Proteins Involved in Endothelial Function and Inflammation Are Implicated in Cerebral Small Vessel Disease.

Background: Endothelial dysfunction and inflammation have been implicated in the pathophysiology of cerebral small vessel disease (SVD). However, whether they are causal, and if so which components of the pathways represent potential treatment targets, remains uncertain.

Methods: Two-sample Mendelian randomization (MR) was used to test the association between the circulating abundance of 996 proteins involved in endothelial dysfunction and inflammation and SVD.

Infection Reinforces the Defense Reactions in - Roots to the Detriment of Nodules.

, able to establish symbiosis with mutualistic bacteria of the genus , is one of the main species in European riparian environments, where it performs numerous biological and socio-economic functions. However, riparian ecosystems face a growing threat from , a highly aggressive waterborne pathogen causing severe dieback in . To date, the tripartite interaction between the host plant, the symbiont and the pathogen remains unexplored but is critical for understanding how pathogen-induced stress influences the nodule molecular machinery and so on the host-symbiont metabolism.

Systematic Approach to Parametrization of Disaccharides for the Martini 3 Coarse-Grained Force Field.

Sugars are ubiquitous in biology; they occur in all kingdoms of life. Despite their prevalence, they have often been somewhat neglected in studies of structure-dynamics-function relationships of macromolecules to which they are attached, with the exception of nucleic acids. This is largely due to the inherent difficulties of not only studying the conformational dynamics of sugars using experimental methods but indeed also resolving their static structures.

Kinetic and Theoretical Studies of 3,5-Dicyanothiophene Reactivity with Cyclic Secondary Amines in Water and Acetonitrile: Quantification, Correlation, and Prediction.

The kinetics of the σ-complexation reactions of 3,5-dicyanothiophene with a series of cyclic secondary amines - has been studied in water and acetonitrile at 20 °C. Through the linear free energy relationship (LFER) log = s ( + ), the electrophilicity parameter of 3,5-dicyanothiophene has been determined and then integrated into the electrophilicity scale established by Mayr. Molecular dynamics (MD) simulations have been employed to elucidate the reversal in reactivity order between piperidine and pyrrolidine observed in water.

Nucleophilic and Electrophilic Molybdenum Terminal Oxo Complexes by Coordination-Induced Bond Weakening of Hydroxo O-H Bonds.

The extent of coordination-induced bond weakening in aquo and hydroxo ligands bonded to a molybdenum(III) center complexed by a dianionic, pentadentate ligand system was probed by reacting the known complex (BPzPy)Mo(III)-NTf, , with degassed water or dry lithium hydroxide. The aquo adduct was not observed, but two LiNTf-stabilized hydroxo complexes were fully characterized. Computational and experimental work showed that the O-H bond in these complexes was significantly weakened (to ≈57 kcal mol), such that these compounds could be used to form the diamagnetic, neutral terminal molybdenum oxo complex (BPzPy)Mo(IV)O, , by hydrogen atom abstraction using the aryl oxyl reagent ArO• (Ar = 2,4,6-tri--butylphenyl).

Magnetic Properties, Spin-Vibration Couplings, and Temperature Effects in Phenalenyl and Triangulene.

We introduce a computational methodology for evaluating and analyzing spin-vibration couplings in molecular systems, enabling insights into the interplay between electronic spins and molecular vibrations. By mapping ab initio electronic structure calculations onto molecular spin Hamiltonians, our approach captures those vibrational interactions potentially driving spin relaxation process. Spin-vibration couplings, derived from Holstein and Peierls terms, highlight the pivotal role of vibrational mode symmetry in spin decoherence and efficient energy dissipation.

The Accuracy of Cardiac Surface Conduction Velocity Measurements.

Background: Conduction velocity (CV) is a measure of the health of myocardial tissue. It can be measured by taking differences in local activation times from intracardiac electrodes. Several factors introduce error into the measurement, among which ignoring the 3-dimensional aspect is a major detriment.

Age-Related Ventricular Tachycardia Substrate Characteristics for Repaired Tetralogy of Fallot Before Transcatheter Pulmonary Valve Placement.

Background: Ventricular tachycardia (VT) substrate characteristics before transcatheter pulmonary valve replacement (TPVR) in repaired tetralogy of Fallot (rTOF) are unknown.

Objectives: In this study, the authors sought to evaluate substrates for sustained monomorphic VT before TPVR in rTOF.

Methods: Retrospective (2017 to 2021) and prospective (commencing 2021) rTOF patients with native right ventricular outflow tract referred for electrophysiology study (EPS) before TPVR were included.

ESMO Global Consortium Study on the availability, out-of-pocket costs, and accessibility of cancer medicines: 2023 update.

Background: The availability and affordability of safe, effective cancer therapies are core requirements for effective cancer control. Global disparities exist in access, however, yielding unequal cancer outcomes. The goal of this study was to provide updated data regarding the formulary availability, out-of-pocket costs, and accessibility of cancer medicines in countries across the full spectrum of economic development areas.

The benefits and drawbacks of music in the operating room.

Introduction: A significant proportion of surgeons listen to music in the operating room (MOR) during a surgical procedure. Over the last twenty years, this practice has been widely studied. The aim of this article is to analyze the effects of MOR on surgical performance, postoperative history and, more generally, on communication in the operating theater.

Voice Quality as Digital Biomarker in Bipolar Disorder: A Systematic Review.

Background: Voice analysis has emerged as a potential biomarker for mood state detection and monitoring in bipolar disorder (BD). The systematic review aimed to summarize the evidence for voice analysis applications in BD, examining (1) the predictive validity of voice quality outcomes for mood state detection, and (2) the correlation between voice parameters and clinical symptom scales.

Methods: A PubMed, Scopus, and Cochrane Library search was carried out by two investigators for publications investigating voice quality in BD according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.

Anatomical study of the posterior talofibular ligament: A descriptive analysis of its dual-bundle structure.

Background: The lateral ankle ligament complex, consisting of the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL), is essential for ankle stability. While the ATFL and CFL are frequently studied, the PTFL's role remains less explored.

Methods: Twelve fresh-frozen ankle specimens were dissected to analyze the PTFL's origin, trajectory, and talar insertion, focusing on its bundles and anatomical relationships.

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies.

Bacillary layer detachment: Updates on its clinical and prognostic significance in retinal disease.

Bacillary layer detachment (BALAD) refers to the distinctive splitting at the level of the photoreceptor inner segment myoid and accumulation of intraretinal fluid, as seen on optical coherence tomography (OCT).BALAD is an increasingly recognized OCT biomarker of numerous heterogeneous chorioretinal diseases, including posterior uveitis, age-related macular degeneration and macular neovascularization, neoplastic and paraneoplastic retinal disorders, rhegmatogenous retinal detachment, blunt ocular trauma, and miscellaneous conditions. The recognition of BALAD is clinically relevant because, based on the specific etiology, BALAD may require simple observation, ocular or systemic medical treatment, or even surgical intervention, with subsequent different prognosis.

Off-axis electron holography of unstained bacteriophages: Toward electrostatic potential measurement of biological samples.

Transmission electron microscopy, especially at cryogenic temperature, is largely used for studying biological macromolecular complexes. A main difficulty of TEM imaging of biological samples is the weak amplitude contrasts due to electron diffusion on light elements that compose biological organisms. Achieving high-resolution reconstructions implies therefore the acquisition of a huge number of TEM micrographs followed by a time-consuming image analysis.

Chapter 15: RECURRENT OR PERSISTENT PRIMARY HYPERPARATHYROIDISM, PARATHYROMATOSIS.

Persistent primary hyperparathyroidism is defined as the persistence or recurrence of hypercalcemia within 6 months of parathyroid surgery. Recurrent primary hyperparathyroidism is defined as the recurrence of primary hyperparathyroidism more than 6 months after an initially curative parathyroidectomy. In these situations, it is essential to rule out differential diagnoses, and in particular secondary hyperparathyroidism and familial hypocalciuric hypercalcemia.

Chapter 5: THE ROLE OF GENETICS IN PRIMARY HYPERPARATHYROIDISM.

Around 10% of cases of primary hyperparathyroidism are thought to be genetic in origin, some of which are part of a syndromic form such as multiple endocrine neoplasia types 1, 2A or 4 or hyperparathyroidism-jaw tumor syndrome, while the remainder are cases of isolated familial primary hyperparathyroidism. Recognition of these genetic forms is important to ensure appropriate management according to the gene and type of variant involved, but screening for a genetic cause is not justified in all patients presenting primary hyperparathyroidism. The indications for genetic analysis have made it possible to propose a decision tree that takes into account whether the presentation is familial or sporadic, syndromic or isolated, patient age, and histopathological type of parathyroid lesion.

Chapter 8: MANAGEMENT OF AGGRESSIVE FORMS OF PRIMARY HPT: PARATHYROID CARCINOMA AND ATYPICAL PARATHYROID TUMOR.

Parathyroid carcinoma is extremely rare, affecting 1% of cases of primary hyperparathyroidism. For this reason, management is poorly codified and requires expertise in specialized center. PC is genetically determined in a quarter to a third of cases, notably involving the CDC73 gene coding for parafibromin.

Chapter 14: POST-SURGICAL FOLLOW-UP.

Primary hyperparathyroidism is treated surgically. Postoperatively, close monitoring of blood calcium levels is necessary to detect any hypocalcemia. Postoperative PTH assays can be performed within 24 hours to identify patients who will not develop permanent hypoparathyroidism.

Chapter 6: SYNDROMIC PRIMARY HYPERPARATHYROIDISM.

Syndromic primary hyperparathyroidism has several features in common: younger age at diagnosis when compared with sporadic primary hyperparathyroidism, often synchronous or metachronous multi-glandular involvement, higher possibility of recurrence, association with other endocrine or extra-endocrine disorders, and suggestive family background with autosomal dominant inheritance. Hyperparathyroidism in multiple endocrine neoplasia type 1 is the most common syndromic hyperparathyroidism. It is often asymptomatic in adolescents and young adults, but may be responsible for recurrent lithiasis and/or bone loss.