Mitochondrial dynamics and bioenergetics in Alzheimer's induced pluripotent stem cell-derived neurons.

Mitochondrial (MT) dysfunction is a hallmark of Alzheimer's Disease (AD), but the scope and severity of these specific deficits across forms of AD are not well characterized. We designed a high-throughput, longitudinal, phenotypic assay to track MT dynamics and bioenergetics in glutamatergic iPSC-derived human neurons possessing mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2) and the amyloid beta precursor protein (APP). Each gene set was comprised of iPSC-derived neurons from an AD patient as well as two to three engineered mutations with appropriate isogenic and age matched controls.

Dielectrophoretic bead-droplet reactor for solid-phase synthesis.

Solid-phase synthesis underpins many advances in synthetic and combinatorial chemistry, biology, and material science. The immobilization of a reacting species on the solid support makes interfacing of reagents an important challenge in this approach. In traditional synthesis columns, this leads to reaction errors that limit the product yield and necessitates excess consumption of the mobile reagent phase.

Oxidative Stress is a shared characteristic of ME/CFS and Long COVID.

More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset.

Longitudinal cytokine and multi-modal health data of an extremely severe ME/CFS patient with HSD reveals insights into immunopathology, and disease severity.

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents substantial challenges in patient care due to its intricate multisystem nature, comorbidities, and global prevalence. The heterogeneity among patient populations, coupled with the absence of FDA-approved diagnostics and therapeutics, further complicates research into disease etiology and patient managment. Integrating longitudinal multi-omics data with clinical, health,textual, pharmaceutical, and nutraceutical data offers a promising avenue to address these complexities, aiding in the identification of underlying causes and providing insights into effective therapeutics and diagnostic strategies.

Active forgetting and neuropsychiatric diseases.

Recent and pioneering animal research has revealed the brain utilizes a variety of molecular, cellular, and network-level mechanisms used to forget memories in a process referred to as "active forgetting". Active forgetting increases behavioral flexibility and removes irrelevant information. Individuals with impaired active forgetting mechanisms can experience intrusive memories, distressing thoughts, and unwanted impulses that occur in neuropsychiatric diseases.

Decolonial interventions: Intentional emergence, Black Shoals, and the pedagogical possibilities.

Using Black Shoals as a theoretical guide, we explore how intentional emergence (IE) can help erode the colonial and capitalist underpinnings of leadership education. Informed by Black Shoals and IE, we offer three pedagogical recommendations we frame as decolonial interventions-dissolving the center, weaving the margins, and collective imagining. Attending to these, and other, interventions stand to disrupt the normative structures and cultures of leadership learning, catalyze new relations and relationships, and engendering new possibilities for leadership development and social change.

Spectral tweezers: Single sample spectroscopy using optoelectronic tweezers.

A scheme that combines optoelectronic tweezers (OET) with spectroscopic analysis is presented. Referred to as , the approach uses a single focused light beam that acts both as the trapping beam for OET and the probe beam for spectroscopy. Having simultaneous manipulation and spectral characterization ability, the method is used to isolate single micro-samples from clusters and perform spectral measurements.

Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS and could explain symptoms of nerve pain and muscle weakness.

Risk factors for infection and acute urinary retention following transperineal prostate biopsy.

Purpose: To calculate the frequency of infection and acute urinary retention (AUR) following transperineal (TP) prostate biopsy at a single high-volume academic institution and determine risk factors for developing these post-biopsy conditions.

Methods: Men undergoing TP prostate biopsy from 2012 to 2022 at our institution were retrospectively identified and chart reviewed. TP biopsies were performed with TR ultrasound (TRUS) guidance with anesthesia using a brachytherapy grid template.

Microparticle electrical conductivity measurement using optoelectronic tweezers.

When it comes to simulate or calculate an optoelectronic tweezer (OET) response for a microparticle suspended in a given medium, a precise electrical conductivity (later referred to as conductivity) value for the microparticle is critical. However, there are not well-established measurements or well-referenced values for microparticle conductivities in the OET realm. Thus, we report a method based on measuring the escape velocity of a microparticle with a standard OET system to calculate its conductivity.

Less is more: single dose versus extended antibiotic prophylaxis for transperineal prostate biopsy.

Introduction: There is an ongoing debate as to the appropriate regimen of antibiotic prophylaxis with transperineal (TP) biopsy. The objective of this study was to report the rate of infection following TP biopsy at a high-volume institution and assess the impact of single dose antibiotics at the time of biopsy versus outpatient antibiotics in preventing postprocedural infections.

Materials And Methods: Records of men undergoing TP prostate biopsy from 2012 to 2022 were reviewed.

Establishing and sustaining an acute care for elders unit: An incremental journey to success.

Acute Care for Elders (ACE) units reduce hospital-associated delirium, functional decline, and lengths of stay. However, establishing and sustaining such units have proven difficult. There are only 43 ACE units among the >3500 hospitals in the United States.

Resolution improvement of optoelectronic tweezers using patterned electrodes.

An optoelectronic tweezer (OET) device is presented that exhibits improved trapping resolution for a given optical spot size. The scheme utilizes a pair of patterned physical electrodes to produce an asymmetric electric field gradient. This, in turn, generates an azimuthal force component in addition to the conventional radial gradient force.

Beyond the symptom: the biology of fatigue.

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.

Learning and memory using Drosophila melanogaster: a focus on advances made in the fifth decade of research.

In the last decade, researchers using Drosophila melanogaster have made extraordinary progress in uncovering the mysteries underlying learning and memory. This progress has been propelled by the amazing toolkit available that affords combined behavioral, molecular, electrophysiological, and systems neuroscience approaches. The arduous reconstruction of electron microscopic images resulted in a first-generation connectome of the adult and larval brain, revealing complex structural interconnections between memory-related neurons.

Innate and learned odor-guided behaviors utilize distinct molecular signaling pathways in a shared dopaminergic circuit.

Odor-based learning and innate odor-driven behavior have been hypothesized to require separate neuronal circuitry. Contrary to this notion, innate behavior and olfactory learning were recently shown to share circuitry that includes the Drosophila mushroom body (MB). But how a single circuit drives two discrete behaviors remains unknown.

Early Mitochondrial Defects in the 5xFAD Mouse Model of Alzheimer's Disease.

Background: Mitochondrial (MT) dysfunction is a hallmark of Alzheimer's disease (AD). Amyloid-β protein precursor and amyloid-β peptides localize to MT and lead to MT dysfunction in familial forms of AD. This dysfunction may trigger subsequent types of pathology.

Controlled Transport of Individual Microparticles Using Dielectrophoresis.

A dielectrophoretic device employing a planar array of microelectrodes is designed for controlled transport of individual microparticles. By exciting the electrodes in sequence, a moving dielectrophoretic force is created that can drag a particle across the electrodes in a straight line. The electrode shapes are designed to counter any lateral drift of the trapped particle during transport.

Genetics and Molecular Biology of Memory Suppression.

The brain is designed not only with molecules and cellular processes that help to form memories but also with molecules and cellular processes that suppress the formation and retention of memory. The latter processes are critical for an efficient memory management system, given the vast amount of information that each person experiences in their daily activities and that most of this information becomes irrelevant with time. Thus, efficiency dictates that the brain should have processes for selecting the most critical information for storage and suppressing the irrelevant or forgetting it later should it escape the initial filters.

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study.

Objective: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS).

Methods: Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .

Active forgetting requires Sickie function in a dedicated dopamine circuit in .

Forgetting is an essential component of the brain's memory management system, providing a balance to memory formation processes by removing unused or unwanted memories, or by suppressing their expression. However, the molecular, cellular, and circuit mechanisms underlying forgetting are poorly understood. Here we show that the memory suppressor gene, , functions in a single dopamine neuron (DAn) by supporting the process of active forgetting in .

Phenotypic characteristics of peripheral immune cells of Myalgic encephalomyelitis/chronic fatigue syndrome via transmission electron microscopy: A pilot study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic multi-systemic disease characterized by extreme fatigue that is not improved by rest, and worsens after exertion, whether physical or mental. Previous studies have shown ME/CFS-associated alterations in the immune system and mitochondria. We used transmission electron microscopy (TEM) to investigate the morphology and ultrastructure of unstimulated and stimulated ME/CFS immune cells and their intracellular organelles, including mitochondria.

A community-based adapted exercise program to increase quality of life and self-efficacy among adults with physical disabilities: A mixed-method study.

Background: Self-efficacy is one of the key constructs that directly influence physical activity, community participation, and mental health while acting as a strong influence on the quality of life (QOL) for adults with physical disabilities (AWPDs). There are relatively few studies focusing on a community-based exercise program in this population.

Objective: This study aims to quantitatively examine a community-based adapted exercise program on the QOL and self-efficacy of AWPDs.

Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome: A Randomized Clinical Trial.

Importance: New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy.

Objective: To evaluate the efficacy and safety of fenfluramine in patients with LGS.

Design, Setting, And Participants: This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration.

A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome.

Objective: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).

Methods: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo.