signals that allow for estimating the position of the recorded neurons by triangulation. Here we set out to study whether recording from 3D-tts would improve the quality of sorting and hence allow for the extraction of more information about the stimulus. Based on single trial firing rate values, we calculated one-way ANOVAs at 1 significance thresholds and performed subsequent posthoc comparison (Scheffé) in order to detect stimulus selectivity and determine stimulus specificity for the activity at each single site, respectively. In order to investigate the coding of distributed neuronal ensembles, we computed binary activity patterns for all active electrodes in the array and determined their stimulus selectivity and specificity. Compared to what we found previously in single microelectrode recordings, the number of object selective or even specific recording sites increased up to 3 times which provides highly specific sites in 3 out of 4 sessions (3000 trials, 13.5 million spikes). Given that our monkeys always performed the memory task with a set of twenty visual stimuli, we found highly specific sites coding for only one object which revealed up to 18 of 19 possible pairwise comparisons. According to the proposal that single neurons participate in more than one specific object representation we also found bi- or even tri-object-dependant sites (average 27 significant pairwise comparisons per session) and never non-systematic object specificity. As clusters of triangulation-reconstructed spikes tend to have inter-cluster regions with smooth transitions which could potentially reflect synchronous spikes, we wanted to know how much information could be carried by these signals. After removing spikes between clusters, we found object specificity highly decreased (in one session only 6 out of previous 38 significant pairwise comparisons remained). These results suggest that the use of tetrodes with a real 3D-structure provides more information about neuronal object representations

Splitting local ensembles by spike-sorting degrades the quality of neuronal object representations in macaque prefrontal cortex

As most cortical neurons are broadly tuned to various stimulus parameters, accurate representations of individual objects in short-term memory that can support the monkey’s decision need to be based on the activity of neuronal ensembles. We have in the past (Städtler et al., SfN 2006) analyzed simultaneously recorded multi-unit signals and found to our surprise that stimulus selectivity at individual sites was higher than what had been published for single units. We had expected that a signal that consists of the activity of several neurons should provide less selectivity because combining broadly tuned activity should result in even broader tuning by blurring. In order to test whether splitting up the multi-unit signal improves or degrades stimulus selectivity, we sorted multi-unit activity from 97 sites by means of semi-automatic PCA-based clustering (Chen et al., in prep.) into 413 sorted units. As for the multi-unit analysis, we calculated one-way ANOVAs (p<0.01) to detect stimulus selectivity and determined stimulus specificity by subsequent posthoc comparison (Scheffé). Only 11.6 of responsive sorted-units exhibited object-selective responses compared to 18.6 of responsive multi-units. Even more detrimental was the effect of sorting on stimulus specificity: only 2.9 of sorted units allowed for the discrimination of objects compared to 7.2 of the unsorted multi-unit signals. If this result is not due to a problem with detectability of weak signals, it suggests that the selectivity of local ensembles might be caused by coordination of their members. However, before we can directly address this possibility we need to improve our spike sorting methods such that temporally overlapping spike waveforms can unequivocally assigned to subsets of local neurons. For the time being we asked whether selectivity and specificity of distributed activity patterns based on sorted units combined across sites would profit from the contribution of a larger number of units, the prediction being that more independent signals could in principle provide more differentiating patterns. We therefore calculated binary activity patterns derived from epochs with a significant difference in firing rate compared to baseline. Distributed patterns of sorted activity provided a lower percentage of distinguishable patterns than the same analysis revealed for multi-unit signals. These results show that decomposition of local ensemble activity has direct impact on the quality of stimulus representations which in turn suggests that stimulus coding in the short-term memory of prefrontal cortex seems to depend on the coordinated activity of neuronal populations

Prefrontal firing rates reflect the number of stimuli processed for visual short-term memory

The way a system reacts to increased task demands can reveal information about its functional mechanism. We therefore assessed the question how non human primates process information about visual stimuli by driving two rhesus monkeys to their cognitive limits in a visual memory task. The monkeys were first trained to successfully perform the visual memory task (> 80 correct responses). Then the number of stimuli shown to the monkey (load) was increased to up to 4. The stimulus presentation period (SP) was 900 milliseconds long. Thus, in the load 4 condition each single stimulus was only shown for less than 225ms. After a three second delay period, a test stimulus was shown. The task of the monkey was then to decide via differential button press, whether the test stimulus matched any of the previously shown stimuli. Neuronal firing rates were recorded using up to 16 multi electrodes placed in the prefrontal cortex. For every trial in which the monkey responded correctly, the average multi unit rate during the SP was estimated. We then assessed the question whether the firing rates in the SP during the distinct load conditions were significantly different. To minimize the effect of non-stationarities present in the data, we paired the data so that the trials of one pair were maximally 2.5 minutes apart. We tested against the null-hypothesis that the firing rates during the SP did not differ significantly among the load conditions using the nonparametric Friedman-test for paired data. For every recording site where we could reject the null-hypothesis (p<0.05), we investigated in which direction the rates of the different load conditions differed, correcting for multiple tests using the Tukey-Kramer-correction. A total of 12681 correct trials were recorded with a total of 160 recording positions (6 to 16 per session). In total, 23 positions showed significant effects from which 20 were consistent. The firing rate differences were called consistent if the difference compared to load 1 were stronger the higher the load. Out of these 20 consistent recording sites 14 showed a firing rate which monotonically increased with the load, 6 showed a monotonous decrease. This means that 12 of the recording sites in prefrontal cortex show a significant modulation of firing rates with respect to the load condition during a delayed match to sample task. However this modulation is not necessarily excitatory. Interestingly, it seems that the majority of sites showed a load-consistent modulation i.e. the higher the load, the stronger the modulation. This could be a possible mechanism to code the number of stimuli or their sequence