VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia-reperfusion injury in rats.

Clinical evidence has indicated a possible link between renal injury and remote liver injury. We investigated whether extracellular histone mediates remote hepatic damage after renal graft ischemia-reperfusion injury, while vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preservation solution for 24 hours and then transplanted into a Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery. Prolonged cold ischemia in renal grafts enhanced liver injury 24 hours after engraftment. Caspase-1, ASC, NLRP3, and AIM2 expressions in hepatocyte, CD68+ -infiltrating macrophages, tissue, and serum interleukin-1ß and -18 were greatly elevated, indicating that pyroptosis occurred in the liver and resulted in acute liver functional impairment. Blocking the caspase-1 pathway decreased the number of necrotic hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver function was partially restored. Our data suggested that renal allograft ischemia-reperfusion injury is likely associated with acute liver damage due to hepatocyte pyroptosis induced by histone and such injury may be protected by VEGF administration. VEGF, therefore, may serve as a new strategy against other remote organ injuries related to renal transplantation.

Xenon Treatment Protects against Remote Lung Injury after Kidney Transplantation in Rats.

BACKGROUND: Ischemia-reperfusion injury (IRI) of renal grafts may cause remote organ injury including lungs. The authors aimed to evaluate the protective effect of xenon exposure against remote lung injury due to renal graft IRI in a rat renal transplantation model. METHODS: For in vitro studies, human lung epithelial cell A549 was challenged with H2O2, tumor necrosis factor-α, or conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. For in vivo studies, the Lewis renal graft was stored in 4°C Soltran preserving solution for 24 h and transplanted into the Lewis recipient, and the lungs were harvested 24 h after grafting. Cultured lung cells or the recipient after engraftment was exposed to 70% Xe or N2. Phospho (p)-mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α), Bcl-2, high-mobility group protein-1 (HMGB-1), TLR-4, and nuclear factor κB (NF-κB) expression, lung inflammation, and cell injuries were assessed. RESULTS: Recipients receiving ischemic renal grafts developed pulmonary injury. Xenon treatment enhanced HIF-1α, which attenuated HMGB-1 translocation and NF-κB activation in A549 cells with oxidative and inflammatory stress. Xenon treatment enhanced p-mTOR, HIF-1α, and Bcl-2 expression and, in turn, promoted cell proliferation in the lung. Upon grafting, HMGB-1 translocation from lung epithelial nuclei was reduced; the TLR-4/NF-κB pathway was suppressed by xenon treatment; and subsequent tissue injury score (nitrogen vs. xenon: 26 ± 1.8 vs. 10.7 ± 2.6; n = 6) was significantly reduced. CONCLUSION: Xenon treatment confers protection against distant lung injury triggered by renal graft IRI, which is likely through the activation of mTOR-HIF-1α pathway and suppression of the HMGB-1 translocation from nuclei to cytoplasm.

Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair.

Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD. With growing evidence supporting the key role of neuroinflammation in PD pathogenesis, new molecular targets are being found that could potentially prevent or delay nigrostriatal DA neuron loss. Hence, this creates the opportunity for disease modifying treatment, to currently what is an incurable disease.

Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.

Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

Assessment of cesarean delivery availability in 26 low- and middle-income countries: a cross-sectional study.

OBJECTIVE: We sought to assess the capacity to provide cesarean delivery (CD) in health facilities in low- and middle-income countries. STUDY DESIGN: We conducted secondary analysis of 719 health facilities, in 26 countries in Africa, the Pacific, Asia, and the Mediterranean, using facility-based cross-sectional data from the World Health Organization Situational Analysis Tool to Assess Emergency and Essential Surgical Care. RESULTS: A total of 531 (73.8%) facilities reported performing CD. In all, 126 (17.5%) facilities did not perform but referred CD; the most common reasons for doing so were lack of skills (53.2%) and nonfunctioning equipment (42.9%). All health facilities surveyed had at least 1 operating room. Of the facilities performing CD, 47.3% did not report the presence of any type of anesthesia provider and 17.9% did not report the presence of any type of obstetric/gynecological or surgical care provider. In facilities reporting a lack of functioning equipment, 26.4% had no access to an oxygen supply, 60.8% had no access to an anesthesia machine, and 65.9% had no access to a blood bank. CONCLUSION: Provision of CD in facilities in low- and middle-income countries is hindered by a lack of an adequate anesthetic and surgical workforce and availability of oxygen, anesthesia, and blood banks.

Do trauma courses change practice? A qualitative review of 20 courses in East, Central and Southern Africa.

BACKGROUND: Trauma courses have been shown to improve clinical knowledge and patient outcomes. However, little is known about the individual drivers of change in practice amongst course participants in their home clinic environment. METHODS: Front-line healthcare workers participated in a two-day Primary Trauma Care (PTC) course. Immediately after the course participants completed an evaluation survey on intended change in the management of trauma patients. Six months after the course, participants completed a survey on actual changes that had occurred. RESULTS: A total of 451 participants were sampled, with 321 responding at 6 months, from 40 courses across East, Central and Southern Africa. The most commonly reported intended change was the adoption of an ABCDE/systematic approach (53%). Six months after the course, 92.7% of respondents reported that they had made changes in their management, with adoption of an ABCDE/systematic approach (50.0%) remaining most common. 77% of participants reported an improvement in departmental trauma management, 26% reported an increase in staffing, 29% an increase in equipment and 68% of participants had gone on to train other healthcare workers in PTC. CONCLUSION: The findings suggest that PTC courses not only improve individual management of trauma patients but also but is also associated with beneficial effects for participants' host institutions with regards to staffing, equipment and training.

Plastic surgery and the biometric e-passport: implications for facial recognition.

This correspondence comments on the challenges of plastic reconstructive and aesthetic surgery on the facial recognition algorithms employed by biometric passports. The limitations of facial recognition technology in patients who have undergone facial plastic surgery are also discussed. Finally, the advice of the UK HM passport office to people who undergo facial surgery is reported.

Inspiring tomorrow's surgeons: the benefits of student surgical society membership☆?

OBJECTIVES: To assess the perceived value of medical school student surgical society membership and its effect on determining future career aspirations. DESIGN: Cross-sectional survey. SETTING: Three UK medical school student surgical societies. PARTICIPANTS: Undergraduate and postgraduate students. RESULTS: Of 119 students, 60 (50.4%) completed the survey. Of the respondents, 62.3% indicated that the surgical society had increased their awareness and knowledge about the different surgical specialties. Of the respondents who had decided on a career in surgery before joining the society, 67.6% stated that participating in society events had better prepared them for the career. Plastic surgery (13.3%), general surgery (11.7%), and neurosurgery (11.7%) were the 3 most popular specialties for future careers. Surgical skills workshops (21.9%), conferences (21.1%), and careers talks (16.4%) were chosen by students as the most useful career-guiding events organized by surgical societies. CONCLUSION: Participation in medical school surgical societies is perceived as a valuable part of undergraduate and postgraduate medical education in aiding students to decide on future careers.

A review of oral and maxillofacial surgery journals' contribution to undergraduate surgical education.

We searched the Medline database of 4 leading international journals of oral and maxillofacial surgery (OMFS) for all articles containing the terms "undergraduate", "medical student", or "dental student" in the abstract, title, or keywords, from the earliest paper to 2013, to identify and review publications that related to the education of undergraduate medical and dental students. We found 130 articles, of which 22 (17%) met the inclusion criteria. Most were published by teams based in the United States, followed by those from the United Kingdom and Germany. The earliest was published in 1986. Since then, most have been published in the Journal of Oral and Maxillofacial Surgery (0.33/year) and the least in the International Journal of Oral and Maxillofacial Surgery (0.11/year). Eleven original research articles concerned dental students and 4 concerned medical students. Three studies looked at both groups and compared them with their qualified counterparts. There is a relative paucity of articles relating to the education of undergraduates, particularly medical students, in OMFS journals, although the number has increased over the last decade. There is a need for more educational papers to be aimed at students interested in pursuing OMFS as a career.

Surgical care in low and middle-income countries: burden and barriers.

Surgically correctable pathology accounts for a sizeable proportion of the overall global burden of disease. Over the last decade the role of surgery in the public health agenda has increased in prominence and attempts to quantify surgical capacity suggest that it is a significant public health issue, with a great disparity between high-income, and low- and middle-income countries (LMICs). Although barriers such as accessibility, availability, affordability and acceptability of surgical care hinder improvements in LMICs, evidence suggests that interventions to improve surgical care in these settings can be cost-effective. Currently, efforts to improve surgical care are mainly coordinated by academia and intuitions with strong surgical and global health interests. However, with the involvement of various international organisations, policy makers, healthcare managers and other stakeholders, a collaborative approach can be achieved in order to accelerate progress towards improved and sustainable surgical care. In this article, we discuss the current burden of global surgical disease and explore some of the barriers that may be encountered in improving surgical capacity in LMICs. We go on to consider the role that international organisations can have in improving surgical care globally. We conclude by discussing surgery as a global health priority and possible solutions to improving surgical care globally.

Organ cross talk and remote organ damage following acute kidney injury.

Increasing evidence suggests that acute kidney injury (AKI) mediates a systemic response that can lead to multiple organ failure. AKI may manifest in a variety of clinical scenarios including kidney transplantation and is associated with a significantly high mortality. It has been postulated that specific pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, may mediate a systemic response, resulting in recruitment of pro-inflammatory cells leading to organ failure. However, the specific mechanism by which the cytokine cascade results in distant organ damage is yet to be determined. Furthermore, it remains unclear as to whether cytokines mediate similar or differing responses in different end organs. This review summarizes the effects of AKI on remote organs and explores the role of systemic cytokines in mediating distant organ damage.

Is Health Care a Right? Health Reforms in the USA and their Impact Upon the Concept of Care.

In 2008 United States President Barack Obama declared that health care "should be a right for every American".(1) This statement, although noble, does not reflect US healthcare statistics in recent times, with the number of uninsured reaching over 50 million in 2010.(2) Such disparity has sparked a political drive towards change, and the introduction of the Patient Protection and Affordable Care Act (PPACA).(3) These changes have been highly polemical, raising the fundamental question of whether health care is a right; a contract between the nation and its inhabitants granted at birth, or an entitlement; a privilege that must be earned as opposed to universally provided. Access to healthcare in the US is mediated by insurance coverage, either in the form of private or employer based cover, which may be government based for public sector employees or private for private sector employees. The majority of spending on healthcare however, comes from government expenditure on health programs such as Medicare, Medicaid, Tricare, and the State Children's Health Insurance Program (SCHIP).(4) Medicare is a federal government funded social insurance program that provides health insurance to people aged 65 and older, younger people with disabilities, and those with end stage renal failure requiring dialysis. Medicaid is a means tested insurance coverage program for individuals with low incomes and their families, and is jointly funded by state and federal governments. Tricare is a healthcare program that provides healthcare insurance for military personnel, retirees, and their dependents. The SCHIP provides states with federal government funding to provide health insurance to children from families with modest incomes that do not qualify for Medicaid. As such, although the majority of the US population is insured by federal, state, employer, or private health insurance, the remainders go uninsured.

Do inhalational anesthetics cause cognitive dysfunction?

Increasing evidence indicates that inhalational anesthetics may cause or increase the risk of developing postoperative cognitive dysfunction (POCD), especially in the elderly population. POCD may exist as a transient or long-term complication of surgery and anesthesia and is associated with reduced quality of life. There remains great discrepancy between clinical studies investigating the prevalence of POCD and inhalational anesthetics as many fail to show an association. However, numerous animal studies have suggested that inhalational anesthetics may alter cognitive function via amyloid ß accumulation, modified neurotransmission, synaptic changes and dysregulated calcium homeostasis. Other factors such as neuroinflammation and pro-inflammatory cytokines may also play a role. This paper reviews the role of inhalational anesthetics in the etiology and underlying mechanisms that result in POCD.