Noninvasive Imaging of Transgene Expression in Neurons Using Chemical Exchange Saturation Transfer MRI.

Advances in gene therapy, especially for brain diseases, have created new imaging demands for noninvasive monitoring of gene expression. While reporter gene imaging using co-expression of fluorescent protein-encoding gene has been widely developed, these conventional methods face significant limitations in longitudinal in vivo applications. Magnetic resonance imaging (MRI), specifically chemical exchange saturation transfer (CEST) MRI, provides a robust noninvasive alternative that offers unlimited depth penetration, reliable spatial resolution, and specificity toward particular molecules.

Toward quantitative CEST imaging of glutamate in the mouse brain using a multi-pool exchange model calibrated by H-MRS.

Purpose: To develop a CEST quantification model to map glutamate concentration in the mouse brain at 11.7 T, overcoming the limitations of conventional glutamate-weighted CEST (gluCEST) contrast (magnetization transfer ratio with asymmetric analysis).

Methods: H-MRS was used as a gold standard for glutamate quantification to calibrate a CEST-based quantitative pipeline.

Fast vibrational analysis of molecular systems.

The development of infrared difference spectroscopy provides unprecedented insights on structures of complex molecules like metalloproteins. However, the relevant information can be hard to find among the many bands of the vibrational spectra. The ab initio modeling is very helpful to assign the frequencies to vibrational modes but it is a challenge to process the huge quantity of data into descriptors useful for experimentalists.

Paracetamol overdose causing acute kidney injury without hepatotoxicity: a case report.

Background: Paracetamol is a widely used analgesic and antipyretic. Paracetamol-induced hepatotoxicity is well known, but nephrotoxicity without hepatotoxicity is rarely seen.

Case Presentation: We present a case of acute kidney injury without hepatotoxicity in paracetamol overdose.

Predicting Matrix Test Effectiveness for Evaluating Auditory Performance in Noise Using Pure-Tone Audiometry and Speech Recognition in Quiet in Cochlear Implant Recipients.

Introduction: Auditory performance in noise of cochlear implant recipients can be assessed with the adaptive Matrix test (MT); however, when the speech-to-noise ratio (SNR) exceeds 15 dB, the background noise has any negative impact on the speech recognition. Here, we aim to evaluate the predictive power of aided pure-tone audiometry and speech recognition in quiet and establish cut-off values for both tests that indicate whether auditory performance in noise can be assessed using the Matrix sentence test in a diffuse noise environment.

Methods: Here, we assessed the power of pure-tone audiometry and speech recognition in quiet to predict the response to the MT.

The contribution of preclinical magnetic resonance imaging and spectroscopy to Huntington's disease.

Huntington's disease is an inherited disorder characterized by psychiatric, cognitive, and motor symptoms due to degeneration of medium spiny neurons in the striatum. A prodromal phase precedes the onset, lasting decades. Current biomarkers include clinical score and striatal atrophy using Magnetic Resonance Imaging (MRI).

Longitudinal MRI and 1H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction.

SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein, which is part of the transcriptional coactivator complex SAGA. The mutation primarily causes neurodegeneration in the cerebellum and retina, as well as several forebrain structures. The SCA7140Q/5Q knock-in mouse model recapitulates key disease features, including loss of vision and motor performance.

Antisense oligonucleotide-mediated disruption of HTT caspase-6 cleavage site ameliorates the phenotype of YAC128 Huntington disease mice.

In Huntington disease, cellular toxicity is particularly caused by toxic protein fragments generated from the mutant huntingtin (HTT) protein. By modifying the HTT protein, we aim to reduce proteolytic cleavage and ameliorate the consequences of mutant HTT without lowering total HTT levels. To that end, we use an antisense oligonucleotide (AON) that targets HTT pre-mRNA and induces partial skipping of exon 12, which contains the critical caspase-6 cleavage site.

SPICT as a predictive tool for risk of 1-year health degradation and death in older patients admitted to the emergency department: a bicentric cohort study in Belgium.

Background: Older patients are increasingly showing multi-comorbidities, including advanced chronic diseases. When admitted to the emergency department (ED), the decision to pursue life-prolonging treatments or to initiate a palliative care approach is a challenge for clinicians. We test for the first time the diagnostic accuracy of the Supportive and Palliative Care Indicators Tool (SPICT) in the ED to identify older patients at risk of deteriorating and dying, and timely address palliative care needs.

Perturbation Theory Treatment of Spin-Orbit Coupling. III: Coupled Perturbed Method for Solids.

A previously proposed noncanonical coupled-perturbed Kohn-Sham density functional theory (KS-DFT)/Hartree-Fock (HF) treatment for spin-orbit coupling is here generalized to infinite periodic systems. The scalar-relativistic periodic KS-DFT/HF solution, obtained with a relativistic effective core potential, is taken as the zeroth-order approximation. Explicit expressions are given for the total energy through third-order, which satisfy the 2N + 1 rule (i.

Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis.

Background: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet.

Objectives: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis.

CRYSTAL23: A Program for Computational Solid State Physics and Chemistry.

The Crystal program for quantum-mechanical simulations of materials has been bridging the realm of molecular quantum chemistry to the realm of solid state physics for many years, since its first public version released back in 1988. This peculiarity stems from the use of atom-centered basis functions within a linear combination of atomic orbitals (LCAO) approach and from the corresponding efficiency in the evaluation of the exact Fock exchange series. In particular, this has led to the implementation of a rich variety of hybrid density functional approximations since 1998.

Long-term outcomes of retrospective case series of middle ear implantation with Vibrant Soundbridge in children with congenital aural atresia.

Purpose: to assess audiological performance in quiet and noise, quality of life and side effects of Vibrant Soundbridge (VSB) in children with congenital aural atresia (CAA).

Methods: A retrospective study including consecutive patients with unilateral or bilateral CAA implanted with VSB from 2009 to 2020 in a tertiary referral centre.

Results: 18 patients with CAA and a present stapes were included (3 simultaneous bilateral VSB implants) and 21 ears: 17 VSB were attached to the short incus process, and four to the stapes.

Do Non-COVID-19 Patients' Behaviour Towards Emergency Changed During the COVID-19 Outbreak? A Severity-Based Approach.

Objective: During the COVID-19 pandemic, the number of patients presenting to the emergency department (ED) declined. The main goal of this study was to compare and describe the non-COVID-19 patient's disease severity presentation during the pandemic with its pre-pandemic severity.

Methods: We conducted a retrospective observational study.

Reactive astrocytes promote proteostasis in Huntington's disease through the JAK2-STAT3 pathway.

Huntington's disease is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in Huntington's disease that involves morphological, molecular and functional changes. How reactive astrocytes contribute to Huntington's disease is still an open question, especially because their reactive state is poorly reproduced in experimental mouse models.

Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington's disease reveals early gray and white matter alterations.

Pathogenesis of the inherited neurodegenerative disorder Huntington's disease (HD) is progressive with a long presymptomatic phase in which subtle changes occur up to 15 years before the onset of symptoms. Thus, there is a need for early, functional biomarker to better understand disease progression and to evaluate treatment efficacy far from onset. Recent studies have shown that white matter may be affected early in mutant HTT gene carriers.

Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI.

(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe); (2) Methods: glucose consumption, lactate secretion and extracellular acidification rate (ECAR) were measured in vitro after exposure of cervix cancer SiHa cells and breast cancer 4T1 cells to UK-5099 (10 µM). Mice bearing the 4T1 tumor model were treated daily during four days with UK-5099 (3 mg/kg).

Perturbation Theory Treatment of Spin-Orbit Coupling, Part I: Double Perturbation Theory Based on a Single-Reference Initial Approximation.

We develop a perturbation theory for solving the many-body Dirac equation within a given relativistic effective-core potential approximation. Starting from a scalar-relativistic unrestricted Hartree-Fock (SR UHF) solution, we carry out a double perturbation expansion in terms of spin-orbit coupling (SOC) and the electron fluctuation potential. Computationally convenient energy expressions are derived through fourth order in SOC, second order in the electron fluctuation potential, and a total of third order in the coupling between the two.

Perturbation Theory Treatment of Spin-Orbit Coupling II: A Coupled Perturbed Kohn-Sham Method.

A noncanonical coupled perturbed Kohn-Sham density functional theory (KS-DFT)/Hartree-Fock (HF) treatment of spin-orbit coupling (SOC) is provided. We take the scalar-relativistic KS-DFT/HF solution, obtained with a relativistic effective core potential, as the zeroth-order approximation. Explicit expressions are given for the total energy through the 4th order, which satisfy the 2 + 1 rule.

Spin-orbit coupling from a two-component self-consistent approach. II. Non-collinear density functional theories.

We revise formal and numerical aspects of collinear and non-collinear density functional theories in the context of a two-component self-consistent treatment of spin-orbit coupling. Theoretical and numerical analyses of the non-collinear approaches confirm their ability to yield the proper collinear limit and provide rotational invariance of the total energy for functionals in the local-density or generalized-gradient approximations (GGAs). Calculations on simple molecules corroborate the formal considerations and highlight the importance of an effective screening algorithm to provide the sufficient level of numerical stability required for a rotationally invariant implementation of non-collinear GGA functionals.

Broad Influence of Mutant Ataxin-3 on the Proteome of the Adult Brain, Young Neurons, and Axons Reveals Central Molecular Processes and Biomarkers in SCA3/MJD Using Knock-In Mouse Model.

Spinocerebellar ataxia type 3 (SCA3/MJD) is caused by CAG expansion mutation resulting in a long polyQ domain in mutant ataxin-3. The mutant protein is a special type of protease, deubiquitinase, which may indicate its prominent impact on the regulation of cellular proteins levels and activity. Yet, the global model picture of SCA3 disease progression on the protein level, molecular pathways in the brain, and neurons, is largely unknown.

Influence of post-COVID-19 deconfinement on psychiatric visits to the emergency department.

Objective: During the deconfinement period after the coronavirus disease-2019 (COVID-19) pandemic, the number and characteristics of psychiatric visits changed in our emergency department (ED). We aimed to assess changes in the number of visits and characterize the profiles of these patients.

Methods: In this retrospective observational study, we examined the number of psychiatric ED visits and their proportion among the total number of ED visits.