Amyloid-related changes in fluency in patients with subjective cognitive decline.

Introduction: We examined semantic and phonemic fluency in individuals with subjective cognitive decline (SCD) in relation to amyloid status and clinical progression.

Methods: A total of 490 individuals with SCD (62 ± 8 years, 42% female, 28% amyloid-positive, 17% clinical progression) completed annual fluency assessments (mean ± SD follow-up 4.3 ± 2.

Long-term mortality of Dutch COVID-19 patients admitted to the intensive care medicine: a retrospective analysis from a national quality registry.

Objective: To describe the 12-month mortality of Dutch COVID-19 intensive care unit patients, the total COVID-19 population and various subgroups on the basis of the number of comorbidities, age, sex, mechanical ventilation, and vasoactive medication use.

Methods: We included all patients admitted with COVID-19 between March 1, 2020, and March 29, 2022, from the Dutch National Intensive Care (NICE) database. The crude 12-month mortality rate is presented via Kaplan-Meier survival curves for each patient subgroup.

Patient-reported outcomes in conservatively managed cerebral cavernous malformations.

Background: There is a paucity of studies on patient-reported outcomes and quality of life (QoL) in conservatively managed patients with a cerebral cavernous malformation (CCM).

Methods: This single-center observational study included consecutive adult CCM patients, diagnosed in 2000-2023, managed conservatively, and with at least 6 months of follow-up. Patients completed two validated patient-reported outcome measures (PROMs): EuroQol 5-dimensions 5-levels (EQ-5D-5L), and Patient-Reported Outcome Measurement Information System 29 (PROMIS-29).

Acute pilonidal abscess: Prospective nationwide audit in the Netherlands.

Aim: The aim of this study was to assess Dutch surgical practice and outcomes for acute pilonidal abscess.

Method: Patients with pilonidal sinus disease (PSD) who underwent surgical treatment between 1 March 2020 and 1 March 2021 at 36 participating hospitals were included in a prospective observational cohort study. For the present study, only patients with an acute abscess were included for analysis.

A nationwide snapshot study on outcomes one year after surgery for chronic pilonidal sinus disease.

Aim: Managing pilonidal sinus disease (PSD) remains challenging due to high recurrence rates and morbidity associated with treatment. The aim of this study was to evaluate the outcomes one year after surgical treatment for chronic PSD in the Netherlands.

Method: Patients with PSD who underwent surgical treatment between March 1, 2020, and March 1, 2021, at 36 participating hospitals were included in a prospective observational cohort study.

Prediction of Survival After Pediatric Cardiac Arrest Using Quantitative EEG and Machine Learning Techniques.

Background And Objectives: Early neuroprognostication in children with reduced consciousness after cardiac arrest (CA) is a major clinical challenge. EEG is frequently used for neuroprognostication in adults, but has not been sufficiently validated for this indication in children. Using machine learning techniques, we studied the predictive value of quantitative EEG (qEEG) features for survival 12 months after CA, based on EEG recordings obtained 24 hours after CA in children.

The association of spinal morning stiffness with lumbar disc degeneration and C-reactive protein: The back complaints in older adults (BACE) study.

Objective: To determine the association between patient-reported spinal morning stiffness and lumbar disc degeneration (LDD) and systemic inflammation, as measured by C-reactive protein (CRP), in older patients with non-specific back pain. The ultimate objective is to help shape a future definition of spinal osteoarthritis (OA).

Design: Baseline data from the Dutch "Back Complaints in the Older Adults" (BACE) study was used.

The association of limited or painful spinal range of motion with lumbar disc degeneration: the back complaints in older adults (BACE) study.

Background: We currently lack clear definitions for structural and symptomatic spinal osteoarthritis (OA). To define spinal OA and create diagnostic criteria for this condition, it is necessary to determine the relationship between clinical signs and symptoms of back pain and radiographic features of OA. Notably, recent studies suggest a defining sign of spinal OA could be a limited or painful spinal range of motion (ROM).

Further perceptions of probability: Accurate, stepwise updating is contingent on prior information about the task and the response mode.

To adapt to an uncertain world, humans must learn event probabilities. These probabilities may be stationary, such as that of rolling a 6 on a die, or changing over time, like the probability of rainfall over the year. Research on how people estimate and track changing probabilities has recently reopened an old epistemological issue.

Reading Performance Following Contralateral Implantation of an Extended Depth of Focus (EDOF) IOL and a Hybrid EDOF Multifocal IOL.

Purpose: To assess objective reading performance at intermediate and near distances using the Salzberg Reading Desk (SRD) (SRD Vision) in patients with cataract who underwent the implantation of a diffractive extended depth of focus intraocular lens (EDOF IOL) in the dominant eye and a hybrid multifocal EDOF IOL in the non-dominant eye.

Methods: This prospective, non-comparative, interventional study included 46 eyes of 23 patients with cataract who underwent bilateral cataract surgery with implantation of the DFR00V Tecnis Synergy IOL (Johnson & Johnson Surgical Vision) in the non-dominant eye and the DXR00V Tecnis Symfony OptiBlue IOL (Johnson & Johnson Surgical Vision) in the dominant eye. At postoperative 6 months, the Salzburg Reading Desk was used to assess distance-corrected reading performance at near and intermediate distances.

Synergistic polytherapy for the broad-spectrum treatment of chemically-induced seizures in rats.

Chemically-induced seizures, as a result of exposure to a neurotoxic compound, present a serious health concern. Compounds can elicit seizure activity through disruption of neuronal signaling by neurotransmitters, either by mimicking, modulating or antagonizing their action at the receptor or interfering with their metabolism. Benzodiazepines, such as diazepam and midazolam, and barbiturates are the mainstay of treatment of seizures.

Prospective Evaluation of Clinical and Patient-Reported Outcomes Following Contralateral Implantation of an Extended Depth of Focus (EDOF) and Hybrid EDOF-Multifocal IOL.

Purpose: To evaluate clinical outcomes following contralateral implantation of a diffractive extended depth of focus (EDOF) and a hybrid EDOF-multifocal intraocular lens (IOL) with a violet filter in a U.S.-based population.

Prophylactic Mesh-related Reoperations and Mesh-related Problems During Subsequent Relaparotomies: Long-term Results From the PRIMA Trial.

Objective: This study aimed to evaluate all mesh-related problems during reoperations after mesh-reinforcement 15 years after the start of the PRIMA trial. SUMMARY BACKGROUND DATA Prophylactic mesh reinforcement during closure of a midline laparotomy has proven to reduce the incidence of incisional hernia, especially in high-risk patients, but long-term mesh-related morbidity is largely unknown.

Methods: Patients receiving a prophylactic onlay or retro-rectus mesh in the PRIMA trial between 2009 and 2012 were included on an as-treated basis from participating centers that made reoperation notes available.

-Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses.

The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication of a broad range of viruses that rely on ER protein quality control. We found, by screening a panel of deoxynojirimycin and cyclitol glycomimetics, that the mechanism-based ER α-glucosidase II inhibitor, 1,6--cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 replication in lung epithelial cells, halting intracellular generation of mature spike protein, reducing production of infectious progeny, and leading to reduced syncytium formation. Through activity-based protein profiling, we confirmed ER α-glucosidase II inhibition in primary airway epithelial cells, grown at the air-liquid interface.

Is surgeon annual case volume related with intra and postoperative complications after ventral hernia repair? Uni- and multivariate analysis of prospective registry-based data.

Background: Literature on a potential relationship between surgeon case volume and intra- or postoperative complications after ventral hernia repair remains scarce.

Methods: Patients who underwent ventral hernia repair between 2011 and 2023 were selected from the prospectively maintained French Hernia-Club Registry. Outcome variables were: intraoperative events, postoperative general complications, surgical site occurrences, surgical site infections, length of intensive care unit (ICU), and patient-reported scar bulging during follow-up.

Digital remote assessment of speech acoustics in cognitively unimpaired adults: feasibility, reliability and associations with amyloid pathology.

Background: Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer's disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting.

Methods: Fifty cognitively unimpaired adults (Age 68 ± 6.

Structure-Activity Relationship Studies of Aryl Sulfoxides as Reversible Monoacylglycerol Lipase Inhibitors.

Monoacylglycerol lipase (MAGL) is the key enzyme for the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). The central role of MAGL in the metabolism of 2-AG makes it an attractive therapeutic target for a variety of disorders, including inflammation-induced tissue injury, pain, multiple sclerosis, and cancer. Previously, we reported , an aryl sulfoxide, as a peripherally restricted, covalent reversible MAGL inhibitor that reduced neuropathic pain and inflammation in preclinical models.

Resilience After High-Grade Subarachnoid Hemorrhage: A Prospective Cohort Study on Quality of Life.

Background And Objectives: Treatment of patients who present with poor clinical condition is often postponed until neurological improvement is observed. Despite previous studies, it is still unclear how survivors perceive their quality of life (QoL). This study aimed to evaluate self-perceived QoL in patients with aneurysmal subarachnoid hemorrhage who present with poor clinical condition, as defined by World Federation of Neurosurgical Societies (WFNS) grades 4 to 5, compared with those who present in more favorable clinical condition (WFNS 1-3).

Discovery of isoquinoline sulfonamides as allosteric gyrase inhibitors with activity against fluoroquinolone-resistant bacteria.

Bacteria have evolved resistance to nearly all known antibacterials, emphasizing the need to identify antibiotics that operate via novel mechanisms. Here we report a class of allosteric inhibitors of DNA gyrase with antibacterial activity against fluoroquinolone-resistant clinical isolates of Escherichia coli. Screening of a small-molecule library revealed an initial isoquinoline sulfonamide hit, which was optimized via medicinal chemistry efforts to afford the more potent antibacterial LEI-800.

Establishing Correlates of Maternal-Fetal Cytomegalovirus Transmission-One Step Closer Through Predictive Modeling.

Background: Determinants of maternal-fetal cytomegalovirus (CMV) transmission and factors influencing the severity of congenital CMV (cCMV) infection are not well understood.

Methods: We conducted a descriptive, multicenter study in pregnant women ≥18 years old with primary CMV infection and their newborns to explore maternal immune responses to CMV and determine potential immunologic/virologic correlates of cCMV following primary infection during pregnancy. We developed alternative approaches looking into univariate/multivariate factors associated with cCMV, including a participant clustering/stratification approach and an interpretable predictive model-based approach using trained decision trees for risk prediction (post hoc analyses).

Examination of Particulate Contamination in Parenteral Injections and Infusions Following Fluid Withdrawal Utilizing Conventional Needles and Filter Needles: Assessment of Compliance and Comparative Analysis.

Particulate contamination, the unintentional presence of particles in parenteral fluids, is associated with potential risks such as phlebitis and thrombophlebitis. Recent guidelines recommend the use of filter needles when withdrawing parenteral fluid from vials with a rubber stopper. However, the literature is limited and lacks clarity regarding the advantages of filter needles over conventional needles.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

Background And Objectives: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH.