Predicting intraoperative feasibility of combined TES-mMEP and cSSEP monitoring during scoliosis surgery based on preoperative neurophysiological assessment

Background contextCombined monitoring of muscle motor evoked potentials elicited by transcranial electric stimulation (TES-mMEP) and cortical somatosensory evoked potentials (cSSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, TES-mMEP/cSSEP is not always feasible. Predictors of feasibility would help to plan the monitoring strategy.PurposeTo identify predictors of the feasibility of TES-mMEP/cSSEP during scoliosis surgery.Study design/settingProspective cohort study in a clinical neurophysiology unit and pediatric orthopedic department of a French university hospital.Patient sampleA total of 103 children aged 2 to 19 years scheduled for scoliosis surgery.Outcome measuresFeasibility rate of intraoperative TES-mMEP/cSSEP monitoring.MethodsAll patients underwent a preoperative neurological evaluation and preoperative mMEP and cSSEP recordings at both legs. For each factor associated with feasibility, we computed sensitivity, specificity, positive predictive value (PPV), and negative predictive value. A decision tree was designed.ResultsPresence of any of the following factors was associated with 100% feasibility, 100% specificity, and 100% PPV: idiopathic scoliosis, normal preoperative neurological findings, and normal preoperative mMEP and cSSEP recordings. Feasibility was 0% in the eight patients with no recordable mMEPs or cSSEPs during preoperative testing. A decision tree involving three screening steps can be used to identify patients in whom intraoperative TES-mMEP/cSSEP is feasible.ConclusionsPreoperative neurological and neurophysiological assessments are helpful for identifying patients who can be successfully monitored by TES-mMEP/cSSEP during scoliosis surgery.     

Efficient in situ N-heterocyclic carbene palladium(ii) generated from Pd(OAc)2 catalysts for carbonylative Suzuki coupling reactions of arylboronic acids with 2-bromopyridine under inert conditions leading to unsymmetrical arylpyridine ketones: synthesis,characterization and cytotoxic activities

N,N-Substituted benzimidazole salts were successfully synthesized and characterized by ¹H-NMR, ¹³C {¹H} NMR and IR techniques, which support the proposed structures. Catalysts generated in situ were efficiently used for the carbonylative cross-coupling reaction of 2 bromopyridine with various boronic acids. The reaction was carried out in THF at 110 °C in the presence of K₂CO₃ under inert conditions and yields unsymmetrical arylpyridine ketones. All N,N-substituted benzimidazole salts 2a–i and 4a–i studied in this work were screened for their cytotoxic activities against human cancer cell lines such us MDA-MB-231, MCF-7 and T47D. The N,N-substituted benzimidazoles 2e and 2f exhibited the most cytotoxic effect with promising cytotoxic activity with IC₅₀ values of 4.45 μg mL⁻¹ against MDA-MB-231 and 4.85 μg mL⁻¹ against MCF7 respectively.

The in situ prepared four component system Pd(OAc)₂, 1,3-dialkylbenzimidazolium halides 2a–i and 4a–i, K₂CO₃ under CO atmosphere catalyses carbonylative cross-coupling reaction of 2-bromopyridine with various boronic acids to yield unsymmetrical arylpyridine ketones.     

Serum positive cagA in patients with non-ulcer dyspepsia and peptic ulcer disease from two centers in different regions of Turkey

AIM: To investigate and compare frequencies of serum positive cagA in patients from two separate regions of Turkey who were grouped according to the presence of peptic ulcer disease or non-ulcer dyspepsia. METHODS: One hundred and eighty Helicobacter pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia were included in the study. One hundred and fourteen patients had non-ulcer dyspepsia and 66 had peptic ulcer disease (32 with gastric ulcers and/or erosions and 34 with duodenal ulcers). Each patient was tested for serum antibody to H. pylori cagA protein by enzyme immunoassay. RESULTS: The total frequency of serum positive cagA in the study group was 97.2 %. The rates in the patients with peptic ulcers and in those with non-ulcer dyspepsia were 100 % and 95.6 %, respectively. These results were similar to those reported in Asian studies, but higher than those that have been noted in other studies from Turkey and Western countries. CONCLUSION: The high rates of serum positive cagA in these patients with peptic ulcer disease and non-ulcer dyspepsia were similar to results reported in Asia. The fact that there was high seroum prevalence regardless of ulcer status suggests that factors other than cagA might be responsible for ulceration or other types of severe pathology in H. pylori-positive individuals.     

Taurine attenuates lung ischemia–reperfusion injury after lung transplantation in rats

Purpose

Taurine, the major intracellular free amino acid found in high concentrations in mammalian cells, is known to be an endogenous antioxidant and a membrane-stabilizing agent. It was hypothesized that taurine may be effective in reducing ischemia–reperfusion injury after lung transplantation and an experimental study was conducted in a rat model.

Methods

The number of Sprague–Dawley rats used in the study was 35. Animals were randomized into five groups of 7 rats each, including control, donor I, donor II, ischemia–reperfusion injury, and treatment groups. All animals were exposed to the same experimental conditions in the preoperative period. Rats were fixed in a supine position after the induction. After the rats were shaved, a left pneumonectomy was performed following sternotomy in control, donor I, and donor II groups. The harvested grafts in donor I and donor II groups were transplanted to the rats of the ischemia–reperfusion group and treatment group, respectively. However, taurine was administered intraperitoneally for 3 days before the harvesting procedure in donor II. All harvested lungs were kept in a Euro-Collins solution at +4 °C for 24 h in a half-inflated manner. After harvesting and transplantation, lungs were sampled for histopathological and biochemical analysis.

Results

Malondialdehyde and superoxide dismutase, glutathione peroxidase, and catalase levels were lower in the treatment group than the other groups (p < 0.05). Histopathological findings were better in treatment group than the ischemia–reperfusion group (p < 0.05).

Conclusion

It was demonstrated that donor treatment with taurine resulted in preservation of transplanted lung tissue in respect to histopathological and biochemical findings.     

The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behçet's disease. A randomized clinical trial

Objective. Because exposure to streptococcal antigens might be a major disease activity—provoking factor in Behçet's disease, this study was undertaken to evaluate the effectiveness of benzathine penicillin in the prophylaxis of recurrent arthritis episodes during the course of this disease. Methods. A prospective, randomized study design was used to allocate patients to receive colchicine alone or colchicine plus benzathine penicillin for 24 months. Results. The duration, severity, and pattern of arthritis episodes were found to be similar in the 2 treatment groups, but the number of arthritis episodes was significantly reduced, and the duration of episode-free time significantly prolonged, in the penicillin group compared with the colchicine-alone group. Conclusion. Penicillin treatment was demonstrated to offer adjunctive benefits in the prevention of arthritis episodes which are not obtainable with colchicine monotherapy. This finding could provide additional evidence for antigen triggering in the pathogenesis of Behçet's disease.     

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t)ide analogs after liver transplantation.     

Intima-media thickness and arterial distensibility in Behçet's disease

The etiology of Beh?et's disease, a systemic vasculitis, is unknown. Vascular involvement may be seen in 25% of patients with Beh?et's disease. Vasculitis make the prognosis of Beh?et's disease severe. The aim of this study is to examine the structural and functional changes and relations of these changes with progression and prognosis of Beh?et's disease. For this purpose, 40 patients with Beh?et's disease and 40 healthy volunteer control subjects were analyzed, additionally patients with Beh?et's disease were divided into 2 subgroups as those with vascular complications and those without vascular complications. Intima-media thickness and arterial distensibility were measured in all subjects with carotid artery ultrasonography. Carotid artery distensibility was significantly lower in the patient group compared to the control group (0.67 +/- 0.2, 0.93 +/- 0.4, p < 0.05), and carotid artery IMT was significantly higher (0.59 +/- 12, 0.80 +/- 0.11, p < 0.05). A statistically significant increase in IMT has been detected (0.77 +/- 11, 0.86 +/- 11, p < 0.05) in patients with Beh?et's disease with vascular involvement compared to patients with Beh?et's disease without vascular involvement, arterial distensibility in patients with vascular disease was similar with those who has no vascular disease (0.69 +/- 0.25, 0.63 +/- 0.25, p > 0.05). There was a significant negative linear regression between arterial distensibility and systolic blood pressure (SBP) (B = -1 x 10(-2), p < 0.05), and a significant positive linear regression has also been found between IMT and SBP and diastolic blood pressure (DBP) and pulse pressure (PP) (B = 6.8 x 10(-3) for SBP, p < 0.05, B = 6.9 x 10(-3) for DBP, p < 0.05, B = 6 x 10(-3) for PP, p < 0.05). As a result, IMT increases and AD decreases in patients with Beh?et's disease compared to results in the control group. Although more studies are required for this subject, use of noninvasive parameters such as IMT and AD, which reflect the structural and functional characteristics of vasculature, may be useful to define disease progression and subjects at high risk.     

Atrioventricular Nodal Reentrant Tachycardia with Paroxysmal Atrial Fibrillation: Clinical and Electrophysiological Features and Predictors of Atrial Fibrillation Recurrence Following Elimination of Atrioventricular Nodal Reentrant Tachycardia

Introduction: Clinical and electrophysiological characteristics of patients with atrioventricular nodal reentrant tachycardia (AVNRT) and paroxysmal atrial fibrillation (AF) have not been studied in a large patient cohort. We aimed to define the clinical features and cardiac electrophysiological characteristics of these patients, and to examine the incidence and identify predictors of AF recurrences after elimination of AVNRT. Methods and Results: Thirty-six patients with AVNRT and documented paroxysmal AF (Group 1) and 497 patients with AVNRT alone undergoing ablation in the same period (Group 2) were studied. There were no significant differences between groups regarding clinical features, except age, which was higher in Group 1 (p < 0.001). Presence of atrial vulnerability (induction of AF lasting > 30 seconds) and multiple AH jumps (≥50 ms) before ablation were significantly more prevalent in Group 1 (p < 0.001, p = 0.010 respectively). During follow-up of 34 ± 11 months, AF recurred in 10 patients (28%) in Group 1, while 2 patients in Group 2 (0.4%) developed paroxysmal AF (p < 0.001). Univariate predictors of AF were: left atrial diameter > 40 mm (p = 0.001), presence of mitral or aortic calcification (p = 0.003), atrial vulnerability after ablation (p = 0.015) and valvular disease (p = 0.042). However, independent predictors of AF recurrences were left atrial diameter > 40 mm (p = 0.002) and the presence of atrial vulnerability after ablation (p = 0.034). Conclusion: In patients with both AVNRT and paroxysmal AF, the recurrence rate of AF after elimination of AVNRT is 28%. Left atrial diameter greater than 40 mm and atrial vulnerability after elimination of AVNRT are independent predictors of AF recurrences in the long term.     

A proposed unified interphase nucleus chromosome structure: Preliminary preponderance of evidence

Cryoelectron tomography of the cell nucleus using scanning transmission electron microscopy and deconvolution processing technology has highlighted a large-scale, 100- to 300-nm interphase chromosome structure, which is present throughout the nucleus. This study further documents and analyzes these chromosome structures. The paper is divided into four parts: 1) evidence (preliminary) for a unified interphase chromosome structure; 2) a proposed unified interphase chromosome architecture; 3) organization as chromosome territories (e.g., fitting the 46 human chromosomes into a 10-μm-diameter nucleus); and 4) structure unification into a polytene chromosome architecture and lampbrush chromosomes. Finally, the paper concludes with a living light microscopy cell study showing that the G1 nucleus contains very similar structures throughout. The main finding is that this chromosome structure appears to coil the 11-nm nucleosome fiber into a defined hollow structure, analogous to a Slinky helical spring [https://en.wikipedia.org/wiki/Slinky; motif used in Bowerman et al., eLife 10, e65587 (2021)]. This Slinky architecture can be used to build chromosome territories, extended to the polytene chromosome structure, as well as to the structure of lampbrush chromosomes.

A recent publication introduced iterative deconvolution for scanning transmission electron microscopy (TEM) tomograms of cryopreserved cellular structures (ref. 1 and references therein). Micron-thick areas of the vitrified cells were accessible without prior cryosectioning or lamella preparation. The deconvolution computation simplified interpretation of the tomograms by substantially filling the missing wedges of information that result from incomplete tilts. The effect was a substantial improvement in resolution along the depth (Z) direction. This technology made it possible to assess a tomogram from an area of the nucleus intact, in which large-scale interphase chromosome structures were noted (1).Here, the chromosome structures observed in these nuclear tomograms are further documented and analyzed. This paper is divided into four parts. The first part presents the evidence, preliminary but compelling, for a unified interphase chromosome structure. The second part presents the proposed unified interphase chromosome architecture. The third part shows that this interphase chromosome structure could be further organized as chromosome territories: for example, by fitting the 46 human chromosomes into a 10-μm-diameter nucleus. The fourth part unifies this structure into a polytene chromosome architecture and lampbrush chromosomes. The paper concludes with a living light microscopy cell study showing that the G1 nucleus has very similar structures throughout this organelle.The interphase nucleus encloses the genomic DNA, as well as the machinery for regulation of gene expression, RNA synthesis, and DNA replication (2). DNA is packaged into chromatin, the in vivo structure of which remains unclear. While mitotic chromosomes are highly condensed, interphase chromosomes decondense but remain in distinct territories with little overlap. Interphase chromatin is organized in a number of ways, including immutable gene-rich and -poor domains in the primary sequence and expression-promoting or -suppressing regions that may vary during the cell cycle or reflect cell differentiation (2). A classic distinction is drawn between euchromatin and heterochromatin, with the former more “open” and prone to expression, while the latter is more “closed” and prone to silencing (but see ref. 3). However, different methods, such as fluorescence and electron microscopy (EM), or posttranslational histone modifications, are sensitive to different parameters and do not necessarily agree in their identification.The predominant model to describe the path of the DNA strand in the interphase nucleus is the constrained random walk (4) or fractal globule (5, 6). At prophase, the dispersed polymers must recondense without entangling. During mitosis, the space-filling interphase chromatin condenses into a compact micrometer-sized structure. The degree of order in these structures remains undefined.The double-stranded DNA polymer itself, which in isolation appears as a semiflexible, right-hand helix 2 nm in diameter, winds tightly around core histones to form nucleosomes. Each nucleosome has a DNA footprint of 146 base pairs and a geometric diameter of ∼11 nm (7–9). Nucleosomes appear as beads on a string, but the density and spacing of nucleosomes along the DNA sequence may be highly variable (10). In the next stage, the nucleosomes are supposed to coil up into a 30-nm filament, possibly as a tight solenoid or alternatively with a zig-zag structure (11, 12). Today, the 30-nm filament is largely considered an artifact (13, 14). It has been observed in vitro, in isolated or ruptured nuclei, and in cases of deliberate manipulation of divalent cation concentration, but not in intact nuclei (13–15).Current insights into chromatin structure arise primarily from methods based on sequencing. With a number of significant variations, chromatin is cross-linked, cleaved, captured, and sequenced in order to determine which sequences lie in close proximity (5, 16). These methods have revealed a genetic structure of chromosome territories at the largest scale, active and inactive compartments at the multimega base level, followed by topologically associated domains (also known as TADs) whose regulation is controlled concomitantly even if they appear to be distant in sequence (16, 17). An overall, three-dimensional (3D) spatial map of the genome can be generated from the proximity constraints. Extension of the methods to analysis of individual cells revealed a strong heterogeneity, however, making it difficult to connect proximity data to local structure.Microscopy offers the most direct observations of structure, but specimen preparation may be disruptive. Classic EM requires fixation, followed by solvent-based dehydration and impregnation with a hardening polymer. Heavy metal salts are added to generate image contrast based on electron scattering; the indirect nature makes it difficult to interpret apparent density in terms of molecular composition (18). This limitation was circumvented by electron spectroscopic imaging, which distinguishes protein from nucleic acid on the basis of nitrogen and phosphorus concentrations (19). A recent advance used a DNA-binding dye to induce a localized polymerization of diaminobenzidine, which in turn binds an osmium stain (15). A modest density difference between euchromatin and heterochromatin was found, but no evidence was seen for long-range order (15). Fluorescence microscopy has made great advances with the introduction of superresolution methods. The combination with in situ hybridization permits even a degree of sequencing in situ. Still, long exposures and biochemical manipulations require strong cross-linking, which necessarily influences local structure. Cryoelectron tomography offers the most direct and pristine view of cellular structure, including chromatin, but conventional TEM requires thin sectioning or lamella fabrication using the focused ion beam microscope.Cryoscanning transmission electron tomography is a new addition to the toolkit of cellular imaging techniques. The most obvious advantages in relation to conventional defocus phase-contrast TEM are the ability to accommodate thicker specimens and the quantitative contrast based on electron scattering cross-sections. As implemented for cellular tomography, it provides: 1) a unipolar optical transfer function with the specimen in focus, 2) a long depth of field, and most importantly, 3) strong contrast for low spatial frequencies (20). We have recently demonstrated the application of cryoscanning transmission electron tomography in combination with 3D iterative deconvolution processing to whole-cell tomography and obtained a view of the cell nucleus that revealed unexpected large-scale structures (1).Data Considerations and Their Complexity.The primary data for this paper have considerably different attributes, such as the close-spaced 3D pixels with subtle gray level differences and textures, requiring new ways to display its details and architecture. This is a common problem for various imaging technologies (e.g., cellular cryoelectron tomography and MRI). The usual methods to visualize 3D data, such as moving up and down in the Z-dimension through two-dimensional (2D) slices, do not adequately show 3D relationships. Therefore, we propose the extensive use of stereo with extensions to circumvent this problem. Evidence for the chromosome structure is presented primarily in 3D stereo movies of various kinds (Movie S1 and rocking angular stereo pairs A to C′ presented in Movies S2–S8). Visualization guidance and challenges for the stereo movies are also discussed in depth in SI Appendix.