Vestibular Infant Screening-Rehabilitation (VIS-REHAB): protocol for a randomised controlled trial on Vestibular Rehabilitation Therapy (VRT) in vestibular-impaired children.

Introduction: A vestibular deficit can have a substantial impact on the overall development of children. Therefore, it is of utmost importance that vestibular-impaired problems are treated early and effectively through Vestibular Rehabilitation Therapy (VRT). Although VRT is sufficiently proven and standardised in adults, there remains a lack of research examining its efficacy in children.

Discovery and Development of an Advanced Lead for the Treatment of African Trypanosomiasis.

African trypanosomiasis is a widespread disease of human and veterinary importance caused by various with a globally devastating impact and a need for novel treatment options. We here provide a comprehensive preclinical evaluation of nucleoside analogues, 6-thioether-modified tubercidins, with curative activity against African trypanosomiasis. Promising hits were identified following screening against the most relevant trypanosome species.

Cell signaling and tissue remodeling in the pulmonary autograft after the Ross procedure: A computational study.

In the Ross procedure, a patient's pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale.

Synthesis and Anti- Activity of 3-Cyanopyridine Derivatives.

Chagas disease (CD) is a parasitic neglected tropical disease (NTD) caused by the protozoan that affects 6 million people worldwide, often resulting in financial burden, morbidity, and mortality in endemic regions. Given a lack of highly efficient and safe treatments, new, affordable, and fit-for-purpose drugs for CD are urgently needed. In this work, we present a hit-to-lead campaign for novel cyanopyridine analogues as antichagasic agents.

Disorder-Not CHARGE Syndrome-Presenting as Isolated Cochleovestibular Dysfunction.

CHARGE syndrome, characterized by a distinct set of clinical features, has been linked primarily to mutations in the gene. Initially defined by specific clinical criteria, including coloboma, heart defects, choanal atresia, delayed growth, and ear anomalies, CHARGE syndrome's diagnostic spectrum has broadened since the identification of . Variants in this gene exhibit considerable phenotypic variability, leading to the adoption of the term " disorder" to encompass a wider range of associated symptoms.

Hemodynamics and wall shear metrics in a pulmonary autograft: Comparing a fluid-structure interaction and computational fluid dynamics approach.

Objective: In young patients, aortic valve disease is often treated by placement of a pulmonary autograft (PA) which adapts to its new environment through growth and remodeling. To better understand the hemodynamic forces acting on the highly distensible PA in the acute phase after surgery, we developed a fluid-structure interaction (FSI) framework and comprehensively compared hemodynamics and wall shear-stress (WSS) metrics with a computational fluid dynamic (CFD) simulation.

Methods: The FSI framework couples a prestressed non-linear hyperelastic arterial tissue model with a fluid model using the in-house coupling code CoCoNuT.

Bioluminescence Imaging Reveals Differences in Parasite Killing Kinetics by Antileishmanial Reference Drugs.

The bioluminescent BALB/c mouse model was used to evaluate the parasiticidal drug action kinetics of the reference drugs miltefosine, paromomycin, sodium stibogluconate, and liposomal amphotericin B. Infected mice were treated for 5 days starting from 7 days post-infection, and parasite burdens were monitored over time bioluminescence imaging (BLI). Using nonlinear regression analyses of the BLI signal, the parasite elimination half-life () in the liver, bone marrow, and whole body was determined and compared for the different treatment regimens.

Long-term hematopoietic stem cells trigger quiescence in Leishmania parasites.

Addressing the challenges of quiescence and post-treatment relapse is of utmost importance in the microbiology field. This study shows that Leishmania infantum and L. donovani parasites rapidly enter into quiescence after an estimated 2-3 divisions in both human and mouse bone marrow stem cells.

A Clinical Framework for Video Head Impulse Testing and Vestibular Evoked Myogenic Potential Assessments in Primary School-Aged Children.

Objectives: This study aimed to offer normative data and age trends of an age-appropriate vestibular test protocol in a large group (n = 140) of school-aged children (6 to 13 years old) as well as to provide a practical and clinical framework for accurate performance and interpretation of vestibular test results in this specific age group.

Design: The typically developing participants (mean age of 9.51 ± 2.

Chemoselective Synthesis and Anti-Kinetoplastidal Properties of 2,6-Diaryl-4-tetrahydro-thiopyran-4-one -Oxides: Their Interplay in a Cascade of Redox Reactions from Diarylideneacetones.

2,6-Diaryl-4-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related -oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4-tetrahydro-thiopyran-4-ones, and their -sulfoxide and sulfone metabolites were evaluated against , , and various species in comparison with their cytotoxicity against human fibroblasts MRC-5.

Synthesis and Anti-Chagas Activity Profile of a Redox-Active Lead 3-Benzylmenadione Revealed by High-Content Imaging.

Chagas disease, or American trypanosomiasis, is a neglected tropical disease which is a top priority target of the World Health Organization. The disease, endemic mainly in Latin America, is caused by the protozoan and has spread around the globe due to human migration. There are multiple transmission routes, including vectorial, congenital, oral, and iatrogenic.

Effect of Porosity on the Colonization of Digital Light-Processed 3D Hydrogel Constructs toward the Development of a Functional Intestinal Model.

With the rapid increase of the number of patients with gastrointestinal diseases in modern society, the need for the development of physiologically relevant in vitro intestinal models is key to improve the understanding of intestinal dysfunctions. This involves the development of a scaffold material exhibiting physiological stiffness and anatomical mimicry of the intestinal architecture. The current work focuses on evaluating the scaffold micromorphology of gelatin-methacryloyl-aminoethyl-methacrylate-based nonporous and porous intestinal 3D, intestine-like constructs, fabricated via digital light processing, on the cellular response.

Lead Optimization of the 5-Phenylpyrazolopyrimidinone NPD-2975 toward Compounds with Improved Antitrypanosomal Efficacy.

Human African trypanosomiasis (HAT) still faces few therapeutic options and emerging drug resistance, stressing an urgency for novel antitrypanosomal drug discovery. Here, we describe lead optimization efforts aiming at improving antitrypanosomal efficacy and better physicochemical properties based on our previously reported optimized hit NPD-2975 (pIC 7.2).

Cognitive outcomes in Susac syndrome: A 2-year neuropsychological follow-up study.

Background And Purpose: Susac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long-term neuropsychological outcomes of patients with SuS.

Immediate Carotid Artery Stenting or Deferred Treatment in Patients With Tandem Carotid Lesions Treated Endovascularly for Acute Ischaemic Stroke.

Fifteen to 20% of patients with an acute ischaemic stroke have a tandem lesion defined by the combination of an intracranial large vessel thrombo-embolic occlusion and a high grade stenosis or occlusion of the ipsilateral internal carotid artery. These patients tend to have worse outcomes than patients with isolated intracranial occlusions, with higher rates of disability and death. The introduction of endovascular thrombectomy to treat the intracranial lesion clearly improved the outcome compared with treatment with intravenous thrombolysis alone.

Uncertainty quantification of the wall thickness and stiffness in an idealized dissected aorta.

Personalized treatment informed by computational models has the potential to markedly improve the outcome for patients with a type B aortic dissection. However, existing computational models of dissected walls significantly simplify the characteristic false lumen, tears and/or material behavior. Moreover, the patient-specific wall thickness and stiffness cannot be accurately captured non-invasively in clinical practice, which inevitably leads to assumptions in these wall models.

Stiffness matters: Improved failure risk assessment of ascending thoracic aortic aneurysms.

Objectives: Rupture and dissection are feared complications of ascending thoracic aortic aneurysms caused by mechanical failure of the wall. The current method of using the aortic diameter to predict the risk of wall failure and to determine the need for surgical resection lacks accuracy. Therefore, this study aims to identify reliable and clinically measurable predictors for aneurysm rupture or dissection by performing a personalized failure risk analysis, including clinical, geometrical, histologic, and mechanical data.

Public preferences for the allocation of societal resources over different healthcare purposes.

Objective: Increasing healthcare expenditures require governments to make difficult prioritization decisions. Considering public preferences can help raise citizens' support. Previous research has predominantly elicited preferences for the allocation of public resources towards specific treatments or patient groups and principles for resource allocation.

Novel Targets for Molecular Imaging of Inflammatory Processes of Carotid Atherosclerosis: A Systematic Review.

Computed tomography angiography (CTA), magnetic resonance angiography (MRA) and F-FDG-PET have proven clinical value when evaluating patients with carotid atherosclerosis. In this systematic review, we will focus on the role of novel molecular imaging tracers in that assessment and their potential strengths to stratify stroke risk. We systematically searched PubMed, Embase, the Web of Science Core Collection, and Cochrane Library for articles reporting on molecular imaging to noninvasively detect or characterize inflammation in carotid atherosclerosis.

Growth and remodeling of the dissected membrane in an idealized dissected aorta model.

While transitioning from the acute to chronic phase, the wall of a dissected aorta often expands in diameter and adaptations in thickness and microstructure take place in the dissected membrane. Including the mechanisms, leading to these changes, in a computational model is expected to improve the accuracy of predictions of the long-term complications and optimal treatment timing of dissection patients. An idealized dissected wall was modeled to represent the elastin and collagen production and/or degradation imposed by stress- and inflammation-mediated growth and remodeling, using the homogenized constrained mixture theory.

Drivers of vascular growth and remodeling: A computational framework to promote benign adaptation in the Ross procedure.

In the sixties, Dr Donald Ross designed a surgical solution for young patients with aortic valve disease by using the patients' own pulmonary valve. The Ross procedure is the only aortic valve replacement technique that can restore long-term survival and preserve quality of life. The main failure mode of the Ross procedure is wall dilatation, potentially leading to valve regurgitation and leakage.

The impact of vestibular function on cognitive-motor interference: a case-control study on dual-tasking in persons with bilateral vestibulopathy and normal hearing.

Bilateral vestibulopathy (BV) is a chronic vestibular disorder, characterized by bilaterally absent or significantly impaired vestibular function. Symptoms typically include, but are not limited to, unsteadiness and movement-induced blurred vision (oscillopsia). This prospective case-control study aimed to elucidate the impact of BV on cognitive and motor performance and on cognitive-motor interference.

Chirp-Evoked VEMPs: A Test-Retest Reliability Study.

Objectives: To determine the test-retest reliability of cervical and ocular vestibular-evoked myogenic potentials (c&oVEMP) evoked by 500 Hz narrowband (NB) CE-Chirp and broadband (BB) CE-Chirp stimuli.

Design: Twenty healthy participants (10 female) were tested twice on the same day to determine the within-session reliability and 1 week later to determine the between-session reliability. The latency, amplitude, and asymmetry ratio of c&oVEMPs elicited by 95 dB nHL air-conducted (AC) 500 Hz NB CE-Chirp and BB CE-Chirp were recorded bilaterally.