Project description:In the British feline breed a golden coat modification, called light-gold, akita or copper, was reported by breeders during the 2010s. This modification restricted eumelanin to the tip of the tail and hairs showed a wideband modification. Pedigree analyses revealed an autosomal recessive inheritance pattern. A single candidate region was identified using a genome-wide association study. Within that region, we identified CORIN (Corin, serine peptidase) as the strongest candidate gene, since two CORIN variants have previously been identified in Siberian cats with a golden phenotype. A homozygous CORIN:c.2425C>T nonsense variant was identified in copper British cats. Segregation of the variant was consistent with recessive inheritance. This nonsense CORIN:c.2425C>T variant, located in CORIN exon 19, was predicted to produce a truncated CORIN protein - CORIN:p.(Arg809Ter) - that would lack part of the scavenger receptor domain and the trypsine-like serine protease catalytic domain. All 30 copper cats were T/T homozygous for the variant, which was also found in 20 C/T heterozygous British control cats but was absent in 340 cats from the 99 Lives dataset. Finally, genotyping of 218 cats from 12 breeds failed to identify carriers in cats from other breeds. We propose that this third CORIN:c.2425C>T variant represents the wbBSH (British recessive wideband) allele in the domestic cat.
Project description:The most severe complication of Kawasaki disease, an inflammatory disorder of young children, is the formation of coronary artery aneurysms. It is known that patients with coronary artery aneurysms, particularly those with medium and large lesions, have a higher risk of future major cardiovascular events. In contrast, there is a lack of data on the cardiovascular status in long-term follow-up for Kawasaki disease patients without coronary involvement or with self-limited coronary artery aneurysms, resulting in most patients being discharged after 5 years. Even though some paediatricians may believe these patients should not be followed at all, studies indicating a dysfunctional endothelium show the need for further investigation. Consequently, a review of the most significant aspects of Kawasaki disease, and the necessity of correctly identifying, treating and monitoring these patients, particularly those with a higher risk of complications, was conducted.
Project description:Glaucoma is one of the principal causes of irreversible blindness worldwide. Yet, intraocular pressure (IOP) is the main modifiable risk factor for disease progression. In the never-ending challenge to develop new and effective drugs, several molecules have been tested as anti-glaucoma agents thanks to their pressure-lowering capabilities. Among these molecules, the cannabinoids have been investigated as possible anti-glaucoma drugs since the early 1970s. Cannabinoids are a large class of chemical compounds that exploit their effects by interaction with cannabinoid receptors 1 and 2. These receptors are widely expressed in the human retina where they may influence important functions such as photo-transduction, amacrine cell network maintenance, and IOP regulation. Therefore, in past years several studies have been conducted in order to assess the IOP lowering effects of cannabinoids. PRISMA guidelines have been used to perform a literature search on Pubmed and Scopus aiming to investigate the mechanism of IOP lowering effects and the potential benefits of orally administered, inhaled, topical, and intravenous cannabinoids in the treatment of glaucoma patients.
Project description:Homology modelling is normally the technique of choice when experimental structure data are not available but three-dimensional coordinates are needed, for example, to aid with detailed interpretation of results of spectroscopic studies. Herein, the state of the art of homology modelling will be described in the light of a series of recent developments, and an overview will be given of the problems and opportunities encountered in this field. The major topic, the accuracy and precision of homology models, will be discussed extensively due to its influence on the reliability of conclusions drawn from the combination of homology models and spectroscopic data. Three real-world examples will illustrate how both homology modelling and spectroscopy can be beneficial for (bio)medical research.
Project description:BackgroundThe diagnostic process of pulmonary fibrosis (PF) is often challenging, requires a collaborative effort of several experts, and often requires bioptic material, which can be difficult to obtain, both in terms of quality and technique. The main procedures available to obtain such samples are transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB).ObjectiveThe purpose of this paper is to review the evidence for the role of TBLC in the diagnostic-therapeutic process of PF.MethodsA comprehensive review was performed to identify articles to date that addressed the role of TBLC in the diagnostic-therapeutic process of PF using the PubMed® database.ResultsThe reasoned search identified 206 papers, including 21 manuscripts (three reviews, one systematic review, two guidelines, two prospective studies, three retrospective studies, one cross-sectional study, one original article, three editorials, three clinical trials, and two unclassifiable studies), which were included in the final review.ConclusionsTBLC is gaining increasing efficacy and improving safety profile; however, there are currently no clear data demonstrating its superiority over SLB. Therefore, the two techniques should be considered with careful rationalization on a case-by-case basis. Further research is needed to further optimize and standardize the procedure and to thoroughly study the histological and molecular characteristics of PF.
Project description:This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung cancer. It also systematically reviews the current evidence, the international recommendations in the most relevant guidelines, the most controversial aspects in clinical and pathological staging, the specific technical aspects of radiotherapy treatment, and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients, evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical evolution. Finally, currently active trials that aspire to provide more evidence on this topic are reviewed.
Project description:Six novel cyclodextrin (CD)-based metal-organic frameworks (MOFs) were synthesized using distinct crystallization methodologies. A modified vapor diffusion method is introduced for the first time, termed fast crystallization, which enables the rapid solid-state formation of MOF compounds. This innovative method yielded four of the newly synthesized MOFs. The crystal structures of five obtained frameworks were structurally characterized through single-crystal X-ray diffraction, while one, compound 5 (γ-CD-K-5), was additionally characterized as a bulk powder. Structural analysis revealed that two of the newly obtained MOFs, namely, compound 2 (α-CD-K-2) and compound 3 (α-CD-Rb-3), exhibited isostructural characteristics, forming a three-dimensional (3D) framework. Compound 1 (α-CD-K-1) shared the same space group as EVEGET (α-CD-K) and displayed the same framework type. Furthermore, the crystal packing of compound 4 (β-CD-K-4) closely resembled that of compound 1 and EVEGET, with the only distinction lying in the type of CD employed. Notably, compound 6 (γ-CD-K-6) incorporated an iodine ion with an occupancy of 0.2. To discern the intermolecular interactions within the obtained MOFs, the Hirshfeld surface was calculated using Crystal Explorer software.
Project description:Background/Objectives: This study aimed to determine if MRI features can distinguish between spinal infections caused by pyogenic bacteria and Mycobacterium tuberculosis. Methods: Patients underwent an MRI of the thoracolumbar spine with and without contrast. Three blinded observers assessed the images, using statistical tests for analysis. Results: Demographic characteristics and symptom duration were similar between patients with tuberculous and pyogenic spinal infections. In 36 cases of pyogenic infections, the MRI showed weakly delineated paravertebral tissue enhancement (76%), a hyperintense signal in the T2 TIRM sequences (89%), and homogeneous vertebral body enhancement (89%). In 32 cases of Mycobacterium infections, the MRI revealed well-delineated paravertebral changes, mixed vertebral body signals, and variable enhancement. Pyogenic infections were more often found in the lumbar spine (67%) and typically involved two vertebrae, while tuberculous infections preferred the thoracic spine (75%) and often involved two vertebrae, with 25% affecting three or more vertebrae. Conclusions: The MRI features can help differentiate between pyogenic and tuberculous spine infections, though none are definitive. The study suggests that MRI can be used for initial differentiation or as a diagnostic tool when biopsy or surgical exploration is not possible.