Vision Threatening Raised Intracranial Pressure Associated with Recreational Nitrous Oxide Use

Nitrous oxide is used as an anaesthetic and analgesic agent in the medical setting and is known to cause raised intracranial pressure. The use of nitrous oxide recreationally for the drug’s euphoric and relaxant properties has been linked to multiple neurological and psychiatric sequelae including neuropathy, myelopathy, and psychosis. We describe a case of a young person who declared heavy nitrous oxide use resulting in vision-threatening papilloedema secondary to raised intracranial pressure. He underwent emergency lumbar drainage alongside high-dose acetazolamide and parenteral vitamin B12 injections. To our knowledge, there have yet to be other reports of cases where heavy nitrous oxide use has caused secondary pseudotumor cerebri syndrome

The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation

Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na+ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na+ pump function modulates neuronal excitability to maintain normal sleep behaviour

Dynamic causal modelling of immune heterogeneity

An interesting inference drawn by some Covid-19 epidemiological models is that there exists a proportion of the population who are not susceptible to infection -- even at the start of the current pandemic. This paper introduces a model of the immune response to a virus. This is based upon the same sort of mean-field dynamics as used in epidemiology. However, in place of the location, clinical status, and other attributes of people in an epidemiological model, we consider the state of a virus, B and T-lymphocytes, and the antibodies they generate. Our aim is to formalise some key hypotheses as to the mechanism of resistance. We present a series of simple simulations illustrating changes to the dynamics of the immune response under these hypotheses. These include attenuated viral cell entry, pre-existing cross-reactive humoral (antibody-mediated) immunity, and enhanced T-cell dependent immunity. Finally, we illustrate the potential application of this sort of model by illustrating variational inversion (using simulated data) of this model to illustrate its use in testing hypotheses. In principle, this furnishes a fast and efficient immunological assay--based on sequential serology--that provides a (i) quantitative measure of latent immunological responses and (ii) a Bayes optimal classification of the different kinds of immunological response (c.f., glucose tolerance tests used to test for insulin resistance). This may be especially useful in assessing SARS-CoV-2 vaccines

Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms

Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers.Fifty-one population-based MSS colon cancers were assessed for ACVR1, ACVR2 and pSMAD2 protein. Consensus mutation-prone portions of ACVR2 were sequenced in primary cancers and all exons in colon cancer cell lines. Loss of heterozygosity (LOH) was evaluated for ACVR2 and ACVR1, and ACVR2 promoter methylation by methylation-specific PCR and bisulfite sequencing and chromosomal instability (CIN) phenotype via fluorescent LOH analysis of 3 duplicate markers. ACVR2 promoter methylation and ACVR2 expression were assessed in colon cancer cell lines via qPCR and IP-Western blots. Re-expression of ACVR2 after demethylation with 5-aza-2'-deoxycytidine (5-Aza) was determined. An additional 26 MSS colon cancers were assessed for ACVR2 loss and its mechanism, and ACVR2 loss in all tested cancers correlated with clinicopathological criteria.Of 51 MSS colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression. No somatic ACVR2 mutations were detected. Loss of ACVR2 expression was associated with LOH at ACVR2 (p<0.001) and ACVR2 promoter hypermethylation (p<0.05). ACVR2 LOH, but not promoter hypermethylation, correlated with CIN status. In colon cancer cell lines with fully methylated ACVR2 promoter, loss of ACVR2 mRNA and protein expression was restored with 5-Aza treatment. Loss of ACVR2 was associated with an increase in primary colon cancer volume (p<0.05).Only a small percentage of MSS colon cancers lose expression of activin signaling members. ACVR2 loss occurs through LOH and ACVR2 promoter hypermethylation, revealing distinct mechanisms for ACVR2 inactivation in both MSI and MSS subtypes of colon cancer

Double insurance transfacetal screws for lumbar spinal stabilization

Aim: The authors report experience with 14 cases where two screws or ′′double insurance′′ screws were used for transfacetal fixation of each joint for stabilization of the lumbar spinal segment. The anatomical subtleties of the technique of insertion of screws are elaborated. Materials and Methods: During the period March 2011 to June 2014, 14 patients having lumbar spinal segmental instability related to lumbar canal stenosis were treated by insertion of two screws into each articular assembly by transfacetal technique. After a wide surgical exposure, the articular cartilage was denuded and bone chips were impacted into the joint cavity. For screw insertion in an appropriate angulation, the spinous process was sectioned at its base. The screws (2.8 mm in diameter and 18 mm in length) were inserted into the substance of the medial or inferior articular facet of the rostral vertebra via the lateral limit of the lamina approximately 6-8 mm away from the edge of the articular cavity. The screws were inserted 3 mm below the superior edge and 5 mm above the inferior edge of the medial (inferior) facets and directed laterally and traversed through the articular cavity into the lateral (superior) articular facet of the caudal vertebra toward and into the region of junction of base of transverse process and of the pedicle. During the period of follow-up all treated spinal levels showed firm bone fusion. There was no complication related to insertion of the screws. There was no incidence of screw misplacement, displacementor implant rejection. Conclusions: Screw insertion into the firm and largely cortical bones of facets of lumbar spine can provide robust fixation and firm stabilization of the spinal segment. The large size of the facets provides an opportunity to insert two screws at each spinal segment. The firm and cortical bone material and absence on any neural or vascular structure in the course of the screw traverse provides strength and safety to the process

Quantitative morphometric analysis of the lumbar vertebral facets and evaluation of feasibility of lumbar spinal nerve root and spinal canal decompression using the Goel intraarticular facetal spacer distraction technique: A lumbar/cervical facet comparison

Objective : The authors evaluate the anatomic subtleties of lumbar facets and assess the feasibility and effectiveness of use of ′Goel facet spacer′ in the treatment of degenerative spinal canal stenosis. Materials and Methods : Twenty-five lumbar vertebral cadaveric dried bones were used for the purpose. A number of morphometric parameters were evaluated both before and after the introduction of Goel facet spacers within the confines of the facet joint. Results : The spacers achieved distraction of facets that was more pronounced in the vertical perspective. Introduction of spacers on both sides resulted in an increase in the intervertebral foraminal height and a circumferential increase in the spinal canal dimensions. Additionally, there was an increase in the disc space or intervertebral body height. The lumbar facets are more vertically and anteroposteriorly oriented when compared to cervical facets that are obliquely and transversely oriented. Conclusions : Understanding the anatomical peculiarities of the lumbar and cervical facets can lead to an optimum utilization of the potential of Goel facet distraction arthrodesis technique in the treatment of spinal degenerative canal stenosis