Search

As international attention continues to focus on large dam projects across Asia, it is worth noting that conflicts over the politics of and environmental changes caused by dams in India are not new. Population dislocation, siltation, disease, floods caused by catastrophic dam failure, raised water tables, high costs and low returns-all of these concerns, and others, can be discussed in the context of reservoir projects ten, one hundred, or even one thousand years old. In this paper, I identify some of the major issues in the political ecology of contemporary dam projects and show how these same issues have played out in southern India over the last thousand years, suggesting that historical attention to the cultural and political context of reservoir construction might help us to understand some aspects of contemporary conflicts.

New advances in collaborative technologies, often grouped under the umbrella term ‘web 2.0’, are changing the opportunity space for organisational collaboration and decision making. Research and development can now be outsourced to external self-organising communities of scientists, new business models rely wholly on content created by end users and customers are increasingly asked for input to the development of new products and services. The way in which many strategic and operational decisions are made, once the sole prevail of executive management, is being challenged by new forms of knowledge, expertise and opinion from non-management employees, and increasingly, from those outside the organisation such as customers, partners and suppliers. The widespread adoption of web 2.0 technologies and their increasing use in the business context, in other words, is creating an inevitable tension between traditional ‘top-down’ strategic decision-making principles and ‘bottom-up’, ad hoc and sometimes unstructured collaborative processes.

Abstract Background The Caribbean region, like other developing regions of the world, faces significant challenges in conducting research, especially in the context of limited resource capacities and capabilities. Further, due to its diverse and multiple island states, research capacity is scattered and unevenly spread within the region. The Caribbean EcoHealth Programme (CEHP) is a research program that is structured to improve the capacity and capability of health professionals in the Caribbean region to respond in integrative and innovative ways to on-going and emerging environmental health challenges by means of multi-sectoral interventions. Methods Core parts of the CEHP’s mission are to (1) conduct collaborative research in areas that the region has identified as critical; (2) build and strengthening integrated approaches to research; and (3) develop and enhance basic research capacity within the Caribbean region. Fundamental to the success of the CEHP’s human and resource development mission has been its use of the Atlantis Mobile Laboratory (AML). The AML has allowed the CEHP program to move throughout the Caribbean and be able to respond to calls for specific research and capacity building opportunities. Results The CEHP’s five main research projects have generated the following results: (1) the Persistent Organic Pollutants (POPs) study has evaluated human exposures to POPs, heavy metals, pesticides, and zoonotic infections; (2) the Burden of Illness (BOI) studies have developed protocols for the testing of foodborne microorganisms, strengthen laboratory analytical capabilities, and determined the prevalence and incidence of food-borne illness; (3) the Rainwater Harvesting (RWH) study has evaluated the microbial and chemical quality of rainwater harvesting systems; (4) the Ecotoxicology Water (ETW) studies have provided much needed data on the quality of recreational and drinking water supplies, and (5) the Food Safety Training Program has developed Diploma and M.Sc Agri-Food Safety and Quality Assurance programmes. Conclusions The CEHP program provides a successful example of how a collaborative instead of researcher driven research agenda can lead to not only the generation of needed information, but also leave within the region where the research has been carried out the capacity and capabilities to continue to do so independent of outside interventions.

The ARC Centre of Excellence in Creative Industries and Innovation (CCi) commissioned two jams –online collaborative events – to discover new ideas for improving outcomes in two important aspects of the Centre’s work.

Abstract Background People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada. Methods Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada. Summary The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada.

Abstract Background At least two million Canadian children meet established criteria for weight management. Due to the adverse health consequences of obesity, most pediatric weight management research has examined the efficacy and effectiveness of interventions to improve lifestyle behaviors, reduce co-morbidities, and enable weight management. However, little information is available on families’ decisions to initiate, continue, and terminate weight management care. This is an important knowledge gap since a substantial number of families fail to initiate care after being referred for weight management while many families who initiate care discontinue it after a brief period of time. This research aims to understand the interplay between individual, family, environmental, and systemic factors that influence families’ decisions regarding the management of pediatric obesity. Methods/Design Individual interviews will be conducted with children and youth with obesity (n = 100) and their parents (n = 100) for a total number of 200 interviews with 100 families. Families will be recruited from four Canadian multi-disciplinary pediatric weight management centers in Vancouver, Edmonton, Hamilton, and Montreal. Participants will be purposefully-sampled into the following groups: (i) Non-Initiators (5 families/site): referred for weight management within the past 6 months and did not follow-up the referral; (ii) Initiators (10 families/site): referred for weight management within the past 6 months and did follow-up the referral with at least one clinic appointment; and (iii) Continuers (10 families/site): participated in a formal weight management intervention within the past 12 months and did continue with follow-up care for at least 6 months. Interviews will be digitally recorded and analyzed using an ecological framework, which will enable a multi-level evaluation of proximal and distal factors that underlie families’ decisions regarding initiation, continuation, and termination of care. Demographic and anthropometric/clinical data will also be collected. Discussion A better understanding of family involvement in pediatric weight management care will help to improve existing health services in this area. Study data will be used in future research to develop a validated survey that clinicians working in pediatric obesity management can use to understand and enhance their own health services delivery.

Abstract Background Motor neurone disease (MND) is a devastating illness which leads to muscle weakness and death, usually within 2-3 years of symptom onset. Respiratory insufficiency is a common cause of morbidity, particularly in later stages of MND and respiratory complications are the leading cause of mortality in MND patients. Non Invasive Ventilation (NIV) is the current standard therapy to manage respiratory insufficiency. Some MND patients however do not tolerate NIV due to a number of issues including mask interface problems and claustrophobia. In those that do tolerate NIV, eventually respiratory muscle weakness will progress to a point at which intermittent/overnight NIV is ineffective. The NeuRx RA/4 Diaphragm Pacing System was originally developed for patients with respiratory insufficiency and diaphragm paralysis secondary to stable high spinal cord injuries. The DiPALS study will assess the effect of diaphragm pacing (DP) when used to treat patients with MND and respiratory insufficiency. Method/Design 108 patients will be recruited to the study at 5 sites in the UK. Patients will be randomised to either receive NIV (current standard care) or receive DP in addition to NIV. Study participants will be required to complete outcome measures at 5 follow up time points (2, 3, 6, 9 and 12 months) plus an additional surgery and 1 week post operative visit for those in the DP group. 12 patients (and their carers) from the DP group will also be asked to complete 2 qualitative interviews. Discussion The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND with respiratory muscle weakness. The project is funded by the National Institute for Health Research, Health Technology Assessment (HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association and the Henry Smith Charity. Trial Registration: Current controlled trials ISRCTN53817913. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

Abstract Background There is a growing recognition that many public health issues are complex and can be best understood by examining the relationship between human health and the health of the ecosystems in which people live. Two approaches, One Health and Ecosystem Approaches to Health (EcoHealth), can help us to better understand these intricate and complex connections, and appear to hold great promise for tackling many modern public health dilemmas. Although both One Health and EcoHealth have garnered recognition from numerous health bodies in Canada and abroad, there is still a need to better understand how these approaches are shaping the practice of public health in Ontario. The purpose of this study was to characterize how public health actors in Ontario are influenced by the holistic principles which underlie One Health and EcoHealth, and to identify important lessons from their experiences. Methods Ten semi-structured interviews were conducted with ten participants from the public health sphere in Ontario. Participants encompassed diverse perspectives including infectious disease, food systems, urban agriculture, and environmental health. Interviews were recorded, transcribed and analyzed using qualitative content analysis to identify major themes and patterns. Results Four major themes emerged from the interviews: the importance of connecting human health with the environment; the role of governance in promoting these ideas; the value of partnerships and collaborations in public health practice; and the challenge of operationalizing holistic approaches to public health. Overall study participants were found to be heavily influenced by concepts couched in EcoHealth and One Health literature, despite a lack of familiarity with these fields. Conclusions Although One Health and EcoHealth are lesser known approaches in the public health sphere, their holistic and systems-based principles were found to influence the thoughts, values and experiences of public health actors interviewed in this study. This study also highlights the critical role of governance and partnerships in facilitating a holistic approach to health. Further research on governance and partnership models, as well as systems-based organizational working practices, is needed to close the gap between One Health and EcoHealth theory and public health practice.

Abstract Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Discussion Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Trial registration Current controlled trials ISRCTN83178718

Abstract Background Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology. Methods In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR. Results No methylation or sequence variation of the MHC2TA promoter pIV was found. Conclusion The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.

Abstract Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.

Study Design: Retrospective observational study., Objective: This study analyzes the epidemiology of pediatric Le Fort fractures and assesses the incidence of concomitant injuries and acute-level hospital course using the largest, national pediatric trauma database to date., Methods: Pediatric midface and Le Fort fractures from 2016-2019 were identified in the National Trauma Data Bank. Descriptive analyses of Le Fort compared to non-Le Fort midface fractures were performed. Multivariable regression assessed whether Le Fort fractures were risk factors for ICU admission, intracranial injury, cervical spine (C-spine) fracture, tracheostomy, and mortality., Results: A total of 1489 patients with Le Fort fractures were identified. There were 520 Le Fort I, 632 Le Fort II, and 609 Le Fort III fractures. Fracture incidence increased with age. Le Fort fractures showed higher rates of concomitant intracranial injury ( P < 0.001), ICU admission ( P < 0.001), C-spine fracture ( P < 0.001), and tracheostomy ( P < 0.001). Incidence of all the above increased with higher-grade Le Fort fractures. Le Fort III fractures had higher rates of mortality than non-Le Fort midface fractures (7.6% vs 3.2%). Multivariable regression showed that all Le Fort patterns were independent risk factors for tracheostomy and ICU admission, but only Le Fort I for C-spine fractures., Conclusions: The incidence of Le Fort fractures appears to increase with age. Higher category Le Fort fractures are associated with greater morbidity., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

A 3-year-old patient sustained a tripartite mandibular fracture, including bilateral condylar fractures with lateral dislocation of the left condyle and symphyseal fracture. Staged lower jaw reconstruction with closed reduction of the laterally dislocated condyle, transfacial pinning between the mandibular angles, MMF using circummandibular wiring and intermaxillary fixation screws was performed., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, or publication of this article., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Currently, there is an increasing trend in women seeking aesthetic flat closure after mastectomy. To date, there is no plastic surgery literature on specific techniques to achieve an aesthetic flat closure after mastectomy. As plastic surgeons, we need to continue to innovate and to iterate new surgical techniques in our reconstructive armamentarium to address the desires of and to optimize the outcomes for our reconstructive breast surgery patients. Herein, we seek to delineate key considerations and employed techniques for reconstructive plastic surgeons performing aesthetic flat closure after mastectomy. Namely, it is crucial to listen to the patient, and to fully understand the patient's concerns, wishes, and particular aesthetic desired. From a technical perspective, the key surgical pearls include completely obliterating the inframammary fold, ensuring the same size and flap thickness bilaterally, appropriately de-fatting medially on the chest wall to allow for a smooth contour, obviating any presence of dog ears medially or laterally with precise tissue excision, and confirming that the incisions are entirely symmetric bilaterally. Intraoperatively, it is important to sit these patients up to assess soft tissue re-draping, and to confirm that there are no dog ears nor any excess tissue that could compromise the perfectly flat aesthetic chest closure. With the increasing demand for flat closures after mastectomy, plastic surgeons need to be keen on employing modified surgical techniques to best optimize the desired aesthetic flat closure reconstructions for these patients, as these reconstructions are not simply linear closures., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Extraction of integral membrane proteins with poly(styrene-co-maleic acid) provides a promising alternative to detergent extraction. A major advantage of extraction using copolymers rather than detergent is the retention of the lipid bilayer around the proteins. Here we report the first functional investigation of the mammalian insulin receptor which was extracted from cell membranes using poly(styrene-co-maleic acid). We found that the copolymer efficiently extracted the insulin receptor from 3T3L1 fibroblast membranes. Surprisingly, activation of the insulin receptor and proximal downstream signalling was detected upon copolymer extraction even in the absence of insulin stimulation. Insulin receptor and IRS1 phosphorylations were above levels measured in the control extracts made with detergents. However, more distal signalling events in the insulin signalling cascade, such as the phosphorylation of Akt were not observed. Following copolymer extraction, in vitro addition of insulin had no further effect on insulin receptor or IRS1 phosphorylation. Therefore, under our experimental conditions, the insulin receptor is not functionally responsive to insulin. This study is the first to investigate receptor tyrosine kinases extracted from mammalian cells using a styrene-maleic acid copolymer and highlights the importance of thorough functional characterisation when using this method of protein extraction., (© 2022. The Author(s).)

Background: Small angle scattering techniques are beginning to be more widely utilised for structural analysis of biological systems. However, applying these techniques to study membrane proteins still remains problematic, due to sample preparation requirements and analysis of the resulting data. The development of styrene-maleic acid co-polymers (SMA) to extract membrane proteins into nanodiscs for further study provides a suitable environment for structural analysis., Methods: We use small angle neutron scattering (SANS) with three different contrasts to determine structural information for two different polymer nanodisc-incorporated proteins, Outer membrane protein F (OmpF) and gramicidin. Ab initio modelling was applied to generate protein/lipid structures from the SANS data. Other complementary structural methodologies, such as DLS, CD and TEM were compared alongside this data with known protein crystal structures., Results: A single-phase model was constructed for gramicidin-containing nanodiscs, which showed dimer formation in the centre of the nanodisc. For OmpF-nanodiscs we were able to construct a multi-phase model, providing structural information on the protein/lipid and polymer components of the sample., Conclusions: Polymer-nanodiscs can provide a suitable platform to investigate certain membrane proteins using SANS, alongside other structural methodologies. However, differences between the published crystal structure and OmpF-nanodiscs were observed, suggesting the nanodisc structure could be altering the folding of the protein., General Significance: Small angle scattering techniques can provide structural information on the protein and polymer nanodisc without requiring crystallisation of the protein. Additional complementary techniques, such as ab initio modelling, can generate alternative models both the protein and nanodisc system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©2021TheAuthors.PublishedbyElsevierB.V.)

Extraction of membrane proteins from biological membranes has traditionally involved detergents. In the past decade, a new technique has been developed, which uses styrene maleic acid (SMA) copolymers to extract membrane proteins into nanodiscs without the requirement of detergents. SMA nanodiscs are compatible with analytical techniques, such as small-angle scattering, NMR spectroscopy, and DLS, and are therefore an attractive medium for membrane protein characterization. While mass spectrometry has also been reported as a technique compatible with copolymer extraction, most studies have focused on lipidomics, which involves solvent extraction of lipids from nanodiscs prior to mass-spectrometry analysis. In this study, mass spectrometry proteomics was used to investigate whether there are qualitative or quantitative differences in the mammalian plasma membrane proteins extracted with SMA compared to a detergent control. For this, cell surface proteins of 3T3L1 fibroblasts were biotinylated and extracted using either SMA or detergent. Following affinity pull-down of biotinylated proteins with NeutrAvidin beads, samples were analyzed by nanoLC-MS. Here, we report for the first time, a global proteomics protocol for detection of a mammalian cell "SMALPome", membrane proteins incorporated into SMA nanodiscs. Removal of SMA from samples prior to processing of samples for mass spectrometry was a crucial step in the protocol. The reported surface SMALPome of 3T3L1 fibroblasts consists of 205 integral membrane proteins. It is apparent that the detergent extraction method used is, in general, quantitatively more efficient at extracting proteins from the plasma membrane than SMA extraction. However, samples prepared following detergent extraction contained a greater proportion of proteins that were considered to be "non-specific" than in samples prepared from SMA extracts. Tantalizingly, it was also observed that proteins detected uniquely or highly preferentially in pull-downs from SMA extracts were primarily multi-spanning membrane proteins. These observations hint at qualitative differences between SMA and detergent extraction that are worthy of further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morrison, Heesom, Edler, Doutch, Price, Koumanov and Whitley.)

Knowing accurate saturated vapor pressures of explosives at ambient conditions is imperative to provide realistic boundaries on available vapor for ultra-trace detection. In quantifying vapor content emanating from low-volatility explosives, we observed discrepancies between the quantity of explosive expected based on literature vapor pressure values and the amount detected near ambient temperatures. Most vapor pressure measurements for low-volatility explosives, such as RDX (1,3,5-trinitro-1,3,5-triazinane) and HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane), have been made at temperatures far exceeding 25 °C and linear extrapolation of these higher temperature trends appears to underestimate vapor pressures near room temperature. Our goal was to measure vapor pressures as a function of temperature closer to ambient conditions. We used saturated RDX and HMX vapor sources at controlled temperatures to produce vapors that were then collected and analyzed via atmospheric flow tube-mass spectrometry (AFT-MS). The parts-per-quadrillion (ppq v ) sensitivity of AFT-MS enabled measurement of RDX vapor pressures at temperatures as low as 7 °C and HMX vapor pressures at temperatures as low as 40 °C for the first time. Furthermore, these vapor pressures were corroborated with analysis of vapor generated by nebulizing low concentration solutions of RDX and HMX. We report updated vapor pressure values for both RDX and HMX. Based on our measurements, the vapor pressure of RDX at 25 °C is 3 ± 1 × 10 -11 atm (i.e., 30 parts per trillion by volume, ppt v ), the vapor pressure of HMX is 1.0 ± 0.6 × 10 -14 atm (10 ppq v ) at 40 °C and, with extrapolation, HMX has a vapor pressure of 1.0 ± 0.6 × 10 -15 atm (1.0 ppq v ) at 25 °C.

Introduction: Resurfacing complex full thickness wounds requires free tissue transfer which creates donor site morbidity. We describe a method to fabricate a skin flap equivalent with a hierarchical microvascular network. Materials & methods: We fabricated a flap of skin-like tissue containing a hierarchical vascular network by sacrificing Pluronic ® F127 macrofibers and interwoven microfibers within collagen encapsulating human pericytes and fibroblasts. Channels were seeded with smooth muscle and endothelial cells. Constructs were topically seeded with keratinocytes. Results: After 28 days in culture, multiphoton microscopy revealed a hierarchical interconnected network of macro- and micro-vessels; larger vessels (>100 μm) were lined with a monolayer endothelial neointima and a subendothelial smooth muscle neomedia. Neoangiogenic sprouts formed in the collagen protodermis and pericytes self-assembled around both fabricated vessels and neoangiogenic sprouts. Conclusion: We fabricated a prevascularized scaffold containing a hierarchical 3D network of interconnected macro- and microchannels within a collagen protodermis subjacent to an overlying protoepidermis with the potential for recipient microvascular anastomosis.

Over recent years, there has been a rapid development of membrane-mimetic systems to encapsulate and stabilize planar segments of phospholipid bilayers in solution. One such system has been the use of amphipathic copolymers to solubilize lipid bilayers into nanodiscs. The attractiveness of this system, in part, stems from the capability of these polymers to solubilize membrane proteins directly from the host cell membrane. The assumption has been that the native lipid annulus remains intact, with nanodiscs providing a snapshot of the lipid environment. Recent studies have provided evidence that phospholipids can exchange from the nanodiscs with either lipids at interfaces, or with other nanodiscs in bulk solution. Here we investigate kinetics of lipid exchange between three recently studied polymer-stabilized nanodiscs and supported lipid bilayers at the silicon-water interface. We show that lipid and polymer exchange occurs in all nanodiscs tested, although the rate and extent differs between different nanodisc types. Furthermore, we observe adsorption of nanodiscs to the supported lipid bilayer for one nanodisc system which used a polymer made using reversible addition-fragmentation chain transfer polymerization. These results have important implications in applications of polymer-stabilized nanodiscs, such as in the fabrication of solid-supported films containing membrane proteins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Insufficient vascularization of currently available clinical biomaterials has limited their application to optimal wound beds. We designed a hydrogel scaffold with a unique internal microstructure of differential collagen densities to induce cellular invasion and neovascularization., Methods: Microsphere scaffolds (MSS) were fabricated by encasing 1% (w/v) type 1 collagen microspheres 50-150 μm in diameter in 0.3% collagen bulk. 1% and 0.3% monophase collagen scaffolds and Integra® disks served as controls. Mechanical characterization as well as in vitro and in vivo invasion assays were performed. Cell number and depth of invasion were analyzed using Imaris™. Cell identity was assessed immunohistochemically., Results: In vitro, MSS exhibited significantly greater average depth of cellular invasion than Integra® and monophase collagen controls. MSS also demonstrated significantly higher cell counts than controls. In vivo, MSS revealed significantly more cellular invasion spanning the entire scaffold depth at 14 days than Integra®. CD31+ expressing luminal structures suggestive of neovasculature were seen within MSS at 7 days and were more prevalent after 14 days. Multiphoton microscopy of MSS demonstrated erythrocytes within luminal structures after 14 days., Conclusion: By harnessing simple architectural cues to induce cellular migration, MSS holds great potential for clinical translation as the next generation dermal replacement product., Statement of Significance: Large skin wounds require tissue engineered dermal substitutes in order to promote healing. Currently available dermal replacement products do not always adequately incorporate into the body, especially in complex wounds, due to poor neovascularization. In this paper, we present a hydrogel with an innovative microarchitecture that is composed of dense type I collagen microspheres suspended in a less-dense collagen bulk. We show that cell invasion into the scaffold is driven solely by mechanical cues inherent within this differential density interface, and that this induces robust vascular cell invasion both in vitro and in a rodent model. Our hydrogel performs favorably compared to the current clinical gold standard, Integra®. We believe this hydrogel scaffold may be the first of the next generation of dermal replacement products., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction., Competing Interests: LJB is a co-founder and equity holder in 3D BioCorp. Remaining authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Diabetes is an increasingly prevalent comorbidity in patients presenting for surgery, impacting nearly 14% of adults in the United States. Although it is known that diabetic patients are at an increased risk for postoperative complications, there is a paucity of literature on the specific ramifications of diabetes on different surgical procedures., Methods: Using the American College of Surgeons National Surgical Quality Improvement Program dataset, demographics, outcomes, and length of in-patient hospitalization were examined for patients who underwent plastic surgery between 2007 and 2012. Adjusted multivariable logistic regression models were used to assess the relationship between diabetes status and a spectrum of medical and surgical postoperative outcomes., Results: Thirty-nine thousand four hundred seventy-five plastic surgery patients were identified, including 1,222 (3.10%) with insulin-dependent diabetes mellitus (IDDM) and 1,915 (4.75%) with non-insulin-dependent diabetes mellitus (NIDDM), who had undergone breast, hand/upper and lower extremity, abdominal, or craniofacial procedures. Logistic regression analyses showed that only insulin-dependent diabetics had a higher likelihood of surgical complications (IDDM: P value < 0.0001; NIDDM: P value < 0.103), whereas patients with both IDDM and NIDDM had increased likelihoods of medical complications (IDDM: P value < 0.001; NIDDM: P value = 0.0093) compared with nondiabetics. Average hospital stay for diabetics was also longer than for nondiabetics., Conclusions: Diabetes is associated with an increase in a multitude of postoperative complications and in hospital length of stay, in patients undergoing plastic surgery. Diabetes status should thus be evaluated and addressed when counseling patients preoperatively. Risks may be further stratified based on IDDM versus NIDDM status.

Secure closure of the fascial layers after entry into the peritoneal cavity is crucial to prevent incisional hernia, yet appropriate purchase of the tissue can be challenging due to the proximity of the underlying protuberant bowel which may become punctured by the surgical needle or strangulated by the suture itself. Devices currently employed to provide visceral protection during abdominal closure, such as the metal malleable retractor and Glassman Visceral Retainer, are unable to provide complete protection as they must be removed prior to complete closure. A puncture resistant, biocompatible, and degradable matrix that can be left in place without need for removal would facilitate rapid and safe abdominal closure. We describe a novel elastomer (CC-DHA) that undergoes a rapid but controlled solid-to-liquid phase transition through the application of a destabilized carbonate cross-linked network. The elastomer is comprised of a polycarbonate cross-linked network of dihydroxyacetone, glycerol ethoxylate, and tri(ethylene glycol). The ketone functionality of the dihydroxyacetone facilitates hydrolytic cleavage of the carbonate linkages resulting in a rapidly degrading barrier that can be left in situ to facilitate abdominal fascial closure. Using a murine laparotomy model we demonstrated rapid dissolution and metabolism of the elastomer without evidence of toxicity or intraabdominal scarring. Furthermore, needle puncture and mechanical properties demonstrated the material to be both compliant and sufficiently puncture resistant. These unique characteristics make the biomaterial extraordinarily useful as a physical barrier to prevent inadvertent bowel injury during fascial closure, with the potential for wider application across a variety of medical and surgical applications., Statement of Significance: Fascial closure after abdominal surgery requires delicate maneuvers to prevent incisional hernia while minimizing risk for inadvertent bowel injury. We describe a novel biocompatible and biodegradable polycarbonate elastomer (CC-DHA) comprised of dihydroxyacetone, glycerol ethoxylate, and tri(ethylene glycol), for use as a rapidly degrading protective visceral barrier to aid in abdominal closure. Rapid polymer dissolution and metabolism was demonstrated using a murine laparotomy model without evidence of toxicity or intraabdominal scarring. Furthermore, mechanical studies showed the material to be sufficiently puncture resistant and compliant. Overall, this new biomaterial is extraordinary useful as a physical barrier to prevent inadvertent bowel injury during fascial closure, with the potential for wider application across a variety of medical and surgical applications., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Aortic insufficiency (AI) is increasingly recognized as a complication of continuous flow left ventricular assist device support; however, its long-term prevalence, clinical significance, and efficacy of potential interventions are not well known., Methods and Results: We studied the prevalence and management of AI in 232 patients with continuous flow left ventricular assist device at our institution. Patients with aortic valve (AV) surgery before left ventricular assist device implantation were excluded from analysis. To examine the prevalence of de novo AI, patients without preoperative AI were divided into a retrospective and a prospective cohort based on whether a dedicated speed optimization study had been performed at the time of discharge. Forty-three patients underwent AV repair at the time of implant, and 3 subsequently developed greater than mild AI. In patients without surgical AV manipulation and no AI at the time of implant, Kaplan-Meier analysis revealed that freedom from greater than mild de novo AI at 1 year was 77.6±4.2%, and that at least moderate AI is expected to develop in 37.6±13.3% after 3 years. Nonopening of the AV was strongly associated with de novo AI development in patients without prospective discharge speed optimization. Seven of 21 patients with at least moderate AI developed symptomatic heart failure requiring surgical intervention., Conclusions: AI is common in patients with continuous flow left ventricular assist devices and may lead to clinical decompensation requiring surgical correction. The prevalence of AI is substantially less in patients whose AV opens, and optimized loading conditions may reduce AI prevalence in those patients in whom AV opening cannot be achieved.

Objectives: This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF)., Background: Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated., Methods: Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography., Results: Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p = 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p = 0.069). CRI correlated with the exercise-induced increase in FFA (r = 0.41; p < 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group., Conclusions: Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to develop a novel approach to optimizing continuous-flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions., Background: In CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp test., Methods: We devised a unique ramp test protocol to be routinely used at the time of discharge for speed optimization and/or if device malfunction was suspected. The patient's left ventricular end-diastolic dimension, frequency of aortic valve opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded in increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for left ventricular end-diastolic dimension, pulsatility index, and power were calculated., Results: Fifty-two ramp tests for 39 patients were prospectively collected and analyzed. Twenty-eight ramp tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424 ± 211 rpm. Seventeen patients had ramp tests performed for suspected device thrombosis, and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplantation. Device thrombosis was confirmed in 8 of 10 cases at the time of emergent device exchange or transplantation. All patients with device thrombosis, but none of the remaining patients had a left ventricular end-diastolic dimension slope >-0.16., Conclusions: Ramp tests facilitate optimal speed changes and device malfunction detection and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Previous studies have shown that albino rats born and raised in bright cyclic light are protected from light-induced apoptosis. The present study was designed to determine if bright cyclic rearing provides protection against retinal degeneration caused by acute light exposure in albino mice., Methods: BALB/c mice were born in dim cyclic light (5 lux, 12 h ON/OFF). At 1 week of age, half of the litters were moved into 400 lux cyclic light. At 5 weeks of age, mice raised in the dim or bright cyclic conditions were divided into two groups. One group was placed in constant light (3,000 lux for 72 h) and the other was maintained in its original cyclic light environment. Control and constant light-stressed mice were dark-adapted for 24 and 48 h, respectively, after which their eyes were removed immediately for morphologic evaluation or preparation of rod outer segment (ROS) membranes. ROS lipids were extracted and fatty acid methyl esters were analyzed by gas-liquid chromatography. Eyes used for TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labeling) and DNA fragmentation assays were enucleated immediately after the 72 h light exposure., Results: Measurement of outer nuclear layer (ONL) thickness indicated there was no difference in the number of viable photoreceptor cells in the dim-reared controls compared to bright-reared controls. Constant light exposure significantly reduced the ONL thickness in dim- and bright-reared groups, with the largest change occurring in the dim-reared mice. TUNEL assay showed no apoptotic photoreceptor cells in either control group; however, apoptotic nuclei could be detected in both exposed groups, with the largest number found in the dim-reared mice. After light exposure, DNA fragmentation was prominent in dim-reared mice, but was not present in bright-reared animals. There was no significant difference in the fatty acid composition of ROS membranes in the dim- and bright-reared control mice. However, constant light exposure resulted in a greater loss of docosahexaenoic acid (22:6n-3) in the ROS of dim-reared animals., Conclusions: Mice raised in a bright cyclic light environment are protected against light-induced apoptosis. We suggest that the protection is due to the up-regulation of cell survival pathways or the down-regulation of pathways that are vulnerable to acute cell stress.

1. The aim of our study was to demonstrate the existence, location and functional importance of an alternative angiotensin II-forming pathway other than angiotensin converting enzyme (ACE) in the human saphenous vein (SV). 2. Vascular reactivity studies using an in vitro organ bath technique showed that the SV (n=20) produced similar maximum contractions in response to angiotensin I (41.5+/-5.4 mN) compared to those observed to angiotensin II (46.7+/-10.9 mN). The response to angiotensin I could be significantly inhibited (P<0.05) by incubation with the AT1 receptor antagonist losartan (1 microM). 3. Prior incubation of segments of SV with either captopril (1 microM) (n=6), quinaprilat (1 microM) (n=7), or the chymase inhibitor soya bean trypsin inhibitor (SBTI) (10 microM) (n=7) singularly failed to have any inhibitory effect on the response to angiotensin I. However when vessel segments (n=7) were co-incubated with quinaprilat (1 microM) and SBTI (10 microM), the SV exhibited a rightward shift in curve profile to angiotensin I and a markedly reduced maximum response 12.5+/-2.4 mN, when compared to control (30.4+/-7.6 mN), quinaprilat (24.5+/-9.4 mN), and SBTI (31.6+/-10.7 mN) on their own. 4. An immunohistochemical technique employing streptavidin biotin peroxidase localised ACE to both endothelial cells and smooth muscle cells while chymase was confined to mast cells in the adventitia of the vessel wall. 5. In conclusion, our results demonstrate the existence of an alternative angiotensin I converting pathway to that of ACE, involving chymase. Therefore, there is the capacity for a continuation of angiotensin II formation, in the presence of ACE inhibition.