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1.
Proc Natl Acad Sci U S A ; 119(20): e2117184119, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35549552

ABSTRACT

Gaze understanding­a suggested precursor for understanding others' intentions­requires recovery of gaze direction from the observed person's head and eye position. This challenging computation is naturally acquired at infancy without explicit external guidance, but can it be learned later if vision is extremely poor throughout early childhood? We addressed this question by studying gaze following in Ethiopian patients with early bilateral congenital cataracts diagnosed and treated by us only at late childhood. This sight restoration provided a unique opportunity to directly address basic issues on the roles of "nature" and "nurture" in development, as it caused a selective perturbation to the natural process, eliminating some gaze-direction cues while leaving others still available. Following surgery, the patients' visual acuity typically improved substantially, allowing discrimination of pupil position in the eye. Yet, the patients failed to show eye gaze-following effects and fixated less than controls on the eyes­two spontaneous behaviors typically seen in controls. Our model for unsupervised learning of gaze direction explains how head-based gaze following can develop under severe image blur, resembling preoperative conditions. It also suggests why, despite acquiring sufficient resolution to extract eye position, automatic eye gaze following is not established after surgery due to lack of detailed early visual experience. We suggest that visual skills acquired in infancy in an unsupervised manner will be difficult or impossible to acquire when internal guidance is no longer available, even when sufficient image resolution for the task is restored. This creates fundamental barriers to spontaneous vision recovery following prolonged deprivation in early age.


Subject(s)
Fixation, Ocular , Vision, Ocular , Attention , Blindness , Child , Humans , Visual Acuity
2.
J Neurosci Res ; 101(3): 316-326, 2023 03.
Article in English | MEDLINE | ID: mdl-36434794

ABSTRACT

The effects of MgSO4 as an anti-inflammatory agent in pregnant women have been investigated in the last few years. Infections can cause an inflammatory reaction involving the placenta membranes and amniotic cavity. They may have short-term effects on the mother and her fetuses, like preterm birth, cerebral palsy, and developmental delay. Despite the alleged advantages of MgSO4 as a neuroprotective agent in the preterm brain, the long-term molecular and behavioral function of MgSO4 has not been fully elucidated. Here, we investigated the long-term effect of antenatal MgSO4 , during late gestation, on offspring's behavior focusing on cognitive function, motor activity, and social cognition in adolescence and adulthood, and explored its influence on brain gene expression (e.g., ErbB signaling, pro-inflammatory, and dopaminergic markers) in adulthood. A significant abnormal exploratory behavior of offspring of MgSO4 -treated dams was found compared to the control group in both adolescence and adulthood. Furthermore, we found that adult females exposed to MgSO4 under inflammation displayed working and recognition memory impairment. A reduction in IL-6 expression was detected in the prefrontal cortex, and hippocampus specimens derived from LPS-Mg-treated group. In contrast, an imbalanced expression of dopamine 1 and 2 receptors was detected only in prefrontal cortex specimens. Besides, we found that MgSO4 ameliorated the overexpression of the Nrg1 and Erbb4 receptors induced by LPS in the hippocampus. Thus, MgSO4 treatment for preventing brain injuries can adversely affect offspring cognition behavior later in life, depending on the sex and age of the offspring.


Subject(s)
Magnesium Sulfate , Premature Birth , Infant, Newborn , Animals , Pregnancy , Female , Humans , Magnesium Sulfate/pharmacology , Magnesium Sulfate/metabolism , Rodentia , Lipopolysaccharides/pharmacology , Brain/metabolism , Inflammation/metabolism
3.
Ophthalmic Physiol Opt ; 43(3): 337-346, 2023 05.
Article in English | MEDLINE | ID: mdl-36660882

ABSTRACT

PURPOSE: Ultra-Orthodox Jewish men are known to have a high prevalence of myopia, which may be due to intense near-work from an early age. This study objectively assessed near-viewing behaviours in ultra-Orthodox and non-ultra-Orthodox men in Israel for different tasks. METHODS: Ultra-Orthodox (n = 30) and non-ultra-Orthodox (n = 38) men aged 18-33 years participated. Autorefraction, visual acuity, height and Harmon distance were measured. An objective range-finding sensor was mounted on their spectacles while they performed four 10-min tasks in a randomised order: (1) reading printed material, (2) writing printed material, (3) passive electronic and (4) active electronic tasks. Near-viewing distance and the number of viewing breaks were calculated for each task. Statistical analyses included Student t-tests and the Mann-Whitney test between groups and repeated measures ANOVA or Friedman between tasks. RESULTS: For all tasks combined, a significantly shorter viewing distance was observed for the ultra-Orthodox group (36.2 ± 7.0 cm) than for the non-ultra-Orthodox group (39.6 ± 6.7 cm, p < 0.05). Viewing distances for the passive reading and electronic tasks were shorter for the ultra-Orthodox group (36.9 ± 7.7 cm vs. 41.3 ± 8.1 cm, p < 0.03 and 39.0 ± 10.1 vs. 43.9 ± 9.3, p < 0.05, respectively). Viewing distances were significantly different between all four tasks, with writing having the closest distance. No correlation was found between working distance and spherical equivalent or Harmon distance. However, a significant correlation was found in the ultra-Orthodox group between working distance and height for each task (p < 0.04, R < 0.42 for all). There was no difference in the number of viewing breaks between the groups. CONCLUSION: When reading a book and viewing an iPad, ultra-Orthodox men demonstrated a closer objective working distance than non-ultra-Orthodox men. This shorter viewing distance may contribute to the high prevalence and degree of myopia in this population.


Subject(s)
Jews , Myopia , Male , Humans , Myopia/therapy , Refraction, Ocular , Visual Acuity , Israel/epidemiology
4.
Int J Mol Sci ; 23(9)2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35563336

ABSTRACT

Stressful unpredictable life events have been implicated in numerous diseases. It is now becoming clear that some life periods are more vulnerable than others. As adolescence is a sensitive period in brain development, the long-term effects of stress during this period could be significant. We investigated the long-term effects of exposure to unpredictable chronic mild stress in adolescent mice on alternative splicing of Sirtuin 1. One-month-old mice were exposed to 4 weeks of UCMS and examined for anxiety and cognition at the age of 2, 4 and 6 months. We found a rise in anxious behavior immediately after the exposure to stress. Notably, there was a long-term impairment of performance in cognitive tasks and an imbalance in Sirtuin 1 and TrkB receptor alternative splicing in the stress-exposed mice compared with controls. To conclude, our results show that exposure to unpredictable chronic mild stress during adolescence affects cognition in adulthood. Understanding pathways affiliated with stress may help minimize the long-term emotional effects of an unpredictable, stressful event.


Subject(s)
Alternative Splicing , Sirtuin 1 , Stress, Psychological , Alternative Splicing/genetics , Alternative Splicing/physiology , Animals , Anxiety/genetics , Anxiety/metabolism , Cognition/physiology , Female , Mice , Sirtuin 1/genetics , Sirtuin 1/metabolism , Stress, Psychological/genetics , Stress, Psychological/metabolism
5.
Int J Mol Sci ; 23(16)2022 Aug 21.
Article in English | MEDLINE | ID: mdl-36012711

ABSTRACT

Alzheimer's disease (AD) is the most common form of dementia, but there is still no available treatment. Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus. We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC. The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Cognitive Dysfunction/drug therapy , Disease Models, Animal , Dronabinol/pharmacology , Dronabinol/therapeutic use , Mice , Mice, Transgenic , Receptor, trkB
6.
Optom Vis Sci ; 98(8): 959-970, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34387583

ABSTRACT

SIGNIFICANCE: Evidence supporting the contributions of near work in myopia is equivocal. Findings from this pilot study suggest that a high prevalence of myopia in ultra-Orthodox boys may be attributed to intense near work at school and learning to read in preschool at an early age. PURPOSE: This study aimed to assess factors that may influence myopia in three groups of Jewish boys with different educational demands. METHODS: Healthy ultra-Orthodox, religious, and secular Jewish boys (n = 36) aged 8 to 12 years participated. Refractive status, education, time spent reading and writing, and electronic device use were assessed using a questionnaire, and time outdoors and physical activity were assessed objectively using an Actiwatch. Data were analyzed with χ2 and Kruskal-Wallis tests with Bonferroni post hoc comparisons. RESULTS: Ultra-Orthodox (n = 14) and religious (n = 13) children had greater myopia prevalence compared with secular children (n = 9; P = .01), despite no differences in parental myopia. Actigraph data showed that there were no differences in activity (P = .52) or time spent outdoors (P = .48) between groups. Ultra-Orthodox children learned to read at a younger age and spent more hours at school (P < .001 for both). All groups engaged in a similar amount of near work while not in school (P = .52). However, ultra-Orthodox boys had less electronic device use than did religious (P = .007) and secular children (P < .001). CONCLUSIONS: This pilot study demonstrates that ultra-Orthodox, religious, and secular children have distinct educational demands but similar time outdoors, physical activity, and near work while not in school. The findings suggest that near work at school and/or learning to read in preschool at an early age may contribute to previously reported differences in refractive error between groups. However, conclusions should be confirmed in a larger sample size.


Subject(s)
Myopia , Child , Humans , Jews , Judaism , Male , Myopia/epidemiology , Pilot Projects , Vision Tests
7.
J Vis ; 15(8): 5, 2015.
Article in English | MEDLINE | ID: mdl-26057548

ABSTRACT

Young children are characterized by poor visual performances. Visual crowding, lateral interactions, and contour detection are critical functions for visual perception, context effect, and recognition that develop over the years up to maturity. The age at which the maturation's onset of the functions can be observed and the functions' underlying neural basis remain unclear. Here we used a development approach to investigate the onset of the foveal visual functions in order to learn about their neuronal basis and their relationships. We measured lateral interactions, crowding, and contour integration in participants aged 3-15 years. The results show that very young children do not exhibit collinear facilitation; rather, their vision is dominated by suppression and a high degree of crowding. Our results show sequential changes in the visual functions in parallel with the development of facilitation-that is, a significant reduction in crowding and an improved contour detection threshold. Our data suggest that the correlation between the onset age of maturation of collinear facilitation with crowding reduction and improvement of contour integration has underlying mutual neuronal mechanisms.


Subject(s)
Crowding , Form Perception/physiology , Pattern Recognition, Visual/physiology , Perceptual Masking/physiology , Adolescent , Child , Child, Preschool , Contrast Sensitivity/physiology , Female , Humans , Male , Visual Acuity/physiology , Visual Cortex/physiology
8.
Ageing Res Rev ; 99: 102349, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823488

ABSTRACT

Age-related cognitive and affective disorders pose significant public health challenges. Notably, emotional and cognitive symptoms co-occur across multiple age-associated conditions like normal aging, Alzheimer's disease (AD), and mood disorders such as depression and anxiety. While the intricate interplay underlying this relationship remains poorly understood, this article highlights the possibility that an imbalance between full-length (TrkB.FL) and truncated (TrkB.T1) isoforms of tyrosine kinase receptor TrkB in the neurotrophic system may significantly affect age-associated emotional and cognitive functions, by altering brain-derived neurotrophic factor (BDNF) signaling, integral to neuronal health, cognitive functions and mood regulation. While the contribution of this imbalance to pathogenesis awaits full elucidation, this review evaluates its potential mediating role, linking emotional and cognitive decline across age-related disorders The interplay between TrkB.T1 and TrkB.FL isoforms may be considered as a pivotal shared regulator underlying this complex relationship. The current review aims to synthesize current knowledge on TrkB isoform imbalance, specifically its contribution to age-related cognitive decline and mood disorders. By examining shared pathogenic pathways between aging, cognitive decline, and mood disorders through the lens of TrkB signaling, this review uncovers potential therapeutic targets not previously considered, offering a fresh perspective on combating age-related mental health issues as well as cognitive deficits.


Subject(s)
Aging , Cognitive Dysfunction , Receptor, trkB , Humans , Receptor, trkB/metabolism , Aging/metabolism , Aging/psychology , Aging/physiology , Cognitive Dysfunction/metabolism , Animals , Protein Isoforms/metabolism , Cognition/physiology , Emotions/physiology , Brain-Derived Neurotrophic Factor/metabolism
9.
J Optom ; 17(1): 100483, 2024.
Article in English | MEDLINE | ID: mdl-37797567

ABSTRACT

PURPOSE: To describe the performance of the Actiwatch Spectrum Plus (Philips, Respironics) for determining real world indoor and outdoor environments and physical activity in children. METHODS: Children wore the device while performing 10 different activities, ranging from sedentary to vigorous physical-activity, and under different indoor and outdoor conditions. Repeated measures ANOVA was implemented via mixed effects modeling to determine illuminance (lux) and physical activity (counts per 15 s, CP15) across conditions. Receiver operator characteristics (ROC) analysis assessed the accuracy to detect indoor versus outdoor settings. RESULTS: Illuminance was found to be statistically different across indoor (793 ± 348 lux) and outdoor (4,413 ± 518 lux) conditions (P<.0001), with excellent diagnostic accuracy to detect indoor versus outdoor settings (Area under the ROC Curve, AUC 0.94); 1088 lux was identified as the optimal threshold for outdoor illuminance (sensitivity: 93.0%; specificity: 85.0%). Using published activity ranges, we found that when children were sitting, 94% of the physical-activity readings were classified as sedentary or light. When children were walking, 88% of readings were classified as light, and when children were running, 77% of readings were classified as moderate or vigorous. CONCLUSION: The Actiwatch Spectrum Plus performed well during real world activities in children, showing excellent diagnostic accuracy at 1088 lux as a threshold to detect indoor versus outdoor environments and in categorizing physical activity.


Subject(s)
Exercise , Light , Child , Humans
10.
J Optom ; 16(3): 199-205, 2023.
Article in English | MEDLINE | ID: mdl-36400680

ABSTRACT

PURPOSE: Optometry education strives to develop competencies required for reflective practice in its pupils. The forced changes in academia during COVID-19 pandemic, rapid switching to online methods imposed serious challenges on the training of reflective skills. We hypothesize that the synchronous online sessions of case-based reflections are effective in imparting training for reflective practice in optometry students. METHODS: A prospective study was done with planned, synchronous, online, small group workshops for case-based reflections through the second year of optometry program during 'introduction to patient care' course. The reflective competencies were measured with a modified Groningen Reflection Ability Scale (GRAS) at the beginning and towards conclusion. Data was analysed with Mann-Whitney one tail test and qualitative thematic methods. RESULTS: Total of 104 students participated in the study. The aggregate score showed significant improvement (p<0.05) in students' reflective ability. A rising trend was seen in each component namely self-reflection, empathetic and communication reflections. DISCUSSIONS: The results demonstrate that the reflective skills can be developed using virtual patient experiences, case-based reflective practices conducted in synchronous small group workshops in online mode. Students perceived it as useful activity in developing themselves as healthcare professionals.


Subject(s)
COVID-19 , Education, Distance , Optometry , Humans , Pandemics , Prospective Studies , Students
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