A Unique Enoxaparin Derived from Bovine Intestinal Heparin: A Single Purification Step of the Starting Material Assures a Bovine Enoxaparin Like the Standard from Porcine Origin.

Low-molecular-weight heparin represent a significant advancement in anticoagulant therapy with enoxaparin being a prominent example obtained exclusively through the fragmentation of porcine intestinal heparin. However, escalating demand and limited resources have raised concerns about enoxaparin supplementation. The current challenge involves exploring alternative heparin sources for large-scale enoxaparin production with bovine intestinal heparin emerging as a promising option. Our study demonstrates that enoxaparin derived from the available bovine heparin preparation differs significantly from the reference compound. Yet, the implementation of a straightforward purification step yields a preparation termed "high-anticoagulant bovine heparin". Fragmentation of this purified product through ß-elimination produces enoxaparin akin to the standard from a porcine origin. To ensure physicochemical similarity, we employed various spectroscopic, enzymatic, and chromatographic tests to compare the new bovine-derived enoxaparin with the original porcine compound. Biological activity was confirmed through in vitro coagulation assays and assessments using an animal model of venous thrombosis. Our study affirms that the ß-elimination reaction cleaves the bovine heparin chain without preferential breaks in regions with different sulfation patterns. Additionally, we scrutinized decasaccharides purified from enoxaparin preparations, providing a comprehensive demonstration of the similarity between products obtained from porcine and bovine heparin. In summary, our findings indicate that an enoxaparin equivalent to the original porcine-derived product can be derived from bovine heparin, given that the starting material undergoes a simple purification step.

Unraveling the Oxidation Kinetics Through Electronic Structure Regulation of MnCo2O4.5@Ni3S2 p-n Junction for Urea-Assisted Electrocatalytic Activity.

A promising strategy to boost electrocatalytic performance is via assembly of hetero-nanostructured electrocatalysts that delivers the essential specific surface area and also active sites by lowering the reaction barrier. However, the challenges associated with the intricate designs and mechanisms remain underexplored. Therefore, the present study constructs a p-n junction in a free-standing MnCo2O4.5@Ni3S2 on Ni-Foam. The space-charge region's electrical characteristics is dramatically altered by the formed p-n junction, which enhances the electron transfer process for urea-assisted electrocatalytic water splitting (UOR). The optimal MnCo2O4.5@Ni3S2 electrocatalyst results in greater oxygen evolution reactivity (OER) than pure systems, delivering an overpotential of only 240 mV. Remarkably, upon employing as UOR electrode the required potential decreases to 30 mV. The impressive performance of the designed catalyst is attributed to the enhanced electrical conductivity, greater number of electrochemical active sites, and improved redox activity due to the junction interface formed between p-MnCo2O4.5 and n-Ni3S2. There are strong indications that the in situ formed extreme-surface NiOOH, starting from Ni3S2, boosts the electrocatalytic activity, i.e., the electrochemical  surface reconstruction generates the active species. In conclusion, this work presents a high-performance p-n junction design for broad use, together with a viable and affordable UOR electrocatalyst.

An Efficient and Scalable "Second Generation" Total Synthesis of the Marine Polyketide Limaol Endowed with Antiparasitic Activity.

The cluster of four skipped exo-methylene substituents on the "northern" wing of limaol renders this dinoflagellate-derived marine natural product unique in structural terms. This arguably non-thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty-fold per run. Key-to-success was a gold-catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate-controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much-improved route to the "northern" sector was established by leveraging the power of asymmetric hydrogenation of a 2-pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity.

The marine conservation deposits of Monte San Giorgio (Switzerland, Italy): the prototype of Triassic black shale Lagerstätten.

Marine conservation deposits ('Konservat-Lagerstätten') are characterized by their mode of fossil preservation, faunal composition and sedimentary facies. Here, we review these characteristics with respect to the famous conservation deposit of the Besano Formation (formerly Grenzbitumenzone; including the Anisian-Ladinian boundary), and the successively younger fossil-bearing units Cava inferiore, Cava superiore, Cassina beds and the Kalkschieferzone of Monte San Giorgio (Switzerland and Italy). We compare these units to a selection of important black shale-type Lagerstätten of the global Phanerozoic plus the Ediacaran in order to detect commonalities in their facies, genesis, and fossil content using principal component and hierarchical cluster analyses. Further, we put the Monte San Giorgio type Fossillagerstätten into the context of other comparable Triassic deposits worldwide based on their fossil content. The results of the principal component and cluster analyses allow a subdivision of the 45 analysed Lagerstätten into four groups, for which we suggest the use of the corresponding pioneering localities: Burgess type for the early Palaeozoic black shales, Monte San Giorgio type for the Triassic black shales, Holzmaden type for the pyrite-rich black shales and Solnhofen type for platy limestones.

Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.

Although an increased risk of the skin cancer melanoma in people with Parkinson's Disease (PD) has been shown in multiple studies, the mechanisms involved are poorly understood, but increased expression of the PD-associated protein alpha-synuclein (αSyn) in melanoma cells may be important. Our previous work suggests that αSyn can facilitate DNA double-strand break (DSB) repair, promoting genomic stability. We now show that αSyn is preferentially enriched within the nucleolus in the SK-MEL28 melanoma cell line, where it colocalizes with DNA damage markers and DSBs. Inducing DSBs specifically within nucleolar ribosomal DNA (rDNA) increases αSyn levels near sites of damage. αSyn knockout increases DNA damage within the nucleolus at baseline, after specific rDNA DSB induction, and prolongs the rate of recovery from this induced damage. αSyn is important downstream of ATM signaling to facilitate 53BP1 recruitment to DSBs, reducing micronuclei formation and promoting cellular proliferation, migration, and invasion.

Humanization and functional characterization of enhanced coagulation factor IX variants identified through ancestral sequence reconstruction.

BACKGROUND: Laboratory resurrection of ancient coagulation factor (F) IX variants generated through ancestral sequence reconstruction led to the discovery of a FIX variant, designated An96, which possesses enhanced specific activity independent of and additive to that provided by human p.Arg384Lys, referred to as FIX-Padua. OBJECTIVES: The goal of the current study was to identify the amino acid substitution(s) responsible for the enhanced activity of An96 and create a humanized An96 FIX transgene for gene therapy application. METHODS: Reductionist screening approaches, including domain swapping and scanning residue substitution, were used and guided by one-stage FIX activity assays. In vitro characterization of top candidates included recombinant high-purity preparation, specific activity determination, and enzyme kinetic analysis. Final candidates were packaged into adeno-associated viral (AAV) vectors and delivered to hemophilia B mice. RESULTS: Five of 42 total amino acid substitutions in An96 appear sufficient to retain the enhanced activity of An96 in an otherwise human FIX variant. Additional substitution of the Padua variant further increased the specific activity 5-fold. This candidate, designated ET9, demonstrated 51-fold greater specific activity than hFIX. AAV2/8-ET9 treated hemophilia B mice produced plasma FIX activities equivalent to those observed previously for AAV2/8-An96-Padua, which were 10-fold higher than AAV2/8-hFIX-Padua. CONCLUSION: Starting from computationally inferred ancient FIX sequences, novel amino acid substitutions conferring activity enhancement were identified and translated into an AAV-FIX gene therapy cassette demonstrating high potency. This ancestral sequence reconstruction discovery and sequence mapping refinement approach represents a promising platform for broader protein drug and gene therapy candidate optimization.

Modeling the polychromism of oxide minerals: The case of alexandrite and cordierite.

In this work, we investigate the spectroscopic properties of photochromic alexandrite and cordierite by TD-DFT. The objective is to assess the TD-DFT for the simulation of pleochroism (change of color depending on the crystallographic direction of the observation) and the change of color as a function of the light source. For these simulations, we compared an embedding where dangling bonds are saturated by hydrogen atoms and an electrostatic embedding. The electrostatic embedding provided numerically more stable results and allowed a good reproduction of the pleochroism of cordierite, based on a Fe2+-Fe3+ intervalence charge transfer transition. However, the pleochroism of alexandrite is not as well reproduced, suggesting that TD-DFT has some difficulties to reproduce the anisotropy of the transition dipole moment, an aspect that is not deeply documented in the literature.

Correlation between MRI-based spinal muscle parameters and the vertebral bone quality score in lumbar fusion patients.

Introduction: The vertebral bone quality (VBQ) score that is based on non-contrast enhanced T1-weighted MRI was recently introduced as a novel measure of bone quality in the lumbar spine and shown to be a significant predictor of healthy versus osteopenic/osteoporotic bone. Research question: This study aimed to assess possible correlations between the VBQ score and the functional cross-sectional area (FCSA) of psoas and lumbar spine extensor muscles. Material and methods: Patients who underwent fusion surgery between 2014 and 2017 and had lumbar MRI and CT scans within 6 months prior to surgery were included. The FCSA was assessed at L3-L5 using a pixel intensity threshold method. The VBQ score was calculated by dividing the signal intensity (SI) of the vertebrae L1-L4 through the SI of the cerebrospinal fluid at L3. Volumetric bone mineral density (vBMD) was assessed by quantitative CT. Results: 80 patients (58.8% female, median age 68.8 years) were included. Overall prevalence of osteopenia/osteoporosis was 66.3%, with no significant differences between men and women. The mean (SD) VBQ score was significantly smaller in men, at 2.26 (0.45) versus women at 2.59 (0.39) (p = 0.001). After adjusting for age and BMI, a significant negative correlation was seen between the VBQ score and psoas FCSA at L3 (ß = -0.373; p = 0.022), but only in men. Conclusion: Our results highlight sex differences in the VBQ score that were not demonstrated by vBMD and suggest a potential role of this novel measure to assess not only bone quality, but also spinal muscle quantity.

Gaussian attractive potential for carboxylate/cobalt surface interactions.

Ligand-decorated metal surfaces play a pivotal role in various areas of chemistry, particularly in selective catalysis. Molecular dynamics simulations at the molecular mechanics level of theory are best adapted to gain complementary insights to experiments regarding the structure and dynamics of such organic films. However, standard force fields tend to capture only weak physisorption interactions. This is inadequate for ligands that are strongly adsorbed such as carboxylates on metal surfaces. To address this limitation, we employ the Gaussian Lennard-Jones (GLJ) potential, which incorporates an attractive Gaussian potential between the surface and ligand atoms. Here, we develop this approach for the interaction between cobalt surfaces and carboxylate ligands. The accuracy of the GLJ approach is validated through the analysis of the interaction of oxygen with two distinct cobalt surfaces. The accuracy of this method reaches a root mean square deviation (RMSD) of about 3 kcal/mol across all probed configurations, which corresponds to a percentage error of roughly 4%. Application of the GLJ force field to the dynamics of the organic layer on these surfaces reveals how the ligand concentration influences the film order, and highlights differing mobility in the x and y directions, attributable to surface corrugation on Co(112̄0). GLJ is versatile, suitable for a broad range of metal/ligand systems, and can, subsequently, be utilized to study the organic film on the adsorption/desorption of reactants and products during a catalytic process.

One-Step Electrocatalytic Approach Applied to the Synthesis of ß-Propiolactones from CO2 and Dienes.

ß-Lactones are common substructures in a variety of natural products and drugs, and they serve as versatile synthetic intermediates in the production of valuable chemical derivatives. Traditional ß-lactone synthesis relies on laborious multi-step synthetic methods that use toxic compounds, sophisticated catalysts, expensive, and/or reactive chemicals. Based on the in situ electrochemical formation of metal-based nanoclusters, this paper describes the development of a one-step, room temperature electrocatalytic method for the formation of stable ß-lactone from CO2 and dienes. This one-step "electrosynthesis" method results in the formation of a new class of ß-lactone with high selectivity (up to 100%) and activity (up to 80% yields with respect to the reacted diene) by regulating the applied potential and current density. This work paves the way for more sustainable and environmentally friendly reaction pathways based on the in situ formation of nanoclusters as organic electrosynthesis catalysts.

Decapitation in the long-necked Triassic marine reptile Tanystropheus.

Extreme neck elongation was a common evolutionary strategy among Mesozoic marine reptiles, occurring independently in several lineages1,2. Despite its evolutionary success, such an elongate neck might have been particularly susceptible to predation1, but direct evidence for this possibility has been lacking. Composed of only 13 hyperelongate vertebrae and associated strut-like ribs, the configuration of the long neck of the Triassic archosauromorph Tanystropheus is unique among tetrapods. It was probably stiffened and used to catch prey through an ambush-strategy2. Here, we show that the neck was completely severed in two Tanystropheus specimens (Figure 1), most likely due to a predatory attack, providing vivid evidence of predator-prey interactions among Mesozoic marine reptiles that are rarely preserved in the fossil record. The recurring incidence of decapitation suggests that the elongate neck was a functional weak spot in Tanystropheus, and possibly the long-necked marine reptile bauplan more generally.

Knocking out alpha-synuclein in melanoma cells downregulates L1CAM and decreases motility.

The Parkinson's disease (PD) associated protein, alpha-synuclein (α-syn/SNCA), is highly expressed in aggressive melanomas. The goal of this study was to reveal possible mechanism(s) of α-syn involvement in melanoma pathogenesis. Herein, we asked whether α-syn modulates the expression of the pro-oncogenic adhesion molecules L1CAM and N-cadherin. We used two human melanoma cell lines (SK-MEL-28, SK-MEL-29), SNCA-knockout (KO) clones, and two human SH-SY5Y neuroblastoma cell lines. In the melanoma lines, loss of α-syn expression resulted in significant decreases in the expression of L1CAM and N-cadherin and concomitant significant decreases in motility. On average, there was a 75% reduction in motility in the four SNCA-KOs tested compared to control cells. Strikingly, comparing neuroblastoma SH-SY5Y cells that have no detectable α-syn to SH-SY5Y cells that stably express α-syn (SH/+αS), we found that expressing α-syn increased L1CAM and single-cell motility by 54% and 597%, respectively. The reduction in L1CAM level in SNCA-KO clones was not due to a transcriptional effect, rather we found that L1CAM is more efficiently degraded in the lysosome in SNCA-KO clones than in control cells. We propose that α-syn is pro-survival to melanoma (and possibly neuroblastoma) because it promotes the intracellular trafficking of L1CAM to the plasma membrane.

An Electrostatically Embedded QM/MM Scheme for Electrified Interfaces.

Atomistic modeling of electrified interfaces remains a major issue for detailed insights in electrocatalysis, corrosion, electrodeposition, batteries, and related devices such as pseudocapacitors. In these domains, the use of grand-canonical density functional theory (GC-DFT) in combination with implicit solvation models has become popular. GC-DFT can be conveniently applied not only to metallic surfaces but also to semiconducting oxides and sulfides and is, furthermore, sufficiently robust to achieve a consistent description of reaction pathways. However, the accuracy of implicit solvation models for solvation effects at interfaces is in general unknown. One promising way to overcome the limitations of implicit solvents is going toward hybrid quantum mechanical (QM)/molecular mechanics (MM) models. For capturing the electrochemical potential dependence, the key quantity is the capacitance, i.e., the relation between the surface charge and the electrochemical potential. In order to retrieve the electrochemical potential from a QM/MM hybrid scheme, an electrostatic embedding is required. Furthermore, the charge of the surface and of the solvent regions has to be strictly opposite in order to consistently simulate charge-neutral unit cells in MM and in QM. To achieve such a QM/MM scheme, we present the implementation of electrostatic embedding in the VASP code. This scheme is broadly applicable to any neutral or charged solid/liquid interface. Here, we demonstrate its use in the context of GC-DFT for the hydrogen evolution reaction (HER) over a noble-metal-free electrocatalyst, MoS2. We investigate the effect of electrostatic embedding compared to the implicit solvent model for three contrasting active sites on MoS2: (i) the sulfur vacancy defect, which is rather apolar; (ii) a Mo antisite defect, where the active site is a surface bound highly polar OH group; and (iii) a reconstructed edge site, which is generally believed to be responsible for most of the catalytic activity. According to our results, the electrostatic embedding leads to almost indistinguishable results compared to the implicit solvent for the apolar system but has a significant effect on polar sites. This demonstrates the reliability of the hybrid QM/MM, electrostatically embedded solvation model for electrified interfaces.

Toward a Realistic Surface State of Ru in Aqueous and Gaseous Environments.

Identifying the surface species is critical in developing a realistic understanding of supported metal catalysts working in water. To this end, we have characterized the surface species present at a Ru/water interface by employing a hybrid computational approach involving an explicit description of the liquid water and a possible pressure of H2. On the close-packed, most stable Ru(0001) facet, the solvation tends to favor the full dissociation of water into atomic O and H in contrast with the partially dissociated water layer reported for ultra-high-vacuum conditions. The solvation stabilization was found to reach -0.279 J m2, which results in stable O and H species on Ru(0001) in the presence of liquid water even at room temperature. Conversely, introducing even a small H2 pressure (10-2 bar) results in a monolayer of chemisorbed H at the interface, a general trend found on the three most exposed facets of Ru nanoparticles. While hydroxyls were often hypothesized as possible surface species at the Ru/water interface, this computational study clearly demonstrates that they are not stabilized by liquid water and are not found under realistic reductive catalytic conditions.

A new long-necked archosauromorph from the Guanling Formation (Anisian, Middle Triassic) of southwestern China and its implications for neck evolution in tanystropheids.

A long neck is an evolutionary innovation convergently appearing in multiple tetrapod lineages, including groups of plesiosaurs, non-archosauriform archosauromorphs, turtles, sauropodomorphs, birds, and mammals. Among all tetrapods both extant and extinct, two Triassic archosauromorphs, Tanystropheus and Dinocephalosaurus, have necks that are particularly elongated relative to the lengths of their trunks. However, the evolutionary history of such hyper-elongated necks in these two archosauromorph clades remains unknown, partially because known close relatives such as Macrocnemus and Pectodens possess only moderately elongated necks. Here, we describe a newly discovered early diverging archosauromorph, Gracilicollum latens gen. et sp. nov., based on a specimen comprising a partial neck and an incompletely preserved skull. The long neck is composed of at least 18 cervical vertebrae. The dentition suggests that this new taxon most likely represents an aquatic piscivore, similar to Dinocephalosaurus and Tanystropheus hydroides. Despite possessing a high number of cervical vertebrae, Gracilicollum gen. nov. is recovered as a tanystropheid in an evolutionary grade between Macrocnemus and Tanystropheus rather than as a close relative of Dinocephalosaurus, a result that is primarily attributable to the presence of palatal teeth and the anatomy of the cervical vertebrae in Gracilicollum gen. nov. Considering the information provided by the new specimen, we provide a detailed discussion of the cervical evolution in dinocephalosaurids and tanystropheids, which is shown to be highly complex and mosaic in nature.

Approaches to Assure Similarity between Pharmaceutical Heparins from Two Different Manufacturers.

Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. Heparins obtained from different tissues also differ in their structure and activity. Nevertheless, there is an increased demand for more accurate assessments to ensure the similarities of pharmaceutical heparins. We propose an approach to accurately assess the similarity of these pharmaceutical preparations based on well-defined criteria, which are verified with a variety of refined analytical methods. We evaluate six commercial batches from two different manufacturers which were formulated with Brazilian or Chinese active pharmaceutical ingredients. Biochemical and spectroscopic methods and analysis based on digestion with heparinases were employed to evaluate the purity and structure of the heparins. Specific assays were employed to evaluate the biological activity. We observed minor but significant differences between the constitutive units of the heparins from these two manufacturers, such as the content of N-acetylated α-glucosamine. They also have minor differences in their molecular masses. These physicochemical differences have no impact on the anticoagulant activity but can indicate particularities on their manufacturing processes. The protocol we propose here for analyzing the similarity of unfractionated heparins is analogous to those successfully employed to compare low-molecular-weight heparins.

MRI-based vertebral bone quality score compared to quantitative computed tomography bone mineral density in patients undergoing cervical spinal surgery.

PURPOSE: The vertebral bone quality (VBQ) score based on magnetic resonance imaging (MRI) was introduced as a bone quality marker in the lumbar spine. Prior studies showed that it could be utilized as a predictor of osteoporotic fracture or complications after instrumented spine surgery. The objective of this study was to evaluate the correlation between VBQ scores and bone mineral density (BMD) measured by quantitative computer tomography (QCT) in the cervical spine. METHODS: Preoperative cervical CT and sagittal T1-weighted MRIs from patients undergoing ACDF were retrospectively reviewed and included. The VBQ score in each cervical level was calculated by dividing the signal intensity of the vertebral body by the signal intensity of the cerebrospinal fluid on midsagittal T1-weighted MRI images and correlated with QCT measurements of the C2-T1 vertebral bodies. A total of 102 patients (37.3% female) were included. RESULTS: VBQ values of C2-T1 vertebrae strongly correlated with each other. C2 showed the highest VBQ value [Median (range) 2.33 (1.33, 4.23)] and T1 showed the lowest VBQ value [Median (range) 1.64 (0.81, 3.88)]. There was significant weak to moderate negative correlations between and VBQ Scores for all levels [C2: p < 0.001; C3: p < 0.001; C4: p < 0.001; C5: p < 0.004; C6: p < 0.001; C7: p < 0.025; T1: p < 0.001]. CONCLUSION: Our results indicate that cervical VBQ scores may be insufficient in the estimation of BMDs, which might limit their clinical application. Additional studies are recommended to determine the utility of VBQ and QCT BMD to evaluate their potential use as bone status markers.

Bone collagen quality in lumbar fusion patients: the association between volumetric bone mineral density and advanced glycation endproducts.

PURPOSE: The sole determination of volumetric bone mineral density (vBMD) is insufficient to evaluate overall bone integrity. The accumulation of advanced glycation endproducts (AGEs) stiffens and embrittles collagen fibers. Despite the important role of AGEs in bone aging, the relationship between AGEs and vBMD is poorly understood. We hypothesized that an accumulation of AGEs, a marker of impaired bone quality, is related to decreased vBMD. METHODS: Prospectively collected data of 127 patients undergoing lumbar fusion were analyzed. Quantitative computed tomography (QCT) measurements were performed at the lumbar spine. Intraoperative bone biopsies were obtained and analyzed with confocal fluorescence microscopy for fluorescent AGEs, both trabecular and cortical. Spearman's correlation coefficients were calculated to examine relationships between vBMD and fAGEs, stratified by sex. Multivariable linear regression analysis with adjustments for age, sex, body mass index (BMI), race, diabetes mellitus and HbA1c was used to investigate associations between vBMD and fAGEs. RESULTS: One-hundred and twenty-seven patients (51.2% female, 61.2 years, BMI of 28.7 kg/m2) with 107 bone biopsies were included in the final analysis, excluding patients on anti-osteoporotic drug therapy. In the univariate analysis, cortical fAGEs increased with decreasing vBMD at (r = -0.301; p = 0.030), but only in men. In the multivariable analysis, trabecular fAGEs increased with decreasing vBMD after adjusting for age, sex, BMI, race, diabetes mellitus and HbA1c (ß = 0.99;95%CI=(0.994,1.000); p = 0.04). CONCLUSION: QCT-derived vBMD measurements were found to be inversely associated with trabecular fAGEs. Our results enhance the understanding of bone integrity by suggesting that spine surgery patients with decreased bone quantity may also have poorer bone quality.

Loss of tumor suppressor menin expression in high grade cholangiocarcinomas.

BACKGROUND: MEN1, which codes for the protein menin, is a tumor suppressor in neuroendocrine tissue. In cholangiocarcinoma (CCA) cell lines the overexpression of menin decreased proliferation, angiogenesis, migration, and invasion in vitro and in xenografts, but its expression in CCA tumor tissue samples is not established. OBJECTIVE: Determine whether the expression of menin correlates with disease progression in patient samples of CCA in a tissue microarray (TMA) by immunohistochemical (IHC) staining. RESULTS: IHC analysis of 97 biopsies revealed that low-grade tumors (Grade I) exhibited intense, diffuse, finely granular nuclear menin immunoreactivity with a pronounced linear perinuclear pattern (mean IHC score = 2.00), whereas high-grade tumors (Grade III) mostly lacked such staining (mean IHC score = 0.35). Collectively, there was a significant inverse association between tumor grade and menin staining (P = 0.0005). We also found a significant association between fibrosis status and menin staining, in that, 81.2% (56/69) of patients without fibrosis had no menin staining, whereas 92.9% (26/28) patients with fibrosis exhibited menin staining (P < 0.0001). No association was found between fibrosis status and grade. Overall, menin expression is inversely associated with tumor grade and positively associated with fibrosis status.

Incidence, risk factors, and treatment of incidental durotomy during decompression in degenerative lumbar spine conditions.

BACKGROUND: The purpose of this study was to identify independent risk factors for incidental durotomy (ID) during decompressive lumbar spine surgery, and to describe its treatment. METHODS: This retrospective review includes 650 patients who underwent lumbar decompression at a tertiary institution between January 2015 and October 2019. Data collection was obtained through one independent researcher. The incidence rate and treatment of ID was evaluated by a chart review of operative notes, patient charts, physiotherapy reports, and nursing reports. RESULTS: The incidence rate of ID was 12.6%. The most common reason for admission was disc herniation (63.2%), followed by vertebral stenosis (22.1%). ID resulted in significantly longer operation time (P=0.0001) and length of hospitalization (P=0.0001). A correlation between ID and patient's diagnosis (P=0.0078) as well as the chosen type of surgery (P=0.0404) with an Odds Ratio to cause ID of 1.9 for laminectomy and 1.6 for undercutting compared to microdiscectomy were found. However, age, sex, surgeon experience, lumbar level, revision surgery, as well as multilevel surgery were not significantly correlated with the incidence of ID. Dural tears were closed with dural sealant (47.2%), polyester 4-0 sutures (11.1%) or a combination of both (37.5%) and the majority of patients had bed rest of at least two days. By usage of these treatment methods no patient needed reoperation. CONCLUSIONS: Diagnosis of vertebrostenosis as well as laminectomy were significantly correlated with the incidence of ID. Treatment with intraoperative closure and postoperative bed rest even though not standardized led to complication free outcomes.