Slow GABAA mediated synaptic transmission in rat visual cortex

<p>Abstract</p> <p>Background</p> <p>Previous reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABA_Areceptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABA_Aresponses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABA_Areceptor mediated inhibitory postsynaptic currents (IPSCs). These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABA_AIPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex.</p> <p>Results</p> <p>GABA_Aslow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABA_Aslow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABA_Asubunit-specific antagonist, furosemide, depressed spontaneous and evoked GABA_Afast IPSCs, but not slow GABA_A-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABA_Afast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components.</p> <p>Conclusion</p> <p>GABA_Aslow IPSCs displayed durations that were approximately 4 fold longer than typical GABA_Afast IPSCs, but shorter than GABA_B-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABA_Aslow IPSCs into computational models of cortical function will help improve our understanding of cortical information processing.</p

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children &lt;18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p&lt;0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p&lt;0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p&lt;0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Laminar and Dorsoventral Molecular Organization of the Medial Entorhinal Cortex Revealed by Large-scale Anatomical Analysis of Gene Expression

Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations

Isolated posterior capsular rupture following blunt head trauma

Ahmad M Mansour, Mahmoud O Jaroudi, Rola N Hamam, Fadi C Maalouf Department of Ophthalmology, American University of Beirut, Beirut, Lebanon Abstract: Closed-globe traumatic cataract is not uncommon in males in the pediatric age group. However, there is a relative paucity of literature on isolated posterior lens capsule rupture associated with closed-globe traumatic cataract. We report a case of a 6-year-old boy who presented with white cataract 1 day after blunt trauma to the forehead associated with posterior capsular rupture that was detected by B-scan ultrasonography preoperatively. No stigmata of trauma outside the posterior capsule could be detected by slit-lamp exam, funduscopy, and optical coherence tomography. Phacoemulsification with posterior chamber intraocular lens implant was performed 24 hours after trauma, with the patient achieving 6/6 visual acuity 1 week and 6&nbsp;months after surgery. Our case is unique, being the youngest (amblyogenic age) to be reported, with prompt surgical intervention, and with no signs of trauma outside the posterior capsule. Keywords: posterior capsule rupture, forehead trauma, traumatic cataract, pediatric catarac

Membrane fluxes, bypass flows, and sodium stress in rice: the influence of silicon

Provision of silicon (Si) to roots of rice (Oryza sativa L.) can alleviate salt stress by blocking apoplastic, transpirational bypass flow of Na+ from root to shoot. However, little is known about how Si affects Na+ fluxes across cell membranes. Here, we measured radiotracer fluxes of 24Na+, plasma membrane depolarization, tissue ion accumulation, and transpirational bypass flow, to examine the influence of Si on Na+ transport patterns in hydroponically grown, salt-sensitive (cv. IR29) and salt-tolerant (cv. Pokkali) rice. Si increased growth and lowered [Na+] in shoots of both cultivars, with minor effects in roots; neither root nor shoot [K+] were affected. In IR29, Si lowered shoot [Na+] via a large reduction in bypass flow, while in Pokkali, where bypass flow was small and not affected by Si, this was achieved mainly via a growth dilution of shoot Na+. Si had no effect on unidirectional 24Na+ fluxes (influx and efflux), or on Na+-stimulated plasma-membrane depolarization, in either IR29 or Pokkali. We conclude that, while Si can reduce Na+ translocation via bypass flow in some (but not all) rice cultivars, it does not affect unidirectional Na+ transport or Na+ cycling in roots, either across root cell membranes or within the bulk root apoplast