The ventrolateral medulla and medullary raphe in sudden unexpected death in epilepsy

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by post-ictal central respiratory depression, which could relate to underlying pathology in key respiratory nuclei and/or their neuromodulators. Our aim was to investigate neuronal populations in the ventrolateral medulla (which includes the putative human pre-Bötzinger complex) and the medullary raphe. Forty brainstems were studied comprising four groups: 14 SUDEP, six epilepsy controls, seven Dravet syndrome cases and 13 non-epilepsy controls. Serial sections through the medulla (from obex 1 to 10 mm) were stained for Nissl, somatostatin, neurokinin 1 receptor (for pre-Bötzinger complex neurons) and galanin, tryptophan hydroxylase and serotonin transporter (neuromodulatory systems). Using stereology total neuronal number and densities, with respect to obex level, were measured. Whole slide scanning image analysis was used to quantify immunolabelling indices as well as co-localization between markers. Significant findings included reduction in somatostatin neurons and neurokinin 1 receptor labelling in the ventrolateral medulla in sudden death in epilepsy compared to controls (P < 0.05). Galanin and tryptophan hydroxylase labelling was also reduced in sudden death cases and more significantly in the ventrolateral medulla region than the raphe (P < 0.005 and P < 0.05). With serotonin transporter, reduction in labelling in cases of sudden death in epilepsy was noted only in the raphe (P ≤ 0.01); however, co-localization with tryptophan hydroxylase was significantly reduced in the ventrolateral medulla. Epilepsy controls and cases with Dravet syndrome showed less significant alterations with differences from non-epilepsy controls noted only for somatostatin in the ventrolateral medulla (P < 0.05). Variations in labelling with respect to obex level were noted of potential relevance to the rostro-caudal organization of respiratory nuclear groups, including tryptophan hydroxylase, where the greatest statistical difference noted between all epilepsy cases and controls was at obex 9-10 mm (P = 0.034), the putative level of the pre-Bötzinger complex. Furthermore, there was evidence for variation with duration of epilepsy for somatostatin and neurokinin 1 receptor. Our findings suggest alteration to neuronal populations in the medulla in SUDEP with evidence for greater reduction in neuromodulatory neuropeptidergic and mono-aminergic systems, including for galanin, and serotonin. Other nuclei need to be investigated to evaluate if this is part of more widespread brainstem pathology. Our findings could be a result of previous seizures and may represent a pathological risk factor for SUDEP through impaired respiratory homeostasis during a seizure

Rockfall Hazard Assessment for Access Road to dam “Sveta Petka” using Rockfall Hazard Rating System (RHRS)

Large number of roads in our country are constructed in mountainous and hilly terrains. Execution of cuts in the hard rock masses is inevitable. In light of the geological nature of the rocks, processes like rockfalls and landslides in different forms and magnitude are very usual. They occur during construction activities and afterwards in exploitation of the roads. Correct protective measures must be undertaken in order to secure the safety of traffic and people using this roads. One such case is the access road to Dam “Sv.Petka”, where constant rockfalls, result of great rupture tectonics and steep cut angles built in marbly limestones, endanger the safety of traffic and construction workers using this road. In order to stress out the hazard invoked by rockfalls and the need of protective measures, we used the well established Rockfall Hazard Rating System (RHRS). Posted speed limit has great influence. Along other possibilities that this method offers is the planning of annual programs for protection measures, with separation of most dangerous zones according the classification, before any undertaking of geotechnical analyses of slope stability. Further software modeling is needed in order to get a better understanding of the nature of rockfalls

The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development

The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is not fully understood. Cln7, a major facilitator superfamily domain-containing protein, is affected in a late infantile-onset form of NCL. Cln7 is conserved across species suggesting a common function. Here we demonstrate that Cln7 is required for the normal growth of synapses at the Drosophila larval neuromuscular junction. In a Cln7 mutant, synapses fail to develop fully leading to reduced function and behavioral changes with dysregulation of TOR activity. Cln7 expression is restricted to the post-synaptic cell and the protein localizes to vesicles immediately adjacent to the post-synaptic membrane. Our data suggest an involvement for Cln7 in regulating trans-synaptic communication necessary for normal synapse development

Adult adjustment of survivors of institutional child abuse in Ireland

Method Two hundred and forty-seven adult survivors of institutional abuse with a mean age of 60 were interviewed with a protocol that included the Childhood Trauma Questionnaire, modules from the Structured Clinical Interview for Axis I Disorders of DSM IV and the Structured Clinical Interview for DSM IV Personality Disorders, the Trauma Symptom Inventory, and the Experiences in Close Relationships Inventory. Results The prevalence of psychological disorders among adult survivors of institutional abuse was over 80% and far higher than in the normal population, with anxiety, mood and substance use disorders being the most prevalent diagnoses. Survivors also had high rates of trauma symptoms and insecure adult attachment styles, and these were higher for those who had experienced both institutional and intrafamilial abuse. Conclusions There was an association between the experience of institutional abuse in childhood and the prevalence of adult mental health problems, particularly anxiety, mood and substance use disorders. Practice implications Policies, practices and procedures should be regularly reviewed and revised to maximize protection of young people in institutional care. Evidence-based psychological treatment should be made available to adult survivors of institutional abuse.Commission to Inquire into Child AbuseAuthor has checked copyrightDM, 12/12/201