A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

Background: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer.

Walk with Me Hybrid Virtual/In-Person Walking for Older Adults with Neurodegenerative Disease.

This study presents a protocol for virtual and in-person walking groups for older adults with neurodegenerative diseases and addresses the decline in physical activity and social connectivity during the pandemic. Physical activity, specifically moderate-intensity walking, has been shown to have multiple health benefits for older adults. This methodology was created during the COVID-19 pandemic, contributing to lower physical activity levels and social isolation in older adults.

Parkinson's Disease and Diabetes Mellitus: Individual and Combined Effects on Motor, Cognitive, and Psychosocial Functions.

Background/objective: Understanding the effects of multimorbidity on motor and cognitive function is important for tailoring therapies. Individuals with diabetes mellitus (DM) have a greater risk of developing Parkinson's disease (PD). This study investigated if individuals with comorbid PD and DM experienced poorer functional ability compared to individuals with only PD or DM.

Cell-contact-mediated assembly of contractile airway smooth muscle rings.

Microtissues in the shape of toroidal rings provide an ideal geometry to better represent the structure and function of the airway smooth muscle present in the small airways, and to better understand diseases such as asthma. Here, polydimethylsiloxane devices consisting of a series of circular channels surrounding central mandrels are used to form microtissues in the shape of toroidal rings by way of the self-aggregation and -assembly of airway smooth muscle cell (ASMC) suspensions. Over time, the ASMCs present in the rings become spindle-shaped and axially align along the ring circumference.

Influence of age and sex on microRNA response and recovery in the hippocampus following sepsis.

Sepsis, defined as a dysregulated host immune response to infection, is a common and dangerous clinical syndrome. The excessive host inflammatory response can induce immediate and persistent cognitive decline, which can be worse in older individuals. Sex-specific differences in the outcome of infectious diseases and sepsis appear to favor females.

Adulthood systemic inflammation accelerates the trajectory of age-related cognitive decline.

In order to understand the long-term effects of systemic inflammation, it is important to distinguish inflammation-induced changes in baseline cognitive function from changes that interact with aging to influence the trajectory of cognitive decline. Lipopolysaccharide (LPS; 1 mg/kg) or vehicle was administered to young adult (6 months) male rats via intraperitoneal injections, once a week for 7 weeks. Longitudinal effects on cognitive decline were examined 6 and 12 months after the initial injections.

Achieving natural behavior in a robot using neurally inspired hierarchical perceptual control.

Terrestrial locomotion presents tremendous computational challenges on account of the enormous degrees of freedom in legged animals, and complex, unpredictable properties of natural environments, including the body and its effectors, yet the nervous system can achieve locomotion with ease. Here we introduce a quadrupedal robot that is capable of posture control and goal-directed locomotion across uneven terrain. The control architecture is a hierarchical network of simple negative feedback control systems inspired by the organization of the vertebrate nervous system.

The Utility of Cerebrovascular Reactivity MRI in Brain Rehabilitation: A Mechanistic Perspective.

Cerebrovascular control and its integration with other physiological systems play a key role in the effective maintenance of homeostasis in brain functioning. Maintenance, restoration, and promotion of such a balance are one of the paramount goals of brain rehabilitation and intervention programs. Cerebrovascular reactivity (CVR), an index of cerebrovascular reserve, plays an important role in chemo-regulation of cerebral blood flow.

Protocol for Recording from Ventral Tegmental Area Dopamine Neurons in Mice while Measuring Force during Head-Fixation.

Many studies in systems neuroscience use head-fixation preparations for experimentation. While head-fixation confers several advantages, one major limitation is the lack of behavioral measures that quantify whole-body movements. Here, we detail a step-by-step protocol for using a novel head-fixation device that measures the forces exerted by head-fixed mice in multiple dimensions.

The Role of Nutrition and Inflammation on Cognition in a High-Risk Group for Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disease. Treatments are necessary to target people at high risk for AD. Inflammation, particularly tumor necrosis factor alpha (TNF), appears to be an important marker associated with the development of AD pathophysiology.

Association between anti-inflammatory interleukin-10 and executive function in African American women at risk for Alzheimer's disease.

Introduction: African-Americans (AAs) are 64% more likely to be diagnosed with AD than non-Hispanic Whites. AAs with elevated AD biomarkers exhibit greater neurodegeneration in AD signature regions compared to non-Hispanic Whites with elevated AD biomarkers. This pilot trial examined whether normal or elevated plasma levels of interleukin (IL)-10 are associated with changes in executive function and short-term memory in AA women at risk for developing AD due to parental history.

Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence.

Markers of brain aging and cognitive decline are thought to be influenced by peripheral inflammation. This study compared the effects of repeated lipopolysaccharide (LPS) treatment in young rats to age-related changes in hippocampal-dependent cognition and transcription. Young Fischer 344 X Brown Norway hybrid rats were given intraperitoneal injections once a week for 7 weeks with either LPS or vehicle.

Hippocampal Subregion Transcriptomic Profiles Reflect Strategy Selection during Cognitive Aging.

Age-related cognitive impairments are associated with differentially expressed genes (DEGs) linked to defined neural systems; however, studies examining multiple regions of the hippocampus fail to find links between behavior and transcription in the dentate gyrus (DG). We hypothesized that use of a task requiring intact DG function would emphasize molecular signals in the DG associated with a decline in performance. We used a water maze beacon discrimination task to characterize young and middle-age male F344 rats, followed by a spatial reference memory probe trial test.

A Head-Fixation System for Continuous Monitoring of Force Generated During Behavior.

Many studies in neuroscience use head-fixed behavioral preparations, which confer a number of advantages, including the ability to limit the behavioral repertoire and use techniques for large-scale monitoring of neural activity. But traditional studies using this approach use extremely limited behavioral measures, in part because it is difficult to detect the subtle movements and postural adjustments that animals naturally exhibit during head fixation. Here we report a new head-fixed setup with analog load cells capable of precisely monitoring the continuous forces exerted by mice.

Longitudinal Characterization and Biomarkers of Age and Sex Differences in the Decline of Spatial Memory.

The current longitudinal study examined factors (sex, physical function, response to novelty, ability to adapt to a shift in light/dark cycle, brain connectivity), which might predict the emergence of impaired memory during aging. Male and female Fisher 344 rats were tested at 6, 12, and 18 months of age. Impaired spatial memory developed in middle-age (12 months), particularly in males, and the propensity for impairment increased with advanced age.

Age and Sex Influence the Hippocampal Response and Recovery Following Sepsis.

Although in-hospital mortality rates for sepsis have decreased, survivors often experience lasting physical and cognitive deficits. Moreover, older adults are more vulnerable to long-term complications associated with sepsis. We employed a murine model to examine the influence of age and sex on the brain's response and recovery following sepsis.

Aging in the Brain: New Roles of Epigenetics in Cognitive Decline.

Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic-environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA.

Using Expectancy Theory to quantitatively dissociate the neural representation of motivation from its influential factors in the human brain: An fMRI study.

Researchers have yet to apply a formal operationalized theory of motivation to neurobiology that would more accurately and precisely define neural activity underlying motivation. We overcome this challenge with the novel application of the Expectancy Theory of Motivation to human fMRI to identify brain activity that explicitly reflects motivation. Expectancy Theory quantitatively describes how individual constructs determine motivation by defining motivation force as the product of three variables: expectancy - belief that effort will better performance; instrumentality - belief that successful performance leads to particular outcome, and valence - outcome desirability.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report.

Objectives: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada.

Methods: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology.

An Adverse Reaction in the Pediatric Sleep Laboratory.

We present a case of a 15-month-old boy with Cornelia de Lange Syndrome (NIPBL gene mutation). On a PSG, central sleep apnea (central apnea-hypopnea index of 19/hour) and nocturnal hypoventilation (transcutaneous CO2 > 50 mmHg for 53% of the night) were found. A positive pressure initiation study was aborted because the patient developed a serious adverse reaction.

A GABAergic nigrotectal pathway for coordination of drinking behavior.

The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, during self-initiated drinking in mice. The firing rates of many lateral SNR neurons were time-locked to individual licks.

Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation.

Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation. Building on previous development of fusions of wild-type Gaussia luciferase with channelrhodopsin, here we expanded the utility of luminopsins by fusing bright Gaussia luciferase variants with either channelrhodopsin to excite neurons (luminescent opsin, LMO) or a proton pump to inhibit neurons (inhibitory LMO, iLMO). These improved LMOs could reliably activate or silence neurons in vitro and in vivo.