Development and characterization of fluorescent cholesteryl probes with enhanced solvatochromic and pH-sensitive properties for live-cell imaging.

We present novel fluorescent cholesteryl probes (CNDs) with a modular design based on the solvatochromic 1,8-phthalimide scaffold. We have explored how different modules-linkers and head groups-affect the ability of these probes to integrate into lipid membranes and how they distribute intracellularly in mouse astrocytes and fibroblasts targeting lysosomes and lipid droplets. Each compound was assessed for its solvatochromic behavior in organic solvents and model membranes.

Real-Time Tool Localization for Laparoscopic Surgery Using Convolutional Neural Network.

Partially automated robotic systems, such as camera holders, represent a pivotal step towards enhancing efficiency and precision in surgical procedures. Therefore, this paper introduces an approach for real-time tool localization in laparoscopy surgery using convolutional neural networks. The proposed model, based on two Hourglass modules in series, can localize up to two surgical tools simultaneously.

Modular Fluorescent Cholesterol Naphthalimide Probes And Their Application For Cholesterol Trafficking Studies In Cells.

Development of fluorescent cholesterol analogs to better understand subcellular cholesterol trafficking is of great interest for cell biology and medicine. Our approach utilizes a bifunctional 1,8-naphthalimide scaffold with a push-pull character, modified on one side with a head group and a linker on the other side connecting it to cholesterol an ester bond. Through structure-function studies, we've explored how different substituents-linkers and head groups-affect the ability of these fluorescent cholesterol naphthalimide analogs (CNDs) to mimic natural cholesterol behavior at both molecular and cellular levels.

Adult-onset neurodegeneration in XMEN disease.

Background: XMEN (X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV), and N-linked glycosylation defect) disease results from loss-of-function mutations in MAGT1, a protein that serves as a magnesium transporter and a subunit of the oligosaccharyltransferase (OST) complex. MAGT1 deficiency disrupts N-linked glycosylation, a critical regulator of immune function. XMEN results in recurrent EBV infections and a propensity for EBV-driven malignancies.

Genomic Diagnoses for Ectopic Intracerebral Calcifications.

Background And Objectives: Ectopic intracerebral calcifications (EICs) in the basal ganglia, thalamus, cerebellum, or white matter are seen in a variety of disease states or may be found incidentally on brain imaging. The clinical significance and proportion of cases attributable to an underlying genetic cause is unknown.

Methods: This retrospective cohort study details the clinical, imaging, and genomic findings of 44 patients with EICs who had no established diagnosis despite extensive medical workup.

Quality of life, self-reported outcomes and impact of education among people with moderate and severe hemophilia A: An integrated perspective from a Latin American country.

Collecting and interpreting self-reported outcomes among people with hemophilia A supports the understanding of the burden of the disease and its treatment to improve holistic care. However, in Colombia, this information is limited. Therefore, this study aimed to describe the knowledge, perception and burden of hemophilia A from the patients' perspective.

Patients and Parents' Satisfaction and Self-Reported Evaluation After Single-Event Multilevel Surgery in Cerebral Palsy.

Purpose: The aim of this study was to analyze the results of single-event multilevel surgery (SEMLS) in cerebral palsy (CP) based on objective gait outcomes and self-reported evaluations.

Methods: In total, 258 patients with spastic diplegic CP, GMFCS I-III, who underwent SEMLS and with preoperative and postoperative gait analyses, were included in the SEMLS group (SG). The same database was used to compose the control group (CG) formed of 88 subjects who had performed at least 2 gait analyses and did not undergo surgical intervention between tests.

Role of responsive neurostimulation and immunotherapy in refractory epilepsy due to autoimmune encephalitis: A case report.

Autoimmune encephalitis (AE) frequently presents with seizures in the acute setting. Seizures are often refractory to anti-seizure medications (ASM) but have been shown to be responsive to immunomodulatory therapies. A subset of patients with AE continues to have refractory epilepsy, recently named "autoimmune-associated epilepsy (AAE)," for years after the acute AE presentation.

Regulation of NMDA Receptor Signaling at Single Synapses by Human Anti-NMDA Receptor Antibodies.

The NMDA receptor (NMDAR) subunit GluN1 is critical for receptor function and plays a pivotal role in synaptic plasticity. Mounting evidence has shown that pathogenic autoantibody targeting of the GluN1 subunit of NMDARs, as in anti-NMDAR encephalitis, leads to altered NMDAR trafficking and synaptic localization. However, the underlying signaling pathways affected by antibodies targeting the NMDAR remain to be fully delineated.

Integrated regulation of PKA by fast and slow neurotransmission in the nucleus accumbens controls plasticity and stress responses.

Cortical glutamate and midbrain dopamine neurotransmission converge to mediate striatum-dependent behaviors, while maladaptations in striatal circuitry contribute to mental disorders. However, the crosstalk between glutamate and dopamine signaling has not been entirely elucidated. Here we uncover a molecular mechanism by which glutamatergic and dopaminergic signaling integrate to regulate cAMP-dependent protein kinase (PKA) via phosphorylation of the PKA regulatory subunit, RIIβ.

Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19.

Purpose Of Review: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology.

Recent Findings: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem.

Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD.

Interneuron Dysfunction in a New Mouse Model of SCN1A GEFS.

Advances in genome sequencing have identified over 1300 mutations in the sodium channel gene that result in genetic epilepsies. However, it still remains unclear how most individual mutations within result in seizures. A previous study has shown that the K1270T (KT) mutation, linked to genetic epilepsy with febrile seizure plus (GEFS+) in humans, causes heat-induced seizure activity associated with a temperature-dependent decrease in GABAergic neuron excitability in a knock-in model.

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft.

Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft.

Anti-NMDAR Encephalitis: A Multidisciplinary Approach to Identification of the Disorder and Management of Psychiatric Symptoms.

Background: The novelty of anti-NMDA receptor encephalitis, for which somatic treatments have only recently been developed, has led to a lack of information on assessment and treatment of its variable behavioral manifestations.

Method: In this article, we discuss 4 challenging cases of anti-NMDAR encephalitis, focusing on the importance of a multidisciplinary approach to identification and management of the disorder and the necessity of close collaboration in the acute hospital setting for management of the behavioral symptoms.

Conclusion: The cases we discuss highlight some of the medication and nonpharmacologic treatment strategies that may facilitate management of psychiatric symptoms, both while the medical workup is ongoing and after the diagnosis has been confirmed.

Rumen In Vitro Fermentation and In Situ Degradation Kinetics of Winter Forage Brassicas Crops.

The aim of the present study was to evaluate the nutritional value, the rumen in vitro fermentation, and the in situ degradation of (L.) ssp. (kales) and (L.

Properties of Individual Hippocampal Synapses Influencing NMDA-Receptor Activation by Spontaneous Neurotransmission.

NMDA receptor (NMDAR) activation is critical for maintenance and modification of synapse strength. Specifically, NMDAR activation by spontaneous glutamate release has been shown to mediate some forms of synaptic plasticity as well as synaptic development. Interestingly, there is evidence that within individual synapses each release mode may be segregated such that postsynaptically there are distinct pools of responsive receptors.

Author Correction: Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection).

A dedicated lumbar puncture clinic: performance and short-term patient outcomes.

The purpose of the study was to evaluate patient outcomes, including success rates, factors associated with unsuccessful procedures and frequency of post-lumbar puncture headaches (PLPH), at a dedicated academic outpatient lumbar puncture (LP) clinic. All patients referred to our LP clinic between June 1, 2014 and May 31, 2015 were included in this consecutive observational series. We collected information about patient characteristics, operational parameters of the procedure, and complications.

Quantification of Immune Dysregulation by Next-generation Polymerase Chain Reaction to Improve Sepsis Diagnosis in Surgical Patients.

Objectives: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients.

Background: Immune dysregulation is a central event in sepsis.

Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus.

Objective: To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults.

Methods: We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility.