The Impact of Xanomeline and Trospium Chloride on Cognitive Impairment in Acute Schizophrenia: Replication in Pooled Data From Two Phase 3 Trials.

Objective: Xanomeline and trospium chloride (formerly known as KarXT), a novel M/M muscarinic receptor agonist, demonstrated efficacy across phase 2 and 3 trials as monotherapy for the treatment of inpatients with acute schizophrenia on the Positive and Negative Syndrome Scale total score primary endpoint. In the phase 2 trial, xanomeline/trospium improved performance on a cognitive outcome measure in the subgroup of participants with clinically significant baseline cognitive impairment. The authors sought to confirm this finding using data from two phase 3 trials.

Decrements in Morning and Evening Energy Are Associated With a Higher Symptom Burden in Patients With Gynecologic Cancers Receiving Chemotherapy.

Background: Decrements in energy are a significant problem associated with chemotherapy. To date, no study examined the variability of energy in patients with gynecologic cancers.

Objective: To identify distinct morning and evening energy profiles in patients with gynecologic cancers and evaluate for differences in demographic and clinical characteristics, other common symptoms, and quality-of-life (QOL) outcomes.

The origins of ADNI.

A brief history of events surrounding the conceptualization and original implementation of the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a public-private partnership (PPP) is provided from the perspective of three individuals directly involved from the outset. Potential barriers and how they were addressed are summarized, especially the decision to make all data freely accessible in real-time. Decisions made at the beginning of ADNI are revisited in light of what has been learned over the past 20 years, especially the importance of the investment in cerebrospinal fluid (CSF) and blood measures and the commitment to data sharing.

25-hydroxycholesterol promotes brain cytokine production and leukocyte infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation.

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and, in response to different inflammatory stimuli, overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer's disease as well as various mouse models of neuroinflammation.

Rationale for Adjunctive Treatment Targeting Multiple Mechanisms in Schizophrenia.

Schizophrenia is a complex syndrome with taxing symptoms and for which treatment challenges remain. Current dopamine Dreceptor-blocking antipsychotics have well-known limitations, including ineffectively treating across all symptom domains and generating common side effects such as motor disturbances, weight gain, and metabolic dysfunction. New approaches are sorely needed to address the continued unmet treatment needs for individuals living with schizophrenia.

Worse Morning Energy Profiles Are Associated with Significant Levels of Stress and Decrements in Resilience in Patients Receiving Chemotherapy.

Objectives: Evidence suggests that lower levels of morning energy are associated with higher levels of stress and lower levels of resilience in patients receiving chemotherapy. Study purposes were to identify subgroups of patients with distinct morning energy profiles; evaluate for differences among the profiles in demographic and clinical characteristics, as well as measures of stress, resilience, and coping.

Methods: A total of 1,343 outpatients receiving chemotherapy completed a demographic questionnaire and measures of global, cancer-related, and cumulative life stress, and resilience at study enrollment.

Associations Between Preoperative Shortness of Breath and Potassium Channels Gene Variations in Women With Breast Cancer.

Objectives: Shortness of breath is a common symptom in patients with cancer. However, the mechanisms that underlie this troublesome symptom are poorly understood. Therefore, this study aimed to determine the prevalence of and associated risk factors for shortness of breath in women prior to breast cancer surgery and identify associations between shortness of breath and polymorphisms for potassium channel genes.

Trajectories of Depressive Symptoms Among Patients Undergoing Chemotherapy for Breast, Gastrointestinal, Gynecological, or Lung Cancer.

Background: Individuals who undergo chemotherapy for cancer are at elevated risk of developing depressive symptoms, yet substantial interindividual variation exists in trajectories of these symptoms.

Objective: To examine interindividual variations in trajectories of depressive symptoms during 2 cycles of chemotherapy and to evaluate associations between demographic and clinical characteristics, symptom severity scores, psychological adjustment characteristics (eg, stress and coping), and initial levels and trajectories of depressive symptoms.

Methods: Patients (n = 1323) diagnosed with breast, gynecologic, lung, or gastrointestinal cancer completed the Center for Epidemiological Studies-Depression Scale 6 times, over 2 cycles of chemotherapy.

Gastrointestinal and Neuropsychological Symptoms Are Associated With Distinct Vomiting Profiles in Patients Receiving Chemotherapy.

Objectives: To identify subgroups of patients with distinct chemotherapy-induced vomiting (CIV) profiles; determine how these subgroups differ on several demographic, clinical, and symptom characteristics; and evaluate factors associated with chemotherapy-induced nausea and CIV profiles.

Sample & Setting: Adult patients (N = 1,338) receiving cancer chemotherapy.

Methods & Variables: Data were collected on demographic, clinical, and symptom characteristics.

Palpitations in Women With Breast Cancer Are Associated With Polymorphisms for Neurotransmitter Genes.

Objectives: To evaluate for associations between the occurrence of palpitations reported by women prior to breast cancer surgery and single nucleotide polymorphisms (SNPs) for neurotransmitter genes.

Sample & Setting: A total of 398 women, who were scheduled for unilateral breast cancer surgery, provided detailed information on demographic and clinical characteristics and the occurrence of palpitations prior to breast cancer surgery.

Methods & Variables: The occurrence of palpitations was assessed using a single item (i.

Lower Income, Smoking, Cardiopulmonary Comorbidities, and Higher Symptom Burden Influence the Occurrence of Cough in Patients Receiving Chemotherapy.

Objectives: To identify subgroups of patients with distinct cough occurrence profiles and evaluate for differences among these subgroups.

Sample & Setting: Outpatients receiving chemotherapy (N = 1,338) completed questionnaires six times over two chemotherapy cycles.

Methods & Variables: Occurrence of cough was assessed using the Memorial Symptom Assessment Scale.

Neurosteroids mediate and modulate the effects of pro-inflammatory stimulation and toll-like receptors on hippocampal plasticity and learning.

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10-15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning.

Self-Reported Cancer-Related Cognitive Impairment in Patients With Breast Cancer Is Associated With Potassium Channel Gene Polymorphisms.

Objectives: To evaluate for associations of polymorphisms for potassium channel genes in patients with breast cancer who were classified as having high or low-moderate levels of cancer-related cognitive impairment (CRCI).

Sample & Setting: 397 women who were scheduled to undergo surgery for breast cancer on one breast were recruited from breast care centers located in a comprehensive cancer center, two public hospitals, and four community practices.

Methods & Variables: CRCI was assessed using the Attentional Function Index prior to and for six months after surgery.

Stress and Coping in Patients With Cancer With Depression and Sleep Disturbance.

Objectives: To evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and use of various coping strategies among five groups (no depression or sleep disturbance, no depression and moderate sleep disturbance, subsyndromal depression and very high sleep disturbance, moderate depression and moderate sleep disturbance [Both Moderate]; and high depression and very high sleep disturbance [Both High]).

Sample & Setting: Patients (N = 1,331) receiving chemotherapy were recruited from outpatient oncology clinics.

Methods & Variables: Measures of global, cancer-specific, and cumulative life stress, resilience, and coping were obtained.

Effects of Complete and Partial Loss of the 24S-Hydroxycholesterol-Generating Enzyme on Behavior and Hippocampal Transcription in Mouse.

Brain cholesterol metabolic products include neurosteroids and oxysterols, which play important roles in cellular physiology. In neurons, the cholesterol oxidation product, 24S-hydroxycholesterol (24S-HC), is a regulator of signaling and transcription. Here, we examined the behavioral effects of 24S-HC loss, using global and cell-selective genetic deletion of the synthetic enzyme CYP46A1.

Increases in stress and adverse childhood experiences are associated with the co-occurrence of anxiety and depression in oncology patients.

Purpose: Identify subgroups of patients with distinct joint anxiety AND depression profiles and evaluate for differences in demographic and clinical characteristics, as well as stress, resilience, and coping.

Design: Longitudinal study.

Participants: Patients ( = 1328) receiving chemotherapy.

Stress Exposures Contribute to Worse Joint Morning and Evening Fatigue Profiles in Patients With Cancer During Chemotherapy.

Objectives: To evaluate differences among stress, resilience, and coping strategies related to morning and evening fatigue profiles (both low, low morning and moderate evening, both moderate, and both high).

Sample & Setting: Data were collected from 1,334 adult patients with cancer receiving chemotherapy.

Methods & Variables: Morning and evening fatigue severity were rated over two cycles of chemotherapy using the Lee Fatigue Scale.

Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy.

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown.

Common and distinct risk factors that influence more severe and distressing shortness of breath profiles in oncology outpatients.

Background: Shortness of breath occurs in 10%-70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions.