An Acetylcholine M1 Receptor-Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment: A Phase 2 Randomized Clinical Trial.

Importance: Fall risk and cognitive impairment are prevalent and burdensome in Parkinson disease (PD), requiring efficacious, well-tolerated treatment.

Objective: To evaluate the safety and efficacy of TAK-071, a muscarinic acetylcholine M1 positive allosteric modulator, in participants with PD, increased fall risk, and cognitive impairment.

Design, Setting, And Participants: This phase 2 randomized double-blind placebo-controlled crossover clinical trial was conducted from October 21, 2020, to February 27, 2023, at 19 sites in the US.

Obstetric Outcomes by Hospital Volume of Operative Vaginal Delivery.

Importance: Characterizing hospital-level factors associated with adverse outcomes following operative vaginal delivery (OVD) is crucial for optimizing obstetric care.

Objective: To assess the association between hospital OVD volume and adverse outcomes.

Design, Setting, And Participants: This was a retrospective cohort study of OVDs in California between 2008 and 2020.

Multi Targeted Activity of Cocculus hirsutus through Modulation of DPP-IV and PTP-1B Leading to Enhancement of Glucose Uptake and Attenuation of Lipid Accumulation.

Multi-targeted therapies are gaining attention in the management of multifactorial diseases due to their poly pharmacology, enhanced potency and reduced toxicity. Metabolic disorders like Type 2 diabetes mellitus (T2DM) and obesity necessitate multi-targeted therapy to improve insulin sensitivity, regulate glucose homeostasis and support weight loss. Medicinal plants rich in bioactive compounds exhibit multi-targetted action with minimal side effects.

Validating the revised Attitudes Toward People With Disabilities Scale with health care professionals.

Objective: Disability stigma has been linked with adverse chronic and acute health outcomes in people with disabilities. The present study updated the widely used Attitudes Toward Disabled Persons measure (to the revised Attitudes Toward People With Disabilities [ATPD] scale) among health care professionals and validated the measure using a disability stigma framework.

Design: A survey with 272 health care professionals and students was conducted.

Slab-Specific Projection-Resolved Optical Coherence Tomography Angiography for Enhancing En Face Polyp Detection in Polypoidal Choroidal Vasculopathy.

Purpose: A projection-resolved optical coherence tomography angiography (PR-OCTA) algorithm with slab-specific strategy was applied in polypoidal choroidal vasculopathy (PCV) to differentiate between polyp and branching vascular network (BVN) and improve polyp detection by en face OCTA.

Methods: Twenty-nine participants diagnosed with PCV by indocyanine green angiography (ICGA) and 30 participants diagnosed with typical neovascular age-related macular degeneration (nAMD) were enrolled. Polyps were classified into three categories after using the slab-specific PR algorithm.

The inability to predict futility in hemorrhaging trauma patients using 4-hour transfusion volumes and rates.

Background: Blood shortages and utilization stewardship have motivated the trauma community to evaluate futility cutoffs during massive transfusions (MTs). Recent single-center studies have confirmed meaningful survival in ultra-MT (≥20 U) and super-MT (≥50 U), while others advocate for earlier futility cut points. We sought to evaluate whether transfusion volume and intensity cut points could predict 100% mortality in a multicenter analysis.

A Comparison of Decompression Size and Craniectomy Speed of Reverse Question Mark Versus Retroauricular Incisions for Decompressive Hemicraniectomy: A Cadaver Study.

Background And Objectives: Decompressive hemicraniectomy is a common emergent surgery for patients with stroke, hemorrhage, or trauma. The typical incision is a reverse question mark (RQM); however, a retroauricular (RA) incision has been proposed as an alternative. The widespread adoption ofthe RA incision has been slowed by lack of familiarity and concerns over decompression efficacy.

Genomics-Driven Monitoring of Fraxinus latifolia (Oregon Ash) to Inform Conservation and EAB-Resistance Breeding.

Understanding the evolutionary processes underlying range-wide genomic variation is critical to designing effective conservation and restoration strategies. Evaluating the influence of connectivity, demographic change and environmental adaptation for threatened species can be invaluable to proactive conservation of evolutionary potential. In this study, we assessed genomic variation across the range of Fraxinus latifolia, a foundational riparian tree native to western North America recently exposed to the invasive emerald ash borer (Agrilus planipennis; EAB).

Flow-Through Flaps as a Robust Method for Advanced Free Flap Reconstruction in the Head and Neck: A Multi-Institutional Experience.

Background: Flow-through flaps (FTFs) are an advanced technique in which a free flap is anastomosed to the pedicle of another free flap to reconstruct extensive head and neck defects when recipient vessels are scarce.

Methods: A multi-institutional cohort of FTFs used for head and neck reconstruction were reviewed. For comparison, FTF outcomes were compared to free flaps that required vein grafts (VG) to reach distant recipient vessels.

Linking Fire, Food Webs, and Fish in Stream Ecosystems.

Unlabelled: As wildfire regimes shift, resource managers are concerned about potential threats to aquatic ecosystems and the species they support, especially fishes. However, predicting fish responses can be challenging because wildfires affect aquatic ecosystems via multiple pathways. Application of whole-ecosystem approaches, such as food web modeling, can act as heuristic tools that offer valuable insights that account for these different mechanisms.

Solvatomorphic diversity dictates the stability and solubility of metal-organic polyhedra.

The reaction between molybdenum(ii) acetate and 5-aminoisophthalic acid (HIso-NH) afforded [MoO(μ-O)(Iso-NH)], a novel molybdenum(v) metal-organic polyhedron (MOP) with a triangular antiprismatic shape stabilized by intramolecular N-H⋯O hydrogen bonds. The synthesis conditions, particularly the choice of solvent and reaction time, led to the precipitation of the Mo(v)-MOP in five distinct crystalline forms. These forms vary in their packing arrangements, co-crystallized solvent molecules, and counter-cations, with three phases containing dimethylammonium (dma) and the other two containing diethylammonium (dea).

Traumatic Cystic Artery Pseudoaneurysm After Transjugular Liver Biopsy: A Case Report.

Cystic artery pseudoaneurysms are a rare but life-threatening entity that commonly occurs as a sequela to acute cholecystitis. We present a case of a 52-year-old male with a past medical history of decompensated alcoholic liver cirrhosis who underwent a transjugular liver biopsy (TJLB) after correction of his baseline coagulopathy. On post-operative day one, the patient had significant blood loss with an inappropriate response to blood transfusions and without an identifiable source of bleeding.

The Relationship Between Quantitative Ischemia, Early Revascularization, and Major Adverse Cardiovascular Events: A Multicenter Study.

Background: Observational data have suggested that patients with moderate to severe ischemia benefit from revascularization. However, this was not confirmed in a large, randomized trial.

Objectives: Using a contemporary, multicenter registry, the authors evaluated differences in the association between quantitative ischemia, revascularization, and outcomes across important subgroups.

Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles.

Background: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven.

Objectives: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use.

Multidimensional relationships between sensory perception and cognitive aging.

A growing literature suggests that declines in sensory/perceptual systems predate cognitive declines in aging, and furthermore, they are highly predictive for developing Alzheimer's disease and Alzheimer's related dementias (ADRD). While vision, hearing, olfaction, and vestibular function have each been shown to be related to ADRD, their causal relations to cognitive declines, how they interact with each other remains to be clarified. Currently, there is substantial debate whether sensory/perceptual systems that fail early in disease progression are causal in their contributions to cognitive load and/or social isolation or are simply coincident declines due to aging.

The doctor will polygraph you now.

Artificial intelligence (AI) methods have been proposed for the prediction of social behaviors that could be reasonably understood from patient-reported information. This raises novel ethical concerns about respect, privacy, and control over patient data. Ethical concerns surrounding clinical AI systems for social behavior verification can be divided into two main categories: (1) the potential for inaccuracies/biases within such systems, and (2) the impact on trust in patient-provider relationships with the introduction of automated AI systems for "fact-checking", particularly in cases where the data/models may contradict the patient.

(Black Cumin) Oil: A Case Report and Analysis Exploring Severe Cutaneous Manifestations and Implications for Patient Care.

In the past three decades, there has been a remarkable surge in the popularity and use of herbal medicines. However, despite their widespread use, herbal remedies remain inadequately regulated, exposing consumers to potential adverse effects. This case series examines eight patients with severe cutaneous manifestations resulting from the topical application of (black cumin) oil, emphasizing the critical significance of patch testing, thorough history-taking regarding exposures and herbal supplement usage, and the necessity for enhanced regulatory measures.

Quantifying form resistance is essential for estimating summer low and bankfull flow from stream survey channel morphology.

Reliable estimates of low flow and flood discharge at ungaged locations are required for evaluating stream flow alteration, designing culverts and stream crossings, and interpreting regional surveys of habitat and biotic condition. Very few stream gaging stations are located on small, remote streams, which typically have complex channel morphology. Adequate gaging is also lacking on larger streams that are remote, smaller than those typically gaged, or have channel morphology not conducive to installation of gages.

Egg shape and color mediate acceptance thresholds in diverse avian host species with different rates of antiparasitic egg rejection.

Eggshell recognition in parental birds is vital for nest management, defense against brood parasitism, optimal embryonic development, and minimizing disease and predation risks. This process relies on acceptance thresholds balancing the risk of rejecting own eggs against the benefit of excluding foreign ones, following signal detection theory. We investigated the role of object shape in egg rejection decisions among three host species of the brown-headed cowbird (Molothrus ater), each with a varying known response to parasitic eggs.

Neural Ordinary Differential Equations for Forecasting and Accelerating Photon Correlation Spectroscopy.

Evaluating the quantum optical properties of solid-state single-photon emitters is a time-consuming task that typically requires interferometric photon correlation experiments. Photon correlation Fourier spectroscopy (PCFS) is one such technique that measures time-resolved single-emitter line shapes and offers additional spectral information over Hong-Ou-Mandel two-photon interference but requires long experimental acquisition times. Here, we demonstrate a neural ordinary differential equation model, g2NODE, that can forecast a complete and noise-free interferometry experiment from a small subset of noisy correlation functions.

Deriving Membrane-Water and Protein-Water Partition Coefficients from In Vitro Experiments for Per- and Polyfluoroalkyl Substances (PFAS).

The phospholipid membrane-water partition coefficients () and equilibrium binding affinities for human serum albumin (HSA) of 60 structurally diverse perfluoroalkyl and polyfluoroalkyl substances (PFAS) were evaluated through laboratory measurements and modeling to enhance our understanding of PFAS distribution in organisms. Per- and polyfluoroalkyl carboxylic acids exhibited a 0.36 ± 0.

Gut feelings on short-chain fatty acids to regulate respiratory health.

Respiratory infections and diseases pose significant challenges to society and healthcare systems, underscoring the need for preventative and therapeutic strategies. Recent research in rodent models indicates that short-chain fatty acids (SCFAs), metabolites produced by gut bacteria, may offer medicinal benefits for respiratory conditions. In this opinion, we summarize the current literature that highlights the potential of SCFAs to enhance immune balance in humans.

An Unusual Semiquinone-mediated Self-catalysis Redox Mechanism for the Reaction between Halohydroquinones and N-Substituted Hydroxamic acids.

We found recently that a C-C bonding phenyl-quinone product was produced with high yield (96%) from the reaction between 2,5-dichloro-1,4-Benzoquinone (DCBQ) and N-phenylbenzohydroxamic acid (N-PhBHA) via an unusual Claisen rearrangement mechanism, accompanied with the concurrent formation of the minor byproducts amide (N-phenylBenzamide, N-PhBA; only 2% yield) and hydroxychloroquinone (2% yield). Surprisingly, when DCBQ was replaced with its reduced form 2,5-dichloro-1,4-hydroquinone (DCHQ), no C-C bonding product was detected, whereas N-PhBA (83% yield) and hydroxychloroquinone (80% yield) became the predominant products, indicating a dramatic mechanistic shift. The ascorbate reduction experiment suggested that it was not DCHQ itself, but its corresponding semiquinone radical, that directly reacts with N-PhBHA.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Behavior of compounds leached from tire tread particles under simulated sunlight exposure.

Tire tread particles are microplastics (< 5 mm) and leach organic chemicals into aquatic environments. It is important to understand the behavior of tire wear compounds in sunlight-exposed waters in terms of their persistence, removal, and transformation. Therefore, we conducted photolysis experiments with leachates from laboratory-generated tire tread particles (TTP) over 72 h in a solar simulator to evaluate the behavior of leached compounds and fluorescent components over time.