Association between the Amplification Parameters of the α-Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease.

Background: α-Synuclein seed amplification assay on cerebrospinal fluid (CSF-αSyn-SAA) has shown high accuracy for Parkinson's disease (PD) diagnosis. The analysis of CSF-αSyn-SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.

Objective: To assess differences in CSF-αSyn-SAA amplification parameters in participants with PD stratified by rapid eye movement (REM) sleep behavior disorder (RBD), dysautonomia, GBA, and LRRK2 variants.

Using lifestyle interventions and the gut microbiota to improve PTSD symptoms.

Posttraumatic stress disorder is part of a spectrum of psychological symptoms that are frequently linked with a single defining traumatic experience. Symptoms can vary over the lifespan in intensity based on additional life stressors, individual stability, and connectedness to purpose. Historically, treatment has centered on psychotropic agents and individual and group therapy to increase the individual's window of tolerance, improve emotional dysregulation, and strengthen relationships.

Placental Infections.

This comprehensive review examines the effects of various infections on pregnancy, focusing on maternal symptoms, fetal outcomes, diagnostic methods, and placental pathology. The paper covers bacterial, viral, and parasitic infections, their mechanisms of transmission, clinical presentations, and histopathologic findings in the placenta. It emphasizes the importance of early detection and intervention, highlighting the challenges in diagnosis due to often asymptomatic presentations.

Relationship Between Severity of Ischemia and Coronary Artery Disease for Different Stress Test Modalities in the ISCHEMIA Trial.

Background: The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography.

Methods: Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test.

A 24% Decline in the Utilization of Epidural Procedure Visits for Chronic Spinal Pain Management in the Medicare Population from 2019 to 2022: Updated Analysis of the Effect of Multiple Factors.

Background: The analysis of epidural procedure utilization has revealed several notable trends over recent years. Utilization increased significantly until 2004, then rose minimally until 2011, followed by gradual declines up to 2019 in the Medicare population. The COVID-19 pandemic led to a marked 19% decline in usage from 2019 to 2020.

Escalating Growth to Rapid Decline of Utilization Patterns of Facet Joint Interventions in Managing Spinal Pain in the Medicare Population: Updated Analysis of the Effect of Multiple Factors from 2000 To 2022.

Background: The use of facet joint interventions for spinal pain management experienced rapid growth between 2000 and 2010, with an annual increase of 14.2%. However, this trend slowed significantly from 2010 to 2019, with a reduced growth rate of just 2.

Lipids: Emerging Players of Microglial Biology.

Lipids are small molecule immunomodulators that play critical roles in maintaining cellular health and function. Microglia, the resident immune cells of the central nervous system, regulate lipid metabolism both in the extracellular environment and within intracellular compartments through various mechanisms. For instance, glycerophospholipids and fatty acids interact with protein receptors on the microglial surface, such as the Triggering Receptor Expressed on Myeloid Cells 2, influencing cellular functions like phagocytosis and migration.

Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development.

Introduction: Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells.

Integrative study of lung cancer adeno-to-squamous transition in EGFR TKI resistance identifies RAPGEF3 as a therapeutic target.

Although adeno-to-squamous transition (AST) has been observed in association with resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in clinic, its causality, molecular mechanism and overcoming strategies remain largely unclear. We here demonstrate that squamous transition occurs concomitantly with TKI resistance in PC9-derived xenograft tumors. Perturbation of squamous transition via DNp63 overexpression or knockdown leads to significant changes in TKI responses, indicative of a direct causal link between squamous transition and TKI resistance.

Corneal cross-linking.

First introduced over 20 years ago as a treatment for progressive keratoconus, the original "Dresden" corneal cross-linking (CXL) protocol involved riboflavin saturation of the stroma, followed by 30 min of 3 mW/cm-intensity ultraviolet-A (UV-A) irradiation. This procedure generates reactive oxygen species (ROS) that cross-link stromal molecules, thereby stiffening the cornea and counteracting the ectasia-induced weakening. Due to their large size, riboflavin molecules cannot readily pass through the corneal epithelial cell tight junctions; thus, epithelial debridement was performed.

Mobile App-Facilitated Collaborative Palliative Care Intervention for Critically Ill Older Adults: A Randomized Clinical Trial.

Importance: Few person-centered, scalable models of collaborative intensive care unit (ICU) clinician-palliative care specialist care exist.

Objective: To evaluate the effect of a collaborative palliative care intervention compared to usual care among family members of patients in the ICU.

Design, Setting, And Participants: This parallel-group randomized clinical trial with patient-level randomization was conducted between April 2021 and September 2023.

The Efficacy of Botulinum Toxin Use in Service Members and Veterans with Migraine and Post-Traumatic Headache Disorders: A Scoping Review.

Objective: To delineate the trend of use of botulinum toxin, including onabotulinum toxinA (OTA), in active military personnel and veterans with the diagnoses of migraine and post-traumatic headache (PTH) and describe the efficacy of botulinum toxin administration.

Background: Service members and veterans represent a unique population in the medical management of headache disorders, particularly migraine. They exhibit higher susceptibility to pain of greater intensity and longer durations, possibly due to their history of exposure to combat, trauma, and the associated psychological stresses.

IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.

Lymphatic vessels play a crucial role in activating anti-tumor immune surveillance but also contribute to metastasis and systemic tumor progression. Whether distinct lymphatic phenotypes exist that govern the switch between immunity and metastasis remains unclear. Here we reveal that cytotoxic immunity normalizes lymphatic function and uncouples immune and metastatic potential.

Just-in-Time Simulation Training to Augment Overnight ICU Resident Education.

Patients who decompensate overnight experience worse outcomes than those who do so during the day. Just-in-time (JIT) simulation could improve on-call resident preparedness but has been minimally evaluated in critical care medicine (CCM) to date. To determine whether JIT training can improve residents' performance in simulation and if those skills would transfer to better clinical management in adult CCM.

Phase I study of intratumoral injection of talimogene laherparepvec for the treatment of advanced pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) presents a redoubtable challenge due to late-stage diagnosis and limited treatment options, necessitating innovative therapeutic strategies.

Methods: Here, we report our results investigating the safety and efficacy of talimogene laherparepvec (T-VEC), an FDA-approved oncolytic herpes simplex virus type 1, in patients with advanced PDAC. Nine patients with treatment-refractory advanced PDAC received escalating doses of T-VEC via endoscopic injection.

Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.

Background & Aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons.

A re-look at the relevance of TSH and thyroid autoimmunity for pregnancy outcomes: Analyses of RCT data from PPCOS II and AMIGOS.

Objective: We examined if thyroid autoimmunity is relevant to the relationship between maternal TSH levels and pregnancy outcomes.

Design: Retrospective cohort analysis of data from two randomized controlled trials (RCTs).

Subjects: Participants of the Pregnancy in Polycystic Ovary Syndrome (PPCOS II, n = 746) and the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS, n = 832 with unexplained infertility) RCTs.

A novel mutation, Ile344Asn, in microsomal triglyceride transfer protein abolishes binding to protein disulfide isomerase.

Microsomal triglyceride transfer protein (MTP) plays crucial roles in the assembly and secretion of apolipoprotein B-containing lipoproteins and loss of function MTP variants are associated with abetalipoproteinemia, a disease characterized by the absence of these lipoproteins. MTP is a heterodimeric protein of two subunits, MTP and protein disulfide isomerase (PDI). In this study, we report a proband with abetalipoproteinemia who was monitored annually for 10 years in her third decade and had very low plasma lipids and undetectable apoB-containing lipoproteins.

Lived Experience of Patients and Caregivers in Rare Genetic Neurological Gene Therapy Clinical Trials in Children.

To date, sparse attention has been paid to the importance of the "lived experience" of participants and their caregivers in pediatric gene therapy (GT) trials for rare genetic neurological disorders. Pediatric GT studies differ meaningfully from adult GT studies as the decision to participate involves a dyad: the child participant and their caregiver(s). As a multistakeholder group of authors, we are a diverse group with expert perspectives on the social, emotional, physical, and logistical burdens/benefits of trial participation and the myriad ways they affect pediatric GT research.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017.

Do K channels have a role in immunity?

Ion channels, exchangers and pumps are expressed ubiquitously in cells from all phyla of life. In mammals, their role is best described in excitable cells, where they regulate the initiation and propagation of action potentials. There are over 70 different types of K channels subunits that contribute to these processes.

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.