A novel electromagnetic tracking system for surgery navigation

Objective: This paper proposes the development of a novel electromagnetic tracking system for navigation surgery. Main objective is to provide a system able to operate in a wide tracking volume to make easier and efficient the surgical procedures by assuring high measurement accuracy. Methods: A new field generator consisting in five transmitting coils excited with Frequency Division Multiplexing technique has been developed. Attention is devoted to designing and arrangement of the coils to assure high sensitivity, system scalability and a homogeneous magnetic field inside working volume. A suitable technique based on Look-Up-Table is applied for sensor position calculation and an anthropomorphic robot is used for table calibration. Results: Experimental tests highlight a good repeatability of the measurement data and a negligible noise influence for the proposed system. The obtained tracking volume is wider with respect to the commercial tracking device used in surgical applications and seem promising. Conclusion: The main characteristic of the developed system consists of: scalable and modular configuration of Field Generator, high measured sensitivity due to the increased number of transmitting coils with respect to the classical configuration and large tracking volume. The development of the proposed magnetic tracking systems with high accuracy and wide working volume allows to promote broader utilization of advantaged techniques in surgery procedures for both improving the effectiveness and decreasing the invasiveness of medical interventions

Diagnosis and treatment of urticaria and angioedema: a worldwide perspective

Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

A Fusion Biopsy Framework for Prostate Cancer Based on Deformable Superellipses and nnU-Net

In prostate cancer, fusion biopsy, which couples magnetic resonance imaging (MRI) with transrectal ultrasound (TRUS), poses the basis for targeted biopsy by allowing the comparison of information coming from both imaging modalities at the same time. Compared with the standard clinical procedure, it provides a less invasive option for the patients and increases the likelihood of sampling cancerous tissue regions for the subsequent pathology analyses. As a prerequisite to image fusion, segmentation must be achieved from both MRI and TRUS domains. The automatic contour delineation of the prostate gland from TRUS images is a challenging task due to several factors including unclear boundaries, speckle noise, and the variety of prostate anatomical shapes. Automatic methodologies, such as those based on deep learning, require a huge quantity of training data to achieve satisfactory results. In this paper, the authors propose a novel optimization formulation to find the best superellipse, a deformable model that can accurately represent the prostate shape. The advantage of the proposed approach is that it does not require extensive annotations, and can be used independently of the specific transducer employed during prostate biopsies. Moreover, in order to show the clinical applicability of the method, this study also presents a module for the automatic segmentation of the prostate gland from MRI, exploiting the nnU-Net framework. Lastly, segmented contours from both imaging domains are fused with a customized registration algorithm in order to create a tool that can help the physician to perform a targeted prostate biopsy by interacting with the graphical user interface

Children with Cerebral Palsy can imagine actions like their normally developed peers

The present study aimed at assessing whether children with Cerebral Palsy (CP) can imagine object directed actions similarly to their normally developed peers. We asked children with CP (n = 12) and paired healthy controls (n = 12) to imagine in first person perspective eight daily actions, after observing them through videoclips presented on a computer screen. During motor imagery (MI) children were interrupted at a specific timepoint (e.g., at 2.5 s) from the start. Two frames extracted from the videoclips were then presented on the screen. One of the two depicted the correct timepoint at which the imagined action was interrupted, while the other represented an earlier or later timepoint. Children had to respond by pressing the key associated to the correct frame. Children also underwent VMIQ-2 questionnaire. Both groups performed similarly in the questionnaire and in the requested task, where they showed the same error rate. Errors mainly concerned the later frame, suggesting a similar strategy to solve the task in the two groups. The results support the view that children with CP can imagine actions similarly to their normally developed peers. This encourages the use of MI as a rehabilitative tool in children with motor impairment

Hepatocellular carcinoma treatment over sorafenib: epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?

Introduction: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. Areas covered: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. Expert opinion: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the therapeutic stranding of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its actors (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel. © 2015 Taylor & Francis

Genotype-phenotype spectrum and correlations in Xia-Gibbs syndrome: Report of five novel cases and literature review

Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA-binding motif-containing 1 gene (AHDC1), encoding a protein with a crucial role in transcription and epigenetic regulation, axonogenesis, brain function, and neurodevelopment. AHDC1 variants possibly act through a dominant-negative mechanism and may interfere with DNA repair processes, leading to genome instability and impaired DNA translesion repair. Variants affecting residues closer to the N-terminal are thought to determine a milder phenotype with better cognitive performances. However, clean-cut genotype-phenotype correlations are still lacking