Lewy body diseases and the gut.

Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.

The pyrethroid insecticide deltamethrin disrupts neuropeptide and monoamine signaling pathways in the gastrointestinal tract.

Enteroendocrine cells (EECs) are a rare cell type of the intestinal epithelium. Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants.

Telehealth to Address Preventable Maternal Deaths: A Call to Action.

Over 80% of maternal deaths are preventable. Telehealth approaches can help address disparities by increasing access to quality maternal health care. In this position statement, we advocate for the utility of telehealth to address maternal mortality disparities, focusing specifically on the postpartum period, where most maternal deaths occur.

Diet-microbiome interactions promote enteric nervous system resilience following spinal cord injury.

Spinal cord injury (SCI) results in a plethora of physiological dysfunctions across all body systems, including intestinal dysmotility and atrophy of the enteric nervous system (ENS). Typically, the ENS has capacity to recover from perturbation, so it is unclear why intestinal pathophysiologies persist after traumatic spinal injury. With emerging evidence demonstrating SCI-induced alterations to the gut microbiome composition, we hypothesized that modulation of the gut microbiome could contribute to enteric nervous system recovery after injury.

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology.

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology.

Circulating Extracellular Vesicles as a Potential Mediator of Synuclein Pathology in the Gut.

The spread of pathological alpha-synuclein (aSyn) from the gastrointestinal tract to the brain, or the brain to the intestine, is of increasing interest given observations in experimental models. While there has been a focus on neuronal-mediated spread and propagation, non-neuronal reservoirs of aSyn are also present. In this issue, Yang et al describe the ability of extracellular vesicles, derived from red blood cells in circulation to mediate the deposition of aSyn into the GI tract.

Population fraction of Parkinson's disease attributable to preventable risk factors.

Parkinson's disease is the fastest-growing neurologic disease with seemingly no means of prevention. Intrinsic risk factors (age, sex, and genetics) are inescapable, but environmental factors are not. We identified repeated blows to the head in sports/combat as a potential new risk factor.

Microbial amyloids in neurodegenerative amyloid diseases.

Human-disease associated amyloidogenic proteins are not unique in their ability to form amyloid fibrillar structures. Numerous microbes produce amyloidogenic proteins that have distinct functions for their physiology in their amyloid form, rather than solely detrimental. Emerging data indicate associations between various microbial organisms, including those which produce functional amyloids, with neurodegenerative diseases.

Overview of the Gut Microbiome.

The human gastrointestinal tract is home to trillions of microorganisms-collectively referred to as the gut microbiome-that maintain a symbiotic relationship with their host. This diverse community of microbes grows and changes as we do, with developmental, lifestyle, and environmental factors all shaping microbiome community structure. Increasing evidence suggests this relationship is bidirectional, with the microbiome also influencing host physiological processes.

Population fraction of Parkinson's disease attributable to preventable risk factors.

Parkinson's disease is the fastest growing neurologic disease with seemingly no means for prevention. Intrinsic risk factors (age, sex, genetics) are inescapable, but environmental factors are not. We studied population attributable fraction and estimated fraction of PD that could be reduced if modifiable risk factors were eliminated.

Soluble TNF mediates amyloid-independent, diet-induced alterations to immune and neuronal functions in an Alzheimer's disease mouse model.

Increasing evidence indicates that neurodegenerative diseases, including Alzheimer's disease (AD), are a product of gene-by-environment interplay. The immune system is a major contributor mediating these interactions. Signaling between peripheral immune cells and those within the microvasculature and meninges of the central nervous system (CNS), at the blood-brain barrier, and in the gut likely plays an important role in AD.

Revealing gut microbiome associations with CFS.

The etiology of chronic fatigue syndrome (CFS) is largely unknown. In this issue of Cell Host and Microbe, Guo et al. and Xiong et al.

Introduction: Unraveling the complex contributions of indigenous microbes to neurological health and disease.

The complex interactions between the human body and its indigenous microbes have come into focus as key mediators of neurological health. With both established and emerging association studies, alterations to the gut microbiome are observed to co-occur with many neurological diseases. Whether these associations are due to microbiome-mediated contributions to human health or an effect of the neurological disease itself is largely unknown across conditions.

Traumatic spinal cord injury and the contributions of the post-injury microbiome.

Spinal cord injuries are an enormous burden on injured individuals and their caregivers. The pathophysiological effects of injury are not limited to the spine and limb function, but affect numerous body systems. Growing observations in human studies and experimental models suggest that the gut microbiome is altered following spinal cord injury.

Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms.

Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association, network analysis to identify polymicrobial clusters, and functional profiling.

The gut-brain axis goes viral.

A cloudburst of recent research has revealed important contributions of indigenous microbes to host neurological functions. In this issue of Cell Host & Microbe, Mayberis-Perxachs and Castells-Nobau et al. uncover a role for gut-resident bacteriophages in microbiome structure and metabolism with downstream effects on neuronal gene expression and cognition.

Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.

Objective: This study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer's disease (AD) pathogenesis.

Design: We analysed the gut microbiota composition of 3×Tg mice in an age-dependent manner. We generated germ-free 3×Tg mice and recolonisation of germ-free 3×Tg mice with fecal samples from both patients with AD and age-matched healthy donors.

The effectiveness of peroneal nerve functional electrical simulation for the reduction of bradykinesia in Parkinson's disease: A feasibility study for a randomised control trial.

Objectives: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson's disease.

Design: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up.

Setting: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre.

Findings on repaired full-thickness acetabular articular cartilage defects during revision hip arthroscopy allowing a second look.

Full-thickness acetabular articular cartilage defects (FAACD) are found on most hips with femoroacetabular impingement (FAI) with a wave sign in the acetabulum. When not repaired it can produce pain and catching sensation. Multiple arthroscopic techniques for repairing this chondral lesion exist, but only few show the quality of the repair on a second look.

Editorial Commentary: Can We Derive Any Practical Information From a Study of "The Top 50 Most Influential Papers in Hip Arthroscopy," or Are We Tooting Our Own Horns?

Orthopaedic literature on hip arthroscopy has become more robust primarily from the advent and transformation in the treatment of femoroacetabular impingement syndrome from an open surgical dislocation to an ambulatory arthroscopic procedure. Numerous studies have reviewed the frequency of authors and subjects in particular areas of arthroscopy, but until this article, none had been performed on the most influential in hip arthroscopy. The question to be answered is, Do such studies contribute significantly to our knowledge by suggesting future topics to clinicians and training programs?