A Humanized Yeast Model for Studying TRAPP Complex Mutations; Proof-of-Concept Using Variants from an Individual with a -Associated Neurodevelopmental Syndrome.

Variants in membrane trafficking proteins are known to cause rare disorders with severe symptoms. The highly conserved transport protein particle (TRAPP) complexes are key membrane trafficking regulators that are also involved in autophagy. Pathogenic genetic variants in specific TRAPP subunits are linked to neurological disorders, muscular dystrophies, and skeletal dysplasias.

Lipidomic analysis of human TANGO2-deficient cells suggests a lipid imbalance as a cause of TANGO2 deficiency disease.

TANGO2 deficiency disease (TDD) is a multisystem disease caused by variants in the TANGO2 gene. Symptoms include neurodevelopmental delays, seizures and potentially lethal metabolic crises and cardiac arrhythmias. While the function of TANGO2 remains elusive, vitamin B5/pantothenic acid supplementation has been shown to alleviate symptoms in a fruit fly model and has also been used with success to treat individuals suffering from TDD.

Pilot Study on the Development and Integration of Anthropomorphic Models within the Dental Technician Curriculum.

The effectiveness of modern medical education largely depends on the integration and utilization of digital technologies in teaching various disciplines. In this pilot usability study, we introduced 3D printed anthropomorphic dental models, specifically designed for the elective discipline "Digital and Metal-Free Techniques in Dental Technology" from the curriculum of the Dental Technician specialty in the Medical University of Varna. The evaluation focused on dental technician students' perception of this novel learning environment, its influence on their performance, and the potential for future application of these models and related 3D technologies in their professional practice.

Interdisciplinary Successful Revascularization of Traumatic Occlusion of the Right Common Carotid Artery.

Blunt carotid artery injury (BCI) poses a rare yet severe threat following vascular trauma, often leading to significant morbidity and mortality. We present a case of a 33-year-old male who suffered complete thrombotic occlusion of the right common carotid artery (CCA) following a workplace accident. Clinical evaluation revealed profound neurological deficits, prompting multidisciplinary surgical intervention guided by the Denver criteria (Grade I - disruption inside the vessel that results in a narrowing of the lumen by less than 25%; Grade II - dissection or intramural hematoma causing greater than 25% stenosis; Grade III - comprises pseudoaneurysm formation; Grade IV - causes total vessel occlusion; Grade V - describes vessel transection with extravasation).

The Evaluation of Virtual Reality Neuroanatomical Training Utilizing Photorealistic 3D Models in Limited Body Donation Program Settings.

Background Neuroanatomy is one of the most complex areas of anatomy to teach to medical students. Traditional study methods such as atlases and textbooks are mandatory but require significant effort to conceptualize the three-dimensional (3D) aspects of the neuroanatomical regions of interest. Objectives To test the feasibility of human anatomy teaching medical students in a virtual reality (VR) immersive environment using photorealistic three-dimensional models (PR3DM) of human anatomy, in a limited anatomical body donation program.

Intraoperative Videogrammetry and Photogrammetry for Photorealistic Neurosurgical 3-Dimensional Models Generated Using Operative Microscope: Technical Note.

Background And Objectives: Intraoperative orientation during microsurgery has a prolonged learning curve among neurosurgical residents. Three-dimensional (3D) understanding of anatomy can be facilitated with realistic 3D anatomic models created from photogrammetry, where a series of 2-dimensional images is converted into a 3D model. This study implements an algorithm that can create photorealistic intraoperative 3D models to exemplify important steps of the operation, operative corridors, and surgical perspectives.

How I do it: cervical hemangioblastoma resection. Surgical technique and complication avoidance.

Background: Spinal cord hemangioblastomas are benign, highly vascular neoplasms that affect the brain and, rarely, the spinal cord. They can be solitary or as part of von Hippel-Lindau syndrome. Radiosurgery is not a suitable treatment option.

miRNAs and related genetic biomarkers according to the WHO glioma classification: From diagnosis to future therapeutic targets.

In the 2021 WHO classification of Tumors of the Central Nervous System, additional molecular characteristics have been included, defining the following adult-type diffuse glioma entities: Astrocytoma IDH-mutant, Oligodendroglioma IDH-mutant and 1p/19q-codeleted, and Glioblastoma IDH-wildtype. Despite advances in genetic analysis, precision oncology, and targeted therapy, malignant adult-type diffuse gliomas remain "hard-to-treat tumors", indicating an urgent need for better diagnostic and therapeutic strategies. In the last decades, miRNA analysis has been a hotspot for researching and developing diagnostic, prognostic, and predictive biomarkers for various disorders, including brain cancer.

Photogrammetry Applied to Neurosurgery: A Literature Review.

Photogrammetry refers to the process of creating 3D models and taking measurements through the use of photographs. Photogrammetry has many applications in neurosurgery, such as creating 3D anatomical models and diagnosing and evaluating head shape and posture deformities. This review aims to summarize the uses of the technique in the neurosurgical practice and showcase the systems and software required for its implementation.

Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset.

Ubiquitin-proteasome system (UPS) dysfunction is associated with the pathology of a wide range of human diseases, including myopathies and muscular atrophy. However, the mechanistic understanding of specific components of the regulation of protein turnover during development and disease progression in skeletal muscle is unclear. Mutations in , an E3 ubiquitin ligase cullin3 (CUL3) substrate-specific adapter protein, result in severe congenital nemaline myopathy, but the events that initiate the pathology and the mechanism through which it becomes pervasive remain poorly understood.

Three-Dimensional Printing in Neurosurgery: A Review of Current Indications and Applications and a Basic Methodology for Creating a Three-Dimensional Printed Model for the Neurosurgical Practice.

Introduction Three-dimensional (3D) printing is an affordable aid that is useful in neurosurgery. It allows for better visualization and tactile appreciation of the individual anatomy and regions of interest and therefore potentially lowers the risk of complications. There are various applications of this technology in the field of neurosurgery.

Vitamin B5, a coenzyme A precursor, rescues TANGO2 deficiency disease-associated defects in Drosophila and human cells.

Mutations in the Transport and Golgi Organization 2 (TANGO2) gene are associated with intellectual deficit, neurodevelopmental delay and regression. Individuals can also present with an acute metabolic crisis that includes rhabdomyolysis, cardiomyopathy, and cardiac arrhythmias, the latter of which are potentially lethal. While preventing metabolic crises has the potential to reduce mortality, no treatments currently exist for this condition.

Biallelic variants in TRAPPC10 cause a microcephalic TRAPPopathy disorder in humans and mice.

The highly evolutionarily conserved transport protein particle (TRAPP) complexes (TRAPP II and III) perform fundamental roles in subcellular trafficking pathways. Here we identified biallelic variants in TRAPPC10, a component of the TRAPP II complex, in individuals with a severe microcephalic neurodevelopmental disorder. Molecular studies revealed a weakened interaction between mutant TRAPPC10 and its putative adaptor protein TRAPPC2L.

Contrast-induced neurotoxicity presented as transient cortical blindness after stent-assisted coiling of a medium-sized unruptured basilar artery aneurysm: A case report and review of the literature.

Background: Contrast-induced neurotoxicity is a rare event after endovascular diagnostic procedures or interventions and presents as transient neurological deficit. Herewith, we present a case of reversible complete cortical blindness after uneventful stent-assisted coiling of a medium-sized unruptured basilar artery aneurysm.

Case Description: A 70-year-old woman with a medium-sized 10 mm/6 mm wide neck basilar tip aneurysm was planned for endovascular obliteration of the lesion.

Diagnostic, grading and prognostic role of a restricted miRNAs signature in primary and metastatic brain tumours. Discussion on their therapeutic perspectives.

At present, brain tumours remain one of the "hard-to-treat" malignancies with minimal improvement in patients' survival. Recently, miRNAs have been shown to correlate with oncogenesis and metastasis and have been investigated as potential biomarkers for diagnosis, prognosis and therapy prediction in different brain malignancies. The aim of the current study was to select an accurate and affordable brain tumour detection and grading approach.

TRAPPC11-related muscular dystrophy with hypoglycosylation of alpha-dystroglycan in skeletal muscle and brain.

Aims: TRAPPC11, a subunit of the transport protein particle (TRAPP) complex, is important for complex integrity and anterograde membrane transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. Several individuals with TRAPPC11 mutations have been reported with muscle weakness and other features including brain, liver, skeletal and eye involvement. A detailed analysis of brain and muscle pathology will further our understanding of the presentation and aetiology of TRAPPC11 disease.

A rare case of carotid body tumor associated with near complete cerebral sinus thrombosis and idiopathic intracranial hypertension. Management strategy and review of the literature.

Background: Carotid body tumors (CBTs) are rare hypervascular lesions with critical location which makes them very challenging to treat. In rare occasions, compression of the jugular vein from the tumor mass could predispose to progressive thrombosis of intracranial venous sinuses. The latter consequently leads to intracranial hypertension (pseudotumor cerebri) with the accompanying danger to the vision.

Publisher Correction: Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER-to-Golgi transport and at the mitochondria.

TANGO2 variants result in a complex disease phenotype consisting of recurrent crisis-induced rhabdomyolysis, encephalopathy, seizures, lactic acidosis, hypoglycemia, and cardiac arrhythmias. Although first described in a fruit fly model as a protein necessary for some aspect of Golgi function and organization, its role in the cell at a fundamental level has not been addressed. Such studies are necessary to better counsel families regarding treatment options and nutrition management to mitigate the metabolic aspects of the disease.

A novel homozygous variant in results in a neurodevelopmental disorder and disrupts TRAPP complex function.

Background: Next-generation sequencing has facilitated the diagnosis of neurodevelopmental disorders with variable and non-specific clinical findings. Recently, a homozygous missense p.(Asp37Tyr) variant in a core subunit of TRAPP complexes which function as tethering factors during membrane trafficking, was reported in two unrelated individuals with neurodevelopmental delay, post-infectious encephalopathy-associated developmental arrest, tetraplegia and accompanying rhabdomyolysis.

Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein.

TRAPPC11 was identified as a component of the TRAPP III complex that functions in membrane trafficking and autophagy. Variants in TRAPPC11 have been reported to be associated with a broad spectrum of phenotypes but all affected individuals display muscular pathology. Identifying additional variants will further our understanding of the clinical spectrum of phenotypes and will reveal regions of the protein critical for its functions.

TRAPPC11 functions in autophagy by recruiting ATG2B-WIPI4/WDR45 to preautophagosomal membranes.

TRAPPC11 has been implicated in membrane traffic and lipid-linked oligosaccharide synthesis, and mutations in TRAPPC11 result in neuromuscular and developmental phenotypes. Here, we show that TRAPPC11 has a role upstream of autophagosome formation during macroautophagy. Upon TRAPPC11 depletion, LC3-positive membranes accumulate prior to, and fail to be cleared during, starvation.

TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)-associated proteins.

The movement of proteins between cellular compartments requires the orchestrated actions of many factors including Rab family GTPases, Soluble NSF Attachment protein REceptors (SNAREs) and so-called tethering factors. One such tethering factor is called TRAnsport Protein Particle (TRAPP), and in humans, TRAPP proteins are distributed into two related complexes called TRAPP II and III. Although thought to act as a single unit within the complex, in the past few years it has become evident that some TRAPP proteins function independently of the complex.

Bi-allelic mutations in result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts.

Background: The combination of febrile illness-induced encephalopathy and rhabdomyolysis has thus far only been described in disorders that affect cellular energy status. In the absence of specific metabolic abnormalities, diagnosis can be challenging.

Objective: The objective of this study was to identify and characterise pathogenic variants in two individuals from unrelated families, both of whom presented clinically with a similar phenotype that included neurodevelopmental delay, febrile illness-induced encephalopathy and episodes of rhabdomyolysis, followed by developmental arrest, epilepsy and tetraplegia.

TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy.

Background: Transport protein particle (TRAPP) is a supramolecular protein complex that functions in localizing proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in muscle disease by virtue of homozygous and compound heterozygous deleterious mutations being identified in individuals with limb girdle muscular dystrophy and congenital muscular dystrophy. It remains unclear how this protein leads to muscle disease.