Boiling Histotripsy Ablation of Renal Cell Carcinoma in the Eker Rat Promotes a Systemic Inflammatory Response

Boiling histotripsy (BH) is an experimental focused ultrasound technique that produces non-thermal mechanical ablation. We evaluated the feasibility, short-term histologic effects and the resulting acute inflammatory response to BH ablation of renal cell carcinoma (RCC) in the Eker rat. Genotyped Eker rats were monitored for de novo RCCs with serial ultrasound (US) imaging. When tumors were ≥8 mm, rats underwent ultrasound-guided extracorporeal ablation of the tumor with BH, a pulsed focused US technique that produces non-thermal mechanical ablation of targeted tissues, or a sham US procedure. Treatments targeted approximately 50% of the largest RCC with a margin of normal kidney. BH treated rats were euthanized at 1 (n?=?4) or 48 (n?=?4) h, and sham patients (n?=?4) at 48 h. Circulating plasma cytokine levels were assessed with multiplex assays before and at 0.25, 1, 4, 24 and 48 h following treatment. Kidneys were collected and processed for histologic assessment, immunohistochemistry and intrarenal cytokine concentration measurements. For statistical analysis Student's t-test was used. US-guided BH treatment was successful in all animals, producing hypoechoic regions within the targeted volume consistent with BH treatment effect. Grossly, regions of homogenized tissue were apparent with evidence of focal intra-parenchymal hemorrhage. Histologically, BH produced a sharply demarcated region of homogenized tumor and non-tumor tissue containing acellular debris. BH treatment was associated with significantly increased relative concentration of plasma TNF versus sham treatment (p < 0.05) and transient elevations in high-mobility group box 1 (HMGB1), IL-10 and IL-6 consistent with acute inflammatory response to trauma. Intrarenal cytokine concentrations followed the same trend. At 48 h, enhanced infiltration of CD8⁺ T cells was observed by immunohistochemistry in both the treated and un-treated contralateral RCC/kidneys in BH-treated animals versus sham treatment. BH treatment was well tolerated with transient gross hematuria and a perinephric hematoma developing in one subject each. The study demonstrates the feasibility of BH ablation of de novo RCC and suggests activation of the acute inflammatory cascade following treatment that appears to stimulate CD8+ T cell infiltration of both treated and untreated tumors. Longer duration chronic studies are ongoing to characterize the longevity and robustness of this response.     

游离PSA/总PSA<0.16在总PSA≤4ng/ml的前列腺癌患者中的前列腺穿刺指导价值

目的探讨游离PSA/总PSA(f/t)0.16对于总PSA≤4ng/ml的前列腺癌(PCa)患者是否具有指导前列腺穿刺的意义。方法回顾本院于2008年至2014年收治的总PSA≤4ng/ml的PCa患者的病历资料,分为4组,A组:f/t0.16;B组:f/t0.16且MRI或DRE阳性;C组:f/t≥0.16;D组:f/t≥0.16且MRI或DRE阳性。统计各组穿刺者人数及穿刺阳性率。结果共计73人进入本研究,A组32人,穿刺阳性率23.5%;B组9人,穿刺阳性率33.3%;C组41人,穿刺阳性率11.5%;D组12人,穿刺阳性率16.7%。A组与B组,A组与C组,B组与D组之间穿刺阳性率差别有统计学意义(P0.05)。C组与D组穿刺阳性率差别无统计学意义(P0.05)。结论对于总PSA≤4ng/ml的PCa患者,f/t0.16可以作为前列腺穿刺的指导指标,联合MRI或DRE检查可以提高前列腺穿刺阳性率。     

Innervation zone locations in 43 superficial muscles: Toward a standardization of electrode positioning

Introduction: We describe the innervation zone (IZ) location in 43 muscles to provide information for appropriate positioning of bipolar electrodes for clinical and research applications. Methods: The IZ was studied in 40 subjects (20 men and 20 women) using multichannel surface electromyography (sEMG). Signal quality was checked visually to identify motor unit action potentials and estimate muscle fiber conduction velocity. Results: Results in 33 muscles were classified as excellent or good, because it was possible to identify an area which is favorable for appropriate positioning of an electrode pair without the need to previously determine the IZ location. Conclusions: Knowledge of IZ location will increase standardization and repeatability of sEMG measures. Muscle Nerve 49 :413–421, 2014     

ROLE of exercise in maintaining the integrity of the neuromuscular junction

Physical activity plays an important role in preventing chronic disease in adults and the elderly. Exercise has beneficial effects on the nervous system, including at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and improves recovery from peripheral nerve injuries, whereas decreased physical activity causes degenerative changes in NMJs. Recent studies have begun to elucidate molecular mechanisms underlying the beneficial effects of exercise. These mechanisms involve Bassoon, neuregulin‐1, peroxisome proliferator–activated receptor gamma coactivator 1α, insulin‐like growth factor‐1, glial cell line–derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of activated T cells c1. For example, NMJ denervation and active zone decreases have been observed in aged NMJs, but these age‐dependent degenerative changes can be ameliorated by exercise. In this review we assess the effects of exercise on the maintenance and regeneration of NMJs and highlight recent insights into the molecular mechanisms underlying these exercise effects. Muscle Nerve 49 :315–324, 2014     

Creating a Rapid Assessment Zone with Limited Emergency Department Capacity Decreases Patients Leaving Without Being Seen: A Quality Improvement Initiative

IntroductionPatients leaving the emergency department before treatment (left without being seen) result in increased risks to patients and loss of revenue to the hospital system. Rapid assessment zones, where patients can be quickly evaluated and treated, have the potential to improve ED throughput and decrease the rates of patients leaving without being seen. We sought to evaluate the impact of a rapid assessment zone on the rate of patients leaving without being seen.MethodsA pre- and post-quality improvement process was performed to examine the impact of implementing a rapid assessment zone process at an urban community hospital emergency department. Through a structured, multidisciplinary approach using the Plan, Do, Check, Act Deming Cycle of process improvement, the triage area was redesigned to include 8 rapid assessment rooms and shifted additional ED staff, including nurses and providers, into this space. Rates of patients who left without being seen, median arrival to provider times, and discharge length of stay between the pre- and postintervention periods were compared using parametric and nonparametric tests when appropriate.ResultsImplementation of the rapid assessment zone occurred February 1, 2021, with 42,115 ED visits eligible for analysis; 20,731 visits before implementation and 21,384 visits after implementation. All metrics improved from the 6 months before intervention to the 6 month after intervention: rate of patients who left without being seen (5.64% vs 2.55%; c² = 258.13; P < .01), median arrival to provider time in minutes (28 vs 11; P < .01), and median discharge length of stay in minutes (205 vs 163; P < .01).DiscussionThrough collaboration and an interdisciplinary team approach, leaders and staff developed and implemented a rapid assessment zone that reduced multiple throughput metrics.     

Development of local connections in ferret somatosensory cortex

Ferrets have become recognized as a useful and interesting model for study of neocortical development. Because of their immaturity at birth, it is possible to study very early events in the ontogeny of the brain. We used living slices of ferret somatosensory cortex to study the formation and development of intrinsic elements within the neocortex. A small number of fixed, hemisected brains injected with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) were also used. The slices were obtained from ferret kits aged postnatal day (P)1 to P62 and maintained in a chamber; each slice received injections of fluorescent-labeled dextrans. The injections were made at different ages in several distinct sites, which included the proliferative ventricular zone, the intervening white matter (or intermediate zone), and different sites of developing cortex, including the deeper cortical plate, which incorporated the subplate in young animals, and more superficial cortical sites, depending on the age of the animal. Several animals also received injections into the ventrobasal thalamus. Injections into young animals (P1–7) produced a dominant radial pattern that extended from the ventricular zone into the cortex. Injections into the ventricular zone labeled many cells that appeared morphologically like radial glia as well as presumptive neurons. Although the predominant pattern was radial, injections in the ventricular zone often produced tangentially oriented cells and horizontally arranged fibers at the outer edge of the proliferative zone. These cells and fibers may provide a substrate for tangential dispersion of neurons within the neocortex. More superficial injections within the slice labeled lines of cells that appeared to be stacked upon one another in a radial pile in the cortex; the cortical plate received very few lateral projections. Data obtained from more mature slices indicated that, although the overall pattern of staining remained radial, the precise character of the pattern changed to include more lateral spread into surrounding cortex, which eventually refined and developed into distinct patches by P28, when the overall cortical architecture appeared adult like. The data involving thalamocortical connections were more limited, but they indicated that the thalamus projects precisely to the somatosensory cortex in a point-to-point fashion from the earliest date studied (P0) and that the ventrobasal nucleus terminates upon the somatosensory cortex in a patchy manner during the early postnatal days of development. This study of the development of the somatosensory cortex confirms the ubiquitous nature of column-like connections throughout the neocortex and provides a novel view of the radial nature of early neocortical maturation. © Wiley-Liss, Inc.     

Fundamental Investigations of Bond Behaviour of High-Strength Micro Steel Fibres in Ultra-High Performance Concrete under Cyclic Tensile Loading

The objective of the contribution is to understand the fatigue bond behaviour of brass-coated high-strength micro steel fibres embedded in ultra-high performance concrete (UHPC). The study contains experimental pullout tests with variating parameters like load amplitude, fibre orientation, and fibre-embedded length. The test results show that fibres are generally pulled out of the concrete under monotonic loading and rupture partly under cyclic tensile loading. The maximum tensile stress per fibre is approximately 1176 N/mm², which is approximately one third of the fibre tensile strength (3576 N/mm²). The load-displacement curves under monotonic loading were transformed into a bond stress-slip relationship, which includes the effect of fibre orientation. The highest bond stress occurs for an orientation of 30° by approximately 10 N/mm². Under cyclic loading, no rupture occurs for fibres with an orientation of 90° within 100,000 load changes. Established S/N-curves of 30°- and 45°-inclined fibres do not show fatigue resistance of more than 1,000,000 load cycles for each tested load amplitude. For the simulation of fibre pullout tests with three-dimensional FEM, a model was developed that describes the local debonding between micro steel fibre and the UHPC-matrix and captures the elastic and inelastic stress-deformation behaviour of the interface using plasticity theory and a damage formulation. The model for the bond zone includes transverse pressure-independent composite mechanisms, such as adhesion and micro-interlocking and transverse pressure-induced static and sliding friction. This allows one to represent the interaction of the coupled structures with the bond zone. The progressive cracking in the contact zone and associated effects on the fibre load-bearing capacity are the decisive factors concerning the failure of the bond zone. With the developed model, it is possible to make detailed statements regarding the stress-deformation state along the fibre length. The fatigue process of the fibre-matrix bond with respect to cyclic loading is presented and analysed in the paper.