Lessons from Deep Learning Structural Prediction of Multistate Multidomain Proteins-The Case Study of Coiled-Coil NOD-like Receptors.

We test here the prediction capabilities of the new generation of deep learning predictors in the more challenging situation of multistate multidomain proteins by using as a case study a coiled-coil family of Nucleotide-binding Oligomerization Domain-like (NOD-like) receptors from and a few extra examples for reference. Results reveal a truly remarkable ability of these platforms to correctly predict the 3D structure of modules that fold in well-established topologies. A lower performance is noticed in modeling morphing regions of these proteins, such as the coiled coils.

Differential Inhibition by Cenobamate of Canonical Human Nav1.5 Ion Channels and Several Point Mutants.

Cenobamate is a new and highly effective antiseizure compound used for the treatment of adults with focal onset seizures and particularly for epilepsy resistant to other antiepileptic drugs. It acts on multiple targets, as it is a positive allosteric activator of γ-aminobutyric acid type A (GABA) receptors and an inhibitor of neuronal sodium channels, particularly of the late or persistent Na current. We recently evidenced the inhibitory effects of cenobamate on the peak and late current component of the human cardiac isoform hNav1.

Probiotics in the Prophylaxis of Premature Rupture of Membranes and Cervical Incompetence.

Unlabelled: Premature rupture of membranes (PROM) and cervical incompetence (CI) are major contributors to preterm birth, a leading cause of neonatal morbidity and mortality.

Background/objectives: Disorders of the vaginal microbiota, such as bacterial vaginosis, have been associated with an increased risk of PROM, CI, and subsequent preterm birth. Probiotics, particularly Lactobacillus strains, have been proposed as a preventive strategy to restore and maintain a healthy vaginal microbiome.

TSPO-PET in pre-surgical evaluations: Correlation of neuroinflammation and SEEG epileptogenicity mapping in drug-resistant focal epilepsy.

Objectives: Resective surgery in drug-resistant focal epilepsy (DRFE) requires extensive evaluation to localize the epileptogenic zone (EZ). When non-invasive phase 1 assessments (electroencephalography, EEG; magnetic resonance imaging, MRI; and F-Fluorodeoxyglucose-positron emission tomography, [F]FDG-PET) are inconclusive for EZ localization, invasive investigations such as stereo-EEG (SEEG) are necessary. Epileptogenicity maps (Ems) visualize the EZ using SEEG-identified ictal high-frequency oscillations (iHFOs).

Imaging Aspects in a Case of Persistent Müllerian Duct Syndrome (PMDS): A Case Report and Overview.

Persistent Müllerian duct syndrome (PMDS) is a rare kind of internal male pseudohermaphroditism. The patient, who has a male karyotype and phenotypic characteristics, exhibits Müllerian duct derivatives such as the uterus, cervix, fallopian tubes, and upper two-thirds of the vagina. This article provides a comprehensive analysis of the CT and MRI characteristics of a case of PMDS in a 35-year-old male patient who sought medical attention at our clinic due to pain in the left inguinal region and the presence of undescended testes on both sides.

Vasogenic oedema during stereoelectroencephalography: intracranial pattern and late-onset clinical repercussion.

In patients suffering from focal drug-resistant epilepsy, intracranial explorations are the gold standard for identifying the epileptogenic zone and evaluating the possibility of a surgical resection. Amongst them, stereoelectroencephalography (SEEG), using depth electrodes, is a safe procedure. However, complications occur on average in 2% of cases, notably haemorrhages or infections.

Evolution of Natural Myocardial Shear Wave Behavior in Young Hearts: Determinant Factors and Reproducibility Analysis.

Background: Myocardial diastolic function assessment in children by conventional echocardiography is challenging. High-frame rate echocardiography facilitates the assessment of myocardial stiffness, a key factor in diastolic function, by measuring the propagation velocities of myocardial shear waves (SWs). However, normal values of natural SWs in children are currently lacking.

Clinical impact of novel cardiovascular magnetic resonance technology on patients with congenital heart disease: a scientific statement of the Association for European Pediatric and Congenital Cardiology and the European Association of Cardiovascular Imaging of the European Society of Cardiology.

Cardiovascular magnetic resonance (CMR) imaging is recommended in patients with congenital heart disease (CHD) in clinical practice guidelines as the imaging standard for a large variety of diseases. As CMR is evolving, novel techniques are becoming available. Some of them are already used clinically, whereas others still need further evaluation.

Exposure to Gulf war illness-related chemicals exacerbates alcohol-induced liver damage in rodents.

Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war, consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on the pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB-treated mice.

Sympathetic Nervous Influences Are Negative Prognostic Factors in Stomach Cancer.

(1) Background: The aim of our study was to assess the involvement of the sympathetic nervous system in the progression of patients with gastric carcinoma by analyzing the sympathetic neuronal fibers and beta 2 adrenoreceptors. (2) Methods: We performed a retrospective study in which we analyzed the clinical, biological, and histological data from a total of 104 patients diagnosed with stomach cancer. (3) Results: After analyzing the immunoreactivity of beta 2 adrenoreceptors, we observed increased values in patients with tumors larger than 5 cm in diameter ( = 0.

Exposure to Gulf war illness-related chemicals exacerbates alcohol- induced liver damage in rodents.

Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB- treated mice.

Aggressive Male Breast Cancer-Clinical and Therapeutic Aspects Correlated with the Histopathological Examination: A Case Report and Literature Review.

Breast cancer is often seen as a disease that occurs in women, but it can also appear in men in a very small percentage, below 1%. Men have a minimal amount of breast tissue compared to women, which has the potential to become malignant in a similar way to women, although much less frequently. A patient presented with advanced local invasion due to the low amount of breast tissue, with the tumor quickly invading the adjacent structures.

Deep retroinsular and parieto-opercular origin of vestibular symptoms: A stereoelectrocenphalography (SEEG) study.

Several studies have shown that the retroinsular and posterior parietal operculum regions play a central role in vestibular processing. Electrical stimulations performed during stereoelectroencephalography (SEEG) in patients with focal drug-resistant epilepsy could contribute to the analysis of this area. Among the 264 SEEGs performed in both an adult and a paediatric epilepsy surgery centre, we retrospectively identified 24 patients (9%) reporting vertigo during electrical stimulations (ES).

[F]DPA-714 PET Imaging in the Presurgical Evaluation of Patients With Drug-Resistant Focal Epilepsy.

Background And Objectives: Translocator protein 18 kDa (TSPO) PET imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [F]DPA-714 PET and [F]FDG PET for localizing the EZ during presurgical assessment of DRFE, when phase 1 presurgical assessment does not provide enough information.

[Echocardiography with high frame rates in the clinical practice : Principles, applications and perspectives].

Continuous developments in cardiovascular imaging, software and hardware have led to technological advancements that open new ways for assessing myocardial mechanics, hemodynamics, and function. Through new scan modalities, echocardiographic scanners can nowadays achieve very high frame rates up to 5000 frames s which enables a wide variety of new applications, including shear wave elastography, ultrafast speckle tracking, the visualization of intracardiac blood flow and myocardial perfusion imaging. This review provides an overview of these advances and demonstrates possible applications and their potential added value in the clinical practice.

Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen.

The impact of the peptide amino acids side-chain modifications on the immunological recognition has been scarcely explored. We investigate here the effect of methionine oxidation on the antigenicity of the melanoma immunodominant peptide 369-YMDGTMSQV-377 (YMD). Using CD8 T cell activation assays, we found that the antigenicity of the sulfoxide form is higher when compared to the YMD peptide.

Clinical Outcomes Depending on Sympathetic Innervation in Pancreatic Cancer.

Background: The aim of our study was to evaluate sympathetic neuronal remodeling in patients with pancreatic cancer, together with its correlation with clinical outcomes.

Methods: In this descriptive, retrospective study, we analyzed pancreatic cancer specimens and peritumoral pancreatic tissue from 122 patients. We also investigated tyrosine hydroxylase immunoreactivity for the analysis of sympathetic nerve fibers and beta 2 adrenoreceptors immunoreactivity.

H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.

During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as biomarkers for diagnosis, staging, prognosis, and even as therapeutic targets.

Confirmation of Heart Malformations in Fetuses in the First Trimester Using Three-Dimensional Histologic Autopsy.

Background: We aimed to evaluate the usefulness of three-dimensional (3D) reconstruction of histology slides to confirm congenital heart disease (CHD) detected by first-trimester fetal cardiac ultrasonography. Conventional autopsy is hindered by the small size of the first-trimester fetal heart, and current CHD confirmation studies employ the use of highly specialized and expensive methods.

Technique: An extended first-trimester ultrasound examination protocol was used to diagnose fetal heart anomalies.

Oncogenic CALR mutant C-terminus mediates dual binding to the thrombopoietin receptor triggering complex dimerization and activation.

Calreticulin (CALR) frameshift mutations represent the second cause of myeloproliferative neoplasms (MPN). In healthy cells, CALR transiently and non-specifically interacts with immature N-glycosylated proteins through its N-terminal domain. Conversely, CALR frameshift mutants turn into rogue cytokines by stably and specifically interacting with the Thrombopoietin Receptor (TpoR), inducing its constitutive activation.

Bladder Wall Structure Alterations in Patients Treated With Botulinum Toxin for Detrusor Overactivity - A Morphological Study.

Background/aim: The overactive bladder syndrome (OAB) is a bothersome condition that affects up to 33% of the population. In up to 69% of the cases, the underlying condition is an overactive detrusor (DO). Treatment options rely on behavioral changes, medical treatment, neuromodulation, and invasive treatment, such as injecting botulinum toxin (BoNT) in the detrusor or augmentation cystoplasty.