Rele Ologunde

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

Neuroinflammation in Parkinsons 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.

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 β 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.

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-1β, 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.

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-&agr;, 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-1&agr; (HIF-1&agr;), Bcl-2, high-mobility group protein-1 (HMGB-1), TLR-4, and nuclear factor &kgr;B (NF-&kgr;B) expression, lung inflammation, and cell injuries were assessed. Results:Recipients receiving ischemic renal grafts developed pulmonary injury. Xenon treatment enhanced HIF-1&agr;, which attenuated HMGB-1 translocation and NF-&kgr;B activation in A549 cells with oxidative and inflammatory stress. Xenon treatment enhanced p-mTOR, HIF-1&agr;, 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-&kgr;B 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-1&agr; pathway and suppression of the HMGB-1 translocation from nuclei to cytoplasm.

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.

Surgical follow-up in low-income and middle-income countries

The poorest third of the world’s population is estimated to receive only 3·5% of the 234 million surgical procedures undertaken annually. Despite being a small proportion of global surgical output, such procedures represent a substantial challenge for health-care providers in low-resource settings. This challenge is compounded by the burden of managing postoperative complications (particularly delayed complications), which patients might not present with, as evidenced by the low rates of follow-up in many lowincome and middle-income countries. In the context of cataract surgery, Nathan Congdon and colleagues (August, p e37) propose the possibility of using early postoperative assessment of all patients or late assessment only of those who return for follow-up without additional prompting as practicable methods to improve long-term patient outcomes in settings where barriers to adequate post-operative follow-up exist. Such approaches would be feasible in many resource-limited settings, and where appropriate should be extended to postoperative follow-up of other surgical procedures. However, a potential exists for many patients to slip through the net by not returning for followup assessment despite developing harmful postoperative complications. Paternalistic medicine persists in many developing countries. Yousuf and colleagues reported that most patients in Srinigar, India, avoid the responsibility of decision making and defer this responsibility to the doctor. Where self-reporting contradicts socially and culturally mediated beliefs, systems that rely on this mechanism might not be able to ensure continuity in patient care. We therefore recommend a protocol wherein the doctor explicitly advises the patient to return should they experience predefi ned complications. Furthermore, the health-care provider should attempt to facilitate travel and rebooking where possible.

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 Childrens 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.

Surgical Care: Addressing the Barriers to Access in Low-Income Countries

We read with interest, in the October 2013 issue of World Journal of Surgery, the article by Samad et al. [1], which highlighted the barriers encountered by patients trying to access surgical care in a tertiary hospital in Pakistan. These challenges are ubiquitous across the health systems of many lowand middle-income countries [2]. Samad and colleagues identified some of the reasons that these barriers to accessing surgical care exist. They characterized the barriers as contributing to first-interval delay (from the onset of symptoms to seeking initial health care) and second-interval delay (from when surgery was first advised to when it was performed). Even when patients do access care, however, they may be lost to follow-up despite having developed potentially harmful postoperative complications [3]. Thus, there may be a ‘‘third interval’’ (time from surgery to follow-up) when factors exist that further complicate the patient’s experience of accessing care. Such adverse events may influence other patients not to seek care, thus adding to the important and potentially large group of patients who never receive care for surgical illness. With surgery previously identified as a necessary component of primary care to achieve universal health coverage [4], we applaud the authors’ call to integrate general practitioners (GPs) into a better surgical referral network and to improve their training to be able to make surgical diagnoses. This resounds well with the Declaration of Alma Ata on Primary Health Care [5], celebrating its 35th anniversary this year. Its message of an integrated health system with primary health care as the first point of contact for patients reiterates the need for outreach initiatives in the name of primary health care to increase equitable access to specialized health care services as well. GPs are also able to act as a conduit to help patients overcome barriers to seeking specialist care as well as to follow up and maintain long-term rehabilitation. The most prominent such barrier to surgical care described in this article was the lack of knowledge about disease implications and treatment options. Interestingly, such lack of knowledge was found to be the most likely factor hindering patients from initially seeking care. Additionally, we would argue that long-standing lack of access could have led patients to become less inclined to seek care. Samad and colleagues highlighted the role of poor literacy and faulty disease perceptions. They suggested initiating a focused education campaign to address these issues. As GPs were found to be the first point of contact for up to 80 % of the study population, their potential role in educating patients about their ailments, treatment options, and disease implications should be examined further. A well-informed population is more likely to seek care when it is needed and more inclined to comply with a proposed treatment. Financial constraints remain a challenge to individuals in many low-income countries. Efforts to decrease the costs involved in treatment (including follow-up)—e.g., transportation, lost earnings, diagnosis, treatment costs—are likely to potentiate any effort to increase access to health care for underserved populations. R. Ologunde (&) Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK e-mail: rele.ologunde09@imperial.ac.uk

The post-2015 development agenda: the role of surgical care in improving health.

During the past decade and a half, the global health landscape has been characterised by efforts to achieve the millennium development goals (MDGs). These eight health-related objectives agreed upon by the international health community were established in the millennium declaration. The formalisation of these goals and the predefined essential services needed to achieve them has garnered political priority and has been promoted through multiple institutions and organizations [1]. However, as the year 2015 approaches, and with it the target date to achieve the MDGs, attention is increasingly been drawn to the health architecture of the post-MDG era and the health priorities for this next chapter of international health promotion [2]. Key considerations include how to best place health in the post-2015 agenda. With a sizeable proportion of disease burden reducible by surgical intervention [3] coupled with the current inequitable distribution of surgical services globally [4], it is clear that surgical care should play an important role in improving health in the post-2015 era. The challenge of improving access to surgical care in many lowand middle-income countries (LMICs) is well documented in the literature [3]; barriers to care include insufficient accessibility, affordability, availability, and acceptability of care, compounded by a lack of an adequate surgical workforce [5]. Despite these challenges, improving access to surgical care has been shown to be a cost-effective and sustainable intervention that can have simultaneous and reciprocal benefits within a health system [3], and for society as a whole by promoting development through the enhancement of equity, improving economic status by limiting time spent out of work due to disability, and strengthening health systems. Achieving universal health coverage alone, in the 15 years following 2015, will not be enough to ensure that populations currently burdened with disease begin to experience improvements in health. Prevention programmes (for example to reduce road traffic accidents) and continued public health promotion and education accompanied by timely access to healthcare must be imperative to discussion on the post-2015 development agenda. To adequately comprehend the burden of surgical disease in LMICs and evaluate progress towards tackling it, there is a need to establish appropriate metrics to quantify the burden. The utility of relevant metrics will be evident in their ability to aid identification of areas for improvement in terms of operative and postoperative care, infrastructure, human resources, availability of surgical procedures, and essential surgical equipment. Such metrics can also aid in informing global health discourse on surgical care priority setting and advocacy to achieve sustained global awareness in the role of surgery as a post-MDG global health priority. In the year 2000, 189 countries adopted the millennium declaration and set international objectives, which have resulted in tangible gains in global health. In the year 2030, will we acknowledge that our post-MDG era achieved comparable improvements in global health, or will we lament a missed opportunity?