An Alzheimer's Disease Mechanism Based on Early Pathology, Anatomy, Vascular-Induced Flow, and Migration of Maximum Flow Stress Energy Location with Increasing Vascular Disease.

This paper suggests a chemical mechanism for the earliest stages of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) flow stresses provide the energy needed to induce molecular conformation changes leading to AD by initiating amyloid-ß (Aß) and tau aggregation. Shear and extensional flow stresses initiate aggregation in the laboratory and in natural biophysical processes. Energy-rich CSF flow regions are mainly found in lower brain regions. MRI studies reveal flow stress "hot spots" in basal cisterns and brain ventricles that have chaotic flow properties that can distort molecules such as Aß and tau trapped in these regions into unusual conformations. Such fluid disturbance is surrounded by tissue deformation. There is strong mapping overlap between the locations of these hot spots and of early-stage AD pathology. Our mechanism creates pure and mixed protein dimers, followed by tissue surface adsorption, and long-term tissue agitation ultimately inducing chemical reactions forming more stable, toxic oligomer seeds that initiate AD. It is proposed that different flow stress energies and flow types in different basal brain regions produce different neurotoxic aggregates. Proliferating artery hardening is responsible for enhanced heart systolic pulses that drive energetic CSF pulses, whose critical maximum systolic pulse energy location migrates further from the heart with increasing vascular disease. Two glymphatic systems, carotid and basilar, are suggested to contain the earliest Aß and tau AD disease pathologies. A key to the proposed AD mechanism is a comparison of early chronic traumatic encephalopathy and AD pathologies. Experiments that test the proposed mechanism are needed.

Virtual Reality in the Management of Chronic Low Back Pain: A Scoping Review.

Virtual reality (VR) is a burgeoning treatment option for chronic pain. Its use has been heterogenous in the literature. This scoping review assesses the current literature for the use of VR in the treatment of chronic low back pain (CLBP). The following themes were identified by the analysis: safety and feasibility of VR, quality of life associated with VR treatment for CLBP, efficacy of VR to treat CLBP, and efficacy of VR to treat functional changes associated with CLBP. Gaps were identified after analysis of the extant literature. Although the nascent research uncovered in this scoping review found good evidence for safety and tolerability of VR, more studies of safety, acceptance, and satisfaction are recommended including focused studies of spinal pain risks specific to use of VR. Overall, the methodological quality of studies reviewed in this scoping review was poor and outcomes were limited to short-term posttreatment outcomes.

The Epidemiology, Risk Factors, and Nonsurgical Treatment of Injuries Related to Endurance Running.

ABSTRACT: Running is a popular form of exercise that is easily accessible to various populations; endurance running, defined as distances beyond 5 km, continues to grow within the sport. Endurance running-related injuries are common in the lower extremities and are primarily overuse related. A multitude of risk factors for injury exist, including extrinsic factors, such as running distance and frequency, and intrinsic factors, such as biomechanics and nutrition status. Training and rehabilitation techniques vary with a general focus on strengthening and gradual increase in activity, but evidence is mixed, and it is difficult to generalize programs across different running populations. Management of specific running groups, including youth runners, is an area in which additional research is needed. New treatments, such as orthobiologics and wearable technology, have promising potential to optimize performance and recovery and minimize injury. However, they need to be further evaluated with high-quality studies.

Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection.

Cerebrospinal fluid (CSF) flowing through periarterial spaces is integral to the brain's mechanism for clearing metabolic waste products. Experiments that track tracer particles injected into the cisterna magna (CM) of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces surrounding pial arteries, with a bulk flow in the same direction as blood flow. However, the driving mechanism remains elusive. Several studies have suggested that the bulk flow might be an artifact, driven by the injection itself. Here, we address this hypothesis with new in vivo experiments where tracer particles are injected into the CM using a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure. Yet, particle-tracking reveals flows that are consistent in all respects with the flows observed in earlier experiments with single-syringe injection.

Simulated microgravity in the ring-sheared drop.

The ring-sheared drop is a module for the International Space Station to study sheared fluid interfaces and their influence on amyloid fibril formation. A 2.54-cm diameter drop is constrained by a stationary sharp-edged ring at some latitude and sheared by the rotation of another ring in the other hemisphere. Shearing motion is conveyed primarily by the action of surface shear viscosity. Here, we simulate microgravity in the laboratory using a density-matched liquid surrounding the drop. Upon shearing, the drop's deformation away from spherical is found to be a result of viscous and inertial forces balanced against the capillary force. We also present evidence that the deformation increases with increasing surface shear viscosity.

Predicting Steady Shear Rheology of Condensed-Phase Monomolecular Films at the Air-Water Interface.

Predicting the non-Newtonian shear response of soft interfaces in biophysical systems and engineered products has been compromised by the use of linear (Newtonian) constitutive equations. We present a generalized constitutive equation, with tractable material properties, governing the response of Newtonian and non-Newtonian interfaces subjected to a wide range of steady shear. With experiments spanning six decades of shear rate, we capture and unify divergent reports of shear-thinning behavior of monomolecular films of the lipid dipalmitoylphosphatidylcholine, the primary constituent of mammalian cell walls and lung surfactant, at near-physiological packing densities.

Surface shear viscosity as a macroscopic probe of amyloid fibril formation at a fluid interface.

Amyloidogenesis of proteins is of wide interest because amyloid structures are associated with many diseases, including Alzheimer's and type II diabetes. Dozens of different proteins of various sizes are known to form amyloid fibrils. While there are numerous studies on the fibrillization of insulin induced by various perturbations, shearing at fluid interfaces has not received as much attention. Here, we present a study of human insulin fibrillization at room temperature using a deep-channel surface viscometer. The hydrodynamics of the bulk flow equilibrates in just over a minute, but the proteins at the air-water interface exhibit a very slow development during which the surface (excess) shear viscosity deduced from a Newtonian surface model increases slightly over a period of a day and a half. Then, there is a very rapid increase in the surface shear viscosity to effectively unbounded levels as the interface becomes immobilized. Atomic force microscopy shows that fibrils appear at the interface after it becomes immobilized. Fibrillization in the bulk does not occur until much later. This has been verified by concurrent atomic force microscopy and circular dichroism spectroscopy of samples from the bulk. The immobilized interface has zero in-plane shear rate, however due to the bulk flow, there is an increase in the strength of the normal component of the shear rate at the interface, implicating this component of shear in the fibrillization process ultimately resulting in a thick weave of fibrils on the interface. Real-time detection of fibrillization via interfacial rheology may find utility in other studies of proteins at sheared interfaces.

Differential diagnosis considerations of sickness after rapid pressure changes at altitude.

INTRODUCTION: Aviation has undergone significant advancement over time; despite our best practices, injuries can still occur. Occasionally aviators will suffer from injuries of barotrauma, decompression sickness, or arterial gas embolism. The history and physical examination are important when evaluating the injury and its subsequent treatment. This article will help readers identify key components of the history and physical examination in a patient to recognize decompression sickness and arterial gas embolism. CASE REPORT: This case report is of a Naval F/A-18C pilot who demonstrated acute and delayed neurologic symptoms when his cockpit underwent four rapid decompression cycles from 11,000 to 29,000 ft (3353 to 8839 m) in a 20-s period. He was subsequently treated with hyperbaric oxygen via a standard U.S. Navy TreatmentTable 6 with complete neurological recovery as determined by his improved neurological abilities. DISCUSSION: Naval aviators are exposed to multiple stresses during flight. When injuries occur it is important to obtain a careful history and physical examination. A broad differential diagnosis, including decompression sickness, hypoxia, and arterial gas embolism, should be considered to ensure prompt and appropriate evaluation and treatment. In this case report, the pilot had acute neurological injuries concerning for arterial gas embolism or an hypoxic episode, as well as a delayed recurrence of symptoms consistent with decompression sickness.