Maternal smoking during pregnancy and long-term ophthalmic morbidity of the offspring.

OBJECTIVE: To examine whether smoking during pregnancy is correlated with long-term ophthalmic complications of the offspring. STUDY DESIGN: A population-based cohort analysis was performed comparing all deliveries of mothers who reported smoking during pregnancy and non-smoking mothers between 1991 and 2014 at a single tertiary medical center. Hospitalizations of the offspring up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan-Meier curve was used to compare cumulative hospitalization rate in exposed and unexposed offspring and a Cox proportional hazards model was used to control for confounders. RESULTS: During the study period, 243,680 deliveries met the inclusion criteria. Of them, 2965 (1.2%) were children of smoking mothers. Ophthalmic-related hospitalizations were significantly higher in children born to smoking mothers, as compared with the non-smoking group (1.4% vs. 0.1%, p < 0.01). Specifically, these hospitalizations were due to higher rates of visual disturbance rate and ophthalmic infections. The Kaplan-Meier curve demonstrated a significant higher cumulative incidence of ophthalmic-related hospitalizations in the smoking group (log rank p < 0.001). Using a Cox proportional hazards model, controlling for potential confounders, maternal tobacco use was found to be independently associated with long-term ophthalmic morbidity of the offspring (adjusted HR = 1.51, CI 1.11-2.04). CONCLUSION: Maternal smoking during pregnancy is an independent risk factor for long-term ophthalmic morbidity of the offspring. These results are in line with many recent studies that strongly support maternal smoking cessation during pregnancy due to high offspring morbidity risk.

Mild Cognitive Impairment and Neurofeedback: A Randomized Controlled Trial.

Background and Objectives: Mild cognitive impairment (MCI) is often a precursor of dementia, and in particular of Alzheimer's Disease (AD) which is the most common cause of dementia. Individuals with amnestic MCI are several-fold more likely to develop AD than the general population. Therefore, MCI comprises a well-detectable, early stage time-point for therapeutic intervention and strategic prevention. Based on common electroencephalographical (EEG) pattern changes seen in individuals with MCI, we postulated that EEG-based neurofeedback could help improve the memory performance of patients with MCI. Memory performance is of particular importance in these patients, since memory decline is the most prominent symptom in most patients with MCI, and is the most predictive symptom for cognitive deterioration and the development of AD. Methods: In order to improve the memory performance of patients with MCI we used a system of EEG-based neurofeedback in an attempt to reverse alterations of the EEG that are known to be common in patients with MCI. Our protocol comprised the provision of positive feedback in order to enhance the activity level of the upper alpha band. Participants were divided to two groups receiving either neurofeedback training to enhance the upper alpha frequency (Experimental group) or random feedbacks (Sham group) Results: We witnessed a significant improvement in memory performance in subjects in the experimental group compared to those in the sham group. This improvement was maintained for at least 1 month. Conclusions: Neurofeedback may be a promising and affordable novel approach for treating the decline in memory witnessed in patients with MCI.

Assisted reproductive technology and long-term ophthalmic morbidity of the offspring.

In this study, we investigate if children born following assisted reproduction technologies (ARTs) are at an increased risk for long-term ophthalmic complications. For this purpose, a population-based cohort analysis was conducted which included all deliveries between 1991 and 2014 at a single tertiary medical center. Offspring were classified relative to conception method as ART or spontaneous pregnancies. Offspring hospitalizations up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan-Meier survival curve was used to compare cumulative hospitalization rates in exposed (ART) and unexposed offspring (spontaneous), and a Cox proportional hazards model was used to control for potential confounders. A total of 243,682 deliveries were included in the study. In that, 1.8% of the deliveries (4364) were of mothers who underwent fertility treatments and 98.2% (239,318) were conceived spontaneously. Offspring born to mothers who underwent fertility treatments had a significantly higher hospitalization rate involving ophthalmic morbidity, as compared to spontaneously conceived offspring (1.2% vs. 1.0%, p = 0.04). The Kaplan-Meier survival curve pointed to a significantly higher cumulative incidence of ophthalmic morbidity following ART (log rank p = 0.02). Cox proportional hazards model was adjusted for maternal age, preterm delivery, maternal hypertensive disorders, diabetes, and mode of delivery which demonstrated ART as an independent risk factor for long-term pediatric ophthalmic morbidity (adjusted hazard ratio = 1.37, CI 1.04-1.80, p-value = 0.02). We concluded that ART is an independent risk factor for long-term ophthalmic morbidity of the offspring.

Neurofeedback Improves Memory and Peak Alpha Frequency in Individuals with Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is a syndrome characterized by a decrease in cognitive abilities, while daily function is maintained. This condition, which is associated with an increased risk for the development of Alzheimer's disease, has no known definitive treatment at present. In this open-label pilot study we explored the possible benefits of neurofeedback for subjects with MCI. Eleven participants diagnosed with MCI were trained to increase the power of their individual upper alpha band of the electroencephalogram (EEG) signal over the central parietal region. This was achieved using an EEG-based neurofeedback training protocol. Training comprised ten 30-min sessions delivered over 5 weeks. Cognitive and electroencephalographic assessments were conducted before and after training and at 30 days following the last training session. A dose-dependent increase in peak alpha frequency was observed throughout the period of training. Memory performance also improved significantly following training, and this improvement was maintained at 30-day follow-up, while peak alpha frequency returned to baseline at this evaluation. Our findings suggest that neurofeedback may improve memory performance in subjects with mild cognitive impairment, and this benefit may be maintained beyond the training period.

Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals.

Presynaptic terminals are specialized sites for information transmission where vesicles fuse with the plasma membrane and are locally recycled. Recent work has extended this classical view, with the observation that a subset of functional vesicles is dynamically shared between adjacent terminals by lateral axonal transport. Conceptually, such transport would be expected to disrupt vesicle retention around the active zone, yet terminals are characterized by a high-density vesicle cluster, suggesting that counteracting stabilizing mechanisms must operate against this tendency. The synapsins are a family of proteins that associate with synaptic vesicles and determine vesicle numbers at the terminal, but their specific function remains controversial. Here, using multiple quantitative fluorescence-based approaches and electron microscopy, we show that synapsin is instrumental for resisting vesicle dispersion and serves as a regulatory element for controlling lateral vesicle sharing between synapses. Deleting synapsin disrupts the organization of presynaptic vesicle clusters, making their boundaries hard to define. Concurrently, the fraction of vesicles amenable to transport is increased, and more vesicles are translocated to the axon. Importantly, in neurons from synapsin knock-out mice the resting and recycling pools are equally mobile. Synapsin, when present, specifically restricts the mobility of resting pool vesicles without affecting the division of vesicles between these pools. Specific expression of synapsin IIa, the sole isoform affecting synaptic depression, rescues the knock-out phenotype. Together, our results show that synapsin is pivotal for maintaining synaptic vesicle cluster integrity and that it contributes to the regulated sharing of vesicles between terminals.

Inhibition of exocytosis or endocytosis blocks activity-dependent redistribution of synapsin.

The synaptic vesicle cycle encompasses the pre-synaptic events that drive neurotransmission. Influx of calcium leads to the fusion of synaptic vesicles with the plasma membrane and the release of neurotransmitter, closely followed by endocytosis. Vacated release sites are repopulated with vesicles which are then primed for release. When activity is intense, reserve vesicles may be mobilized to counteract an eventual decline in transmission. Recently, interplay between endocytosis and repopulation of the readily releasable pool of vesicles has been identified. In this study, we show that exo-endocytosis is necessary to enable detachment of synapsin from reserve pool vesicles during synaptic activity. We report that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity-dependent redistribution of synapsin from the pre-synaptic terminal into the axon. Likewise, perturbation of endocytosis with dynasore or by a dynamin dominant-negative mutant fully prevents synapsin redistribution. Such inhibition of synapsin redistribution occurred despite the efficient phosphorylation of synapsin at its protein kinase A/CaMKI site, indicating that disengagement of synapsin from the vesicles requires exocytosis and endocytosis in addition to phosphorylation. Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool.