The expansion of liquid biopsies to vascular care: an overview of existing principles, techniques and potential applications to vascular malformation diagnostics

Vascular malformations are congenital lesions that occur due to mutations in major cellular signalling pathways which govern angiogenesis, cell proliferation, motility, and cell death. These pathways have been widely studied in oncology and are substrates for various small molecule inhibitors. Given their common molecular biology, there is now a potential to repurpose these cancer drugs for vascular malformation care; however, a molecular diagnosis is required in order to tailour specific drugs to the individual patient’s mutational profile. Liquid biopsies (LBs), emerging as a transformative tool in the field of oncology, hold significant promise in this feat. This paper explores the principles and technologies underlying LBs and evaluates their potential to revolutionize the management of vascular malformations. The review begins by delineating the fundamental principles of LBs, focusing on the detection and analysis of circulating biomarkers such as cell-free DNA, circulating tumor cells, and extracellular vesicles. Subsequently, an in-depth analysis of the technological advancements driving LB platforms is presented. Lastly, the paper highlights the current state of research in applying LBs to various vascular malformations, and uses the aforementioned principles and techniques to conceptualize a liquid biopsy framework that is unique to vascular malformation research and clinical care

Hidden aqueductal stenosis associated to bilateral idiopathic foramina of Monro stenosis mimicking a Chiari I malformation? Case report

A 39-year old man came to our outpatient clinic with long history of unspecific symptoms and signs. Cerebral MRI showed herniation of the cerebellar tonsils of more than 1cm below the foramen magnum and a triventricular hydrocephalus. A diagnosis of Chiari I malformation was retained. After an osteo-dural decompression of the posterior fossa, post-operative MRI revealed an aqueductal stenosis with triventricular hydrocephalus. An endoscopic-third- ventriculostomy showed an idiopathic stenosis of the right foramen of Monro. Residual symptoms and persistence of biventricular hydrocephalus justified a ventriculo-peritoneal shunt. Aqueductal and foramina of Monro stenosis can mimick a Chiari I malformatio

THE EFFECTS OF SPECIFIC TRAINING ON CARDIORESPIRATORY ENDURANCE AMONG YOUNG JUDOKAS

ABSTRACT The primary aim of this research was to determine the changes in cardiorespiratory endurance of young judokas during an eight-week specificallydesigned trainingprogram. The research was carried out on a sample of 25 young, highly selected judokas, all members of the extended list of cadet and junior national team members of Serbia, aged 14 to 18. All of the participants were included in a specificallydesigned training program which lasted for eight weeks, and represented a combination of highly-intense activities of very short duration, specific strength exercises, the improvement of specific judo techniques and judo matches (randori). The results of the analysis indicated that cardiorespiratory endurance among young judokas after an eight-week specificallydesigned training program had not undergone any statistically significant changes. Furthermore, the value of VO2peakwas somewhat elevated at the final measuring. The explanations for these results can be found in the fact that young judokas were not subjected to a rapid reduction in body weight, and instead through increased intensity of the training load were able to decrease their body fat percentage. In addition, we can justifiably assume that the level of training load, during this specificallydesigned training program, was sufficient for the previously achieved level of cardiorespiratory endurance to be maintained. The results of this research confirm that the basis for daily planning and programming should consist of precisely diagnosed procedures for the evaluation of the characteristics of athletes, since they offer insight into the proper application of training load. Key words: judo, cardiorespiratory endurance, training, adaptation

The Extended Lateral Supraorbital Approach and Extradural Anterior Clinoidectomy Through a Frontopterio-Orbital Window : Technical Note and Pilot Surgical Series

BACKGROUND: Lateral approaches to treat anterior cranial fossa lesions have evolved since the first frontotemporal approach described by Dandy in 1918. We describe a less invasive approach to perform extradural anterior clinoidectomy through a lateral supraorbital (LSO) approach for anterior circulation aneurysms and anterolateral skull base lesions. METHODS: The extended LSO approach involves performing a standard lateral supraorbital craniotomy followed by drilling of the sphenoid wing and lateral wall of the orbit through the frontal bony opening of the LSO approach, without any temporal extension of the craniotomy. This creates a frontopterio-orbital window exposing the periorbita; superior, medial, and anterior aspect of the temporal dura mater; and superior orbital fissure. After unroofing the superior orbital fissure, the meningo- orbital fold is cut, and the temporal dura mater is peeled from the lateral wall of the cavernous sinus to expose the anterior clinoid process allowing a standard opening of the optic canal and anterior clinoidectomy. RESULTS: The extended LSO approach and extradural anterior clinoidectomy allowed access to 4 sphenoid wing/anterior clinoidal meningiomas, 5 anterior circulation aneurysms, 2 temporomesial lesions, and 1 orbital/cavernous sinus abscess. Postoperatively, 2 patients had transient hemiparesis, 2 patients had transient third nerve palsy, and 1 patient had minimal visual field deterioration. All patients had a modified Rankin Scale score CONCLUSION: The extended LSO approach opens a new route (frontopterio-orbital window) to perform extradural anterior clinoidectomy safely and increases surgical exposure, angles, and operability of a less invasive keyhole craniotomy (LSO approach) to treat anterior cranial fossa lesions.Peer reviewe

Thyroid hormones affect the proliferation and/or mobilization of bulge stem cell population

Thyroid hormones (TH) play a pivotal role in the development of mammalian skin, and are necessary for both the initiation and maintenance of hair growth. Adult hypothyroid rats showed impaired epidermal proliferation, hair growth and wound healing. Stem cells (SCs) located at the bulges of the hair follicles are responsible for hair cycling, and contribute to the regeneration of the new epidermis after wounding. Therefore a reduction in the number or function of bulge stem cells could be a cause of disturbed skin reepithelization and hair follicle maintenance. We hypothesized that a decrease in TH during prenatal development would affect the bulge stem cell population. Subclinical hypothyroidism was induced with propylthiouracil through drinking water in a dose of 1.5 mg/l in pregnant Albino Oxford rats, from the first day of gravidity and during lactation. The control group was untreated. Five, seven-day-old pups were euthanized and skin samples were taken from the dorsal part of their bodies. The number of hair follicles was estimated on an area of 1mm2 of dermis. For the immunohistochemical study, proliferating cell nuclear antigen (PCNA) (Santa Cruz Biotechnology) and NANOG (Thermo Scientific) antibodies were used. The number of PCNA and NANOG positive cells was estimated on the area of 1mm2 of hair follicle. The number of hair follicles was reduced and the expression of PCNA was decreased in the cells of the inner and outer sheath of hair follicles in the hypothyroid pups compared to the controls. They also had an increased number of NANOG positive bulge cells which we presume are multipotent SCs. Decreased expression of PCNA demonstrates low proliferation and increased expression of NANOG, which may be explained in two ways: 1) the inhibited differentiation of putative SCs and/or 2) the reduction of mobilization of these cells to the epidermis or sebaceous gland. Our results confirm that the lack of TH influences the formation of hair follicles in early infantile rat pups

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system

Functionally Relevant Domains of the Prion Protein Identified In Vivo

The prion consists essentially of PrPSc, a misfolded and aggregated conformer of the cellular protein PrPC. Whereas PrPC deficient mice are clinically healthy, expression of PrPC variants lacking its central domain (PrPΔCD), or of the PrP-related protein Dpl, induces lethal neurodegenerative syndromes which are repressed by full-length PrP. Here we tested the structural basis of these syndromes by grafting the amino terminus of PrPC (residues 1–134), or its central domain (residues 90–134), onto Dpl. Further, we constructed a soluble variant of the neurotoxic PrPΔCD mutant that lacks its glycosyl phosphatidyl inositol (GPI) membrane anchor. Each of these modifications abrogated the pathogenicity of Dpl and PrPΔCD in transgenic mice. The PrP-Dpl chimeric molecules, but not anchorless PrPΔCD, ameliorated the disease of mice expressing truncated PrP variants. We conclude that the amino proximal domain of PrP exerts a neurotrophic effect even when grafted onto a distantly related protein, and that GPI-linked membrane anchoring is necessary for both beneficial and deleterious effects of PrP and its variants

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Identification of Degrading Effects in the Operation of Neighboring Photovoltaic Systems in Urban Environments

As photovoltaics technologies have emerged as one of the most promising renewable energy resources in urban environments, monitoring and maintaining of such systems have gained significance. In order to support reliable system operation during the projected in-field operation lifetime, effective strategies for identifying potential problems in photovoltaic systems operation are needed. In this paper, novel methods for the identification of degrading effects in the operation of neighboring photovoltaic systems are presented. The proposed methods are applicable for identifying panel aging properties, soiling effects, and the operation of photovoltaic systems under different shading scenarios. Since the proposed methods are based on the cross-correlation of the operation of neighboring systems, they are particularly suitable performance assessment in urban environments. The proposed identification methods are integrated according to the adopted fog computing model, providing a scalable solution capable of uniform integration into the distributed applications for monitoring and maintenance of photovoltaic systems in urban areas. The details regarding the implementation of the identification methods in the form of data processing services and service operation and dependencies are also provided in this paper. The identification methods, integration concept, and related service operation are verified through the presented case study