Excellent Clinical Outcomes From a National Donation‐After‐Determination‐of‐Cardiac‐Death Lung Transplant Collaborative

Donation‐after‐Determination‐of‐Cardiac‐Death (DDCD) donor lungs can potentially increase the pool of lungs available for Lung Transplantation (LTx). This paper presents the 5‐year results for Maastricht category III DDCD LTx undertaken by the multicenter Australian National DDCD LTx Collaborative. The Collaborative was developed to facilitate interaction with the Australian Organ Donation Authority, standardization of definitions, guidelines, education and audit processes. Between 2006 and 2011 there were 174 actual DDCD category III donors (with an additional 37 potentially suitable donors who did not arrest in the mandated 90 min postwithdrawal window), of whom 71 donated lungs for 70 bilateral LTx and two single LTx. In 2010 this equated to an “extra” 28% of donors utilized for LTx. Withdrawal to pulmonary arterial flush was a mean of 35.2 ± 4.0 min (range 18–89). At 24 h, the incidence of grade 3 primary graft dysfunction was 8.5%[median PaO₂/FiO₂ ratio 315 (range 50–507)]. Overall the incidence of grade 3 chronic rejections was 5%. One‐ and 5‐year actuarial survival was 97% and 90%, versus 90% and 61%, respectively, for 503 contemporaneous brain‐dead donor lung transplants. Category III DDCD LTx therefore provides a significant, practical, additional quality source of transplantable lungs.     

Evaluation of Hyphecan (1‐4,2‐acetamide‐deoxy‐B‐D‐glucan polymer) on wound healing in a rodent model

Objective: To evaluate the effect of an artificial skin Hyphecan (1‐4,2‐acetamide‐deoxy‐B ‐D ‐glucan polymer) on wound healing in a rodent model. Materials and Method: The prospective study was conducted at a basic science laboratory at a tertiary teaching hospital. Two 4 cm × 4 cm full‐thickness wounds were created on the dorsal surface of 10 Spraque–Dawley rats and covered with Hyphecan and Kaltostat, respectively. Wounds were examined and measured on days 4, 10, 21 and 28, and would continue after day 28 until healed up completely. Punch biopsies (3 mm) were taken on days 4, 10 and 28 for histological examination of the response of healing and repair. Results: Despite the fact that the wound healing rate was similar for both groups on days 4, 10, 21 and 28, the average healing time for the Hyphecan group (29.1 ± 1.7 days) was significantly shorter statistically (P = 0.03) than the Kaltostat group (30.7 ± 2.8 days). Conversely, the marked healing response elicited by Hyphecan on day 4 persisted on days 10 and 28 in contrast to Kaltostat, which had only a mild degree of healing response on days 10 and 28. The study suggests that wounds treated by Hyphecan heal faster than Kaltostat. Conclusion: The findings provide basic scientific evidence supporting the clinical use of Hyphecan in different wounds and might also reduce the cost of wound management as Hyphecan is cheaper than Kaltostat and requires a shorter treatment time.      

Investigation of High‐Speed Erythrocyte Flow and Erythrocyte‐Wall Impact in a Lab‐on‐a‐Chip

To better understand erythrocyte high‐speed motion, collision characteristics, and collision‐induced hemolysis probability in rotary blood pumps, a visual experimental investigation of high‐speed erythrocyte flow and erythrocyte‐wall collision in a lab‐on‐a‐chip was performed. The erythrocyte suspension was driven by a microsyringe pump connected to the microchip, and the erythrocyte flow and erythrocyte‐wall impact process were observed and imaged by an optical microscope and a high‐speed camera. Two types of microchips with different impact surfaces (flat and curved) were employed. The motion and deformation features before and after collision were studied in detail. The results show that erythrocytes not only move along the flow direction in the flow plane but also rotate and roll in three‐dimensional space. Erythrocytes keep discoid shape during the movement in the straight channel, but their deformations during collision are mainly classified into two types: erythrocyte structure is still stable and the erythrocyte performance can be ensured to a certain extent in the TypeA deformation, while the TypeB deformation makes the membrane more likely to fracture on the stretched side, increasing the probability of hemolysis. Furthermore, the movements and deformations of the erythrocytes after collision are analyzed and classified into two types: bouncing and slipping. Moreover, a simulation method for the flow in microchip was performed and validated through a comparison of the streamlines and experimental erythrocytes tracks, which can be further employed to predict the high‐speed blood flow, associated with collision process in mechanical blood pump.     

Manipulator‐driven selection of semi‐active MR‐visible markers

Background

A method for the identification of semi‐active fiducial magnetic resonance (MR) markers is presented based on selectively optically tuning and detuning them.

Methods

Four inductively coupled solenoid coils with photoresistors were connected to light sources. A microcontroller timed the optical tuning/detuning of coils and image collection. The markers were tested on an MR manipulator linking the microcontroller to the manipulator control to visibly select the marker subset according to the actuated joint.

Results

In closed‐loop control, the average and maximum were 0.76° ± 0.41° and 1.18° errors for a rotational joint, and 0.87 mm ± 0.26 mm and 1.13 mm for the prismatic joint.

Conclusions

This technique is suitable for MR‐compatible actuated devices that use semi‐active MR‐compatible markers.     

Enhanced healing of goat femur‐defect using BMP7 gene‐modified BMSCs and load‐bearing tissue‐engineered bone

Segmental defect regeneration is still a clinical challenge. In this study, we investigated the feasibility of bone marrow stromal cells (BMSCs) infected with adenoviral vector containing the bone morphogenetic protein 7 gene (AdBMP7) and load‐bearing to enhance bone regeneration in a critically sized femoral defect in the goat model. The defects were implanted with AdBMP7‐infected BMSCs/coral (BMP7 group) or noninfected BMSCs/coral (control group), respectively, stabilized with an internal fixation rod and interlocking nails. Bridging of the segmental defects was evaluated by radiographs monthly, and confirmed by biomechanical tests. Much callus was found in the BMP7 group, and nails were taken off after 3 months of implantation, indicating that regenerated bone in the defect can be remodeled by load‐bearing, whereas after 6 months in control group. After load‐bearing, it is about 5 months; the mechanical property of newly formed bone in the BMP7 group was restored, but 8 months in control group. Our data suggested that the BMP7 gene‐modified BMSCs and load‐bearing can promote bone regeneration in segmental defects. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:412–418, 2010     

Role of Toll‐like receptor 4 signaling in cutaneous chronic graft‐versus‐host disease

Cutaneous damage is one of the characterized manifestations in chronic graft‐versus‐host disease (cGVHD). When local effective immunity in the skin is altered to a dysimmune reaction, cutaneous injuries occur. Toll‐like receptor 4 signaling is regarded as a central mediator of inflammation and organ injury. In this study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous cGVHD was markedly increased compared with that from non‐GVHD patients and healthy controls. In addition, NF‐κB expression, TLR4 downstream signaling, and TLR4‐mediated cytokines, including IL‐6 and ICAM‐1, were upregulated. Moreover, ICAM‐1 was widely distributed in skin biopsies from patients with cutaneous cGVHD. We also found that LPS induced TLR4‐mediated NF‐κB activation and IL‐6 and ICAM‐1 secretion in human fibroblasts in vitro. Thus, TLR4, NF‐κB, IL‐6, and ICAM‐1 contribute to the inflammatory response that occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for cutaneous cGVHD therapy.     

Epidemiological Patterns of Foot‐and‐Mouth Disease Worldwide

Foot‐and‐Mouth Disease (FMD) is a clinical syndrome in animals due to FMD virus that exists in seven serotypes, whereby recovery from one sero‐type does not confer immunity against the other six. So when considering intervention strategies in endemic settings, it is important to take account of the characteristics of the different serotypes in different ecological systems. FMD serotypes are not uniformly distributed in the regions of the world where the disease still occurs. For example, the cumulative incidence of FMD serotypes show that six of the seven serotypes of FMD (O, A, C, SAT‐1, SAT‐2, SAT‐3) have occurred in Africa, while Asia contends with four sero‐types (O, A, C, Asia‐1), and South America with only three (O, A, C). Periodically there have been incursions of Types SAT‐1 and SAT‐2 from Africa into the Middle East. This paper describes the global dynamics for the seven sero‐types and attempts to define FMD epidemiological clusters in the different regions of the world. These have been described on a continent by continent basis. The review has reaffirmed that the movement of infected animals is the most important factor in the spread of FMD within the endemically infected regions. It also shows that the eco‐system based approach for defining the epidemiological patterns of FMD in endemic, which was originally described in South America, can apply readily to other parts of the world. It is proposed that any coordinated regional or global strategy for FMD control should be based on a sound epidemiological assessment of the incidence and distribution of FMD, identifying risk sources as either primary or secondary endemic eco‐systems.     

Dynamical analysis of dislocation‐associated factors in total hip replacements by hardware‐in‐the‐loop simulation

Since dislocation of total hip replacements (THR) remains a clinical problem, its mechanisms are still in the focus of research. Previous studies ignored the impact of soft tissue structures and dynamic processes or relied on simplified joint contact mechanics, thus, hindered a thorough understanding. Therefore, the purpose of the present study was to use hardware‐in‐the‐loop (HiL) simulation to analyze systematically the impact of varying implant positions and designs as well as gluteal and posterior muscle function on THR instability under physiological‐like loading conditions during dynamic movements. A musculoskeletal multibody model emulated the in situ environment of the lower extremity during deep sit‐to‐stand with femoral adduction maneuver while a six‐axis robot moved and loaded a THR accordingly to feed physical measurements back to the multibody model. Commercial THRs with hard‐soft bearings were used in the simulation with three different head diameters (28, 36, 44 mm) and two offsets (M, XL). Cup inclination of 45°, cup anteversion of 20°, and stem anteversion of 10° revealed to be outstandingly robust against any instability‐related parameter variation. For the flexion motion, higher combined anteversion angles of cup and stem seemed generally favorable. Total hip instability was either deferred or even avoided even in the presence of higher cup inclination. Larger head diameters (>36 mm) and femoral head offsets (8 mm) deferred occurrence of prosthetic and bone impingement associated with increasing resisting torques. In summary, implant positioning had a much higher impact on total hip stability than gluteal insufficiency and impaired muscle function. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2557–2566, 2017.

     

Effects of Nano‐hydroxyapatite/Poly(DL‐lactic‐co‐glycolic acid) Microsphere‐Based Composite Scaffolds on Repair of Bone Defects: Evaluating the Role of Nano‐hydroxyapatite Content

The aim of the current study was to prepare microsphere‐based composite scaffolds made of nano‐hydroxyapatite (nHA)/poly (DL‐lactic‐co‐glycolic acid) (PLGA) at different ratios and evaluate the effects of nHA on the characteristics of scaffolds for tissue engineering application. First, microsphere‐based composite scaffolds made of two ratios of nHA/PLGA (nHA/PLGA = 20/80 and nHA/PLGA = 50/50) were prepared. Then, the effects of nHA on the wettability, mechanical strength, and degradation of scaffolds were investigated. Second, the biocompatibility and osteoinductivity were evaluated and compared by co‐culture of scaffolds with bone marrow stromal stem cells (BMSCs). The results showed that the adhesion, proliferation, and osteogenic differentiation of BMSCs with nHA/PLGA (50/50) were better than those with nHA/PLGA (20/80). Finally, we implanted the scaffolds into femur bone defects in a rabbit model, then the capacity of guiding bone regeneration as well as the in vivo degradation were observed by micro‐CT and histological examinations. After 4 weeks' implantation, there was no significant difference on the repair of bone defects. However, after 8 and 12 weeks' implantation, the nHA/PLGA (20/80) exhibited better bone formation than nHA/PLGA (50/50). These results suggested that a proper concentration of nHA in the nHA/PLGA composite should be taken into account when the composite scaffolds were prepared, which plays an important role in the biocompatibility, degradation rate and osteoconductivity.     

Hamiltonian two‐degrees‐of‐freedom control of chemical reactors

A novel unified approach to two‐degrees‐of‐freedom control is devised and applied to a classical chemical reactor model. The scheme is constructed from the optimal control point of view and along the lines of the Hamiltonian formalism for nonlinear processes. The proposed scheme optimizes both the feedforward and the feedback components of the control variable with respect to the same cost objective. The original Hamiltonian function governs the feedforward dynamics, and its derivatives are part of the gain for the feedback component. The optimal state trajectory is generated online, and is tracked by a combination of deterministic and stochastic optimal tools. The relevant numerical data to manipulate all stages come from a unique off‐line calculation, which provides design information for a whole family of related control problems. This is possible because a new set of PDEs (the variational equations) allow to recover the initial value of the costate variable, and the Hamilton equations can then be solved as an initial‐value problem. Perturbations from the optimal trajectory are abated through an optimal state estimator and a deterministic regulator with a generalized Riccati gain. Both gains are updated online, starting with initial values extracted from the solution to the variational equations. The control strategy is particularly useful in driving nonlinear processes from an equilibrium point to an arbitrary target in a finite‐horizon optimization context. Copyright © 2010 John Wiley & Sons, Ltd.