Consequences of polyploidy and divergence as revealed by cytogenetic mapping of tandem repeats in African clawed frogs (Xenopus, Pipidae).

Repetitive elements have been identified in several amphibian genomes using whole genome sequencing, but few studies have used cytogenetic mapping to visualize these elements in this vertebrate group. Here, we used fluorescence in situ hybridization and genomic data to map the U1 and U2 small nuclear RNAs and histone H3 in six species of African clawed frog (genus Xenopus), including, from subgenus Silurana, the diploid Xenopus tropicalis and its close allotetraploid relative X. calcaratus and, from subgenus Xenopus, the allotetraploid species X. pygmaeus, X. allofraseri, X. laevis, and X. muelleri. Results allowed us to qualitatively evaluate the relative roles of polyploidization and divergence in the evolution of repetitive elements because our focal species include allotetraploid species derived from two independent polyploidization events - one that is relatively young that gave rise to X. calcaratus and another that is older that gave rise to the other (older) allotetraploids. Our results demonstrated conserved loci number and position of signals in the species from subgenus Silurana; allotetraploid X. calcaratus has twice as many signals as diploid X. tropicalis. However, the content of repeats varied among the other allotetraploid species. We detected almost same number of signals in X. muelleri as in X. calcaratus and same number of signals in X. pygmaeus, X. allofraseri, X. laevis as in the diploid X. tropicalis. Overall, these results are consistent with the proposal that allopolyploidization duplicated these tandem repeats and that variation in their copy number was accumulated over time through reduction and expansion in a subset of the older allopolyploids.

Necessity of fusion following decompression surgery in patients with single-level lumbar stenosis: study protocol for an open-label multicentre non-inferiority randomized controlled clinical trial.

BACKGROUND: The necessity of spinal segment fusion after decompression is one of the most controversial and unresolved issues in single-level lumbar spinal stenosis surgery. To date, only one trial carried out 15 years ago focused on this problem. The key purpose of the current trial is to compare the long-term clinical results of the two surgical methods (decompression vs. decompression and fusion) in patients with single-level lumbar stenosis. METHODS: This study is focused on the non-inferior clinical results of decompression compared with the standard fusion procedure. In the decompression group, the spinous process, the interspinous and supraspinous ligaments, part of the facet joints, and corresponding parts of the vertebral arch are to be preserved intact. In the fusion group, decompression is to be supplemented with transforaminal interbody fusion. Participants meeting the inclusion criteria will be randomly divided into two equal groups (1:1), depending on the surgical method. The final analysis will include 86 patients (43 per group). The primary endpoint is Oswestry Disability Index dynamics at the end of the 24-month follow-up compared to the baseline level. Secondary outcomes included those estimated using the SF-36 scale, EQ-5D-5L, and psychological scales. Additional parameters will include sagittal balance of the spine, fusion results, total cost of surgery, and hospital stay followed by two-year treatment. Follow-up examinations will be performed at 3, 6, 12, and 24 months DISCUSSION: Authors suggest that this study will improve the evidence for application of various surgical techniques for lumbar spine stenosis surgery and verify the existing protocol for surgical management. TRIAL REGISTRATION: ClinicalTrials.gov NCT05273879 . Registered on March 10, 2022.

Teachability of lower cervical spine injury classifications.

OBJECTIVES: To compare the teachability of the Allen-Ferguson, Harris, Argenson, AOSpine, Subaxial Cervical Spine Injury Classification (SLIC), Subaxial Cervical Spine Injury Classification (CSISS) and to identify the classification that a group of residents and junior neurosurgeons find easiest to learn. METHODS: We used data from 64 consecutive patients. Answers of nine residents and junior neurosurgeons and four experienced surgeons in two assessment procedures were used. Six raters (workshop group) participated in special seminars between assessments. Three other raters formed the control group. Experienced surgeon's answers were used for comparison. Teachability was measured as the median value of the difference (ΔK) in the interrater agreement on the same patients by the same pairs of subjects. RESULTS: Median Δ K for the Allen-Ferguson, Harris, Argenson and AOSpine classifications were: (1) 0.01, 0.02, 0.29, and 0.39 for the workshop group; (2). 0.09, -0.03, 0.06 and 0.04 for the control group, respectively. Between numerical scales, median ΔK was higher for SLIC but did not exceed 0.16. Interrater consistency with expert's opinion was increased in the workshop group for Allen-Ferguson, Argenson and AOSpine and did not differ in either group for SLIC and CSISS. CONCLUSION: The AOSpine classification was the most teachable. Among numeric scales, SLIC demonstrated better results. The successful application of these classifications by residents and junior neurosurgeons was possible after a short educational course. The use of these scales in educational cycles at the stage of residency can significantly simplify the communication between specialists, especially at the stage of patient admission.

Divergent subgenome evolution in the allotetraploid frog Xenopus calcaratus.

Allopolyploid genomes are divided into compartments called subgenomes that are derived from lower ploidy ancestors. In African clawed frogs of the subgenus Xenopus (genus Xenopus), allotetraploid species have two subgenomes (L and S) with morphologically distinct homoeologous chromosomes. In allotetraploid species of the sister subgenus Silurana, independently evolved subgenomes also exist, but their cytogenetics has not been investigated in detail. We used a diverse suite of cytogenetic and molecular FISH techniques on an allotetraploid species in Silurana-Xenopus calcaratus-to explore evolutionary dynamics of chromosome morphology and rearrangements. We find that the subgenomes of X. calcaratus have distinctive characteristics, with a more conserved a-subgenome resembling the closely related genome of the diploid species X. tropicalis, and a more rapidly evolving b-subgenome having more pronounced changes in chromosome structure, including diverged heterochromatic blocks, repetitive sequences, and deletion of a nucleolar secondary constriction. Based on these cytogenetic differences, we propose a chromosome nomenclature for X. calcaratus that may apply to other allotetraploids in subgenus Silurana, depending on as yet unresolved details of their evolutionary origins. These findings highlight the potential for large-scale asymmetry in subgenome evolution following allopolyploidization.

Efficacy and Safety of Goel-Harms Technique in Upper Cervical Spine Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The main purpose of this systematic review and meta-analysis was to estimate the incidence of implant-associated complications and fusion rates for the Goel-Harms technique (GHT) and to show potential factors affecting the complications and nonunion development. METHODS: A systematic search of the PubMed database according to PRISMA guidance was performed. The main inclusion criteria comprised description of fusion rate and/or implant-associated complications rate. RESULTS: This systematic review included 86 articles focused on the results of surgery in 4208 patients. The rate of screw-related complications was as follows: 1) vertebral artery (VA) injury, 2.8%; 2) screw malposition in the direction of the VA, 5.8%; and 3) C2 nerve root irritation, 6.1%. The nonunion rate was 4.2%. Transpedicular screw insertion to the C1 and C2 vertebrae were the safest regarding VA injury and correlated with lower blood loss. For C1-C2 fusion, there was no statistical difference for the different bone graft localization. C2 nerve root irritation rate did not depend on screw insertion technique. The use of a freehand technique did not correlate with a high rate of screw-related complications. CONCLUSIONS: The Goel-Harms technique is a promising method of C1-C2 fusion, with a relatively low nonunion and VA injury rate. It can be performed safely without C-arm or navigation system assistance. Transpedicular screw insertion trajectories to the C1 and C2 vertebrae were safest regarding VA injury and blood loss volume. Further comparative studies of various C1-C2 stabilization methods with a high level of significance should be carried out to identify the optimal approach.

Factors Affecting the Outcomes of Traumatic Atlanto-Occipital Dislocations in Adults: A Systematic Review.

OBJECTIVE: The objectives of this study were to conduct a systematic review of the literature to determine the optimal treatment method for patients with atlanto-occipital dislocation (AOD) and to identify possible factors influencing their outcomes. METHODS: We conducted a systematic review of the PubMed database between January 1966 and December 2020. The main inclusion criterion was articles that discussed AOD treatment methods, and outcome descriptions were selected for analysis. Intergroup differences were assessed using nonparametric statistical methods. RESULTS: Of the 657 articles identified initially, only 54 met the inclusion criteria, resulting in data from 139 patients. Type I or II AODs were more frequent in patients injured in road traffic accidents, whereas type III AODs were more frequent in patients with catatrauma (P = 0.027). Spinal cord injury was more frequently observed in patients with types I and II AODs than in those with type III AOD (P = 0.026). Improved outcomes were more common in the surgical treatment group (P < 0.001). Significant differences in treatment outcomes between the halo device and orthosis groups were not observed (P = 0.32). CONCLUSIONS: Prognosis of AOD is unfavorable in adults with dislocations resulting from road traffic accidents, those with types I and II AOD, and patients younger than 22 years and older than 47 years. Surgical treatment was optimal for adult patients with an AOD, and treatment outcomes did not depend on the number of occipitocervical fusion levels. Immobilization with the halo device showed no advantages over use of an external orthosis.

The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results.

The treatment of glial brain tumors is an unresolved problem in neurooncology, and all existing methods (tumor resection, chemotherapy, radiotherapy, radiosurgery, fluorescence diagnostics, photodynamic therapy, etc.) are directed toward increasing progression-free survival for patients. Fluorescence diagnostics and photodynamic therapy are promising methods for achieving gross total resection and additional treatment of residual parts of the tumor. However, sometimes the use of one photosensitizer for photodynamic therapy does not help, and the time until tumor relapse barely increases. This translational case report describes the preliminary results of the first combined use of 5-ALA and chlorin e6 photosensitizers for fluorescence-guided resection and photodynamic therapy of glioblastoma, which allowed us to perform total resection of tumor tissue according to magnetic resonance and computed tomography images, remove additional tissue with increased fluorescence intensity without neurophysiological consequences, and perform additional therapy. Two months after surgery, no recurrent tumor and no contrast uptake in the tumor bed were detected. Additionally, the patient had ischemic changes in the access zone and along the periphery and cystic-glial changes in the left parietal lobe.

Xenogeneic Sertoli cells modulate immune response in an evolutionary distant mouse model through the production of interleukin-10 and PD-1 ligands expression.

BACKGROUND: Immunomodulatory mechanisms of Sertoli cells (SCs) during phylogeny have not been described previously. This study attempted to reveal mechanisms of SC immune modulation in an evolutionary distant host. METHODS: The interaction of the SC cell line derived from Xenopus tropicalis (XtSC) with murine immune cells was studied in vivo and in vitro. The changes in the cytokine production, the intracellular and surface molecules expression on murine immune cells were evaluated after co-culturing with XtSCs. Migration of XtSCs in mouse recipients after intravenous application and subsequent changes in spleen and the testicular immune environment were determined by flow cytometry. RESULTS: The in vitro co-culture model was established, allowing the study of XtSCs interaction with murine immune cells. Intracellular staining of interleukin (IL-)10 revealed a significant increase in its expression in macrophages and B cells co-cultured with XtSCs, compared to both unstimulated cells and xenogeneic control. On the contrary, a significant decrease in Th lymphocytes expressing interferon-gamma was observed. The expression of both PD-1 ligands (PD-L1 and PD-L2) was upregulated on the macrophage surfaces after co-culture with XtSCs, but not with the controls. XtSCs migrated specifically to testes when administered intravenously and modulated systemic and local testicular microenvironment; this was detected by the expression of molecules associated with suppressive phenotype by CD45+ cells in both spleen and testes. CONCLUSION: We have demonstrated for the first time that SCs can migrate and modulate immune response in a phylogenetically distant host. It was further observed that SCs induce expression of molecules associated with immunosuppression, such as IL-10 and PD-1 ligands.

A Pilot Study of Fluorescence-Guided Resection of Pituitary Adenomas with Chlorin e6 Photosensitizer.

Fluorescence diagnostics is one of the promising methods for intraoperative detection of brain tumor boundaries and helps in maximizing the extent of resection. This paper presents the results of a pilot study on the first use of the chlorin e6 photosensitizer and a two-channel video system for fluorescence-guided resection of pituitary adenomas. The study's clinical part involved two patients diagnosed with hormonally inactive pituitary macroadenomas and one patient with a hormonally active one. All neoplasms had different sizes and growth patterns. The data showed accumulation of chlorin e6 in tumor tissues in high concentrations: Patient 1: 2 mg/kg, Patient 2: 5 mg/kg, and Patient 3: 4 mg/kg. For Patient 1, the residual part of the tumor was not resected since it was intimately attached to the anterior genu of the internal carotid artery. For Patients 2 and 3, no regions of increased Ce6 accumulation were detected in the tumor foci after resection. Therefore, the use of the Ce6 and a two-channel video system helped to achieve a high degree of tumor resection in each case.

Fluoroscopic landmarks and trajectories for safe posterior percutaneous transarticular C1-C2 screw insertion: a CT-based simulation study.

PURPOSE: To determine the safe screw trajectory for posterior transarticular fixation of C1-C2 without direct visualisation of C2 lateral masses and by using fluoroscopic landmarks only. METHODS: Fluoroscopic models of the craniovertebral region in frontal and sagittal planes were reconstructed using 1-mm interval computed tomography scans of the cervical spine in 30 patients. The imitation model of the screw trajectory was then applied with verification of the exact screw localisation using multiplanar reconstruction. Twenty-seven trajectories for 60 oblique C1-C2 reformations were tested. RESULTS: In the frontal plane, all correct trajectories passed through the medial waistline point (WstP) of C3 and through the middle of the lateral mass of C1. In the lateral plane, the posterior spinal process-lateral mass (SpLM) point-middle C1 anterior tuberculum point (ATP), middle SpLM-upper ATP, and lower SpLM-odontoid point (ODP)-had relatively low rates of vertebral artery (VA) injury (2.3%, 4.6%, and 7%, respectively) and other screw malpositions (6.9%, 4.6%, and 4.6%, respectively). In cases of an isthmus height exceeding 8 mm, there were no incidences of VA injury. Patients with an isthmus width greater than 7 mm had a lower risk of screw malposition. CONCLUSION: We identified potentially safe trajectories for percutaneous posterior transarticular fixation of C1-C2. Using SpLM, ATP, and ODP landmarks in the lateral plane, and WstP and C1 middle landmarks in the frontal plane, it is possible to achieve an acceptable screw position without direct visualisation of the C2 lateral mass.

The impact of odontoid screw fixation techniques on screw-related complications and fusion rates: a systematic review and meta-analysis.

PURPOSE: The primary goal of this study was to conduct a systematic review and meta-analysis of articles focused on odontoid screw fixation (OSF) and screw-related complications or non-union rates. METHODS: We conducted a systematic review of the PubMed and Crossref databases between January 1982 and December 2019. Inclusion criteria comprised detailed descriptions of the surgical technique and screw-related complications (screw cut-out, loosening, breakage, malposition) or fusion rates. RESULTS: The initial selection consisted of 683 abstracts. A total of 150 full texts were chosen for detailed study, and 83 articles were included in the analysis. The point estimates for screw-related complications were as follows: 1. screw malposition frequency-4.8%; 2. screw cut-out rate-5.0%; 3. screw loosening/pull-out-3.8%; and 4. screw fracture rate-3.1%. The point estimate for the non-union rate was 9.7%. Statistical analysis of the screw-related complications rate based on surgical technique details was also performed CONCLUSIONS: Double-screw OSF performance in elder patients resulted in a higher risk of post-operative screw cut-out. In other cases, the development of screw-related complications did not depend on the method of intraoperative head fixation, selection of the implant entry point for OSF, type of the used screws, or cannulated instruments application. The outcomes of single-screw fixation through the anterior lip of the C2 vertebra were comparable to other techniques of OSF. Further, statistically reliable studies should be carried out to identify the optimal technique of OSF.

Transcervical approach with endoscopic assistance for surgical treatment of patient with irreducible atlantoaxial dislocation: a case report.

We demonstrate the case of a surgery in a patient with irreducible atlantoaxial dislocation (IrAAD) after C2 fracture. The challenges of this case were the flexed head in a forced position, impossibility of neck extension, and revision operation after posterior occipito-cervical fixation. The patient underwent the following surgeries: 1. A ventral release of C1-C2 using transcervical endoscopy; 2. Removal of occipito-cervical system and fibrous block resection in the posterior surfaces of the C1-C2; 3. Reducing of AAD and odontoid screw fixation; 4. Posterior C1-C2-C3 screw fixation. Ankylosing of C1-C2 and C2-C3-C4 fusion was verified by computed tomography scan. There was an improvement in patient status as observed by the increase of the SF-36 scale scores. The use of endoscopic transcervical approach is a good alternative to the transoral approach. Comparative studies of these methods should be performed regarding the choice of an optimal method of decompression in cases of IrAAD.

Posterior percutaneous transarticular stand-alone screw instrumentation of C1-C2 with endoscopic assistance: A report of two cases.

We present two cases of minimally invasive posterior transarticular screw fixation of C1-C2. The points for screw insertion were visualized by endoscopy via the instrumental port. A patient with a type III odontoid fracture with subluxation underwent a minimally invasive posterior stand-alone transarticular screw fixation. Despite the application of compression screws, for technical reasons, only minimal compression on the anterior third of the C1-C2 lateral joint was achieved. However, complete fracture fusion was achieved with stable fibrous C1-C2 fusion 2.5 years postoperatively. A second patient with a chronic type II odontoid fracture underwent percutaneous C1-C2 fixation by the same method. After 2 years, fracture fusion and C1-C2 lateral mass ankylosis were achieved. The use of a tubular retractor and endoscopy in stand-alone screw fixation of C1-C2 allows direct visualization of the screw entry point and decreases surgical trauma. This procedure might be an alternative to other methods of transarticular instrumentation.

External Multicenter Study of Reliability and Reproducibility for Lower Cervical Spine Injuries Classification Systems-Part 2: An Analysis of the Subaxial Cervical Spine Injury Classification and Cervical Spine Injury Severity Score Scale.

STUDY DESIGN: A multicenter observational survey. OBJECTIVE: To quantify and compare inter- and intraobserver reliability of the subaxial cervical spine injury classification (SLIC) and the cervical spine injury severity score (CSISS) in a multicentric survey of neurosurgeons with different experience levels. METHODS: Data concerning 64 consecutive patients who had undergone cervical spine surgery between 2013 and 2017 was evaluated, and we surveyed 37 neurosurgeons from 7 different clinics. All raters were divided into 3 groups depending on their level of experience. Two assessment procedures were performed. RESULTS: For the SLIC, we observed excellent agreement regarding management among experienced surgeons, whereas agreement among less experienced neurosurgeons was moderate and almost twice as unlikely. The sensitivity of SLIC relating to treatment tactics reached as high as 92.2%. For the CSISS, agreement regarding management ranged from medium to substantial, depending on a neurosurgeon's experience. For less experienced neurosurgeons, the level of agreement concerning surgical management was the same as for the SLIC in not exceeding a moderate level. However, this scale had insufficient sensitivity (slightly exceeding 50%). The reproducibility of both scales was excellent among all raters regardless of their experience level. CONCLUSIONS: Our study demonstrated better management reliability, sensitivity, and reproducibility for the SLIC, which provided moderate interrater agreement with moderate to excellent intraclass correlation coefficient indicators for all raters. The CSISS demonstrated high reproducibility; however, large variability in answers prevented raters from reaching a moderate level of agreement. Magnetic resonance imaging integration may increase sensitivity of CSISS in relation to fracture management.

Sex chromosome evolution in frogs-helpful insights from chromosome painting in the genus Engystomops.

The differentiation of sex chromosomes is thought to be interrupted by relatively frequent sex chromosome turnover and/or occasional recombination between sex chromosomes (fountain-of-youth model) in some vertebrate groups as fishes, amphibians, and lizards. As a result, we observe the prevalence of homomorphic sex chromosomes in these groups. Here, we provide evidence for the loss of sex chromosome heteromorphism in the Amazonian frogs of the genus Engystomops, which harbors an intriguing history of sex chromosome evolution. In this species complex composed of two named species, two confirmed unnamed species, and up to three unconfirmed species, highly divergent karyotypes are present, and heteromorphic X and Y chromosomes were previously found in two species. We describe the karyotype of a lineage estimated to be the sister of all remaining Amazonian Engystomops (named Engystomops sp.) and perform chromosome painting techniques using one probe for the Y chromosome and one probe for the non-centromeric heterochromatic bands of the X chromosome of E. freibergi to compare three Engystomops karyotypes. The Y probe detected the Y chromosomes of E. freibergi and E. petersi and one homolog of chromosome pair 11 of Engystomops sp., suggesting their common evolutionary origin. The X probe showed no interspecific hybridization, revealing that X chromosome heterochromatin is strongly divergent among the studied species. In the light of the phylogenetic relationships, our data suggest that sex chromosome heteromorphism may have occurred early in the evolution of the Amazonian Engystomops and have been lost in two unnamed but confirmed candidate species.

A Translational Study on Acute Traumatic Brain Injury: High Incidence of Epileptiform Activity on Human and Rat Electrocorticograms and Histological Correlates in Rats.

BACKGROUND: In humans, early pathological activity on invasive electrocorticograms (ECoGs) and its putative association with pathomorphology in the early period of traumatic brain injury (TBI) remains obscure. METHODS: We assessed pathological activity on scalp electroencephalograms (EEGs) and ECoGs in patients with acute TBI, early electrophysiological changes after lateral fluid percussion brain injury (FPI), and electrophysiological correlates of hippocampal damage (microgliosis and neuronal loss), a week after TBI in rats. RESULTS: Epileptiform activity on ECoGs was evident in 86% of patients during the acute period of TBI, ECoGs being more sensitive to epileptiform and periodic discharges. A "brush-like" ECoG pattern superimposed over rhythmic delta activity and periodic discharge was described for the first time in acute TBI. In rats, FPI increased high-amplitude spike incidence in the neocortex and, most expressed, in the ipsilateral hippocampus, induced hippocampal microgliosis and neuronal loss, ipsilateral dentate gyrus being most vulnerable, a week after TBI. Epileptiform spike incidence correlated with microglial cell density and neuronal loss in the ipsilateral hippocampus. CONCLUSION: Epileptiform activity is frequent in the acute period of TBI period and is associated with distant hippocampal damage on a microscopic level. This damage is probably involved in late consequences of TBI. The FPI model is suitable for exploring pathogenetic mechanisms of post-traumatic disorders.

External Multicenter Study of Reliability and Reproducibility for Lower Cervical Spine Injuries Classification Systems-Part 1: A Comparison of Morphological Schemes.

STUDY DESIGN: Multicenter observational survey study. OBJECTIVES: To quantify and compare the inter- and intraobserver reliability of Allen-Fergusson (A-F), Harris, Argenson, and AOSpine (AOS) classifications for cervical spine injuries, in a multicentric survey of neurosurgeons with different levels of experience. METHODS: We used data of 64 consecutive patients. Totally, 37 surgeons (from 7 centers), were included in the study. The initial assessment was returned by 36 raters. The second assessment performed after 1.5 months included 24 raters. RESULTS: We received 15 111 answers for 3840 evaluations. Raters reached a fair general agreement of the A-F scale, while the experienced group achieved κ = 0.39. While all groups showed moderate interrater reliability for primary assessment of Harris scale (κ = 0.44), the κ value for experts decreased from 0.58 to 0.49. The Argenson scale demonstrated moderate and substantial agreement among all raters (κ = 0.47 and κ = 0.55, respectively). The AOS scheme primary assessment general kappa value for all types of injuries and across all raters was 0.49, reaching substantial agreement among experts (κ = 0.62) with moderate agreement across beginner and intermediate groups (κ = 0.48 and κ = 0.44, respectively). The second assessment general agreement kappa value reached 0.56. CONCLUSIONS: We found the highest values of interobserver agreement and reproducibility among surgeons with different levels of experience with Argenson and AOSpine classifications. The AOSpine scale additionally incorporated more detailed description of compression injuries and facet-joint fractures. Agreement levels reached for Allen-Fergusson and Harris scales were fair and moderate, respectively, indicating difficulty of their application in clinical practice, especially by junior specialists.

Appliance of Navigated Transcranial Magnetic Stimulation in Radiosurgery for Brain Metastases.

PURPOSE: Navigated transcranial magnetic stimulation (nTMS) provides noninvasive visualization of eloquent brain areas. The nTMS is usually applied in presurgical planning to minimize the risk of surgery-related neurological deterioration. The aim of this study was to evaluate the usefulness of nTMS data for GammaKnife treatment planning for patients suffering from brain metastases. METHODS: Motor cortex mapping with nTMS was performed in eight patients with brain metastases within or adjacent to the precentral gyrus. The nTMS data set was imported into the planning software and fused with anatomical MRI. Then contouring of the target and critical structures was performed. Treatment plans with and without visualization of the functional structures by nTMS were analyzed and compared by neurosurgeon and medical physicist. RESULTS: The primary motor cortex was successfully delineated even in all cases despite significant peritumoral edema. Beam shaping and combined isocenters were used for conformal dose distribution and steeper dose fall-off near the identified eloquent zone. Compared with plans without nTMS data, treatment plans with integration of cortical nTMS mapping data showed a 2% to 78% (mean, 35.2% ± 22.7%) lower 12-Gy volume within the motor cortex without reduction of the dose applied to the tumor. CONCLUSIONS: The presented approach allows the easy and reliable integration of neurophysiological mapping data into GammaKnife treatment plans by the standard GammaPlan software. Diminishing the dose to critical structures might help to minimize side effects and therefore improve quality of life for brain metastasis patients.

The interconnection between cytokeratin and cell membrane-bound ß-catenin in Sertoli cells derived from juvenile Xenopus tropicalis testes.

Sertoli cells (SCs) play a central role in the determination of male sex during embryogenesis and spermatogenesis in adulthood. Failure in SC development is responsible for male sterility and testicular cancer. Before the onset of puberty, SCs are immature and differ considerably from mature cells in post-pubertal individuals regarding their morphology and biochemical activity. The major intermediate filament (IF) in mature SCs is vimentin, anchoring germ cells to the seminiferous epithelium. The collapse of vimentin has resulted in the disintegration of seminiferous epithelium and subsequent germ cell apoptosis. However, another IF, cytokeratin (CK) is observed only transiently in immature SCs in many species. Nevertheless, its function in SC differentiation is poorly understood. We examined the interconnection between CK and cell junctions using membrane ß-catenin as a marker during testicular development in the Xenopus tropicalis model. Immunohistochemistry on juvenile (5 months old) testes revealed co-expression of CK, membrane ß-catenin and E-cadherin. Adult (3-year-old males) samples confirmed only E-cadherin expression; CK and ß-catenin were lost. To study the interconnection between CK and ß-catenin-based cell junctions, the culture of immature SCs (here called XtiSCs) was employed. Suppression of CK by acrylamide in XtiSCs led to breakdown of membrane-bound ß-catenin but not F-actin and ß-tubulin or cell-adhesion proteins (focal adhesion kinase and integrin ß1). In contrast to the obvious dependence of membrane ß-catenin on CK stability, the detachment of ß-catenin from the plasma membrane via uncoupling of cadherins by Ca2+ chelator EGTA had no effect on CK integrity. Interestingly, CHIR99021, a GSK3 inhibitor, also suppressed the CK network, resulting in the inhibition of XtiSCs cell-to-cell contacts and testicular development in juvenile frogs. This study suggests a novel role of CK in the retention of ß-catenin-based junctions in immature SCs, and thus provides structural support for seminiferous tubule formation and germ cell development.

Avian Expression Patterns and Genomic Mapping Implicate Leptin in Digestion and TNF in Immunity, Suggesting That Their Interacting Adipokine Role Has Been Acquired Only in Mammals

In mammals, leptin and tumor-necrosis factor (TNF) are prominent interacting adipokines mediating appetite control and insulin sensitivity. While TNF pleiotropically functions in immune defense and cell survival, leptin is largely confined to signaling energy stores in adipocytes. Knowledge about the function of avian leptin and TNF is limited and they are absent or lowly expressed in adipose, respectively. Employing radiation-hybrid mapping and FISH-TSA, we mapped TNF and its syntenic genes to chicken chromosome 16 within the major histocompatibility complex (MHC) region. This mapping position suggests that avian TNF has a role in regulating immune response. To test its possible interaction with leptin within the immune system and beyond, we compared the transcription patterns of TNF, leptin and their cognate receptors obtained by meta-analysis of GenBank RNA-seq data. While expression of leptin and its receptor (LEPR) were detected in the brain and digestive tract, TNF and its receptor mRNAs were primarily found in viral-infected and LPS-treated leukocytes. We confirmed leptin expression in the duodenum by immunohistochemistry staining. Altogether, we suggest that whereas leptin and TNF interact as adipokines in mammals, in birds, they have distinct roles. Thus, the interaction between leptin and TNF may be unique to mammals.