Search Results (23)

Introduction: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a benign proliferation of the melanin-producing retinal pigment epithelium (RPE). Although often a benign and incidental finding, multifocal CHRPE may mimic lesions associated with familial adenomatous polyposis (FAP). Case Description: We describe an 8-year-old girl presenting with optic disc pallor and widespread multifocal bear track CHRPE observed bilaterally on dilated fundoscopy. Fundus autofluorescence (FAF) imaging showed uniform areas of hypoautofluorescence corresponding to the bear track lesions. Spectral domain optical coherence tomography (SD-OCT) demonstrated normal lamination without atrophy. The full-field electroretinogram (ffERG) was within normal limits. Whole-genome sequencing (WGS) revealed a likely pathogenic heterozygous variant in the STAG2 gene (c.3222dup, p.Ser1075IlefsTer12). Conclusions: We present a rare case of bilateral, panretinal bear track CHRPE in a child with a likely pathogenic variant in STAG2. Using multimodal imaging, we contrast bear track lesions of the retina with FAP-associated CHRPE. We also present possible ophthalmic manifestations in carriers of pathogenic STAG2 variants. Full article

Waardenburg syndrome (WS) is a rare genetic disorder that affects both hearing and pigmentation. The wide divergence of WS poses significant diagnostic and management challenges. This study investigated type 4 WS within an underrepresented Mongolian population. Whole-exome sequencing revealed that two unique heterozygous variants were identified in the SOX10 gene: c.393C>G (p.Asn131Lys) in a five-year-old female patient presenting with profound sensorineural hearing loss (SNHL), dystopia canthorum, and a white forelock; and c.535A>T (p.Lys179Ter) in a nine-year-old male patient presenting with profound SNHL, dystopia canthorum, and Hirschsprung’s disease. Temporal bone imaging revealed abnormalities in the inner ear structure in both patients. The genotypic and phenotypic characteristics were meticulously delineated, incorporating the deleterious effects of these variants, as evaluated by multiple predictive tools and the American College of Medical Genetics and Genomics (ACMG) criteria. In addition, structural characterizations were also presented using AlphaFold. The findings of this study contribute valuable genetic data to the limited literature on type 4 WS within this ethnic group and highlight the importance of genetic testing and multidisciplinary care for this rare disorder in settings with limited resources. Full article

Background/Objectives: Horseshoe kidney is a congenital anomaly characterized by the fusion of the kidneys at the lower pole. Polycystic kidney disease with horseshoe kidney is called polycystic horseshoe kidney. Genetic testing is essential for the diagnosis of polycystic horseshoe kidney disease because it can result from a number of genetic disorders. Fewer than 20 cases of polycystic horseshoe kidney have been reported to date. However, polycystic horseshoe kidney disease was mostly diagnosed via autopsy or radiologic imaging techniques including computed tomography, magnetic resonance imaging, and angiography. Because polycystic kidney disease has various causes, genetic testing is essential for the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) in patients with polycystic horseshoe kidney disease. At present, the diagnosis of ADPKD is made using genetic approaches, including next-generation sequencing. We reported a potentially pathogenic polycystin 1 (PKD1) gene in a patient with ADPKD and horseshoe kidney. Methods: We performed the sequencing of the PKD1 gene and radiological examinations (computed abdominal tomography). Results: Computed abdominal tomography revealed enlarged kidneys with multiple cysts fused at the lower poles, indicating polycystic HSK. The sequencing of the PKD1 gene revealed a heterozygous pathogenic variant c.165_171del (p.Leu56ArgfsTer15), which genetically confirmed the diagnosis of ADPKD. The patient was treated with an angiotensin II receptor blocker. Conclusions: In this case report, we suggest that genetic testing becomes the key approach to the diagnosis of ADPKD with horseshoe kidney. Additionally, this approach offers the benefit of avoiding the possibility of the condition being mistakenly diagnosed or diagnosed late due to its uncommon occurrence and nonspecific symptoms. Full article

Ataxia-telangiectasia is a rare autosomal recessive disorder that is difficult to diagnose due to its unpredictable presentation. It is characterized by cerebellar degeneration, telangiectasias, immunodeficiency, frequent pulmonary infections, and tumors. Immune system abnormalities manifest as disruptions in both cellular and humoral immunity. The most common findings include decreased levels of immunoglobulin classes (IgA, IgM, IgG, and IgG subclasses) and a reduced number of T and B lymphocytes. A four-year-old girl was initially evaluated and treated for skin lesions that presented as crusts spreading across her body. She was monitored by a pulmonologist due to frequent bronchial obstructions. Over time, she developed bilateral scleral telangiectasia, saccadic eye movements, and impaired convergence. Her gait was wide-based and unstable, with truncal ataxia and a positive Romberg sign. Laboratory tests revealed decreased immunoglobulin G levels, subclass IgG4 levels, elevated alpha-fetoprotein, and a reduced number of T and B lymphocytes. Brain magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing identified heterozygous variants c.1564-165del, p.(Glu5221lefsTer43), and c.7630-2A>C in the serine/threonine-protein kinase ATM (ataxia-telangiectasia mutated) gene, confirming the diagnosis of ataxia-telangiectasia. Following diagnosis, treatment with intravenous immunoglobulin replacement was initiated along with infection prevention and management. The goal of this case report is to raise awareness of the atypical initial presentation that may lead to a diagnostic delay. We emphasize the importance of considering ataxia-telangiectasia in the differential diagnosis, even when classical neurological signs are not yet evident. Full article

Despite their relatively low incidence globally, central nervous system (CNS) tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide surgical interventions and optimize patient outcomes. Frozen sectioning has emerged as a vital intraoperative technique, allowing for highly accurate, rapid analysis of tissue samples, although it poses challenges regarding interpretive errors and tissue distortion. Raman histology, based on Raman spectroscopy, has shown great promise in providing label-free, molecular information for accurate intraoperative diagnosis, aiding in tumor resection and the identification of neurodegenerative disease. Techniques including Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman Scattering (CARS), Surface-Enhanced Raman Scattering (SERS), and Tip-Enhanced Raman Scattering (TERS) have profoundly enhanced the speed and resolution of Raman imaging. Similarly, Confocal Laser Endomicroscopy (CLE) allows for real-time imaging and the rapid intraoperative histologic evaluation of specimens. While CLE is primarily utilized in gastrointestinal procedures, its application in neurosurgery is promising, particularly in the context of gliomas and meningiomas. This review focuses on discussing the immense progress in intraoperative histology within neurosurgery and provides insight into the impact of these advancements on enhancing patient outcomes. Full article

Familial thoracic aortic aneurysms and dissections may occur as an isolated hereditary trait or as part of connective tissue disorders with Mendelian inheritance, but severe cardiovascular disease in pediatric patients is extremely rare. There is growing knowledge on pathogenic variants causing the disease; however, much of the phenotypic variability and gene–gene interactions remain to be discovered. We present a case report of a 5.5-year-old girl with an aortic aneurysm and concomitant polycystic kidney disease. Whole exome sequencing was performed, followed by family screening by amplicon deep sequencing and diagnostic imaging studies. In the proband, two pathogenic variants were identified: p.Tyr257Ter in the LOX gene inherited from her mother, and p.Thr2977Ile in the PKD1 gene inherited from her father. All adult carriers of either of these variants showed symptoms of aortic disease. We conclude that the coexistence of two independent genetic variants in the proband may be the reason for an early onset of disease. Full article

Background: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. Aims: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. Materials and Methods: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Results: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population—c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. Conclusions: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population. Full article

Background and Objectives: Tunnel enlargement (TE) is a widely reported phenomenon after anterior cruciate ligament reconstruction (ACLR). Given the paucity of knowledge in the literature, it remains unclear whether screw position in the tunnel affects TE. This retrospective cohort study evaluated differences in postoperative tunnel enlargement rates (TER) and clinical results between anterior and posterior tibial interference screw insertion during single-bundle ACLR using autologous hamstring grafts. Materials and Methods: A group of consecutive patients that underwent primary arthroscopic single-bundle ACLR in our hospital were screened and divided into two groups based on the position of the tibial interference screw (determined by Computer Tomography within 3 days after surgery): anterior screw position group (A) and posterior screw position group (B). The bone tunnel size was measured using magnetic resonance imaging (MRI) performed 1 year after surgery. International Knee Documentation Committee (IKDC) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were used for clinical results 1 year postoperatively. Results: 87 patients were included. The TER of Group A is higher than that of Group B (43.17% vs. 33.80%, p = 0.024). Group A showed a significant increase (12.1%) in enlargement rates at the joint line level than group B (43.77% vs. 31.67%, p = 0.004). Moreover, KOOS and IKDC scores improved in both groups. There were no significant differences in clinical outcomes between the two groups. Conclusions: One year after ACLR, patients with posterior screw showed significantly lower TE than patients with anterior screw. However, the position of screw did not lead to differences in clinical results over our follow-up period. Posterior screw position in the tibial tunnel maybe a better choice in terms of reducing TE. Whether the different screw positions affect the long-term TE and long-term clinical outcomes needs to be confirmed by further studies. Full article

Nanoparticles have proven to be biocompatible and suitable for many biomedical applications. Currently, hyperthermia cancer treatments based on Fe nanoparticle infusion excited by alternating magnetic fields are commonly used. In addition to this, MRI-based image-guided radiotherapy represents, nowadays, one of the most promising accurate radiotherapy modalities. Hence, assessing the feasibility of combining both techniques requires preliminary characterization of the corresponding dosimetry effects. The present work reports on a theoretical and numerical simulation feasibility study aimed at pointing out preliminary dosimetry issues. Spatial dose distributions incorporating magnetic nanoparticles in MRI-based image-guided radiotherapy have been obtained by Monte Carlo simulation approaches accounting for all relevant radiation interaction properties as well as charged particles coupling with strong external magnetic fields, which are representative of typical MRI-LINAC devices. Two main effects have been evidenced: local dose enhancement (up to 60% at local level) within the infused volume, and non-negligible changes in the dose distribution at the interfaces between different tissues, developing to over 70% for low-density anatomical cavities. Moreover, cellular uptakes up to 10% have been modeled by means of considering different Fe nanoparticle concentrations. A theoretical temperature-dependent model for the thermal enhancement ratio (TER) has been used to account for radiosensitization due to hyperthermia. The outcomes demonstrated the reliability of the Monte Carlo approach in accounting for strong magnetic fields and mass distributions from patient-specific anatomy CT scans to assess dose distributions in MRI-based image-guided radiotherapy combined with magnetic nanoparticles, while the hyperthermic radiosensitization provides further and synergic contributions. Full article

Infrared (IR) thermography is a tool to non-invasively assess the tear film temperature. The aim was to analyze ocular surface temperature (OST) variations in dry eye disease (DED) and control eyes under natural non-controlled blinking conditions. Imaging was performed with a thermal camera (FLIR Systems Inc.) at 30 Hz framerate in 79 participants (39 DED (62.5% women, average age 48 ± 20 years) and 40 control (46.2 % women, average age 38 ± 13 years)) using non-contact IR thermography camera. Data acquisitions were performed in natural blinking conditions for 40 s. IR images were analyzed using a custom algorithm that calculates the OST indexes: mean OST, OST at the start and at the end, minimum and maximum OST, and tear evaporation rate (TER). No significant differences were found between groups in any thermal parameter analyzed (paired comparisons t-test, p > 0.05). In conclusion, the findings of this study did not reveal significant differences between DED and control eyes under natural non-controlled blinking conditions. However, the presence of clinical signs in the control group may affect the results, highlighting the role of DED diagnosis criteria. Full article

Tip-enhanced Raman spectroscopy (TERS) combines the high specificity and sensitivity of plasmon-enhanced Raman spectroscopy with the high spatial resolution of scanning probe microscopy. TERS has gained a lot of attention from many nanoscience fields, since this technique can provide chemical and structural information of surfaces and interfaces with nanometric spatial resolution. Multiwalled carbon nanotubes (MWCNTs) are very versatile nanostructures that can be dispersed in organic solvents or polymeric matrices, giving rise to new nanocomposite materials, showing improved mechanical, electrical and thermal properties. Moreover, MWCNTs can be easily functionalized with polymers in order to be employed as specific chemical sensors. In this context, TERS is strategic, since it can provide useful information on the cooperation of the two components at the nanoscale for the optimization of the macroscopic properties of the hybrid material. Nevertheless, efficient TERS characterization relies on the geometrical features and material composition of the plasmonic tip used. In this work, after comparing the TERS performance of commercial Ag coated nanotips and home-made bulk Au tips on bare MWCNTs, we show how TERS can be exploited for characterizing MWCNTs mixed with conjugated fluorene copolymers, thus contributing to the understanding of the polymer/CNT interaction process at the local scale. Full article

Background and Objectives: Sclerostin is an SOST gene product that inhibits osteoblast activity and prevents excessive bone formation by antagonizing the Wnt signaling pathway. Sclerosteosis has been linked to loss of function mutations in the SOST gene. It is a rare autosomal recessive disorder characterized by craniotubular hyperostosis and can lead to fatal cerebellar herniation. Our aim is to describe the clinical and radiological features and the new underlying SOST mutation in a patient with sclerosteosis. Case: A 25-year-old female who was referred to the endocrine clinic for suspected excess growth hormone. The patient complained of headaches, progressive blurred vision, hearing disturbances, increased size of feet, proptosis, and protrusion of the chin. She had normal antenatal history except for syndactyly. Images showed diffuse osseous thickening and high bone mineral density. Biochemical and hormonal tests were normal. Due to progressive compressive optic neuropathy, optic nerve fenestration with decompression hemicraniotomy was performed. Sclerosteosis was suspected due to the predominant craniotubular hyperostosis with syndactyly. Using peripheral leucocyte DNA, genomic sequencing of the SOST gene was performed. This identified a novel deletion homozygous mutation in the SOST gene (c.387delG, p.Asp131ThrfsTer116) which disrupts sclerostin function, causing sclerosteosis. Conclusions: Discovery of the molecular basis of sclerosteosis represents an important advance in the diagnosis and management of this fatal disease. Full article

Due to their high absorption coefficient and long carrier lifetime, halide perovskites are promising candidates for photocatalysts. For this study, the antisolvent crystallization protocol and the colloidal crystal templating approach were combined to fabricate the highly crystalline cesium lead bromide perovskite with inverse opal morphology (IO-CsPbBr₃). Scanning electron microscopy and transmission electron microscope images demonstrate the three-dimensional well-ordered porous structures of the IO-CsPbBr₃ and their single-crystalline features. The presented approach not only provides hierarchical porous structures but also enhances overall crystallinity. When used as catalysts to promote the polymerization of 2,2′,5′,2″-ter-3,4-ethylenedioxythiophene, the highly crystalline IO-CsPbBr₃ exhibits a superior photocatalytic performance compared to its polycrystalline counterpart. Furthermore, the morphology and the crystalline structure of the highly crystalline IO-CsPbBr₃ are well preserved under photocatalytic conditions. This novel approach enables the preparation of a halide perovskite inverse opal with high crystallinity. Full article

DNA covers the genetic information in all living organisms. Numerous intrinsic and extrinsic factors may influence the local structure of the DNA molecule or compromise its integrity. Detailed understanding of structural modifications of DNA resulting from interactions with other molecules and surrounding environment is of central importance for the future development of medicine and pharmacology. In this paper, we review the recent achievements in research on DNA structure at nanoscale. In particular, we focused on the molecular structure of DNA revealed by high-resolution AFM (Atomic Force Microscopy) imaging at liquid/solid interfaces. Such detailed structural studies were driven by the technical developments made in SPM (Scanning Probe Microscopy) techniques. Therefore, we describe here the working principles of AFM modes allowing high-resolution visualization of DNA structure under native (liquid) environment. While AFM provides well-resolved structure of molecules at nanoscale, it does not reveal the chemical structure and composition of studied samples. The simultaneous information combining the structural and chemical details of studied analyte allows achieve a comprehensive picture of investigated phenomenon. Therefore, we also summarize recent molecular spectroscopy studies, including Tip-Enhanced Raman Spectroscopy (TERS), on the DNA structure and its structural rearrangements. Full article

This study aimed to characterize Korean patients with pseudoxanthoma elasticum (PXE) presenting with angioid streaks. Retinal phenotypes were longitudinally evaluated by multimodal ophthalmic imaging, and targeted gene panel sequencing for inherited retinal diseases was conducted. Seven subjects from unrelated families (median age, 51.2 years) were enrolled and followed for a median of 3.2 years. Four asymptomatic patients were significantly younger than three symptomatic patients with decreased visual acuity at presentation (mean age; 38.1 vs. 61.5 years, p = 0.020). The asymptomatic patients maintained good vision (20/32 or better) and had no choroidal neovascularization (CNV) over the observation period. The symptomatic patients showed additional reduction in visual acuity and bilateral CNV occurrence during the longitudinal follow-up. Pathogenic ABCC6 variants were identified in all patients, leading to a diagnosis of PXE. Heterozygous monoallelic variants were identified in four patients and compound heterozygous variants were detected in three patients. Nine ABCC6 variants were identified, including one novel variant, c.2035G>T [p.Glu679Ter]. This is the first genetic study of Korean patients with PXE. Full article