The afterlife of "doing medicine": Birth planning, chronic illness, and regeneration among the Lisu on the China-Myanmar border.

Between the late 1970s and 1990s, many indigenous Lisu people in the Nu River Valley, an Eastern Himalayan region of China bordering Myanmar and Tibet, underwent what they referred to as "doing medicine"-abortions, vasectomies, and tubal ligations-as part of China's Birth Planning Policy. Lisu, who endured these procedures, struggle with strength loss, nervousness, and pain. Government discourses diminish the Lisu experience, arguing that the policy was lenient toward them. Lisu themselves are reticent to share their experiences but have devised new practices to care for those affected. Drawing on long-term ethnographic fieldwork, I argue that these chronic illnesses and accompanying care practices constitute everyday forms of remembering through which Lisu give shape to their experiences of cultural loss under Chinese colonization while generating new social relationships. This analysis sheds light on Indigenous experiences of birth planning in China with broader implications for understanding the bureaucratic violence of medicine.

Sagittal Spinal Alignment in People with Chronic Spinal Cord Injury and Normal Individual: A Comparison Study Using 3D Ultrasound Imaging.

The aim of this study was to compare the sagittal spinal alignment of people with chronic spinal cord injury (SCI) with normal individuals and to determine whether transcutaneous electrical spinal cord stimulation (TSCS) could cause a change in the thoracic kyphosis (TK) and lumbar lordosis (LL) to re-establish normal sagittal spinal alignment. A case series study was conducted, wherein twelve individuals with SCI and ten neurologically intact subjects were scanned using 3D ultrasonography. In addition, three people with SCI having complete tetraplegia participated further to receive a 12-week treatment (TSCS with task-specific rehabilitation) after evaluation of sagittal spinal profile. Pre- and post-assessments were conducted to evaluate the differences in sagittal spinal alignment. The results showed that the TK and LL values for a person with SCI in a dependent seated posture were greater than those of normal subjects for: standing (by TK: 6.8° ± 1.6°; LL: 21.2° ± 1.9°), sitting straight (by TK: 10.0° ± 4.0°; LL: 1.7° ± 2.6°), and relaxed sitting (by TK: 3.9° ± 0.3°; LL: 7.7° ± 1.4°), respectively, indicating an increased risk for spinal deformity. In addition, TK decreased by 10.3° ± 2.3° after the TSCS treatment, showing a reversible change. These results suggest that the TSCS treatment could be used to restore normal sagittal spinal alignment for individuals with chronic SCI.

Improving the percentage of HIV tests offered to patients admitted to an acute hospital trust with community-acquired pneumonia.

Young people and adults diagnosed with an HIV indicator condition should be offered an HIV test (NICE [National Institute of Clinical Excellence] guidance). Community-acquired pneumonia (CAP) is considered to be an HIV indicator condition as it has an undiagnosed HIV prevalence of 0.76%. We observed however, that the offer of HIV testing to patients with radiologically diagnosed CAP remained low even after a senior respiratory physician review. Our aim was to improve the percentage of patients being offered an HIV test with CAP requiring hospital admission across four acute medical wards at Royal Derby Hospital within 12 months. We identified several key steps in the process. These included the identification of CAP, the role of the medical clerking team and the respiratory infections nursing team that manage pneumonia admissions. After collecting baseline data and staff interviews, we conducted seven plan-do-study-act (PDSA) interventions. These included; iterative communication, educational interventions, system changes that involved a direct HIV test offering by our respiratory infection team and the addition of an HIV test to the electronic CAP bundle. Data collected from 177 patients were analysed over a period of one year. The main outcome measure of the project 'Did patients with a diagnosis of CAP on admission have a documented HIV test offered?' improved from 28% during the first cycle of data collection to 76.4% during the final cycle. Patients were more likely to be offered an HIV test if they had no comorbidity compared with those with a diagnosis of asthma or chronic obstructive pulmonary disease. Our most impactful PDSA interventions were the respiratory infection nurses directly offering an HIV test to patients and adding HIV to the electronic ordering CAP bundle. Our quality improvement programme has shown that educational, communication and system changes can help improve the uptake of HIV testing. Education on HIV testing is now part of our induction programme for new doctors and we are using a new CAP bundle to help streamline the request of HIV testing at the first clinician clerking. Our dedicated respiratory infection nursing team also ensures that patients with CAP have a documented offer of an HIV test.

Mal-positioning of dialysis catheter in anomalous left superior pulmonary vein in a patient with acute type a dissection, a case report

Abstract The partial anomalous pulmonary vein drainage is a rare congenital defect. The pulmonary vein drains in to a systemic vein instead of draining in to the left atrium. In this rare birth defect, the right sided pulmonary vein involvement is more prevalent than the left sided pulmonary veins. We present a case where the anomalous left superior pulmonary vein was diagnosed when a renal dialysis catheter (size = 12F x 16cm) was mal-positioned in to the Anomalous left superior pulmonary vein, demonstrating confusing blood results. We describe how a systematic multidisciplinary approach and use of advanced imaging techniques can recognise and deal with this rare clinical dilemma.

Mal-Positioning of Dialysis Catheter in Anomalous Left Superior Pulmonary Vein in a Patient with Acute Type A Dissection, a Case Report.

The partial anomalous pulmonary vein drainage is a rare congenital defect. The pulmonary vein drains in to a systemic vein instead of draining in to the left atrium. In this rare birth defect, the right sided pulmonary vein involvement is more prevalent than the left sided pulmonary veins. We present a case where the anomalous left superior pulmonary vein was diagnosed when a renal dialysis catheter (size = 12F x 16cm) was mal-positioned in to the Anomalous left superior pulmonary vein, demonstrating confusing blood results. We describe how a systematic multidisciplinary approach and use of advanced imaging techniques can recognise and deal with this rare clinical dilemma.

Release of transgenic progranulin from a living hyaline cartilage graft model: An in vitro evaluation on anti-inflammation.

Osteoarthritis (OA) is a prevalent condition that compromises and even jeopardizes the life quality of millions of people. Common symptoms in OA includes joint stiffness and soreness, and they are often associated with inflammations to various extend. Due to the avascular and aneural nature of articular hyaline cartilage, it has limited self-repair capabilities; especially under inflammatory conditions, damages inflicted on cartilage are often irreversible. Hence, treatment approaches focus on anti-inflammation or articular cartilage replacement. In this study, an engineered, dual-functional living hyaline cartilage graft (LhCG), capable of releasing transgenic anti-inflammatory cytokine-progranulin (PGRN) is developed and envisioned to simultaneously fulfil both requirements. The therapeutic functionality of PGRN releasing LhCG is evaluated by co-culturing the constructs with tumor necrosis factor-alpha (TNFα) secreting THP-1 cells to simulate the inflammatory condition in arthritis. Non-transgenic LhCG constructs and non-coculture sample groups were set up as controls. Gene expression and ECM composition changes across samples were assessed to understand the effects of PGRN as well as inflammatory environment on the cartilage graft. Collectively, the results in this study suggest that in situ release of transgenic recombinant PGRN protects LhCG from induced inflammation in vitro; contrastively, in the absence of PGRN, cartilage grafts are at risk of being degraded and mineralized under exposure to TNFα signaling. This shows that cartilage graft itself can be at risk of degradation or calcification when implanted in arthritic microenvironment. Hence, the inflammatory microenvironment has to be considered in cartilage replacement therapy to increase chances of successful joint mobility restoration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2968-2977, 2016.

Use of Interim Scaffolding and Neotissue Development to Produce a Scaffold-Free Living Hyaline Cartilage Graft.

The fabrication of three-dimensional (3D) constructs relies heavily on the use of biomaterial-based scaffolds. These are required as mechanical supports as well as to translate two-dimensional cultures to 3D cultures for clinical applications. Regardless of the choice of scaffold, timely degradation of scaffolds is difficult to achieve and undegraded scaffold material can lead to interference in further tissue development or morphogenesis. In cartilage tissue engineering, hydrogel is the highly preferred scaffold material as it shares many similar characteristics with native cartilaginous matrix. Hence, we employed gelatin microspheres as porogens to create a microcavitary alginate hydrogel as an interim scaffold to facilitate initial chondrocyte 3D culture and to establish a final scaffold-free living hyaline cartilaginous graft (LhCG) for cartilage tissue engineering.

Optimization of chondrocyte isolation and phenotype characterization for cartilage tissue engineering.

Current protocols for chondrocyte isolation are inconsistent, resulting in suboptimal cell yield and compromised cell quality. Thus, there is a need for an improved isolation protocol that is able to give a maximum yield with optimal cell viability while preserving the chondrocyte phenotype. In light of this, we developed an improved isolation protocol based on enzymatic digestion using 0.1% (w/v) collagenase II. Different from existing methods of digesting minced cartilage for a prolonged period (usually 14-16 h), we performed two additional digestions, with a 5- and 3-h interval in between. The results showed that this multiple digestion method was able to yield a total number of cells that are more than a fivefold increase as compared to any of the common isolation protocols. More importantly, a high percentage of the isolated cells remained viable. Furthermore, an evaluation of the effect of additional digestions on chondrocyte phenotype indicated that cells harvested from the second and third digestion showed a comparable or higher proliferative capacity than the first digestion and all the cells expressed chondrocyte-specific markers tested, with cells from the third digestion showing exceptionally high gene expression levels for collagen type II (Col II), aggrecan, and COMP. Additionally, their ability to produce collagen type II as well as their morphology were not affected by the two additional digestions. Taken together, the results suggested that the use of this isolation protocol resulted in a higher cell yield and the quality of the isolated cells was maintained. Hence, we recommend this isolation protocol to be employed for more efficient cell harvesting especially from limited biopsied cartilage tissue samples.

Hepatogenesis of murine induced pluripotent stem cells in 3D micro-cavitary hydrogel system for liver regeneration.

The discovery of induced pluripotent stem cell (iPSC) technology has raised hopes in circumventing the current limitations in cell-based therapies where autologous stem cells could be generated from terminally differentiated somatic cells. Given the relatively short history of iPSC research, most of the studies are scientific exploratory in nature and hence have minimal practical usage. In this study, we aimed to combine existing knowledge on iPSC differentiation with three-dimensional (3D) scaffold platform so as to fabricate implantable constructs for liver regeneration. A micro-cavitary hydrogel (MCG) platform was employed as a continuous system for both colonies and/or EBs formation and differentiation. The advantage of MCG system is that it further enhances nutrient exchange and also permits greater living space for the encapsulated pluripotent stem cells to rapidly grow into colonies and/or EBs compared to typical non-MCG system. Murine iPSCs and embryonic stem cells (ESCs) were encapsulated respectively in alginate MCG system and after culturing for 10 days; colonies/EBs were formed spontaneously. Differentiation conditions were then introduced to direct the cells toward endodermal lineage and subsequently hepatic lineage and maturation. Up-regulation of endoderm markers and hepatic markers was observed in both iPSCs and ESCs suggesting that iPSC as effectively as the ESCs in MCG system. Urea and albumin production were significantly higher compared to monolayer culture, demonstrating the beneficial effects of MCG system. The results from this work provide foundation in understanding of iPSC differentiation in 3D engineered environment and aid in future biomedical research of iPSC technology.

Bioresponsive hydrogel scaffolding systems for 3D constructions in tissue engineering and regenerative medicine.

Among the diversity of scaffolding systems available, hydrogel remains a popular choice for tissue engineering applications. The current state-of-the-art bioresponsive hydrogels demand intricate designs in pursuit of acquiring desired timely responses, such as controlled release of biological factors, changes in mechanical properties and scaffold degradation, at the same rate as the natural extracellular matrix. In this review, a variety of bioresponsive hydrogels are discussed; in particular, bioactive and biodegradable hydrogels that facilitate cellular development and tissue morphogenesis are highlighted. Bioactive hydrogels are designed to deliver biomolecules such as cell-adhesive moieties and instructive ligands at close proximity to the cell for better uptake or exposure. Biodegradable hydrogels provide transient scaffolding support for therapeutic cell settlement while gradually degrading in response to physical or enzymatic stimuli. In addition, biomechanical stimuli from hydrogels can induce mutual constructive responses on cells and, hence, will also be covered in this review.

A temperature-cured dissolvable gelatin microsphere-based cell carrier for chondrocyte delivery in a hydrogel scaffolding system.

In this study, a novel therapeutic cell delivery methodology in the form of hydrogel encapsulating cell-laden microspheres was developed and investigated. As a model cell for cartilage tissue engineering, chondrocytes were successfully encapsulated in gelatin-based microspheres (mostly of diameter 50-100 µm, centred at 75-100 µm) with high cell viability during the formation of microspheres via a water-in-oil single emulsion process under a low temperature without any chemical treatment. These cell-laden microspheres were then encapsulated in alginate-based hydrogel constructs. By elevating the temperature to 37°C, the cell-laden microspheres were completely dissolved within 2 days, resulting in the same number of same-sized spherical cavities in hydrogel bulk, along with which the encapsulated cells were released from the microspheres and suspended inside the cavities to be cultivated for further development. In this cell delivery system, the microspheres played a dual role as both removable cell vehicles and porogens for creation of the intra-hydrogel cavities, in which the delivered cells were provided with both free living spaces and a better permeable environment. This temperature-cured dissolvable gelatin microsphere-based cell carrier (tDGMC) associating with cell-laden hydrogel scaffold was attempted and evaluated through WST-1, quantitative polymerase chain reaction, biochemical assays and various immunohistochemistry and histology stains. The results indicate that tDGMC technology can facilitate the delivery of chondrocytes, as a non-anchorage-dependent therapeutic cell, with significantly greater efficiency.

Formation of model hepatocellular aggregates in a hydrogel scaffold using degradable genipin crosslinked gelatin microspheres as cell carriers.

Primary hepatocyte is probably the preferred cell for cell therapy in liver regeneration. However, its non-ideal proliferation capacity and rapid loss of phenotype during 2D culture compromises the quality and quantity of the transplanted hepatocytes, resulting in variable success rates of this treatment. Many studies have shown that the formation of 3D hepatocellular spheroids aids in the maintenance of liver-specific functions in hepatocytes. However, many of the methodologies employed require a sophisticated set-up or specialized equipment which makes it uneconomical to scale up for clinical applications. In this study, we have developed dual-functioning genipin crosslinked gelatin microspheres that serve as cell carriers as well as porogens for delivering the model cells and also for creating cavities. The cells were first seeded onto genipin crosslinked gelatin microspheres for attachment, followed by encapsulation in alginate hydrogel. Collagenase, MMP-9, was introduced either in the culture media or mixed with alginate precursor solution to allow microsphere degradation for creating cavities within the gel bulk. Accordingly, the cells proliferate within the cavities, forming hepatocellular aggregates while the alginate hydrogel serves as a confinement, restricting the size and the shape of the aggregates to the size of the cavities. In addition, the final hepatocellular aggregates could be harvested from the system by removing the alginate hydrogel via citrate treatment. Therefore, this versatile platform not only has the advantage of injectability and simplicity, the cellular aggregates generated are in a controlled size and shape and can be extracted from the system.

Inducing ossification in an engineered 3D scaffold-free living cartilage template.

Large and complex bone defects or voids cannot rely on natural bone healing process for recovery. They require natural or engineered grafts to facilitate osteo-progenitor cell recruitment and development. In this study, we have employed an in vitro macro-sized 3D cell-based platform for investigation and application of osteogenesis. The model is based on a porous construct made of engineered living cartilaginous tissue named living hyaline cartilaginous graft (LhCG). It is scaffold-free and is solely made up of living chondrocytes and their extra cellular matrix (ECM). To evaluate the efficiency of LhCG as a viable platform for bone formation, osteoblast and human mesenchymal stem cell (hMSC) were seeded respectively into LhCG constructs, establishing a co-culture system consisting of osteo-progenitors and chondrocytes. The results showed that LhCG could support both osteoblast and hMSC maturation and differentiation to the osteogenic lineage respectively. Successful osteogenesis is also observed after subcutaneous implantation in nude mice model suggesting that bone formation could be achieved both in vitro and in vivo. Additionally, with exposure to osteogenic medium, LhCG construct without any further cell seeding expressed similar levels of osteogenic phenotype markers as the ones with hMSC seeded on. It suggests the existence of an osteoprogenitor sub-population residing within LhCG chondrocytes. Hence, it is demonstrated that LhCG, as a cartilage template, could serve as a dynamic platform to support osteogenesis and its intrinsic phenotypic flexibility may also permit a wide range of applications for stem cell research and processing.

Writing direction affects how people map space onto time.

What determines which spatial axis people use to represent time? We investigate effects of writing direction. English, like Mandarin Chinese in mainland China, is written left to right and then top to bottom. But in Taiwan, characters are written predominantly top to bottom and then right to left. Because being a fluent reader-writer entails thousands of hours of experience with eye and hand movement in the direction dictated by one's writing system, it could be that writing system direction affects the axis used to represent time in terms of space. In a behavioral experiment, we had native speakers of English, Mandarin Chinese from mainland China, and Mandarin Chinese from Taiwan place sets of cards in temporal order. These cards depicted stages of development of plants and animals, for instance: tadpole, froglet, frog. Results showed that English speakers always represented time as moving from left to right (LR). Mainland Chinese participants trended in the same direction, but a small portion laid the cards out from top to bottom. Taiwanese participants were just as likely to depict time as moving from LR as from top to bottom, with a large minority depicting it as moving from right to left. Native writing system affects how people represent time spatially.

Cytocompatibility study of a natural biomaterial crosslinker--Genipin with therapeutic model cells.

Genipin has been widely used as a natural crosslinker to substitute chemical crosslinkers such as glutaraldehyde to crosslink various biomaterials like gelatin, collagen, and chitosan. However, there are contradicting views on the cytotoxicity and safety of genipin in tissue engineering. Therefore in this study, we aimed to evaluate the toxicity of genipin on skeletal tissues cells-osteoblasts and chondrocytes as they are also representatives of typical anchorage-dependent cells (ADCs) and nontypical ADCs. Results suggest that genipin toxicity is dose dependent and acute but not time dependent on both osteoblasts and chondrocytes. In particular, chondrocytes exhibit substantial alterations in the gene expression when exposed to Maximum nontoxic concentration (MaxNC) of genipin but there were no significant changes in the genes tested in osteoblasts. Since osteoblasts are typical ADCs, cellular focal adhesion assessment was carried out with F-actin being more contracted and unorganized when exposed to minimum toxic concentration (MinTC) of genipin. The mechanisms involved in cell deaths in both cell types are believed to be similar and hence using osteoblast as the model, cells were stained positive for Annexin-V and Reactive oxygen species (ROS) level were elevated at MinTC of genipin. Collectively, genipin induced cell apoptosis via ROS production, and apparently, gene expressions could also be altered at MaxNC. For this reason, we recommend the dose of genipin to be controlled within 0.5 mM.

Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine.

INTRODUCTION: Stromal cell-derived factor-1α (SDF-1) is a chemokine that plays a major role in cell trafficking and homing of CD34(+) stem cells. Studies employing SDF-1/CXCR4 have demonstrated its therapeutic potential in tissue engineering. During injury, cells from the injured organ highly express SDF-1, which causes an elevation of localized SDF-1 levels. This leads to recruitment and retention of circulating CD34(+) progenitor cells at the injury site via chemotactic attraction toward a gradient of SDF-1. The general approaches for SDF-1 introduction in tissue engineering are direct protein incorporation into scaffolds and transplantation of SDF-1-overexpressing cells and both methods are successful in improving the regeneration of the damaged tissue/organ. AREAS COVERED: The mechanisms of SDF-1-mediated homing via CXCR4 receptor and the success of SDF-1-based medical applications in mesenchymal stem cell (MSC) homing as well as areas such as therapeutic angiogenesis, wound healing and neuronal and liver regeneration. EXPERT OPINION: Current SDF-1 delivery designs and platforms hold much room for improvement. Regardless of the different techniques of SDF-1 introduction, they have proved to be effective in recruitment of various stem/progenitor cells. The pursuit of SDF-1-related regenerative medicine has already begun. It is thus conceivable that its usage in the clinical setting will be a reality in the near future.

Genipin-crosslinked microcarriers mediating hepatocellular aggregates formation and functionalities.

In engineered regenerative medicine, various types of scaffolds have been customized to pursue the optimal environment for different types of therapeutic cells. In liver therapeutic research, hepatocytes require attachment to solid anchors for survival and proliferation before they could grow into cellular aggregates with enhanced functionalities. Among the various biomaterials scaffolds and vehicles, microspherical cell carriers are suited to these requirements. Individual spheres may provide two-dimensional (2D) cell-affinitive surfaces for cell adhesion and spreading; whereas multiple microcarriers may form three-dimensional (3D) matrices with inter-spherical space for cell expansion and multicellular aggregation. In this study, we culture human liver carcinoma cell line (HepG2) cells on genipin-crosslinked gelatin microspheres of two different sizes. Results suggest that both microcarriers support cell adhesion, proliferation, and spontaneous formation of hepatocellular aggregates, among which the spheres with bigger size (200-300 µm) seem more favorable than the smaller ones in terms of aggregate formation and liver specific functionalities. These findings suggest that the genipin-crosslinked microcarrier is a competent vehicle for liver cell delivery.

Body part representations in verbal semantics.

Embodied theories of language propose that word meaning is inextricably tied to-grounded in-mental representations of perceptual, motor, and affective experiences of the world. The four experiments described in this article demonstrate that accessing the meanings of action verbs like smile, punch, and kick requires language understanders to activate modality-specific cognitive representations responsible for performing and perceiving those same actions. The main task used is a word-image matching task, where participants see an action verb and an image depicting an action. Their task is to decide as quickly as possible whether the verb and the image depict the same action. Of critical interest is participants' behavior when the verb and image do not match, in which case the two actions can use the same effector or different effectors. In Experiment 1, we found that participants took significantly longer to reject a verb-image pair when the actions depicted by the image and denoted by the verb used the same effector than when they used different effectors. Experiment 2 yielded the same result when the order of presentation was reversed, replicating the effect in Cantonese. Experiment 3 replicated the effect in English with a verb-verb near-synonym task, and in Experiment 4, we once again replicated the effect with learners of English as a second language. This robust interference effect, whereby a shared effector slows discrimination, shows that language understanders activate effector-specific neurocognitive representations during both picture perception and action word understanding.

Microcavitary hydrogel-mediating phase transfer cell culture for cartilage tissue engineering.

Hydrogels have been widely used as cell-laden vehicles for therapeutic transplantation in regenerative medicine. Although the advantages of biocompatibility and injectability for in situ grafting have made hydrogel a superior candidate in tissue engineering, there remain challenges in long-term efficacy of tissue development using hydrogel, especially when more sophisticated applications are demanded. The major bottleneck lies in environmental constraints for neo-tissue generation in the gel bulk such as proliferation of encapsulated cells (colonies) per se and also accommodation of their endogenously produced extracellular matrices. In this study, we endeavor to develop an innovative tissue engineering system to overcome these drawbacks through a novel microcavitary hydrogel (MCG)-based scaffolding technology and a novel phase transfer cell culture (PTCC) strategy to enable phenotypically bona fide neo-tissue formation in an injectable artificial graft. For this purpose, microspherical cavities are created in cell-encapsulating hydrogel bulk via a retarded dissolution of coencapsulated gelatin microspheres. Based on proliferation and affinity selection, the encapsulated cell colonies adjacent to the gel-cavity interface will spontaneously outgrow the hydrogel phase and sprout into cavities, enabling neo-tissue islets to fill up the voids and further expand throughout the whole system for full tissue regeneration. The design of MCG-PTCC strategy was elicited from an observation of a spontaneous dynamic outgrowth of chondrocytes from the edge of a cell-laden hydrogel construct over prolonged cultivation--a phenomenon named edge flourish. This MCG-PTCC strategy potentially introduce a new application to hydrogels in the field of regenerative medicine through elevation of its role as a cell vehicle to a three-dimensional transplantable growth-guiding platform for further development of newly generated tissues that better fulfill the demanding criteria of scaffolds in therapeutic tissue regeneration.

Magnetic-based purification system with simultaneous sample washing and concentration.

Simultaneous washing and concentration of magnetic microparticles was demonstrated using a rotational magnetic system under a continuous-flow condition. The rotation of periodically arranged permanent magnets close to a fluidic channel carrying a suspension of magnetic particles allows the trapping and releasing of particles along the fluidic channel in a periodic manner. Each trapping and releasing event resembles one washing cycle in conventional biological assays. Concentration efficiencies of 99.75 +/- 0.083% at a flow rate of 200 microl/min and 88.10 +/- 3.17% at a flow rate of 1,000 microl/min and a purification efficiency of 99.10 +/- 4.3% at a flow rate of 900 microl/min were achieved.