Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination.

Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits.

The amyloid beta 42/38 ratio as a plasma biomarker of early memory deficits in cognitively unimpaired older adults.

The amyloid beta (Aβ) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aβ peptides could also represent relevant biomarkers. We measured levels of Aβ38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aβ levels and amyloid positron-emission-tomography (PET) and performance on a learning and memory task. We found that all Aβ peptides individually and the Aβ42/40 ratio, but not the Aβ42/38 ratio, were significantly correlated with brain amyloid (Aβ-PET).

Anhedonia is associated with higher functional connectivity between the nucleus accumbens and paraventricular nucleus of thalamus.

Background: Anhedonia stands as a life-threatening transdiagnostic feature of many mental illnesses, most notably major depression and involves neural circuits for processing reward information. The paraventricular nucleus of the thalamus (PVT) is associated with reward-seeking behavior, however, links between the PVT circuit and anhedonia have not been investigated in humans.

Methods: In a sample of adults with and without psychiatric symptoms (n = 75, 18-41 years, 55 female), we generated an anhedonia factor score for each participant using a latent factor analysis, utilizing data from depression and anxiety assessments.

Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial.

Background: The rate of antibiotic resistance continues to grow, outpacing small-molecule-drug development efforts. Novel therapies are needed to combat this growing threat, particularly for the treatment of urinary tract infections (UTIs), which are one of the largest contributors to antibiotic use and associated antibiotic resistance. LBP-EC01 is a novel, genetically enhanced, six-bacteriophage cocktail developed by Locus Biosciences (Morrisville, NC, USA) to address UTIs caused by Escherichia coli, regardless of antibiotic resistance status.

Return to Duty in Military Servicemembers After High Tibial Osteotomy Not Associated With Preoperative Radiographic Parameters : A Retrospective Analysis.

Background: Evidence on return to sports/work after high tibial osteotomy (HTO) is limited, especially in a young, high-demand population.

Purpose: To (1) identify whether preoperative knee pathology or intraoperative correction was associated with successful return to duty (RTD) and (2) assess whether postoperative complications and reoperation were associated with failure to RTD.

Study Design: Case series; Level of Evidence, 4.

A pathway linking pulse pressure to dementia in adults with Down syndrome.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy.

Understanding the impact of COVID-19 on women's access to and experiences of contraceptive services in England: a qualitative study.

Background: The COVID-19 pandemic response prompted rapid changes to how contraceptive services were delivered in England. Our aim was to examine women's experiences of accessing contraceptive services since March 2020 and to understand any inequalities of access.

Methods: We conducted telephone interviews with 31 women aged 17-54 years who had accessed contraceptive services in England since March 2020.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

Introduction: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS.

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.

Significance: Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated.

Domain-informed variational neural networks and support vector machines based leakage detection framework to augment self-healing in water distribution networks.

The reduction of water leakage is essential for ensuring sustainable and resilient water supply systems. Despite recent investments in sensing technologies, pipe leakage remains a significant challenge for the water sector, particularly in developed nations like the UK, which suffer from aging water infrastructure. Conventional models and analytical methods for detecting pipe leakage often face reliability issues and are generally limited to detecting leaks during nighttime hours.

Pathways linking pulse pressure to dementia in adults with Down syndrome.

Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS.

Examining the diagnostic value of the mnemonic discrimination task for classification of cognitive status and amyloid-beta burden.

Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs.

Parsing memory and nonmemory contributions to age-related declines in mnemonic discrimination performance: a hierarchical Bayesian diffusion decision modeling approach.

The mnemonic discrimination task (MDT) is a widely used cognitive assessment tool. Performance in this task is believed to indicate an age-related deficit in episodic memory stemming from a decreased ability to pattern-separate among similar experiences. However, cognitive processes other than memory ability might impact task performance.

NODDI-derived measures of microstructural integrity in medial temporal lobe white matter pathways are associated with Alzheimer's disease pathology and cognitive outcomes.

Introduction: Diffusion tensor imaging has been used to assess white matter (WM) changes in the early stages of Alzheimer's disease (AD). However, the tensor model is necessarily limited by its assumptions. Neurite Orientation Dispersion and Density Imaging (NODDI) can offer insights into microstructural features of WM change.

Functional network structure supports resilience to memory deficits in cognitively normal older adults with amyloid-β pathology.

Older adults may harbor large amounts of amyloid-β (Aβ) pathology, yet still perform at age-normal levels on memory assessments. We tested whether functional brain networks confer resilience or compensatory mechanisms to support memory in the face of Aβ pathology. Sixty-five cognitively normal older adults received high-resolution resting state fMRI to assess functional networks, 18F-florbetapir-PET to measure Aβ, and a memory assessment.

Early Impacts of COVID-19 on Select Hospices: Operations, Care Delivery, and Service Utilization.

Objective: The COVID-19 public health emergency (PHE) has important implications for health care service delivery. Little is understood about how the PHE impacted community-based hospice providers and service delivery to hospice-eligible beneficiaries. The aim of this study was to describe hospice response to the PHE and correlated impacts on beneficiary receipt of hospice support services delivered to hospice-eligible beneficiaries participating in the Centers for Medicare & Medicaid Services (CMS) Medicare Care Choices Model (MCCM), a national model testing the provision of certain hospice-like supportive services with concurrent usual care among seriously ill, community-residing Medicare beneficiaries that have not elected to receive hospice care.

Muscle in the caterpillar Manduca sexta responds to an immune challenge, but at a cost, suggesting a physiological trade-off.

Although skeletal muscle is a specialized tissue that provides the motor for movement, it also participates in other functions, including the immune response. However, little is known about the effects of this multitasking on muscle. We show that muscle loses some of its capacity while it is participating in the immune response.

A divide and conquer approach to maximise deep learning mammography classification accuracies.

Breast cancer claims 11,400 lives on average every year in the UK, making it one of the deadliest diseases. Mammography is the gold standard for detecting early signs of breast cancer, which can help cure the disease during its early stages. However, incorrect mammography diagnoses are common and may harm patients through unnecessary treatments and operations (or a lack of treatment).

Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults.

Introduction: We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non-demented older adults through its effects on medial temporal lobe (MTL) subregional volume.

Methods: Thirty-two, non-demented older adults with cerebrospinal fluid (CSF) (amyloid-beta [Aβ]/Aβ, phosphorylated tau [p-tau], total tau [t-tau]), positron emission tomography (PET; 18F-florbetapir), high-resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI).

Insomnia in the Veteran Population: A Sleep Health and Wellness Intervention.

The purpose of this evidence-based project (EBP) was to determine if an evidence-based sleep health and wellness intervention improved sleep in veterans self-reporting a history of insomnia. Insomnia can negatively affect an individual's physical and psychological well-being, as well as increase health-care costs and decrease the overall quality of life. The intervention utilized a combination of insomnia treatments, delivered to two American Legion veteran participant groups: an Alabama American Legion Retreat and individuals at an American Legion Post site.

Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults.

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer's disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults.

Targeted Per- and Polyfluoroalkyl substances (PFAS) assessments for high throughput screening: Analytical and testing considerations to inform a PFAS stock quality evaluation framework.

Per- and polyfluoroalkyl substances (PFAS) represent a large chemical class lacking hazard, toxicokinetic, and exposure information. To accelerate PFAS hazard evaluation, new approach methodologies (NAMs) comprised of in vitro high-throughput toxicity screening, toxicokinetic data, and computational modeling are being employed in read across strategies to evaluate the larger PFAS landscape. A critical consideration to ensure robust evaluations is a parallel assessment of the quality of the screening stock solutions, where dimethyl sulfoxide (DMSO) is often the diluent of choice.

Reduced structural connectivity of the medial temporal lobe including the perforant path is associated with aging and verbal memory impairment.

The perforant path, the white matter bundle connecting the entorhinal cortex (ERC) with the hippocampal formation deteriorates with age-related cognitive decline. Previous investigations using diffusion-weighted MRI to quantify perforant path integrity in-vivo have been limited due to image resolution or have quantified the perforant path using methods susceptible to partial volume effects such as the tensor model and without consideration of its 3-dimensional morphology. In this investigation, we use quantitative-anisotropy informed tractography derived from ultra-high resolution diffusion imaging (ZOOMit) to investigate structural connectivity of the perforant path and other medial temporal lobe (MTL) pathways in older adults (63 to 98 years old, n = 51).