Early Surgery for Traumatic Spinal Cord Injury: Where Are We Now?

Study Design: Narrative review. Objective: There is a strong biological rationale to perform early decompression after traumatic spinal cord injury (SCI). With an enlarging clinical evidence base, most spine surgeons internationally now favor early decompression for the majority of SCI patients; however, a number of pertinent questions remain surrounding this therapy. Methods: A narrative review evaluating the status of early surgery for SCI. In particular, we addressed the following questions: (1) Which patients stand to benefit most from early surgery? 2) What is the most appropriate time threshold defining early surgery? Results: Although heterogeneity exists, the evidence generally seems to support early surgery. While the best evidence exists for cervical SCI, there is insufficient data to support a differential effect for early surgery depending on neurological level or injury severity. When comparing thresholds to define early versus late surgery-including a later threshold (48-72 hours), an earlier threshold (24 hours), and an ultra-early threshold (8-12 hours)-the 2 earlier time points seem to be associated with the greatest potential for improved outcomes. However, existing prehospital and hospital logistics pose barriers to early surgery in a significant proportion of patients. An overview of recommendations from the recent AOSpine guidelines is provided. Conclusion: In spite of increasing acceptance of early surgery post SCI, further research is needed to (1) identify subgroups of patients who stand to derive particular benefit-in particular to develop more evidence-based approaches for central cord syndrome and (2) investigate the efficacy and feasibility of ultra-early surgery targeting more aggressive timelines

Human-specific CpG 'beacons' identify human-specific prefrontal cortex H3K4me3 chromatin peaks

Therefore, CpG-focused comparative sequence analysis can precisely pinpoint chromatin structures that contribute to the human-specific phenotype and further supports an integrated approach in genomic and epigenomic studie

Dynamically-coupled partial-waves in ρπ\rho\pi isospin-2 scattering from lattice QCD

We present the first determination of $\rho \pi$ scattering, incorporating dynamically-coupled partial-waves, using lattice QCD, a first-principles numerical approach to QCD. Considering the case of isospin-2 $\rho \pi$, we calculate partial-wave amplitudes with $J \le 3$ and determine the degree of dynamical mixing between the coupled $S$ and $D$-wave channels with $J^P=1^+$. The analysis makes use of the relationship between scattering amplitudes and the discrete spectrum of states in the finite volume lattice. Constraints on the scattering amplitudes are provided by over one hundred energy levels computed on two lattice volumes at various overall momenta and in several irreducible representations of the relevant symmetry groups. The spectra follow from variational analyses of matrices of correlations functions computed with large bases of meson-meson operators. Calculations are performed with degenerate light and strange quarks tuned to the physical strange quark mass so that $m_\pi \sim 700$ MeV, ensuring that the $\rho$ is stable against strong decay. This work demonstrates the successful application of techniques, opening the door to calculations of scattering processes that incorporate the effects of dynamically-coupled partial-waves, including those involving resonances or bound states.Comment: Minor changes to match the published versio

The ππ→πγ⋆\pi\pi\to\pi\gamma^\star amplitude and the resonant ρ→πγ⋆\rho\to\pi\gamma^\star transition from lattice QCD

We present a determination of the $P$-wave $\pi\pi\to\pi\gamma^\star$ transition amplitude from lattice quantum chromodynamics. Matrix elements of the vector current in a finite-volume are extracted from three-point correlation functions, and from these we determine the infinite-volume amplitude using a generalization of the Lellouch-L\"uscher formalism. We determine the amplitude for a range of discrete values of the $\pi\pi$ energy and virtuality of the photon, and observe the expected dynamical enhancement due to the $\rho$ resonance. Describing the energy dependence of the amplitude, we are able to analytically continue into the complex energy plane and from the residue at the $\rho$ pole extract the $\rho\to \pi \gamma^\star$ transition form factor. This calculation, at $m_\pi\approx 400$ MeV, is the first to determine the form factor of an unstable hadron within a first principles approach to QCD.Comment: 20 pages, 16 figures, 3 table

A Calibrated Method of Massage Therapy Decreases Systolic Blood Pressure Concomitant With Changes in Heart Rate Variability in Male Rats.

ObjectiveThe purpose of this study was to develop a method for applying calibrated manual massage pressures by using commonly available, inexpensive sphygmomanometer parts and validate the use of this approach as a quantitative method of applying massage therapy to rodents.MethodsMassage pressures were monitored by using a modified neonatal blood pressure (BP) cuff attached to an aneroid gauge. Lightly anesthetized rats were stroked on the ventral abdomen for 5 minutes at pressures of 20 mm Hg and 40 mm Hg. Blood pressure was monitored noninvasively for 20 minutes following massage therapy at 5-minute intervals. Interexaminer reliability was assessed by applying 20 mm Hg and 40 mm Hg pressures to a digital scale in the presence or absence of the pressure gauge.ResultsWith the use of this method, we observed good interexaminer reliability, with intraclass coefficients of 0.989 versus 0.624 in blinded controls. In Long-Evans rats, systolic BP dropped by an average of 9.86% ± 0.27% following application of 40 mm Hg massage pressure. Similar effects were seen following 20 mm Hg pressure (6.52% ± 1.7%), although latency to effect was greater than at 40 mm Hg. Sprague-Dawley rats behaved similarly to Long-Evans rats. Low-frequency/high-frequency ratio, a widely-used index of autonomic tone in cardiovascular regulation, showed a significant increase within 5 minutes after 40 mm Hg massage pressure was applied.ConclusionsThe calibrated massage method was shown to be a reproducible method for applying massage pressures in rodents and lowering BP

Solid-Solid Interfacial Contact of Tubing Walls Drives Therapeutic Protein Aggregation During Peristaltic Pumping

Peristaltic pumping during bioprocessing can cause therapeutic protein loss and aggregation during use. Due to the complexity of this apparatus, root-cause mechanisms behind protein loss have been long sought. We have developed new methodologies isolating various peristaltic pump mechanisms to determine their effect on monomer loss. Closed-loops of peristaltic tubing were used to investigate the effects of peristaltic pump parameters on temperature and monomer loss, whilst two mechanism isolation methodologies are used to isolate occlusion and lateral expansion-relaxation of peristaltic tubing. Heat generated during peristaltic pumping can cause heat-induced monomer loss and the extent of heat gain is dependent on pump speed and tubing type. Peristaltic pump speed was inversely related to the rate of monomer loss whereby reducing speed 2.0-fold increased loss rates by 2.0- to 5.0-fold. Occlusion is a parameter that describes the amount of tubing compression during pumping. Varying this to start the contacting of inner tubing walls is a threshold that caused an immediate 20-30% additional monomer loss and turbidity increase. During occlusion, expansion-relaxation of solid-liquid interfaces and solid-solid interface contact of tubing walls can occur simultaneously. Using two mechanisms isolation methods, the latter mechanism was found to be most destructive and a function of solid-solid contact area, where increasing the contact area 2.0-fold increased monomer loss by 1.6-fold. We establish that a form of solid-solid contact mechanism whereby the contact solid interfaces disrupt adsorbed protein films is the root-cause behind monomer loss and protein aggregation during peristaltic pumping

Pressure-dependent regulation of Ca2+ signaling in the vascular endothelium

The endothelium is an interconnected network upon which hemodynamic mechanical forces act to control vascular tone and remodeling in disease. Ca2+ signaling is central to the endothelium's mechanotransduction and networked activity. However, challenges in imaging Ca2+ in large numbers of endothelial cells under conditions that preserve the intact physical configuration of pressurized arteries have limited progress in understanding how pressure-dependent mechanical forces alter networked Ca2+ signaling. We developed a miniature wide-field, gradient-index (GRIN) optical probe designed to fit inside an intact pressurized artery which permitted Ca2+ signals to be imaged with subcellular resolution in a large number (∼200) of naturally-connected endothelial cells at various pressures. Chemical (acetylcholine) activation triggered spatiotemporally-complex, propagating IP3-mediated Ca2+ waves that originated in clusters of cells and progressed from there across the endothelium. Mechanical stimulation of the artery, by increased intraluminal pressure, flattened the endothelial cells and suppressed IP3-mediated Ca2+ signals in all activated cells. By computationally modeling Ca2+ release, endothelial shape changes were shown to alter the geometry of the Ca2+ diffusive environment near IP3 receptor microdomains to limit IP3-mediated Ca2+ signals as pressure increased. Changes in cell shape produce a geometric, microdomain-regulation of IP3-mediated Ca2+ signaling to explain macroscopic pressure-dependent, endothelial-mechanosensing without the need for a conventional mechanoreceptor. The suppression of IP3-mediated Ca2+ signaling may explain the decrease in endothelial activity as pressure increases. GRIN imaging provides a convenient method that provides access to hundreds of endothelial cells in intact arteries in physiological configuration