A Label-Efficient Framework for Automated Sinonasal CT Segmentation in Image-Guided Surgery.

OBJECTIVE: Segmentation, the partitioning of patient imaging into multiple, labeled segments, has several potential clinical benefits but when performed manually is tedious and resource intensive. Automated deep learning (DL)-based segmentation methods can streamline the process. The objective of this study was to evaluate a label-efficient DL pipeline that requires only a small number of annotated scans for semantic segmentation of sinonasal structures in CT scans. STUDY DESIGN: Retrospective cohort study. SETTING: Academic institution. METHODS: Forty CT scans were used in this study including 16 scans in which the nasal septum (NS), inferior turbinate (IT), maxillary sinus (MS), and optic nerve (ON) were manually annotated using an open-source software. A label-efficient DL framework was used to train jointly on a few manually labeled scans and the remaining unlabeled scans. Quantitative analysis was then performed to obtain the number of annotated scans needed to achieve submillimeter average surface distances (ASDs). RESULTS: Our findings reveal that merely four labeled scans are necessary to achieve median submillimeter ASDs for large sinonasal structures-NS (0.96 mm), IT (0.74 mm), and MS (0.43 mm), whereas eight scans are required for smaller structures-ON (0.80 mm). CONCLUSION: We have evaluated a label-efficient pipeline for segmentation of sinonasal structures. Empirical results demonstrate that automated DL methods can achieve submillimeter accuracy using a small number of labeled CT scans. Our pipeline has the potential to improve pre-operative planning workflows, robotic- and image-guidance navigation systems, computer-assisted diagnosis, and the construction of statistical shape models to quantify population variations. LEVEL OF EVIDENCE: N/A.

An endoscopic chisel: intraoperative imaging carves 3D anatomical models.

PURPOSE: Preoperative imaging plays a pivotal role in sinus surgery where CTs offer patient-specific insights of complex anatomy, enabling real-time intraoperative navigation to complement endoscopy imaging. However, surgery elicits anatomical changes not represented in the preoperative model, generating an inaccurate basis for navigation during surgery progression. METHODS: We propose a first vision-based approach to update the preoperative 3D anatomical model leveraging intraoperative endoscopic video for navigated sinus surgery where relative camera poses are known. We rely on comparisons of intraoperative monocular depth estimates and preoperative depth renders to identify modified regions. The new depths are integrated in these regions through volumetric fusion in a truncated signed distance function representation to generate an intraoperative 3D model that reflects tissue manipulation RESULTS: We quantitatively evaluate our approach by sequentially updating models for a five-step surgical progression in an ex vivo specimen. We compute the error between correspondences from the updated model and ground-truth intraoperative CT in the region of anatomical modification. The resulting models show a decrease in error during surgical progression as opposed to increasing when no update is employed. CONCLUSION: Our findings suggest that preoperative 3D anatomical models can be updated using intraoperative endoscopy video in navigated sinus surgery. Future work will investigate improvements to monocular depth estimation as well as removing the need for external navigation systems. The resulting ability to continuously update the patient model may provide surgeons with a more precise understanding of the current anatomical state and paves the way toward a digital twin paradigm for sinus surgery.

Heterochromatin Is Not the Only Place for satDNAs: The High Diversity of satDNAs in the Euchromatin of the Beetle Chrysolina americana (Coleoptera, Chrysomelidae).

The satellitome of the beetle Chrysolina americana Linneo, 1758 has been characterized through chromosomal analysis, genomic sequencing, and bioinformatics tools. C-banding reveals the presence of constitutive heterochromatin blocks enriched in A+T content, primarily located in pericentromeric regions. Furthermore, a comprehensive satellitome analysis unveils the extensive diversity of satellite DNA families within the genome of C. americana. Using fluorescence in situ hybridization techniques and the innovative CHRISMAPP approach, we precisely map the localization of satDNA families on assembled chromosomes, providing insights into their organization and distribution patterns. Among the 165 identified satDNA families, only three of them exhibit a remarkable amplification and accumulation, forming large blocks predominantly in pericentromeric regions. In contrast, the remaining, less abundant satDNA families are dispersed throughout euchromatic regions, challenging the traditional association of satDNA with heterochromatin. Overall, our findings underscore the complexity of repetitive DNA elements in the genome of C. americana and emphasize the need for further exploration to elucidate their functional significance and evolutionary implications.

Management of Urgent Bleeding in Patients with Hemophilia A: Focus on the Use of Emicizumab.

Management of patients with hemophilia A (HA) requires the knowledge and experience of specialized health care professionals. However, these patients may need to be attended in emergencies, outside the referral hospital, where health care professionals do not know about hemophilia and/or new innovative treatments. This study aimed to develop a simple and practical algorithm that could be used in emergency situations by nonspecialized treaters in HA and bleeding with or without factor VIII (FVIII) inhibitors under emicizumab prophylaxis. A group of experts agreed on a simple algorithm, easy to operate, adapted from previous international guidelines, and based on their clinical experience. The proposed algorithm starts with identifying the patient, confirming the diagnosis of HA, prophylaxis with emicizumab, and/or use of other treatments. After stabilizing the patient and stratifying the bleeding risk, the patient is managed according to the presence/absence of FVIII inhibitors. Patients without FVIII inhibitors should receive FVIII concentrate. Dose and follow-up depend on bleeding localization and severity. Patients with FVIII inhibitors should preferably receive recombinant activated factor VII as bypass agent. A basic coagulation assay, FVIII assessment, and FVIII inhibitors detection assays are necessary in an emergency. However, these tests should be interpreted with caution and appropriately chosen, as emicizumab may alter the results. The management of patients with HA is challenging in emergency situations, especially if they are treated with new agents. Nonspecialized in coagulopathies health care professionals have limited understanding of the disease, highlighting the need for an algorithm to assist them in making informed decisions.

Platelet C3G: a key player in vesicle exocytosis, spreading and clot retraction.

C3G is a Rap1 GEF that plays a pivotal role in platelet-mediated processes such as angiogenesis, tumor growth, and metastasis by modulating the platelet secretome. Here, we explore the mechanisms through which C3G governs platelet secretion. For this, we utilized animal models featuring either overexpression or deletion of C3G in platelets, as well as PC12 cell clones expressing C3G mutants. We found that C3G specifically regulates α-granule secretion via PKCδ, but it does not affect δ-granules or lysosomes. C3G activated RalA through a GEF-dependent mechanism, facilitating vesicle docking, while interfering with the formation of the trans-SNARE complex, thereby restricting vesicle fusion. Furthermore, C3G promotes the formation of lamellipodia during platelet spreading on specific substrates by enhancing actin polymerization via Src and Rac1-Arp2/3 pathways, but not Rap1. Consequently, C3G deletion in platelets favored kiss-and-run exocytosis. C3G also controlled granule secretion in PC12 cells, including pore formation. Additionally, C3G-deficient platelets exhibited reduced phosphatidylserine exposure, resulting in decreased thrombin generation, which along with defective actin polymerization and spreading, led to impaired clot retraction. In summary, platelet C3G plays a dual role by facilitating platelet spreading and clot retraction through the promotion of outside-in signaling while concurrently downregulating α-granule secretion by restricting granule fusion.

Exploring horizontal transfer of mariner transposable elements among ants and aphids.

Aphids and ants are mutualistic species with a close space-time relationship, which may facilitate the occurrence of horizontal transfer events between these insect groups. Myrmar-like mariner elements were previously isolated from two ant (Myrmica ruginodis and Tapinoma ibericum) and two aphid species (Aphis fabae and Aphis hederae). The aim of this work is to determine the presence of Myrmar-like mariner elements in new ant and aphid species, as well as to analyze the likelihood of horizontal transfer events between these taxa. To accomplish this, the Myrmar-like element has been isolated from five aphid species and six ant species. Among these new analyzed species, full-length Myrmar-like mariner elements with very high sequence similarity have been isolated from the aphids Aphis nerii, Aphis spiraecola, Brachycaudus cardui, and Rhopalosiphum maidis as well as from the ants Lasius grandis and Lasius niger, even though aphids and ants belong to two insect orders (Hemiptera and Hymenoptera) that have evolved independently for at least 300 million-years. Both Lasius species establish frequent mutualistic relationships with multiple aphid species, including A. nerii, A. spiraecola, and B. cardui. The study of the putative protein encoded by them and the phylogenetic analysis suggests that they could be active transposons shared by aphids and ants through horizontal transfer events. Additionally, mariner elements with internal deletion were found in several aphids and one ant species, showing a high degree of sequence similarity among them. The characteristics of these elements with internal deletion suggest a complex origin involving various evolutionary processes, possibly including also horizontal transfer events. Myrmar-like elements have also been isolated from the other ant species, although without similarity with the aphid mariner sequences. Myrmar-like elements are also present in phylogenetically distant insect species, as well as in one crustacean species. The phylogenetic study carried out with all Myrmar-like elements suggests the probable occurrence of horizontal transfer events.

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry.

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 (p = 6.8 × 103, OR = 7.56[1.64-51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.

SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of "long COVID" neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y MA30 , we demonstrated that intranasal inoculation of SARS2-N501Y MA30 results in viral dissemination to multiple brain regions, including the amygdala and hippocampus. Behavioral assays show a significant increase in anxiety- and depression-like behaviors 14 days following viral infection. Moreover, we observed microglia activation following SARS2-N501Y MA30 infection, along with an augmentation in microglia-dependent neuronal activity in the amygdala. Pharmacological inhibition of microglial activity subsequent to viral spike inoculation mitigates microglia-dependent neuronal hyperactivity. Furthermore, transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating microglia-driven neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. Overall, these data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.

Viral codon optimization on SARS-CoV-2 Spike boosts immunity in the development of COVID-19 mRNA vaccines.

Life-long persistent herpesviruses carry "trans-inducers" to overcome the unusual codon usage of their glycoproteins for efficient expression. Strikingly, this "trans-inducibility" can be achieved by simply changing the codon-usage of acute virus glycoproteins to that of persistent herpesvirus glycoproteins with herpesviral trans-inducer. Here, we apply the "persistent viral codon-usage-trans-inducer" principle to SARS-CoV-2 Spike mRNA vaccine platform, in which the codon-usage of Spike is changed to that of Herpes Simplex Virus-1 (HSV-1) glycoprotein B (gB) with its "trans-inducer" ICP27. The HSVgB-ICP27-codon-optimized Spike mRNA vaccine induced markedly high antigen expression and stability, total IgG, neutralizing antibody, and T cell response, ultimately enhancing protection against lethal SARS-CoV-2 challenge. Moreover, the HSVgB- codon-optimized Delta (B.1.617.2) strain Spike mRNA vaccine provided significant enhancements in antigen expression and long-term protection against SARS-CoV-2 challenge. Thus, we report a novel persistent viral codon-usage-trans-inducer mRNA vaccine platform for enhanced antigen expression and long-term protection against lethal viral infection.

The spread of satellite DNAs in euchromatin and insights into the multiple sex chromosome evolution in Hemiptera revealed by repeatome analysis of the bug Oxycarenus hyalinipennis.

Satellite DNAs (satDNAs) are highly repeated tandem sequences primarily located in heterochromatin, although their occurrence in euchromatin has been reported. Here, our aim was to advance the understanding of satDNA and multiple sex chromosome evolution in heteropterans. We combined cytogenetic and genomic approaches to study, for the first time, the satDNA composition of the genome in an Oxycarenidae bug, Oxycarenus hyalinipennis. The species exhibits a male karyotype of 2n = 19 (14A + 2 m + X1 X2 Y), with a highly differentiated Y chromosome, as demonstrated by C-banding and comparative genomic hybridization, revealing an enrichment of repeats from the male genome. Additionally, comparative analysis between males and females revealed that the 26 identified satDNA families are significantly biased towards male genome, accumulating in discrete regions in the Y chromosome. Exceptionally, the OhyaSat04-125 family was found to be distributed virtually throughout the entire extension of the Y chromosome. This suggests an important role of satDNA in Y chromosome differentiation, in comparison of other repeats, which collectively shows similar abundance between sexes, about 50%. Furthermore, chromosomal mapping of all satDNA families revealed an unexpected high spread in euchromatic regions, covering the entire extension, irrespective of their abundance. Only discrete regions of heterochromatin on the Y chromosome and of the m-chromosomes (peculiar chromosomes commonly observed in heteropterans) were enriched with satDNAs. The putative causes of the intense enrichment of satDNAs in euchromatin are discussed, including the possible existence of burst cycles similar to transposable elements and as a result of holocentricity. These data challenge the classical notion that euchromatin is not enriched with satDNAs.

An asynchronous web-based intervention for neurosurgery residents to improve education on cost-effective care.

OBJECTIVE: To gauge resident knowledge in the socioeconomic aspects of neurosurgery and assess the efficacy of an asynchronous, longitudinal, web-based, socioeconomics educational program tailored for neurosurgery residents. METHODS: Trainees completed a 20-question pre- and post-intervention knowledge examination including four educational categories: billing/coding, procedure-specific concepts, material costs, and operating room protocols. Structured data from 12 index cranial neurosurgical operations were organized into 5 online, case-based modules sent to residents within a single training program via weekly e-mail. Content from each educational category was integrated into the weekly modules for resident review. RESULTS: Twenty-seven neurosurgical residents completed the survey. Overall, there was no statistically significant difference between pre- vs post-intervention resident knowledge of billing/coding (79.2 % vs 88.2 %, p = 0.33), procedure-specific concepts (34.3 % vs 39.2 %, p = 0.11), material costs (31.7 % vs 21.6 %, p = 0.75), or operating room protocols (51.7 % vs 35.3 %, p = 0.61). However, respondents' accuracy increased significantly by 40.8 % on questions containing content presented more than 3 times during the 5-week study period, compared to an increased accuracy of only 2.2 % on questions containing content presented less often during the same time period (p = 0.05). CONCLUSIONS: Baseline resident knowledge in socioeconomic aspects of neurosurgery is relatively lacking outside of billing/coding. Our socioeconomic educational intervention demonstrates some promise in improving socioeconomic knowledge among neurosurgery trainees, particularly when content is presented frequently. This decentralized, web-based approach to resident education may serve as a future model for self-driven learning initiatives among neurosurgical residents with minimal disruption to existing workflows.

Clinical and Biomarker Profile Responses to Rehabilitation Treatment in Patients with Long COVID Characterized by Chronic Fatigue.

Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after SARS-CoV-2 infection. The most frequently associated symptom is fatigue. Physical activity and exercise are recommended, although specific studies are lacking. The objectives of the present work are to analyze the impact of a supervised exercise program on the clinical evolution of LC with fatigue patients and to identify whether certain circulating biomarkers could predict the response to rehabilitation. The rehabilitation treatment response was analyzed in 14 women diagnosed with LC and fatigue, based on the changes in the 6 min walk test and Borg/Fatigue Impact scales. Patients who showed improvement in the meters walked were considered "responders" to the therapy. A total of 65% of patients responded to the exercise program, with an improvement in the meters walked and in oxygen saturation, with stability in the percentage of meters walked. Participants with obesity and those double-vaccinated against SARS-CoV-2 presented a lower degree of fatigue. LC patients presented a favorable response to a supervised exercise program. Differences in creatinine and protein levels were observed between rehabilitation therapy "responders" and "nonresponders". A good state of protein nutrition was related to a better rehabilitation response. The results are promising regarding possible predictive biomarkers of rehabilitation response, such as creatinine.

Intracranial Gliosarcoma: A National Cancer Database Survey of Clinical Predictors for Overall Survival.

OBJECTIVE: Gliosarcoma (GSM) is a variant of glioblastoma, 1 of the most common and aggressive primary brain tumors in adults. Our study seeks to analyze a large cohort of patients with GSM in the National Cancer Database (NCDB) to elucidate clinical predictors of overall survival (OS). METHODS: Data was collected on patients diagnosed with histologically-confirmed GSM using the NCDB (2004-2016). OS was determined via univariate Kaplan-Meier analysis. Bivariate and multivariate Cox proportional-hazards analyses were also utilized. RESULTS: Our cohort of 1015 patients had a median age at diagnosis of 61 years. Six hundred thirty-one (62.2%) were male, 896 (89.0%) were Caucasian, and 698 (68.8%) lacked any comorbidities. Median OS was 11.5 months. Regarding treatment, 264 (26.5%) patients underwent surgery (S) only (OS = 5.19 months), 61 (6.1%) underwent surgery and radiotherapy (S + RT) (OS = 6.87 months), 20 (2.0%) underwent surgery and chemotherapy (S + CT); (OS = 15.51 months), and 653 (65.4%) underwent S + CT + RT (triple) combination therapy (OS = 13.8 months). Notably, on bivariate analysis, S + CT (Hazard ratio [HR] = 0.59, P-value = 0.04) and triple therapy (HR = 0.57, P < 0.01) were associated with increased OS. S + RT was not significantly associated with OS. Similarly, on multivariate Cox proportional-hazards analyses, gross total resection (HR = 0.76, P = 0.02), S + CT (HR = 0.46, P < 0.01), and triple therapy (HR = 0.52, P < 0.01) predicted significantly increased OS. Furthermore, age >60 years old (HR = 1.03, P < 0.01) and the presence of comorbidities (HR = 1.43, P < 0.01) predicted significantly decreased OS. CONCLUSIONS: Despite maximal multimodal treatment, GSMs have poor median OS. NCDB data suggest age, comorbidities, extent of resection, and adjuvant treatment each minimally delays poor outcomes.

The mFI-5 and Postoperative Outcomes in Brain Tumor Patients: A Bayesian Approach to Quantifying Uncertainty.

OBJECTIVE: To the best of our knowledge, prior research has not investigated the uncertainty in the relationship between patient frailty and postoperative outcomes after brain tumor surgery. The present study used Bayesian methods to quantify the statistical uncertainty between the 5-factor modified frailty index (mFI-5) and postoperative outcomes for patients undergoing brain tumor resection. METHODS: The present study used retrospective data collected from patients undergoing brain tumor resection during a 2-year period (2017-2019). Posterior probability distributions were used to estimate the means of model parameters that are most likely given the priors and the data. Additionally, 95% credible intervals (CrIs) were constructed for each parameter estimate. RESULTS: Our patient cohort included 2519 patients with a mean age of 55.27 years. Our multivariate analysis demonstrated that each 1-point increase in the mFI-5 score was associated with an 18.76% (95% CrI, 14.35%-23.36%) increase in hospital length of stay and a 9.37% (CrI, 6.82%-12.07%) increase in hospital charges. We also noted an association between an increasing mFI-5 score and greater odds of a postoperative complication (odds ratio [OR], 1.58; CrI, 1.34-1.87) and a nonroutine discharge (OR, 1.54; CrI, 1.34-1.80). However, no meaningful statistical association was found between the mFI-5 score and 90-day hospital readmission (OR, 1.16; CrI, 0.98-1.36) or between the mFI-5 score and 90-day mortality (OR, 1.12; CrI, 0.83-1.50). CONCLUSIONS: Although mFI-5 scores might be able to effectively predict short-term outcomes such as length of stay, our results demonstrate no meaningful association between mFI-5 scores and 90-day readmission or 90-day mortality. Our study highlights the need for rigorously quantifying statistical uncertainty to safely risk-stratify neurosurgical patients.

Use of tubular retractors to access deep brain lesions: A case series.

BACKGROUND: Deep-seated intracranial lesions can be accessed using blade retractors that may disrupt white matter tracts, exert pressure on adjacent tissue, and lead to post-operative venous injury. Tubular retractors may minimize disruption to white matter tracts by radially dispersing pressure onto surrounding tissue. This study characterizes perioperative outcomes in patients undergoing biopsy or resection of intracranial pathologies using tubular retractors. METHODS: Adult patients (≥18 years) undergoing neurosurgical intervention using tubular retractors at a single health system (January 2016-February 2022) were identified through chart review. Demographics, disease characteristics, management data, and clinical outcomes were collected. RESULTS: A total of 49 patients were included; 23 (47%) had primary brain tumors, 8 (16%) metastases, 6 (12%) intracranial hemorrhage (ICH), 5 (10%) cavernomas, and 7 (14%) other pathologies. Lesions were located subcortically (n = 19, 39%), intraventricularly (n = 15, 31%), and in deep gray matter (n = 11, 22%). Gross total resection (GTR) or near GTR was achieved in 21 of 26 (80.8%) patients with intracranial lesions where GTR was the goal of surgery; 10 of 11 (90.9%) biopsies in patients with masses were diagnostic. Five of six (83.3%) ICHs were totally or near totally evacuated. Seventeen patients (35%) had major complications post-operatively. The most common complications were DVT/PE (n = 7, 14%) and seizures (n = 6, 12%). For patients who experienced post-operative seizures, 3 had seizures preoperatively and 1 had seizures in the context of electrolyte derangements. No patients died of post-operative complications. CONCLUSION: This operative approach may facilitate safe and efficacious biopsy or resection of deep-seated intracranial pathologies.

Expression of STING in Women with Morbid Obesity and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disease. Although mostly benign, this disease can evolve into nonalcoholic steatohepatitis (NASH). The stimulator of interferon genes (STING) plays an important role in the immune response against stressed cells, but this protein may also be involved in liver lipogenesis and microbiota composition. In this study, the role of STING in NAFLD was evaluated by RT-qPCR to analyze STING mRNA abundance and by immunohistochemical analysis to evaluate protein expression in liver biopsies from a cohort composed of 69 women with morbid obesity classified according to their liver involvement (normal liver, n = 27; simple steatosis (SS), n = 26; NASH, n = 16). The results showed that STING mRNA expression in the liver increases with the occurrence of NAFLD, specifically in the SS stage in which the degree of steatosis is mild or moderate. Protein analysis corroborated these results. Positive correlations were observed among hepatic STING mRNA abundance and gamma-glutamyl transferase and alkaline phosphatase levels, hepatic Toll-like receptor 9 expression and some circulating microbiota-derived bile acids. In conclusion, STING may be involved in the outcome and progression of NAFLD and may be related to hepatic lipid metabolism. However, further studies are needed to confirm these findings.

Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.

Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance. Platelets have a half-life in blood ranging from 8 to 11 days, after which they lose the final sialic acid and are recognized by receptors in the liver and eliminated from the bloodstream. This favors the transduction of thrombopoietin, which induces megakaryopoiesis to produce new platelets. More than two hundred enzymes are responsible for proper glycosylation and sialylation. In recent years, novel disorders of glycosylation caused by molecular variants in multiple genes have been described. The phenotype of the patients with genetic alterations in GNE, SLC35A1, GALE and B4GALT is consistent with syndromic manifestations, severe inherited thrombocytopenia, and hemorrhagic complications.

Making the Genome Huge: The Case of Triatoma delpontei, a Triatominae Species with More than 50% of Its Genome Full of Satellite DNA.

The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug 1834, in order to shed light on the karyotypic and genomic evolution of these species. The T. delpontei repeatome analysis showed that the most abundant component in its genome is satellite DNA, which makes up more than half of the genome. The T. delpontei satellitome includes 160 satellite DNA families, most of them also present in T. infestans. In both species, only a few satellite DNA families are overrepresented on the genome. These families are the building blocks of the C-heterochromatic regions. Two of these satellite DNA families that form the heterochromatin are the same in both species. However, there are satellite DNA families highly amplified in the heterochromatin of one species that in the other species are in low abundance and located in the euchromatin. Therefore, the present results depicted the great impact of the satellite DNA sequences in the evolution of Triatominae genomes. Within this scenario, satellitome determination and analysis led to a hypothesis that explains how satDNA sequences have grown on T. delpontei to reach its huge genome size within true bugs.

International Variability in Spinal Metastasis Treatment: A Survey of the AO Spine Community.

STUDY DESIGN: International survey. OBJECTIVES: To assess variability in the treatment practices for spinal metastases as a function of practice setting, surgical specialty, and fellowship training among an international group of spine surgeons. METHODS: An anonymous internet-based survey was disseminated to the AO Spine membership. The questionnaire contained items on practice settings, fellowship training, indications used for spinal metastasis surgery, surgical strategies, multidisciplinary team use, and postoperative follow-up priorities and practice. RESULTS: 341 gave complete responses to the survey with 76.3% identifying spinal oncology as a practice focus and 95.6% treating spinal metastases. 80% use the Spinal Instability Neoplastic Score (SINS) to guide instrumentation decision-making and 60.7% recruit multidisciplinary teams for some or all cases. Priorities for postoperative follow-up are adjuvant radiotherapy (80.9%) and systemic therapy (74.8%). Most schedule first follow-up within 6 weeks of surgery (62.2%). Significant response heterogeneity was seen when stratifying by practice in an academic or university-affiliated center, practice in a cancer center, completion of a spine oncology fellowship, and self-identification as a tumor specialist. Respondents belonging to any of these categories were more likely to utilize SINS (P < .01-.02), recruit assistance from plastic surgeons (all P < .01), and incorporate radiation oncologists in postoperative care (P < .01-.03). CONCLUSIONS: The largest variability in practice strategies is based upon practice setting, spine tumor specialization, and completion of a spine oncology fellowship. These respondents were more likely to use evidenced-based practices. However, the response variability indicates the need for consensus building, particularly for postoperative spine metastasis care pathways and multidisciplinary team use.