Advances in biomarkers for vasospasm - Towards a future blood-based diagnostic test.

Objective: Cerebral vasospasm and the resultant delayed cerebral infarction is a significant source of mortality following aneurysmal SAH. Vasospasm is currently detected using invasive or expensive imaging at regular intervals in patients following SAH, thus posing a risk of complications following the procedure and financial burden on these patients. Currently, there is no blood-based test to detect vasospasm. Methods: PubMed, Web of Science, and Embase databases were systematically searched to retrieve studies related to cerebral vasospasm, aneurysm rupture, and biomarkers. The study search dated from 1997 to 2022. Data from eligible studies was extracted and then summarized. Results: Out of the 632 citations screened, only 217 abstracts were selected for further review. Out of those, only 59 full text articles met eligibility and another 13 were excluded. Conclusions: We summarize the current literature on the mechanism of cerebral vasospasm and delayed cerebral ischemia, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future bloodbased test to detect vasospasm. Efforts should be focused on clinical-translational approaches to create such a test to improve treatment timing and prediction of vasospasm to reduce the incidence of delayed cerebral infarction.

(Re-)Viewing Role of Intracellular Glucose Beyond Extracellular Regulation of Glucose-Stimulated Insulin Secretion by Pancreatic Cells.

For glucose-stimulated insulin secretion (GSIS) by pancreatic ß-cells in animals, it is believed that ATP generated from glucose metabolism is primarily responsible. However, this ignores two well-established aspects in literature: (a) intracellular ATP generation from other sources resulting in an overall pool of ATP, regardless of the original source, and (b) that intracellular glucose transport is 10- to 100-fold higher than intracellular glucose phosphorylation in ß-cells. The latter especially provides an earlier unaddressed, but highly appealing, observation pertaining to (at least transient) the presence of intracellular glucose molecules. Could these intracellular glucose molecules be responsible for the specificity of GSIS to glucose (instead of the widely believed ATP production from its metabolism)? In this work, we provide a comprehensive compilation of literature on glucose and GSIS using various cellular systems - all studies focus only on the extracellular role of glucose in GSIS. Further, we carried out a comprehensive analysis of differential gene expression in Mouse Insulinoma 6 (MIN6) cells, exposed to low and high extracellular glucose concentrations (EGC), from the existing whole transcriptome data. The expression of other genes involved in glycolysis, Krebs cycle, and electron transport chain was found to be unaffected by EGC, except Gapdh, Atp6v0a4, and Cox20. Remarkably, 3 upregulated genes (Atp6v0a4, Cacnb4, Kif11) in high EGC were identified to have an association with cellular secretion. Using glucose as a possible ligand for the 3 proteins, computational investigations were carried out (that will require future 'wet validation', both in vitro and in vivo, e.g., using primary islets and animal models). The glucose-affinity/binding scores (in kcal/mol) obtained were also compared with glucose binding scores for positive controls (GCK and GLUT2), along with negative controls (RPA1, KU70-80, POLA1, ACAA1A, POLR1A). The binding affinity scores of glucose molecules for the 3 proteins were found to be closer to positive controls. Therefore, we report the glucose binding ability of 3 secretion-related proteins and a possible direct role of intracellular glucose molecules in GSIS.

Automated Preoperative and Postoperative Volume Estimates Risk of Retreatment in Chronic Subdural Hematoma: A Retrospective, Multicenter Study.

BACKGROUND AND OBJECTIVES: Several neurosurgical pathologies, ranging from glioblastoma to hemorrhagic stroke, use volume thresholds to guide treatment decisions. For chronic subdural hematoma (cSDH), with a risk of retreatment of 10%-30%, the relationship between preoperative and postoperative cSDH volume and retreatment is not well understood. We investigated the potential link between preoperative and postoperative cSDH volumes and retreatment. METHODS: We performed a retrospective chart review of patients operated for unilateral cSDH from 4 level 1 trauma centers, February 2009-August 2021. We used a 3-dimensional deep learning, automated segmentation pipeline to calculate preoperative and postoperative cSDH volumes. To identify volume thresholds, we constructed a receiver operating curve with preoperative and postoperative volumes to predict cSDH retreatment rates and selected the threshold with the highest Youden index. Then, we developed a light gradient boosting machine to predict the risk of cSDH recurrence. RESULTS: We identified 538 patients with unilateral cSDH, of whom 62 (12%) underwent surgical retreatment within 6 months of the index surgery. cSDH retreatment was associated with higher preoperative (122 vs 103 mL; P < .001) and postoperative (62 vs 35 mL; P < .001) volumes. Patients with >140 mL preoperative volume had nearly triple the risk of cSDH recurrence compared with those below 140 mL, while a postoperative volume >46 mL led to an increased risk for retreatment (22% vs 6%; P < .001). On multivariate modeling, our model had an area under the receiver operating curve of 0.76 (95% CI: 0.60-0.93) for predicting retreatment. The most important features were preoperative and postoperative volume, platelet count, and age. CONCLUSION: Larger preoperative and postoperative cSDH volumes increase the risk of retreatment. Volume thresholds may allow identification of patients at high risk of cSDH retreatment who would benefit from adjunct treatments. Machine learning algorithm can quickly provide accurate estimates of preoperative and postoperative volumes.

Subarachnoid Hemorrhage Outcomes in an Endovascular Right of First Refusal Neurosurgical Environment.

BACKGROUND: Randomized controlled trials demonstrate that endovascular techniques yield improved outcomes compared with microsurgical approaches. However, not all patients are suitable candidates for endovascular management. This study aimed to determine if healthy patients managed microsurgically could achieve functional outcomes comparable to patients managed endovascularly. METHODS: Patients treated for ruptured aneurysmal subarachnoid hemorrhage at 2 level 1 stroke centers from January 2012 through December 2020 were retrospectively reviewed. All cases were evaluated in an endovascular right of first refusal neurosurgical environment. We collected relevant clinical and follow-up data and created a generalized linear model to identify differences between patients treated endovascularly versus microsurgically. A propensity score model accounting for these differences was used to predict patient outcomes. Functional outcomes were independently assessed using the modified Rankin Scale (mRS) with good functional outcome defined as modified Rankin Scale score <3. RESULTS: The study included 588 patients (211 microsurgical, 377 endovascular); median age was 58 years (interquartile range: 40-86 years); in-hospital mortality was 13%. Age, aneurysm size, and aneurysm location significantly predicted treatment modality (all P < 0.05). After greedy-type matching (210 microsurgical, 210 endovascular), patients managed microsurgically were less likely to be discharged home (odds ratio = 0.6, 95% confidence interval 0.4-0.9, P = 0.01). Functional differences disappeared over time; patients in the 2 treatment arms had similar functional outcomes at 3 months (odds ratio = 1.1, 95% confidence interval 0.7-1.8, P = 0.66) and 1 year after subarachnoid hemorrhage (odds ratio = 1.3, 95% confidence interval 0.8-2.1, P = 0.38). CONCLUSIONS: In an endovascular right of first refusal neurosurgical environment, practitioners can treat patients who are not good endovascular candidates microsurgically and achieve functional outcomes comparable to patients managed endovascularly.

Secretory Conservation in Insulin Producing Cells: Is There a System-Level Law of Mass Action in Biology?

Altered secretion of insulin from pancreatic ß-cells can manifest into disorders. For example, a lack of endogenously produced and/or secreted insulin results in Type 1 diabetes (and other associated subtypes). Pancreatic ß-cells are the endocrine secretory cells that promote insulin secretion in response to glucose stimulation. Secretion in response to extracellular triggers is an interplay among various signaling pathways, transcription factors, and molecular mechanisms. The Mouse Insulinoma 6 (MIN6) cell line serves as a model system for gaining mechanistic insights into pancreatic ß-cell functions. It is obvious that higher glucose consumption and increased insulin secretion are correlated. However, it has been reported that intracellular ATP levels remain ∼ constant beyond the extracellular glucose (EG) concentration of 10 mM. Therefore, any cause-effect relationship between glucose consumption (GC) and enhanced insulin secretion (eIS) remains unclear. We also found that total cellular protein, as well as total protein content in the culture "supernatant," remains constant regardless of varying EG concentrations. This indicated that eIS may be at the cost of (a) intracellular synthesis of other proteins and (b) secretion of other secretory proteins, or both (a) and (b), somehow coupled with GC by cells. To gain insights into the above, we carried out a transcriptome study of MIN6 cells exposed to hypoglycemic (HoG = 2.8 mM EG) and hyperglycemic (HyG = 25 mM EG) conditions. Expression of transcripts was analyzed in terms of Fragments Per Kilobase of transcript per Million mapped reads and Transcripts Per Million (FPKM and TPM) as well as values obtained by normalizing w.r.t. "∑(FPKM)" and "∑(TPM)." We report that HyG extracellular conditions lead to an ∼2-fold increase in insulin secretion compared to HoG measured by the enzyme-linked immunosorbent assay (ELISA) and transcripts of secreted proteins as well as their isoforms decreased in HyG conditions compared to HoG. Our results show for the first time that eIS in HyG conditions is at the cost of reduced transcription of other secreted proteins and is coupled with higher GC. The higher GC at increased extracellular glucose also indicates a yet undiscovered role of glucose molecules enhancing insulin secretion, since ATP levels resulting from glucose metabolism have been reported to be constant above an EG concentration of 10 mM. While extrapolation of our results to clinical implications is ambitious at best, this work reports novel cellular level aspects that seem relevant in some clinical observations pertaining to Type 1 diabetes. In addition, the conservatory nature of cellular secretions in insulin-secreting cells, discovered here, may be a general feature in cell biology.

Interaction of admission platelet count with current medications and the risk for chronic subdural recurrence.

OBJECTIVE: Chronic subdural hematoma (cSDH) has a reported 10%-24% rate of recurrence after surgery, and prognostic models for recurrence have produced equivocal results. The objective of this study was to leverage a data mining algorithm, chi-square automatic interaction detection (CHAID), which can incorporate continuous, nominal, and binary data into a decision tree, to identify the most robust predictors of repeat surgery for cSDH patients. METHODS: This was a retrospective cohort study of all patients with SDH from two level 1 trauma centers at a single institution. All patients underwent cSDH evacuation performed by 15 neurosurgeons between 2011 and 2020. The primary outcome was the rate of repeat surgery for recurrent cSDH following the initial evacuation. The authors used CHAID to identify relevant predictors of repeat surgery, including age, sex, comorbidities, postsurgical complications, platelet count prior to the first procedure, midline shift prior to the first procedure, hematoma volume, and preoperative use of anticoagulants, antiplatelets, or statins. RESULTS: Sixty (13.8%) of 435 study-eligible patients (average age 74.0 years) had a cSDH recurrence. These patients had 2.0 times greater odds of having used anticoagulants. The final CHAID model had an overall accuracy of 87.4% and an area under the curve of 0.76. According to the model, the predictor with the strongest association with cSDH recurrence was admission platelet count. Approximately 26% of patients (n = 23/87) with an admission platelet count < 157 × 109/L had a cSDH recurrence, whereas none of the 44 patients with admission platelets > 313 × 109/L had a recurrence. Approximately 17% of patients in the 157-313 × 109/L platelet group who had used preoperative statins required a second procedure, which was associated with a 2.3 times increased risk for repeat surgery compared to those who had not used statins preoperatively. Among those who had not used preoperative statins, a platelet count ≤ 179 × 109/L on admission for the first procedure was the strongest differentiator for a second surgery (n = 5/22 [23%]), which increased the risk of recurrence by 4.5 times. Among the patients using preoperative statins, the use of anticoagulants was the strongest differentiator for requiring repeat surgery (n = 11/33 [33%]). CONCLUSIONS: The described model identified platelet count on admission as the most important predictor of repeat cSDH surgery, followed by preoperative statin use and anticoagulant use. Critical cutoffs for platelet count were identified, which future studies should evaluate to determine if they are modifiable or reflective of underlying disease states.

A Future Blood Test to Detect Cerebral Aneurysms.

Intracranial aneurysms are reported to affect 2-5% of the population. Despite advances in the surgical management of this disease, diagnostic technologies have marginally improved and still rely on expensive or invasive imaging procedures. Currently, there is no blood-based test to detect cerebral aneurysm formation or quantify the risk of rupture. The aim of this review is to summarize current literature on the mechanism of aneurysm formation, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future blood-based test. Efforts should be focused on clinical-translational approaches to create an assay to screen for cerebral aneurysm presence and risk-stratify patients to allow for superior treatment timing and management. Cerebral Aneurysm Blood Test Considerations: There are multiple caveats to development of a putative blood test to detect cerebral aneurysm presence.

Pseudopeptosomes: non-lipidated vesicular assemblies from bispidine-appended pseudopeptides.

We report a novel molecular topology-based approach for creating reproducible vesicular assemblies in different solvent environments (including aqueous) using specifically designed pseudopeptides. Deviating from the classical "polar head group and hydrophobic tail" model of amphiphiles, we showed (reversible) self-assembly of synthesized pseudopeptides into vesicles. Naming these new type/class of vesicles "pseudopetosomes", we characterized them by high-resolution microscopy (scanning electron, transmission electron, atomic force, epifluorescence and confocal) along with dynamic light scattering. While accounting for hydropathy index of the constituent amino acids (side chains) of pseudopeptides, we probed molecular interactions, resulting in assembly of pseudopeptosomes by spectroscopy (fourier-transform infrared and fluorescence). Molecular characterization by X-ray crystallography and circular dichroism revealed "tryptophan (Trp)-Zip" arrangements and/or hydrogen-bonded one-dimensional assembly depending on specific pseudopeptides and solvent environments. Our data indicated that pseudopeptosomes are formed in solutions by self-assembly of bispidine pseudopeptides (of Trp, leucine and alanine amino-acid constituents) into sheets that transform into vesicular structures. Thus, we showed that assembly of pseudopeptosomes utilizes the full spectrum of all four weak interactions essential in biological systems. Our findings have direct implications in chemical and synthetic biology, but may also provide a new avenue of investigations on origins of life via pseudopeptosome-like assemblies. We also showed that these designer peptides can act as carriers for cellular transport.

Molecular dynamics simulation-based trinucleotide and tetranucleotide level structural and energy characterization of the functional units of genomic DNA.

Genomes of most organisms on earth are written in a universal language of life, made up of four units - adenine (A), thymine (T), guanine (G), and cytosine (C), and understanding the way they are put together has been a great challenge to date. Multiple efforts have been made to annotate this wonderfully engineered string of DNA using different methods but they lack a universal character. In this article, we have investigated the structural and energetic profiles of both prokaryotes and eukaryotes by considering two essential genomic sites, viz., the transcription start sites (TSS) and exon-intron boundaries. We have characterized these sites by mapping the structural and energy features of DNA obtained from molecular dynamics simulations, which considers all possible trinucleotide and tetranucleotide steps. For DNA, these physicochemical properties show distinct signatures at the TSS and intron-exon boundaries. Our results firmly convey the idea that DNA uses the same dialect for prokaryotes and eukaryotes and that it is worth going beyond sequence-level analyses to physicochemical space to determine the functional destiny of DNA sequences.

Tetra-compartmental spinal infection with conus medullaris syndrome: illustrative case.

BACKGROUND: Recent literature suggests that spinal infections are increasing in prevalence. Any compartment can be infected in the spine; however, multicompartmental infections are rare. OBSERVATIONS: To the authors' knowledge, this report is the only reported case of a tetra-compartmental spinal infection consisting of epidural, subdural, subarachnoid, and intramedullary components with a contiguous lumbar spondylodiscitis resulting in conus medullaris syndrome requiring surgical intervention. LESSONS: This case highlights the importance of surgical intervention in severe cases such as the one illustrated in this report. Second, magnetic resonance imaging with and without contrast is required to check for spreading of the infection as these findings may change the surgical approach. Last, the use of intraoperative ultrasound is paramount to evaluate the subdural and intramedullary compartments in severe cases.

Hunt-Hess Score at 48 Hours Improves Prognostication in Grade 5 Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Patients with Hunt-Hess (HH)5 aneurysmal subarachnoid hemorrhage (SAH) have high mortality rates. Despite an initial moribund exam, a subset of patients progress to favorable outcomes. OBJECTIVE: To evaluate the utility of delayed HH grading to improve prognostication. METHODS: We retrospectively reviewed patients undergoing treatment of ruptured aneurysms at two level 1 stroke centers from January 2012 through December 2020. We collected relevant clinical information and developed a multivariate cox regression model to identify independent predictors of mortality. To evaluate the utility of delayed examinations in predicting outcomes, we re-assessed the HH grade at 48 hours post admission and constructed a logistic regression model with potential confounders to predict mortality. RESULTS: From 2012 to 2020, 621 patients underwent treatment for aneurysmal SAH. We identified 63 HH5 patients (10%) with a mean age of 58 years. Among these patients, the median length of stay was 14 days, with 3 patients passing away within 48 hours. The overall mortality rate was 63% at 24 months. To predict mortality, our cox regression model found only age to be significant (P = 0.002). Delayed HH grading improved prognostication at 48 hours and remained significant on multivariate analysis as a predictor of mortality (P = 0.0001). We observed a significant difference in mortality between patients HH5 and patients HH4 or lower at 48 hours (P = 0.0003). CONCLUSIONS: Delayed reassessment of HH grade 48 hours postadmission is a predictor of mortality, suggesting reassessment at 48 hours in high grade SAH leads to better prognostication.

Arachnoid webs causing rostral syrinx due to ball-valve effect: an illustrative report of two cases.

An arachnoid web is a pathological formation of the arachnoid membrane. It is a rare phenomenon but is known to lead to syrinx formation in the spinal cord along with pain and neurological deficits. On imaging, the 'scalpel sign' is pathognomonic for an arachnoid web. The etiology of syrinx formation from an arachnoid web is currently unknown. This report documents the only two cases of arachnoid webs with an extensive syrinx in which a likely pathophysiologic mechanism is identified. Both cases presented with motor deficits. The patients had no history of trauma or infection. After extensive workup in both patients and observation of the scalpel sign an arachnoid web was suspected. In both cases, the patients were treated surgically after an arachnoid web was suspected. Intra-operative ultrasound visualized in both cases demonstrates a fenestration in the web that allowed passage of cerebrospinal fluid in a rostral-caudal direction due to a ball-valve effect.

The Era of Onyx Embolization: A Systematic and Literature Review of Preoperative Embolization Before Stereotactic Radiosurgery for the Management of Cerebral Arteriovenous Malformations.

INTRODUCTION: The current treatment paradigm for intracranial arteriovenous malformations (AVMs) focuses on reducing the risk of intracranial hemorrhage using various therapeutic means including embolization, stereotactic radiosurgery (SRS), and microsurgical resection. To improve AVM obliteration rates with SRS, pre-radiosurgical embolization has been trialed in a number of studies to reduce the volume of the AVM nidus prior to radiosurgery. This study aimed to review the efficacy of pre-radiosurgical embolization in the pre-Onyx era compared to the current Onyx era. METHODS: A systematic review was performed using PubMed to identify studies with 20 or more AVM patients, embolization material, and obliteration rates for both embolization + stereotactic radiosurgery (E+SRS) and SRS-only groups. RESULTS: Seventeen articles consisting of 1133 eligible patients were included in this study. A total of 914 (80.7%) patients underwent embolization prior to SRS. Onyx was used as the embolysate in 340 (37.2%) patients in the E+SRS cohorts. Mean obliteration rate for the embolized cohort was 46.9% versus 46.5% in the SRS-only cohort. When comparing obliteration rates based on embolysate material, obliteration rate was 42.1% with Onyx+SRS and 50.0% in the non-Onyx embolysate + SRS cohort. CONCLUSIONS: Onyx (ethylene vinyl-alcohol copolymer dissolved in dimethyl sulfoxide and suspended in micronized tantalum powder) has been increasingly used for the embolization of intracranial AVMs with increased success regarding its ease of use from a technical standpoint and performs similarly to other embolysate materials.

A Three-Dimensional-Based Morphometric Analysis of a Standardized Overcorrection Technique for Fronto-Orbital Advancement in Metopic Craniosynostosis.

INTRODUCTION: The concept of "overcorrection" for trigonocephaly has been reported to achieve both anterior cranial fossa expansion and normalization of craniofacial form. The purpose of this study is to describe in detail a standardized technique to fronto-orbital advancement utilizing the concept of "overcorrection" and objectively evaluate intermediate results. METHODS: This retrospective study included patients with isolated metopic synostosis who underwent surgery via the proposed surgical technique and age and sex-matched unaffected controls. Craniofacial morphometric analysis was performed on pre-, immediate post-, and intermediate postoperative (>2 years) three-dimensional (3D)-rendered computed tomographic (CT) scans and photographs. Key CT-based measurements included interzygomaticofrontal suture distance (IZFS), endocranial bifrontal angle (ECA), and temporal expansion. 3D photogrammetry was performed using established measurements and associated Z-scores converted. A Paired t-test and analysis of variance were performed when appropriate. RESULTS: Forty-one patients were included. A comparison of pre- and immediate postoperative CT scans demonstrated statistically significant increases in all measurements. Subset analysis of 12 patients with intermediate follow-up (age: 39.6 ± 3.6 months) demonstrated significant differences from preoperative values except for IZFS, which decreased from immediate postoperative values and was smaller than age- and sex-matched controls. 3D photogrammetry demonstrated a mean Z-score above the norm for frontal breath. 3D photogrammetry is also positively correlated with CT-based measurements. CONCLUSIONS: This standardized "overcorrection" approach for trigonocephaly can provide the appropriate changes to maintain a normal ECA despite a reduction in bifrontal width over time. 3D photogrammetry positively correlated with CT-based measurements and may provide useful information when following patients clinically. Long-term follow-up assessment to determine the necessary degree of overcorrection at skeletal mature is needed.

The Clinical Significance of Clinocephaly in Late-Presentation Sagittal Craniosynostosis.

The diagnosis of late-presentation sagittal suture craniosynostosis (SCS) can be challenging, especially in the setting of subtle physical exam findings. The clinical significance of clinocephaly-a retro-coronal concavity along the midvault-in this context remains unknown. The aim of this study is to evaluate the predictive value of clinocephaly in identifying late-presentation SCS.A retrospective chart review of all patients >1 year old presenting to the craniofacial clinic with a concern for SCS was performed. The presence or absence of SCS in the setting of clinocephaly was recorded following diagnostic imaging. Student's t test, Chi Square test, and multivariate logistic regression analysis were performed to determine predictors for SCS.75 patients met inclusion criteria. 32 patients (42.7%, 6% female) were diagnosed with SCS. No difference in age between patients with and without SCS was detected. Stratification of patients by age (1-2, 2-4, and >4 years) revealed a higher rate of SCS in younger patients (P = 0.04). The cephalic index (C.I.) of those with sagittal synostosis was significantly smaller but within the normal range, indicating a more scaphocephalic shape (P = 0.003). Logistic regression analysis revealed that C.I. was a strong predictor for SCS (P = 0.003). Of those with SCS, a mix of complete and partial fusion of the sagittal suture was appreciated.This study found that 42.7% of patients with clinocephaly had SCS. C.I. was the only predictor for SCS and unique suture fusion patterns were identified in those with SCS. This study suggests that clinocephaly should be considered a core component of the exam and work-up for SCS. Future studies aimed at evaluating the positive predictive value of this exam finding and identifying risk factors associated with late-presentation SCS are underway.

Intraoperative ultrasound evidence of accidental simultaneous cannulation of the common carotid artery and internal jugular vein: illustrative case.

BACKGROUND: Establishing central venous access is important to provide fluid resuscitation or medications intravenously to patients. OBSERVATIONS: Although accidental cannulation of the internal carotid artery has been reported in the literature, to our knowledge this report is the first documented intraoperative ultrasound video demonstrating accidental and simultaneous common carotid artery and internal jugular cannulation during central line placement in the internal jugular vein. LESSONS: Ultrasound use minimizes accidental carotid cannulation during central line placement in the internal jugular vein. Carotid artery puncture can be managed by external application of pressure or surgical reexploration.

Aspects of Biological Replication and Evolution Independent of the Central Dogma: Insights from Protein-Free Vesicular Transformations and Protein-Mediated Membrane Remodeling.

Biological membrane remodeling is central to living systems. In spite of serving as "containers" of whole-living systems and functioning as dynamic compartments within living systems, biological membranes still find a "blue collar" treatment compared to the "white collar" nucleic acids and proteins in biology. This may be attributable to the fact that scientific literature on biological membrane remodeling is only 50 years old compared to ~ 150 years of literature on proteins and a little less than 100 years on nucleic acids. However, recently, evidence for symbiotic origins of eukaryotic cells from data only on biological membranes was reported. This, coupled with appreciation of reproducible amphiphilic self-assemblies in aqueous environments (mimicking replication), has already initiated discussions on origins of life beyond nucleic acids and proteins. This work presents a comprehensive compilation and meta-analyses of data on self-assembly and vesicular transformations in biological membranes-starting from model membranes to establishment of Influenza Hemagglutinin-mediated membrane fusion as a prototypical remodeling system to a thorough comparison between enveloped mammalian viruses and cellular vesicles. We show that viral membrane fusion proteins, in addition to obeying "stoichiometry-driven protein folding", have tighter compositional constraints on their amino acid occurrences than general-structured proteins, regardless of type/class. From the perspective of vesicular assemblies and biological membrane remodeling (with and without proteins) we find that cellular vesicles are quite different from viruses. Finally, we propose that in addition to pre-existing thermodynamic frameworks, kinetic considerations in de novo formation of metastable membrane structures with available "third-party" constituents (including proteins) were not only crucial for origins of life but also continue to offer morphological replication and/or functional mechanisms in modern life forms, independent of the central dogma.

Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN. METHODS: The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III). RESULTS: A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up. CONCLUSIONS: The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

Isolated traumatic occipital condyle fractures: Is external cervical orthosis even necessary?

BACKGROUND: Occipital condyle fractures (OCFs) have been reported in up to 4-16% of individuals suffering cervical spine trauma. The current management of OCF fractures relies on a rigid cervical collar for 6 weeks or longer. Here, we calculated the rate of acute and delayed surgical intervention (occipitocervical fusion) for patients with isolated OCF who were managed with a cervical collar over a 10-year period at a single institution. METHODS: This was a retrospective analysis performed on all patients admitted to a Level 1 Trauma Center between 2008 and 2018 who suffered traumatic isolated OCF managed with an external rigid cervical orthosis. Radiographic imaging was reviewed by several board-certified neuroradiologists. Demographic and clinical data were collected including need for occipitocervical fusion within 12 months after trauma. RESULTS: The incidence of isolated OCF was 4% (60/1536) for those patients admitted with cervical spine fractures. They averaged 49 years of age, and 58% were male falls accounted for the mechanism of injury in 47% of patients. Classification of OCF was most commonly classified in 47% as type I Anderson and Montesano fractures. Of the 60 patients who suffered isolated OCF that was managed with external cervical orthosis, 0% required occipitocervical fusion within 12 months posttrauma. About 90% were discharged, while the remaining 10% sustained traumatic brain/orthopedic injury that limited an accurate neurological assessment. CONCLUSION: Here, we documented a 4% incidence of isolated OCF in our cervical trauma population, a rate which is comparable to that found in the literature year. Most notably, we documented a 0% incidence for requiring delayed occipital-cervical fusions.

Computed tomography associated radiation exposure in children with craniosynostosis.

BACKGROUND: The role of computed tomography (CT) for diagnosis and surgical planning for craniosynostosis (CS) is well-established. The aim of this study was to quantify the cumulative medical radiation exposure from CT in patients with CS at a tertiary care children's hospital. METHODS: Medical records of patients who presented at < 2 years of age and underwent surgical intervention for CS were examined for demographic information. Effective radiation dose (ERD) in mSv was calculated for each head CT. Descriptive statistics and ANOVA were performed. Mean ± SD is reported; p < 0.05 was considered significant. RESULTS: Two hundred seventy-two patients met inclusion criteria: 241 nonsyndromic and 31 with syndromic diagnoses. For nonsyndromic patients, mean age at first head CT was 6.0 ± 4.9 months, mean number of CT scans obtained was 2.1 ± 1.1, and the mean total combined ERD was 9.1 ± 4.8 mSv. CT scans obtained at < 6 months of age had a significantly greater ERD than those obtained at > 6 months, 5.3 ± 1.9 versus 4.3 ± 1.4 mSv, respectively (p = 0.001). CONCLUSIONS: Patients with nonsyndromic CS undergo 2 CT scans on average related to their diagnosis, with a mean total ERD of 9.1 mSv; this is equivalent to 1.5 years of the average annual background radiation dose a person living in the USA will encounter from environmental radiation, medical exposures, and consumer products. A CT obtained at < 6 months is associated with a higher ERD; thus, we recommend delaying imaging from the initial presentation to the time of pre-operative planning when possible.