New Insights Into the Spectrum of RASopathies: Clinical and Genetic Data in a Cohort of 121 Spanish Patients.

Noonan syndrome and related disorders are a group of well-known genetic conditions caused by dysregulation of the Ras/mitogen-activated protein kinase (RAS/MAPK) pathway. Because of the overlap of clinical and molecular features, they are now called RASopathies. In this study, we retrospectively analyzed the clinical data of 121 patients with a molecularly confirmed diagnosis of RASopathy, describing frequencies for clinical features in all organ systems as well as molecular data.

Total Ankle Arthroplasty as a Correction Tool for Foot Deformities: Analyzing the Impact on Medial Column Alignment Adaptation Through Weightbearing Computed Tomography.

Background: While weightbearing computed tomography (WBCT) has been instrumental in analyzing total ankle arthroplasty (TAA) positioning, there is a notable gap in the literature regarding adaptive changes in the foot's medial column after TAA. This study aims to bridge this gap by comparing preoperative and postoperative alignments of the foot's medial column and analyzing if a correlation exists between TAA coronal alignment correction and medial column alignment adaptation.

Methods: Sixty patients who underwent a lateral approach TAA for end-stage osteoarthritis (OA) between January 2021 and April 2023 were included in this retrospective study.

Engineered autologous nasal cartilage for repair of nasal septal perforations: a case series.

Objective: This phase I clinical trial assessed the use of autologous nasal chondrocyte tissue-engineered cartilage (N-TEC) for functional repair of nasal septal perforations (NSP).

Background: The most widely used technique to treat NSP, namely interposition grafting with a polydioxanone (PDS) plate combined with a deep temporal fascia (DTF) graft, is still suboptimal towards patient satisfaction and revision rates.

Methods: Patients ( n =5, all female, age range: 23-54 years) had a 0.

Terminal Cyclopropylsilyl Alcohols as Useful Key Units to Access 2,3,4,6-Tetrasubstituted Tetrahydropyran Scaffolds by Stereocontrolled Prins Cyclization.

In this study, the use of terminal cyclopropylsilyl alcohols in Prins cyclization is reported as a very efficient methodology for the preparation of polysubstituted tetrahydropyrans, in which three new stereogenic centers have been created in a single pot. The reaction is general for a wide variety of aldehydes (alkylic, vinylic, aromatic, or dialdehydes), different types of alcohols, and halogenation agents providing high yields and excellent diastereoselectivity 2,3,4,6-tetrasubstituted tetrahydropyranyl frameworks. Interestingly, diastereomeric alcohols provide the same tetrahydropyranyl derivatives, showing that the reaction mechanism proceeds through common intermediates.

Isotopic, mycotoxin, and pesticide analysis for organic authentication along the production chain of wheat-derived products.

Wheat-based products are staples in diets worldwide. Organic food frauds continuously threaten consumer trust in the agri-food system. A multi-method approach was conducted for the organic authentication and safety assessment of pasta and bakery products along their production chain.

Regeneration: AT-AMIC Technique: Limits and Indication.

Osteochondral lesion of the talus (OLT) is a commune cause of chronic ankle pain. Symptomatic lesions require surgical treatment. Currently, lesions with diameter less than 107.

Enhancing precision in osteochondral lesions of the talus measurements and improving agreement in surgical decision-making using weight-bearing computed tomography and distance mapping.

Purpose: Weight-bearing computed tomography (WBCT) enables the creation of a three-dimensional (3D) model that represents the ankle morphology in a standing position. Distance mapping (DM) is a complementary feature that uses color coding to represent the relative intraarticular distance and can be used to outline intraarticular defects. Consequently, DM offers a novel approach to delineating osteochondral lesions of the talus (OLT), allowing for the quantification of its surface, volume and depth.

Engineered human osteoarthritic cartilage organoids.

The availability of human cell-based models capturing molecular processes of cartilage degeneration can facilitate development of disease-modifying therapies for osteoarthritis [1], a currently unmet clinical need. Here, by imposing specific inflammatory challenges upon mesenchymal stromal cells at a defined stage of chondrogenesis, we engineered a human organotypic model which recapitulates main OA pathological traits such as chondrocyte hypertrophy, cartilage matrix mineralization, enhanced catabolism and mechanical stiffening. To exemplify the utility of the model, we exposed the engineered OA cartilage organoids to factors known to attenuate pathological features, including IL-1Ra, and carried out mass spectrometry-based proteomics.

Significant Clinical Improvement After Arthroscopic Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus: A 5-Year Follow-Up.

Purpose: This study aims to evaluate the clinical outcomes of arthroscopic autologous matrix-induced chondrogenesis (A-AMIC) for osteochondral lesions of the talus (OLT) at 24 months and 60 months of follow-up. The secondary aim was to assess whether age, body mass index (BMI), and lesion surface affect outcomes.

Design: Sixty-three patients (32 males, 31 females) with a median age of 37 years [interquartile range (IQR): 25-48] were included.

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage.

Implantation of a phenotypically stable cartilage graft could represent a viable approach for repairing osteoarthritic (OA) cartilage lesions. In the present study, we investigated the effects of modulating the bone morphogenetic protein (BMP), transforming growth factor beta (TGFβ), and interleukin-1 (IL-1) signaling cascades in human bone marrow stromal cell (hBMSC)-encapsulated silk fibroin gelatin (SF-G) bioink. The selected small molecules LDN193189, TGFβ3, and IL1 receptor antagonist (IL1Ra) are covalently conjugated to SF-G biomaterial to ensure sustained release, increased bioavailability, and printability, confirmed by ATR-FTIR, release kinetics, and rheological analyses.

Platelets promote human macrophages-mediated macropinocytosis of .

is the main causative agent of hospital-acquired diarrhea and the potentially lethal disease, infection. The cornerstone of the current therapy is the use of antibiotics, which is not fully effective. The molecular mechanisms, inflammatory conditions and host-immune responses that could benefit the persistence or elimination of remain unclear.

Towards an efficient methodology for the synthesis of functionalized dihydropyrans by silyl-Prins cyclization: access to truncated natural products.

We herein present a selective methodology for the synthesis of disubstituted dihydropyrans by silyl-Prins cyclization of -vinylsilyl alcohols mediated by trimethylsilyl trifluoromethanesulfonate (TMSOTf). The reaction features broad substrate scope, short reaction times and ease of process scale-up. Moreover, to showcase the applicability of the proposed method, we also report a facile and linear synthesis of analogues of rhopaloic acid and natural doremox fragrance.

New Spectroelectrochemical Insights into Manganese and Rhenium Bipyridine Complexes as Catalysts for the Electrochemical Reduction of Carbon Dioxide.

This study aimed to demonstrate the behavior of different complexes using IR spectroelectrochemistry (SEC), a technique that combines IR spectroscopy with electrochemistry. Four different Mn and Re catalysts for electrochemical CO reduction were studied in dry acetonitrile. In the case of Mn(apbpy)(CO)Br (apbpy = 4(4-aminophenyl)-2,2'-bipyridine), SEC suggested that a very slow catalytic reduction of CO also occurs in acetonitrile in the absence of proton donors, but at rather negative potentials.

Snijders Blok-Campeau Syndrome: Description of 20 Additional Individuals with Variants in and Literature Review.

Snijders Blok-Campeau syndrome (SNIBCPS, OMIM# 618205) is an extremely infrequent disease with only approximately 60 cases reported so far. SNIBCPS belongs to the group of neurodevelopmental disorders (NDDs). Clinical features of patients with SNIBCPS include global developmental delay, intellectual disability, speech and language difficulties and behavioral disorders like autism spectrum disorder.

Three-Dimensional Distance Mapping to Identify Safe Zones for Lateral Column Lengthening.

Background: Evans (E-LCL) and Hintermann LCL (H-LCL) lateral column lengthening osteotomies are standard surgical solutions for flexible, progressive collapsing feet. E-LCL is performed between the anterior and middle facets and endangers specific os calcis subtalar joint (OCST) subtypes without distinct facets. H-LCL is oriented between the posterior and middle facets and should be suitable for all OCSTs.

Continuous Flow Chemistry: A Novel Technology for the Synthesis of Marine Drugs.

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.

Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer's Disease and Parkinson's Disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases in the elderly. The key histopathological features of these diseases are the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca dyshomeostasis, plays a vital role in the pathophysiology of these neurological disorders.

Evaluation of expanded peripheral blood derived CD34+ cells for the treatment of moderate knee osteoarthritis.

Knee osteoarthritis (OA) is a degenerative joint disease of the knee that results from the progressive loss of articular cartilage. It is most common in the elderly and affects millions of people worldwide, leading to a continuous increase in the number of total knee replacement surgeries. These surgeries improve the patient's physical mobility, but can lead to late infection, loosening of the prosthesis, and persistent pain.

Reliability of Cone Beam Weightbearing Computed Tomography Analysis of Total Ankle Arthroplasty Positioning and Comparison to Weightbearing X-Ray Measurements.

Background: The current reference standard for postoperative evaluation of total ankle arthroplasty (TAA) positioning, weightbearing radiography (WBXR), is subject to technical bias. Weightbearing cone beam computed tomography (WBCT) enables visualization of the foot's complex 3-dimensional (3D) structure under standing load. To date, no WBCT-based system for TAA positioning has been validated.

Changing the Reaction Pathway of Silyl-Prins Cyclization by Switching the Lewis Acid: Application to the Synthesis of an Antinociceptive Compound.

Developing new procedures for the synthesis of tetrahydropyrans in a very stereoselective manner is of great importance for the synthesis of THP-containing natural products. Here, we report an interesting protocol for the synthesis of polysubstituted halogenated tetrahydropyrans by silyl-Prins cyclization of vinylsilyl alcohols, in which the nature of the Lewis acid determines the outcome of the process. The methodology has been applied to the synthesis of a known antinociceptive.

Axial rotation analysis in total ankle arthroplasty using weight-bearing computer tomography and three-dimensional modeling.

Background: Post-operative alignment is the most critical indicator for a successful total ankle arthroplasty (TAA). Total ankle malrotation is associated with an increased risk for polyethylene wear and medial gutter pain. Currently, there is no consensus on the correct way to measure the alignment of the tibial and talar component rotations in the axial plane.

Diastereoselective Synthesis of -2,6-Disubstituted Dihydropyrane Derivatives through a Competitive Silyl-Prins Cyclization versus Alternative Reaction Pathways.

A convenient regioselective synthesis of allyl- and vinylsilyl alcohols, from a common precursor, was described, by selecting the appropriate reaction conditions. Allyl- and vinylsilyl alcohols were tested in silyl-Prins cyclizations for the preparation of disubstituted oxygenated heterocycles in a one-pot sequential reaction. The methodology was sensitive to the structure of the starting alkenylsilyl alcohol and reaction conditions, with competitive pathways observed (particularly for allylsilyl alcohols), such as Peterson elimination and oxonia-Cope reactions.

Classification of the Os Calcis Subtalar Morphology in Symptomatic Flexible Pediatric Pes Planus Deformity Using Weightbearing CT and Distance Mapping.

Background: The etiology of symptomatic pediatric pes planus (PP) deformity is unclear. Reduced os calcis subtalar joint (OCST) anterior facet morphology has been suggested to result in less support to the talar head and a higher propensity to develop PP deformity. Weightbearing computed tomography (WBCT) and distance mapping (DM) offer new opportunities to investigate PP deformity in general and the OCST specifically.