Familial cerebral cavernous malformations caused by a novel germline structural variant in the KRIT1 gene.

The detection of complex structural variants in patients with familial cerebral cavernous malformations (FCCM) remains challenging. Short-read whole genome sequencing was performed for a patient with strong clinical evidence of FCCM but negative results from previous genetic tests. The analysis revealed a large insertion of an intronic KRIT1 fragment into a coding exon of KRIT1.

Platelet-rich plasma - A comprehensive review of isolation, activation, and application.

Platelets and platelet enriched products have been widely studied for their roles in promoting cell proliferation, migration, and tissue regeneration, making them highly interesting for clinical applications such as traumatology, dental, orthopaedic, and plastic surgery. However, their clinical adoption remains limited, partly due to fragmented and inconsistent data. Previous reviews have explored various applications of PRP therapies, but no comprehensive work has systematically mapped their processing methods, treatment modalities, and applications alongside clinical outcomes.

Lifetime Risk of First Symptomatic ICH or Seizure in Familial Cerebral Cavernous Malformations: A Multicenter Patient Data Analysis.

Background And Objectives: Familial cavernous malformations (FCMs) are vascular lesions that pose a lifelong risk of symptomatic hemorrhage (SH) and seizures, yet their natural history remains unclear. This study aims to determine the cumulative lifetime risk of a first SH and/or seizure and assess whether genetic variations influence these risks.

Methods: This international, multicenter retrospective cohort study included data from 16 tertiary referral centers and 1 patient advocacy group.

High-throughput differentiation of human blood vessel organoids reveals overlapping and distinct functions of the cerebral cavernous malformation proteins.

Cerebral cavernous malformations (CCMs) are clusters of thin-walled enlarged blood vessels in the central nervous system that are prone to recurrent hemorrhage and can occur in both sporadic and familial forms. The familial form results from loss-of-function variants in the CCM1, CCM2, or CCM3 gene. Despite a better understanding of CCM pathogenesis in recent years, it is still unclear why CCM3 mutations often lead to a more aggressive phenotype than CCM1 or CCM2 variants.

Oxford Nanopore long-read sequencing with CRISPR/Cas9-mediated target selection for accurate characterization of copy number variants in the LDLR gene.

Introduction: Familial hypercholesterolemia (FH) affects around 1 in 250 people. Most FH cases are caused by pathogenic LDLR variants, with copy number variations (CNVs) accounting for about 10 %. However, short-read gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA) are limited in the specification of CNV breakpoints and the identification of complex structural variants (SVs).

Novel postzygotic mutation in a patient with Parkes Weber syndrome: A case report and literature review.

Key Clinical Message: Not only germline but also postzygotic mutations in the or genes can lead to capillary malformation-arteriovenous malformation (CM-AVM) syndrome. As it is not always possible to clinically distinguish between constitutional variants and postzygotic mosaicism, a sufficiently high sequencing depth must be used in genetic diagnostics to detect both.

Abstract: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome, with or without Parkes Weber syndrome, is a rare autosomal dominant disease caused by pathogenic or variants.

Antibacterial and Antibiofilm Effects of L-Carnitine-Fumarate on Oral Streptococcal Strains and .

is a major pathogenic habitant of oral caries. Owing to its physiological and biochemical features, it prevails in the form of plaque biofilm together with another important mutans streptococci species, . Both species are considered as initiators of cavity lesions, and biofilm is essential to the dental caries process.

Optoelectronic Strain-Measurement System Demonstrated on Scaled-Down Flywheels.

Monitoring the strain in the rotating flywheel in a kinetic energy storage system is important for safe operation and for the investigation of long-term effects in composite materials like carbon-fiber-reinforced plastics. An optoelectronic strain-measurement system for contactless deformation and position monitoring of a flywheel was investigated. The system consists of multiple optical sensors measuring the local relative in-plane displacement of the flywheel rotor.

Aggregates of nonmuscular myosin IIA in erythrocytes associate with GATA1- and GFI1B-related thrombocytopenia.

Background: The transcription factor GATA1 is an essential regulator of erythroid cell gene expression and maturation and is also relevant for platelet biogenesis. GATA1-related thrombocytopenia (GATA1-RT) is a rare X-linked inherited platelet disorder (IPD) characterized by macrothrombocytopenia and dyserythropoiesis. Enlarged platelet size, reduced platelet granularity, and noticeable red blood cell anisopoikilocytosis are characteristic but unspecific morphological findings in GATA1-RT.

Inhibitory effect of theaflavin-3,3'-digallate can involve its binding to the "stem" domain of α-hemolysin of Staphylococcus aureus.

Infections caused by Staphylococcus aureus are currently a worldwide threat affecting millions of individuals. The pathogenicity of S. aureus is associated with numerous virulence factors, including cell surface proteins, polysaccharides, and secreted toxins.

Inhibition of α-hemolysin activity of Staphylococcus aureus by theaflavin 3,3'-digallate.

The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, has resulted in limited treatment options for bacterial infections, including these caused by methicillin-resistant Staphylococcus aureus, leaving the world in a post-antibiotic era. Here, we set out to examine mechanisms by which theaflavin 3,3'-digallate (TF3) might act as an anti-hemolytic compound. In the presented study, we found that TF3 has weak bacteriostatic and bactericidal effects on Staphylococcus aureus, and strong inhibitory effect towards the hemolytic activity of its α-hemolysin (Hla) including its production and secretion.

Phytochemicals and micronutrients in suppressing infectivity caused by SARS-CoV-2 virions and seasonal coronavirus HCoV-229E in vivo.

SARS-CoV-2 infection still poses health threats especially to older and immunocompromised individuals. New emerging variants of SARS-CoV-2, including Omicron and Arcturus, have been challenging the effectiveness of humoral immunity resulting from repeated vaccination and infection. With recent study implying a wave of new mutants in vaccinated people making them more susceptible to the newest variants and fueling a rapid viral evolution, there is a need for alternative or adjunct approaches against coronavirus infections other than vaccines.

Endothelial Differentiation of Knockout iPSCs Triggers the Establishment of a Specific Gene Expression Signature.

Cerebral cavernous malformation (CCM) is a neurovascular disease that can lead to seizures and stroke-like symptoms. The familial form is caused by a heterozygous germline mutation in either the , or gene. While the importance of a second-hit mechanism in CCM development is well established, it is still unclear whether it immediately triggers CCM development or whether additional external factors are required.

Linoleic acid binds to SARS-CoV-2 RdRp and represses replication of seasonal human coronavirus OC43.

Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential.

Hereditary Breast and Ovarian Cancer Service in Sparsely Populated Western Pomerania.

The German Consortium Hereditary Breast and Ovarian Cancer (GC-HBOC) consists of 23 academic centers striving to provide high-quality regional care for affected individuals and healthy at-risk family members. According to the standard operating procedures defined by the GC-HBOC, a Familial Breast and Ovarian Cancer Center was implemented at the University Medicine Greifswald over a four-year period from 2018 to 2021, despite the COVID-19 pandemic. Genetic analyses were performed in a total of 658 individuals, including 41 males, which paved the way to local annual risk-adapted breast cancer surveillance for 91 women and prophylactic surgery for 34 women in 2021.

Inhibition of -Induced TLR2-NFκB Canonical Signaling by Gallic Acid through Targeting the CD14+ Adaptor Protein and p65 Molecule.

The cases of Lyme disease caused by infection have been increasing throughout Northern America and Europe. This pathogen, if not treated in a timely manner with antibiotics, can cause persisting and debilitating health outcomes. In the search for novel agents against , we investigated a phenolic compound-gallic acid-for its anti- and anti-inflammatory effects.

Using CRISPR/Cas9 genome editing in human iPSCs for deciphering the pathogenicity of a novel transcription start site deletion.

Cerebral cavernous malformations are clusters of aberrant vessels that can lead to severe neurological complications. Pathogenic loss-of-function variants in the , , or gene are associated with the autosomal dominant form of the disease. While interpretation of variants in protein-coding regions of the genes is relatively straightforward, functional analyses are often required to evaluate the impact of non-coding variants.

Composition of naturally occurring compounds decreases activity of Omicron and SARS-CoV-2 RdRp complex.

Naturally-occurring compounds are acknowledged for their broad antiviral efficacy. Little is however known about their mutual cooperation. Here, we evaluated in vitro efficacy of the defined mixture of agents against the RdRp complex of the original SARS-CoV-2 and Omicron variant.

Contact-dependent signaling triggers tumor-like proliferation of CCM3 knockout endothelial cells in co-culture with wild-type cells.

Cerebral cavernous malformations (CCM) are low-flow vascular lesions prone to cause severe hemorrhage-associated neurological complications. Pathogenic germline variants in CCM1, CCM2, or CCM3 can be identified in nearly 100% of CCM patients with a positive family history. In line with the concept that tumor-like mechanisms are involved in CCM formation and growth, we here demonstrate an abnormally increased proliferation rate of CCM3-deficient endothelial cells in co-culture with wild-type cells and in mosaic human iPSC-derived vascular organoids.

Pathogenic variants in cause recessive central conducting lymphatic anomaly with lymphedema.

Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Although pathogenic variants in RAS/mitogen activated protein kinase (MAPK) signaling pathway components have been documented in some patients with CCLA, the genetic etiology of the disorder remains uncharacterized in most cases. Here, we identified biallelic pathogenic variants in , encoding the MyoD family inhibitor domain containing protein, in seven individuals with CCLA from six independent families.

Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants.

Despite vaccine availability, the global spread of COVID-19 continues, largely facilitated by emerging SARS-CoV-2 mutations. Our earlier research documented that a specific combination of plant-derived compounds can inhibit SARS-CoV-2 binding to its ACE2 receptor and controlling key cellular mechanisms of viral infectivity. In this study, we evaluated the efficacy of a defined mixture of plant extracts and micronutrients against original SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants.

Uncertainty Analysis of an Optoelectronic Strain Measurement System for Flywheel Rotors.

The strain in a fast spinning carbon fiber flywheel rotor is of great interest for condition monitoring, as well as for studying long-term aging effects in the carbon fiber matrix. Optoelectronic strain measurement is a contactless measurement principle where a special reflective pattern is applied to the rotor which is scanned by a stationary optical setup. It does not require any active electronic components on the rotor and is suited for operation in a vacuum.