Long-Term Outcome and Economic Burden of Aneurysmal Subarachnoid Hemorrhage: Are we Only Seeing the Tip of the Iceberg?

Neurocritical Care -     

Cryptosporidiosis among solid organ transplant recipient attendees at a summer camp

We report a cluster of pediatric cryptosporidiosis infections among solid organ transplant recipients at a summer camp in Georgia, USA. A retrospective cohort study was conducted to investigate the risk factors for infection. A total of 118 campers attended the camp during July 23‐28, 2017. The overall attack rate among campers during the outbreak was 11% (13/118). Sanger‐based amplicon sequencing of stool specimens from 7 (80%) campers identified Cryptosporidium hominis as the suspected etiologic agent. All infected campers were heart or kidney transplant recipients receiving immunosuppressive therapy. The median reported symptom duration was 12 days (range 6‐18 days) and 9 (69.2%) were hospitalized for at least one night (median length of stay 5 days, range 2‐16 days). There were no deaths or acute rejection events attributed to infection. The results of the epidemiologic and environmental investigation suggest a recreational pool as the presumed source, although there was no direct evidence to support this. Many long‐term interventions were implemented, and there have been no further outbreaks at the camp in the following two years. This outbreak demonstrates that cryptosporidiosis may be associated with notable burden in pediatric transplant recipients, and illustrates the challenges associated with source identification and containment.     

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.     

Seizure-Induced Protein Tyrosine Phosphorylation in Rat Brain Regions

Phosphorylation of protein tyrosines is an important modulatory process for cell signaling and other cellular functions. Rat brain regions were examined for altered protein phosphotyrosines, using Western blot analysis and microwave irradiation to limit postmortem alterations, after administration of two convulsants: lithium plus pilocarpine or kainic acid (KA). Most phosphotyrosine proteins were unaltered by these treatments, but there was a large, specific increase in the tyrosine phosphorylation of a 40-Kd protein. This increase was evident in all three regions examined: cerebral cortex, hippocampus, and striatum; it occurred abruptly with onset of generalized status epilepticus (SE) and remained elevated for at least 90 min. Most of the tyrosine phosphorylated 40-Kd protein was in the cytosolic fraction. These results demonstrate a large, specific effect of chemically induced seizures on a single phosphotyrosine protein in rat brain.     

Variations in the locations of the recurrent laryngeal nerve in relation to the ligament of berry

Injury to the recurrent laryngeal nerve (RLN) is one of the most common iatrogenic complications of thyroid surgery. The anatomical course of the nerve also increases its susceptibility to injury and many variations have been documented in the literature. The topographical relationship of the RLN to the ligament of Berry has been extensively studied over the past decades. The consensus in the literature is divided with several authors reporting the nerve to be embedded within the ligament and others reporting a constant finding of the nerve being posterolateral to the ligament. A new operative concept has been recently introduced as a possible resolution for the conflicting reports among authors. Further investigations are needed, however, to assess its reliability and overall effects on clinical outcomes.     

Another (Internal) Epineurium: Beyond the Anatomical Barriers of Nerves

The epineurium has been accepted as the outer anatomical barrier of the peripheral nerves. Our objective was to characterize the microanatomy of the layers surrounding nerves using different tissue-specific staining methods. Two hundred forty-two cross sections of human sciatic and median nerves, and brachial plexuses of eight fresh unembalmed cadavers, were examined. The samples were fixed in formaldehyde solution and stained with hematoxylin–eosin, Masson's trichrome, or epithelial membrane antigen under standard conditions. Because epithelial membrane antigen only stains the perineurium, we demonstrated using hematoxylin–eosin and Masson's trichrome that there were different collagen layers inside and outside the nerves. All fascicles had a collagen layer that surrounded the perineurium and were in close contact with it, with no adipose tissue between them. Unlike the perineurium, this layer, an “internal epineurium,” contained no cells, and it surrounded one or a small group of fascicles. Bundling these fascicles or small groups of fascicles together was the true epineurium, and between the true and internal epineurium, we consistently found an adipose-containing compartment. More proximal to this, the tibial and common peroneal nerves were bundled together by another collagen layer, the circumneurium, which also had a fat-cell-containing compartment deep to it. There were scattered collagen fibers among the adipocytes. Using tissue-specific staining, we were able to demonstrate a collagen layer, the “internal epineurium.” Outside the nerves, we identified several fat-containing concentric compartments. Those compartments were limited by collagen fiber layers that were also similar to the epineurium. Clin. Anat. 33:199–206, 2020. © 2019 Wiley Periodicals, Inc.