Macrophages protect against sensory axon degeneration in diabetic neuropathy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain 1,2 . Although the onset and progression of DPN have been linked with dyslipidemia and hyperglycemia 3 , the contribution of inflammation in the pathogenesis of DPN has not been investigated. Here, we use a High Fat High Fructose Diet (HFHFD) to model DPN and the diabetic metabolic syndrome in mice. Diabetic mice develop persistent heat hypoalgesia after three months, but a reduction in epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, we find that CCR2+ macrophages infiltrate the sciatic nerves of diabetic mice well before axonal degeneration is detectable. We show that these infiltrating macrophages share gene expression similarities with nerve crush-induced macrophages 4 and express neurodegeneration-associated microglia marker genes 5 although there is no axon loss or demyelination. Inhibiting this macrophage recruitment in diabetic mice by genetically or pharmacologically blocking CCR2 signaling results in a more severe heat hypoalgesia and accelerated skin denervation. These findings reveal a novel neuroprotective recruitment of macrophages into peripheral nerves of diabetic mice that delays the onset of terminal axonal degeneration, thereby reducing sensory loss. Potentiating and sustaining this early neuroprotective immune response in patients represents, therefore, a potential means to reduce or prevent DPN.

Collagen Fibril Orientation in Tissue Specimens From Atherosclerotic Plaque Explored Using Small Angle X-Ray Scattering.

Atherosclerotic plaques can gradually develop in certain arteries. Disruption of fibrous tissue in plaques can result in plaque rupture and thromboembolism, leading to heart attacks and strokes. Collagen fibrils are important tissue building blocks and tissue strength depends on how fibrils are oriented. Fibril orientation in plaque tissue may potentially influence vulnerability to disruption. While X-ray scattering has previously been used to characterize fibril orientations in soft tissues and bones, it has never been used for characterization of human atherosclerotic plaque tissue. This study served to explore fibril orientation in specimens from human plaques using small angle X-ray scattering (SAXS). Plaque tissue was extracted from human femoral and carotid arteries, and each tissue specimen contained a region of calcified material. Three-dimensional (3D) collagen fibril orientation was determined along scan lines that started away from and then extended toward a given calcification. Fibrils were found to be oriented mainly in the circumferential direction of the plaque tissue at the majority of locations away from calcifications. However, in a number of cases, the dominant fibril direction differed near a calcification, changing from circumferential to longitudinal or thickness (radial) directions. Further study is needed to elucidate how these fibril orientations may influence plaque tissue stress-strain behavior and vulnerability to rupture.

Functionally Graded, Bone- and Tendon-Like Polyurethane for Rotator Cuff Repair.

Critical considerations in engineering biomaterials for rotator cuff repair include bone-tendon-like mechanical properties to support physiological loading and biophysicochemical attributes that stabilize the repair site over the long-term. In this study, UV-crosslinkable polyurethane based on quadrol (Q), hexamethylene diisocyante (H), and methacrylic anhydride (M; QHM polymers), which are free of solvent, catalyst, and photoinitiator, is developed. Mechanical characterization studies demonstrate that QHM polymers possesses phototunable bone- and tendon-like tensile and compressive properties (12-74 MPa tensile strength, 0.6-2.7 GPa tensile modulus, 58-121 MPa compressive strength, and 1.5-3.0 GPa compressive modulus), including the capability to withstand 10 000 cycles of physiological tensile loading and reduce stress concentrations via stiffness gradients. Biophysicochemical studies demonstrate that QHM polymers have clinically favorable attributes vital to rotator cuff repair stability, including slow degradation profiles (5-30% mass loss after 8 weeks) with little-to-no cytotoxicity in vitro, exceptional suture retention ex vivo (2.79-3.56-fold less suture migration relative to a clinically available graft), and competent tensile properties (similar ultimate load but higher normalized tensile stiffness relative to a clinically available graft) as well as good biocompatibility for augmenting rat supraspinatus tendon repair in vivo. This work demonstrates functionally graded, bone-tendon-like biomaterials for interfacial tissue engineering.

Randomized trial of tourniquet vs blood pressure cuff for target vein dilation in ultrasound-guided peripheral intravenous access.

BACKGROUND: Ten percent of the time, peripheral intravenous access (PIV) is not obtained in 2 attempts in the emergency department. Typically, a tourniquet is used to dilate the target vein; but recent research showed that a blood pressure (BP) cuff improves dilation, which may translate to increased PIV success. OBJECTIVES: We sought to determine if there is improved success in obtaining ultrasound-guided PIV using a BP cuff vs a tourniquet in "difficult stick" patients. METHODS: This is a prospective, randomized, single-blinded trial. Adult patients requiring PIV with at least 2 prior failed attempts were enrolled. Patients were assigned to tourniquet or BP cuff for target vein dilation randomly. Nurses prepared the patient for PIV attempt by either placing a BP cuff inflated to 150 mm Hg or placing a tourniquet on the chosen extremity. The extremity was draped to blind the physician to assignment. Physicians then attempted ultrasound-guided PIV. Failures were defined as IVs requiring greater than 3 ultrasound-guided attempts or 30 minutes, or patient intolerance. If failure occurred, the physician was unblinded; and the patient could be crossed over and reattempted. RESULTS: Thirty-eight patients were enrolled. The success rate for the tourniquet group (n = 17) and BP cuff group (n = 21) was 82.4% and 47.6%, respectively (P = .04). There were no differences between groups for vessel depth, diameter, or procedure time. Six in the BP cuff group were crossed over and had successful PIV obtained with tourniquet. CONCLUSIONS: Tourniquet is superior to BP cuff for target vein dilation in ultrasound-guided PIV.

Bezold abscess: a rare complication of mastoiditis.

Bezold abscess is a rare complication of mastoiditis in which patients are often well appearing but require urgent intervention to prevent serious sequelae. We describe the case of a Bezold abscess in a 12-year-old girl.

Communication gaps in nursing home transfers to the ED: impact on turnaround time, disposition, and diagnostic testing.

INTRODUCTION: This study aims to determine the source of communication gaps in history of present illness (HPI), medical history, and advanced directives in nursing home (NH) patients transferred to the emergency department (ED). We also attempt to determine if these gaps create differences in patient turnaround time (TAT), disposition decision, or diagnostic testing. METHODS: A convenience sample of patients transferred from NHs to a level 1 community trauma center was enrolled by the physicians caring for them. The physicians assessed the adequacy and source of the history for each patient. The patient's chart was then retrospectively reviewed to determine disposition, ED TAT, and diagnostic tests ordered. RESULTS: One hundred patients were enrolled. Physicians found that NH paperwork contained adequate HPI 35% of the time. Patients could provide their own HPI 28% of the time. In 32% of patients, adequate HPI could not be obtained from the patient, NH paperwork, or NH personnel. Comparing patients in whom adequate HPI was available (n = 68) to those in whom HPI was not available (n = 32), there was no difference in TAT (146 vs 173 minutes, P = .22), admissions (60% vs 66%, P = .66), or diagnostic testing (P = .89-1.0). CONCLUSION: Emergency department physicians often do not have adequate HPI in patients transferred from NHs. The absence of adequate information does not affect patient TAT, disposition decision, or ED diagnostic testing.

Techniques for predicting the lifetimes of wave-swept macroalgae: a primer on fracture mechanics and crack growth.

Biomechanical analyses of intertidal and shallow subtidal seaweeds have elucidated ways in which these organisms avoid breakage in the presence of exceptional hydrodynamic forces imposed by pounding surf. However, comparison of algal material properties to maximum hydrodynamic forces predicts lower rates of breakage and dislodgment than are actually observed. Why the disparity between prediction and reality? Most previous research has measured algal material properties during a single application of force, equivalent to a single wave rushing past an alga. In contrast, intertidal macroalgae may experience more than 8000 waves a day. This repeated loading can cause cracks - introduced, for example, by herbivory or abrasion - to grow and eventually cause breakage, yet fatigue crack growth has not previously been taken into account. Here, we present methods from the engineering field of fracture mechanics that can be used to assess consequences of repeated force imposition for seaweeds. These techniques allow quantification of crack growth in wave-swept macroalgae, a first step towards considering macroalgal breakage in the realistic context of repeated force imposition. These analyses can also be applied to many other soft materials.

Death by small forces: a fracture and fatigue analysis of wave-swept macroalgae.

Wave-swept macroalgae are subjected to large hydrodynamic forces as each wave breaks on shore, loads that are repeated thousands of times per day. Previous studies have shown that macroalgae can easily withstand isolated impositions of maximal field forces. Nonetheless, macroalgae break frequently. Here we investigate the possibility that repeated loading by sub-lethal forces can eventually cause fracture by fatigue. We determine fracture toughness, in the form of critical strain energy release rate, for several flat-bladed macroalgae, thereby assessing their resistance to complete fracture in the presence of cracks. Critical energy release rates are evaluated through single-edge-notch, pull-to-break tests and single-edge-notch, repeated-loading tests. Crack growth at sub-critical energy release rates is measured in repeated-loading tests, providing a first assessment of algal breakage under conditions of repeated loading. We then estimate the number of imposed waves required for un-notched algal blades to reach the point of complete fracture. We find that, if not checked by repair, fatigue crack growth from repeated sub-lethal stresses may completely fracture individuals within days. Our results suggest that fatigue may play an important role in macroalgal breakage.

Analysis of Time-Varying Biological Data Using Rainflow Cycle Counting.

A wide range of biological investigations lead to time-history data. The characterization of such data can be difficult particularly in the presence of signal noise or superimposed signals. Several methods are described which can be brought to bear including FFT, thresholding, peak counting, and range counting. However, each of these approaches has significant disadvantages. In this paper we describe a novel method, known as rainflow cycle counting, for characterizing time varying biological time-history data in terms of spiking or oscillation amplitude and frequency. Rainflow counting is a straightforward algorithm for identifying complete cycles in the data and determining their amplitudes. The approach is simple, reliable, easily lends itself to automation, and robust even in the presence of superimposed signals or background noise. After describing the method, its use and behavior are demonstrated on three sample histories of intracellular calcium concentration in chondrocytes exposed to fluid shear stress. The method is also applied to a more challenging data set that has had an artificial random error included. The results demonstrate that the rainflow counting algorithm identifies signal oscillations and appropriately determines their amplitudes even when superimposed or distorted by background noise. These attractive properties make rainflow counting a powerful approach for quantifying and characterizing biological time histories.