Organ transplantation is a definitive therapeutic option for patients with end-stage organ dysfunction and failure.Ischaemia–reperfusion(IR)injury is one of the leading causes of low graft utilization as it significantly increases the risk of primary graft dysfunction and acute rejection following transplantation.This risk is particularly high for organs obtained from donation after circulatory death(DCD)when compared with the organs from donation after brain death(DBD).IR injury exacerbates tissue damage via various mechanisms including the induction of regulated cell death.Regulated cell death and its consequences play critical roles in determining graft survival and function,thereby influencing the overall success of the transplant.Understanding the mechanisms underlying regulated cell death in IR injury is essential for developing therapeutic strategies to minimize tissue damage and improve clinical outcomes in organ transplantation.This review mainly discusses different types of regulated cell death and underlying mechanisms towards preventive cell death strategies in DBD and DCD organ transplantation in preclinical settings.

Background: Sepsis-induced neurodegeneration and cognitive dysfunction remain critical challenges worldwide. Vitamin D was reported to reduce neuronal injury and neurotoxicity and its deficiency was associated with neurocognitive disorders. This study investigates the mechanisms by which vitamin D exerts neuroprotective potential against damage-associated molecular patterns (DAMPs), specifically extracellular histones, in sepsisrelated brain dysfunction. Methods: The cultured mouse hippocampal neuronal HT22 cells were exposed to 20 mu g/ml exogenous histone for 24 h to induce pyroptosis and ferroptosis in the presence or absence of the active form of vitamin D, calcitriol (1 nM). A cecal ligation and puncture mouse sepsis model was used to evaluate histone release and pyroptosis/ ferroptosis biomarkers in the brain together with neurobehavioral performance with or without calcitriol treatment (1 mu g/kg, i.p. injection) at 24 h or 1 week after sepsis onset. Results: In vitro, histone exposure triggered both pyroptosis and ferroptosis in neuronal cells, which was significantly suppressed by calcitriol treatment with the reduced expression of caspase-1 by 38 %, GSDMD by 30 %, ACSL4 by 33 %, and the increased expression of GPX4 by 35 % (n = 6, P < 0.05). Similarly, in vivo, calcitriol treatment inhibited both neuronal pyroptosis and ferroptosis by reducing expression of pyroptosis marker, GSDMD/NeuN (11.6 f 1.2 % vs. 19.4 f 1.1 %) and increasing expression of ferroptosis marker, GPX4/NeuN (21.4 f 1.7 % vs. 13.5 f 1.1 %), in the brain of septic mice (n = 6, P < 0.01). In addition, calcitriol increased survival rate (72 % vs. 41 %) and ameliorated cognitive dysfunction of septic mice (n = 8-13, P < 0.05). Conclusions: This study demonstrates that vitamin D exerts a neuroprotective effect against sepsis by attenuating histone-induced pyroptosis and ferroptosis. These findings highlight the potential therapeutic role of vitamin D supplementation in mitigating brain dysfunction associated with sepsis which needs for further investigation.

Background: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. Patients: 86 patients aged 60- 75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 mu g kg(- 1) for 10 min, followed by 0.5 mu g kg(- 1) hr(- 1) for maintenance until the end of surgery. Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were primary outcomes. Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P< 0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 +/- 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 +/- 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-alpha were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs.

Preventable hospital admissions in elderly home care residents are a major socioeconomic burden, whilst early detection of deterioration may improve outcomes. Our goal was to develop and validate a machine learning-based algorithm to predict hospitalization risk among home care users. Our primary outcome was hospitalization. An existing risk score (1-5) was assessed for its discriminatory capacity over time. We subsequently developed a new machine learning model using carer concerns, service user demographics, and other home care data between January and July 2021. We randomly selected 150 service user records for validation, which were evaluated by both the model and 10 clinicians (9 doctors and 1 nurse) to compare prediction time and accuracy to human experts. Comparison between model and human was via area under the receiver operating characteristic curve (AUC). A score of 5 conferred an 8x higher likelihood of hospitalization in the subsequent 7 days (15.4% vs 1.8%, p < .05), compared to a score of 1. The new model and risk score increased performance, detecting 182 hospitalizations/month (3.7x chance). The AUC for the model was significantly higher than for clinicians (0.87 vs 0.41-0.57, respectively; p < .05). The model took <1 minute, while clinicians typically took over 40 minutes. A risk prediction model using carer concerns and other home care data features detects 3.7x more hospitalizations than chance. The model is faster and more accurate than human clinicians, enabling low-cost scale-up. This study supports linking the model to a triage and intervention service to reduce preventable hospitalizations in the home care sector.

How a new learning platform is revolutionising learning for surgeons to navigate the medtech sector and develop their skills in an accessible and digestible way.

BackgroundAcute kidney injury (AKI) was reported to be one of the initiators of chronic kidney disease (CKD) development. Necroinflammation may contribute to the progression from AKI to CKD. Dexmedetomidine (Dex), a highly selective α2-adrenoreceptor (AR) agonist, has cytoprotective and “anti-” inflammation effects. This study was designed to investigate the anti-fibrotic properties of Dex in sepsis models.MethodsC57BL/6 mice were randomly treated with an i.p. injection of lipopolysaccharides (LPS) (10 mg/kg) alone, LPS with Dex (25 μg/kg), or LPS, Dex and Atipamezole (Atip, an α2-adrenoreceptor antagonist) (500 μg/kg) (n=5/group). Human proximal tubular epithelial cells (HK2) were also cultured and then exposed to LPS (1 μg/ml) alone, LPS and Dex (1 μM), transforming growth factor-beta 1 (TGF-β1) (5 ng/ml) alone, TGF-β1 and Dex, with or without Atip (100 μM) in culture media. Epithelial-mesenchymal transition (EMT), cell necrosis, necroptosis and pyroptosis, and c-Jun N-terminal kinase (JNK) phosphorylation were then determined.ResultsDex treatment significantly alleviated LPS-induced AKI, myofibroblast activation, NLRP3 inflammasome activation, and necroptosis in mice. Atip counteracted its protective effects. Dex attenuated LPS or TGF-β1 induced EMT and also prevented necrosis, necroptosis, and pyroptosis in response to LPS stimulation in the HK2 cells. The anti-EMT effects of Dex were associated with JNK phosphorylation.ConclusionsDex reduced EMT following LPS stimulation whilst simultaneously inhibiting pyroptosis and necroptosis via α2-AR activation in the renal tubular cells. The “anti-fibrotic” and cytoprotective properties and its clinical use of Dex need to be further studied.

Abstract Background: Cancer-induced bone paincaused by advanced tumor bone metastasis remains a clinical challenge, and the underlying mechanisms of BCP remain unknown. This study aimed to screen the expression profile of circular RNAs in a BCP rat model and provide a new theoretical basis for the role of circular RNA in the occurrence and development of BCP. Methods: We established a BCP rat model. The top four differentially expressed circRNAs (DECs) in the model were validated by agarose gel electrophoresis and Sanger sequencing between the BCP group and sham group. A circRNA-miRNA-mRNA network was constructed based on the interactions among circRNAs, microRNA (miRNA), and mRNA, which were predicted by TargetScan. mRNA and circRNA expression levels were detected by quantitative RT-PCR. In addition, Western Blot was performed to identify the protein levels of p-ERK, ERK, and Col8a1. Results: CircRNA parent genes were mainly enriched in MAPK and neurodevelopmental signalling pathways. CircAkt3 and circMap4k1 were significantly up-regulated in the BCP group. CircaAkt3 may increase p-ERK expression by upregulating Col8a1, which may further activate the MAPK pathway. Conclusions: The circAkt3 pathway may influence the development of bone cancer pain by activating the MAPK signaling pathway. This study provided important targets for the development of therapeutic strategy against BCP.

Cera, a homecare provider, uses digital care plans (DCP), to streamline the provision of home care. DCP rollout is part of a larger digitization initiative, including carer visit reports collected through a mobile app and branch actions recorded in a web application supported by a secure central database. This retrospective cohort study aimed to assess the association of a DCP rollout with service user hospitalization rates. his study utilized retrospective data from 2 groups of service users, those for whom their first 30 days of Cera membership occurred prior to DCP rollout (pre-DCP group) versus those whose first 30 days of Cera membership occurred after DCP rollout (post-DCP group). The 30-day hospitalization rate was the primary outcome measure and was determined through a combination of carer reports, reporting from service users or their families, and branch staff follow-up. There were 55 hospitalizations among 392 users in the pre-DCP group in the 30 days after joining Cera (14.0% hospitalization rate), compared to 23 hospitalizations among 297 users in the post-DCP group (7.7% hospitalization rate). This represented a significant reduction in hospitalizations in the post-DCP group (6.3% absolute difference in hospitalization rate; 45% relative reduction; P < .001). This result was robust to multiple sensitivity analyses. The implementation of a DCP was associated with a 45% relative reduction in the 30-day hospitalization rate for new service users when compared to pre-DCP enrollment. These benefits could be further amplified by combining the DCP with additional initiatives aimed at the prediction and prevention of avoidable hospitalizations.

Background: Effective preservation strategies to ameliorate lung graft ischaemia injury are needed to rescue 'extended criteria' or 'marginal' lung grafts, and to improve recipient outcomes after transplantation. Methods: Lung grafts from male Lewis rats were extracted after 40 min of cardiocirculatory death, and healthy human lung tissues were collected from patients undergoing a lobectomy. Lung samples were then preserved in a 4°C preservation solution supplemented with 0.1 nM Dexmedetomidine (Dex, α2-adrenoceptor agonist) for 16 h. In vitro, human lung epithelial A549 cells were preserved in the 4°C preservation solution with 0.1 nM Dex for 24 h, then re-cultured in the cell culture medium at 37°C to mimic the clinical scenario of cold ischaemia and warm reperfusion. Lung tissues and cells were then analysed with various techniques including western blot, immunostaining and electron microscope, to determine injuries and the protection of Dex. Results: Prolonged warm ischaemia after cardiocirculatory death initiated Rip kinase-mediated necroptosis, which was exacerbated by cold storage insult and enhanced lung graft injury. Dex supplementation significantly reduced necroptosis through upregulating Nrf2 activation and reducing oxidative stress, thereby significantly improving lung graft morphology. Dex treatment also attenuated endoplasmic reticulum stress, stabilised lysosomes and promoted cell membrane resealing function, consequently reducing cell death and inflammatory activation after hypothermic hypoxia-reoxygenation in A549 cells. Conclusions: Inhibition of regulated cell death through Dex supplementation to the graft preservation solution improves allograft quality which may aid to expand the donor lung pool and enhance lung transplant outcomes per se.

As of 2018 cancer is responsible for almost 9.6 million deaths annually and, with an aging population, the incidence of cancer is expected to continue to rise. Surgery is an important treatment modality for patients with solid organ cancers. It has been postulated that, due to potentially overlapping processes underlying the development of malignancy and the therapeutic pathways of various anesthetic agents, the choice of anesthetic type and method of administration may affect post-operative outcomes in patients with cancer. This is a literature review of the most recent evidence extracted from various databases including PubMed, EMBASE, and the Cochrane, as well as journals and book reference lists. The review highlights the pathophysiological processes underpinning cancer development and the molecular actions of anesthetic agents, pre-clinical and retrospective studies investigating cancer and anesthetics, as well as ongoing clinical trials. Overall, there are conflicting results regarding the impact of regional vs. general anesthesia on cancer recurrence, whilst the majority of data suggest a benefit of the use of intravenous propofol over inhalational volatile anesthetics. The biological changes associated with the surgical inflammatory response offer a unique opportunity to intervene to counteract any potentially cancer-promoting effects.

The preoperative evaluation of the function of vital organs, including the heart, lungs, liver, and kidneys, is established practice across essentially all surgical specialities and is accepted by both medical professionals and the public. The purpose of preoperative evaluation is to evaluate and implement approaches to prepare and optimise high-risk patients for surgery. Preoperative medical evaluation is designed to achieve a single aim – to make surgery safer. Preoperative evaluation encourages collaboration between surgeons and nonsurgeons, with the use of diagnostic tests and therapeutic interventions to identify and manage modifiable risks. Effective perioperative evaluation and optimisation, particularly of older people undergoing surgery, has been shown to reduce postoperative medical complications, delirium, 30-day mortality, and reduce the length of hospital stay.1 Additionally, 20% of surgeries in older people are delayed for preventable medical reasons, which further highlights the importance of mitigating delays in surgical intervention.1 In terms of preoperative evaluation, most guidelines and approaches focus on risk factors for cardiac, pulmonary, renal, and metabolic-related complications.2 For example, a typical preoperative assessment often includes cardiac investigations, including an electrocardiogram and echocardiogram, respiratory investigations such as spirometry, if there is a history of chronic lung disease, and routine blood tests. However, there is currently a lack of focus on brain health. There is evidence to suggest that surgery, and its associated trauma, may cause significant systemic effects including surgical stress and systemic inflammation, leading to neuroinflammation and subsequent neural connectivity impairment and neurological complications.3 This is an association that remains poorly recognised by the clinical and scientific communities. Surgery has been shown to be associated with delirium, cognitive impairment, and stroke.4 These adverse neurological outcomes associated with surgery significantly impact patients' recovery postoperatively and contribute to poorer outcomes in terms of morbidity and mortality, and are associated with recognised risk factors and morbidities including increasing age, depression, previous stroke, postoperative infection, and the use of sedative drugs. Delirium remains the most common surgical complication in the elderly population, affecting up to 50% of older patients postoperatively and is associated with an increase in mortality, and prolonged intensive care admission and hospital length of stay. Postoperative delirium is thought to be a marker of cerebral vulnerability and points towards the possibility of underlying neurological disease, such as preclinical dementia. Remarkably, the peri-operative period is even thought to be associated with a pro-inflammatory stress response which potentially extends significantly beyond the precise time of surgery, with recent evidence suggesting that postoperative delirium may be associated with delayed neurocognitive recovery.3 In addition to delirium and postoperative cognitive dysfunction, the phenomenon of perioperative covert stroke remains underappreciated and poorly understood, despite being shown to increase the risk of cognitive decline.5 Overall, the traditional perioperative anaesthetic managements focus on cardiac risk optimisation and cardiopulmonary monitoring, alongside the numerous unknown variables within perioperative neuroscience, seems to have resulted in an inadequate appreciation of measures to confer neuroprotection and optimise neurological status within the perioperative period.6 Healthy neurological status is known to be affected by various risk factors such as increasing age and co-morbidities, such as underlying neurodegenerative disease, and all these factors can contribute towards the deterioration of brain function postoperatively and even death. There are also important potentially modifiable risk factors which may negatively impact neurological function, such as poor dietary habits and malnutrition, and poor physical function, which are also inextricably linked to the multifaceted and complex concept of frailty, which should ideally be addressed during the peri-operative period. So, what is the answer? There is no single investigation that will effectively risk stratify each patient's peri-operative neurological status, and there is no single therapeutic tool to confer neuroprotection. For progress to be made, significant financial investment is required to gain a deeper academic understanding of the investigative and therapeutic avenues to ameliorate peri-operative neurological sequalae, and various novel strategies have been investigated for this reason. For example, the use of intraoperative electroencephalography monitoring has recently been advocated to more precisely dictate anaesthetic titration to reduce the rate of perioperative neurocognitive disorders in older patients.7 It has also been suggested that intraoperative electroencephalography monitoring may be used as a warning signal to detect patients with brains vulnerable to neurocognitive disorders.7 Its use in other forms of neurological monitoring, such as to detect cerebral ischaemia intraoperatively, remains debated. Additionally, postoperative biomarkers of neuronal damage have been investigated to potentially predict postoperative cognitive dysfunction and other neurological complications. For example, brain cellular injury, as demonstrated by elevated plasma glial fibrillary acid protein concentrations, has been shown to be associated with a decline in cognition 1 month after shoulder surgery.8 Furthermore, the precise role of preoperative neuroimaging in patients at high-risk of postoperative neurological complications remains controversial and requires further investigation. As well as the need for financial investment to develop further diagnostic and therapeutic tools, costs are also implicated in ensuring that clinical peri-operative services are available to patients that focus on peri-operative neurological optimisation, based on the best available evidence. For example, proactive care of older patients undergoing surgery (POPS) is a geriatrician led service in the United Kingdom which focusses on medically optimising patients peri-operatively and reducing risks and complications in elderly patients undergoing elective surgery using comprehensive geriatric assessment.1 It is vital that the neurological system is not neglected in favour of traditionally optimised organ systems during the peri-operative period. But what are some recommendations which should be considered? Whilst preoperative cognitive screening is frequently performed, evidence is strengthening for the association of delirium with frailty and the need to link frailty screening with preoperative cognitive screening to identify patients at high risk of postoperative delirium.9 Whilst assessing preoperative cognition and frailty is certainly valuable, the question remains as to whether the presence and detection of mental health disorders should also play a role in identifying patients at risk of postoperative neurological complications. For instance, depression screening before cardiac surgery may be effective in identifying patients at higher risk of postoperative delirium, whilst preoperative anxiety has been shown to be associated with an increased risk of executive function decline following oncological surgery.10 Therefore, perhaps a preoperative combination of assessing cognition, frailty and mental health disorders for patients (eg, older than 65 years) may confer a more robust approach to identifying patients at high-risk of postoperative neurological complications. The POPS service is a positive and demonstrable example of the feasibility and efficacy of identifying and optimising elderly patients at high-risk of perioperative complications using comprehensive geriatric assessment.1 Perhaps healthcare systems should consider implementing stratification systems and formalised assessment practices encompassing a combination of additional variables alongside age and physical co-morbidities, such as mental health disorders and frailty, alongside cognition, to identify patients that would benefit most from comprehensive assessment and optimisation, potentially using the POPS model as an example of an established clinical approach to implementing such as service across surgical specialities. Overall, ensuring that patients achieve the best possible peri-operative neurological outcomes will require time, research, financial investment, re-education, and re-organisation of current practice to encourage the safe and expedient recovery of patients back to their families, workplaces, and society.

Letters to the Editor offer ways for readers to engage with authors' publications. Letters are the shortest manuscript for medical students to publish and medical-education journals are best suited. The UK Foundation Programme rewards medical students achieving PubMed ID publications and we hypothesise that this is a main motivation for medical students to submit Letters to the Editor. A review of 15 medical-education journals with an impact factor was conducted to identify numbers and percentages of Letters to the Editor by medical students between July 2018 and June 2020. Affiliation of medical students was collected. Our results show over two years, 299 letters were published by medical students equating to 45.9% of total letters. There was a 60% overall increase in letters by medical students published in the first 12 months compared to second 12 months. During this period overall numbers of letters published increased by 27%. 86% of the letters published by medical students over the two-year period were from UK medical schools. Five schools accounted for 60.5% of these letters. The three medical schools with highest numbers of letters published were King's College London, Imperial College London and University of Oxford for both 2018/19 and 2019/20. The increase in letters published overall with greater numbers published by students, may indicate greater awareness of Letters to the Editor as means of dissemination amongst medical students. UK medical schools published large numbers of letters, perhaps reflecting increasing importance to students of publications due to impacting on subsequent jobs. Results from our quantitative research revealing: large numbers of letters by medical students, increase in letters published from 2018/19 to 2019/20 and overrepresentation of UK medical students supports the hypothesis that medical students are publishing letters to achieve PubMed IDs. Further qualitative research is required to test our hypothesis.

Epithelial–mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. This study aims to investigate the effects of valproic acid (VPA) on EMT in vitro and in vivo. In vitro, EMT was induced by the administration of transforming growth factor-β1 (TGF-β1) in a human alveolar epithelial cell line (A549). The dose effects of VPA (0.1–3 mM) on EMT were subsequently evaluated at different timepoints. VPA (1 mM) was applied prior to the administration of TGF-β1 and the expression of E-cadherin, vimentin, p-Smad2/3 and p-Akt was assessed. In addition, the effects of a TGF-β type I receptor inhibitor (A8301) and PI3K-Akt inhibitor (LY294002) on EMT were evaluated. In vivo, the effects of VPA on bleomycin-induced lung fibrosis were evaluated by assessing variables such as survival rate, body weight and histopathological changes, whilst the expression of E-cadherin and vimentin in lung tissue was also evaluated. A8301 and LY294002 were used to ascertain the cellular signaling pathways involved in this model. The administration of VPA prior to TGF-β1 in A549 cells prevented EMT in both a time- and concentration-dependent manner. Pretreatment with VPA downregulated the expression of both p-Smad2/3 and p-Akt. A8301 administration increased the expression of E-cadherin and reduced the expression of vimentin. LY294002 inhibited Akt phosphorylation induced by TGF-β1 but failed to prevent EMT. Pretreatment with VPA both increased the survival rate and prevented the loss of body weight in mice with pulmonary fibrosis. Interestingly, both VPA and A8301 prevented EMT and facilitated an improvement in lung structure. Overall, pretreatment with VPA attenuated the development of pulmonary fibrosis by inhibiting EMT in mice, which was associated with Smad2/3 deactivation but without Akt cellular signal involvement.

Endovascular aneurysm repair (EVAR) is a well-established minimally invasive technique that relies on x-ray guidance to introduce a stent through the femoral artery and manipulate it into place. The aim of this study was to estimate patient organ and effective doses from EVAR procedures using anatomically realistic computational phantoms and detailed exposure information from radiation dose structured reports (RDSR). Methods: Lookup tables of conversion factors relating kerma area product (P-KA) to organ doses for 49 different beam angles were produced using Monte Carlo simulations (MCNPX2.7) with International Commission on Radiological Protection (ICRP) adult male and female voxel phantoms for EVAR procedures of varying complexity (infra-renal, fenestrated/branched and thoracic EVAR). Beam angle specific correction factors were calculated to adjust doses according to x-ray energy. A MATLAB function was written to find the appropriate conversion factor in the lookup table for each exposure described in the RDSR, perform energy corrections and multiply by the respective exposure P-KA. Using this approach, organ doses were estimated for 183 EVAR procedures in which RDSRs were available. A number of simplified dose estimation methodologies were also investigated for situations in which RDSR data are not available. Results: Mean estimated bone marrow doses were 57 (range: 2-247), 86 (2-328) and 54 (8-250) mGy for infra-renal, fenestrated/branched and thoracic EVAR, respectively. Respective effective doses were 27 (1-208), 54 (1-180) and 37 (5-167) mSv. Dose estimates using non-individualised, average conversion factors, along with those produced using the alternative Monte Carlo code PCXMC, yielded reasonably similar results overall, though variation for individual procedures could exceed 100% for some organs. In conclusion, radiation doses from x-ray guided endovascular aneurysm repairs are potentially high, though this must be placed in the context of the life sparing nature and high success rate for this procedure.

For various end-stage lung diseases, lung transplantation remains one of the only viable treatment options. While the demand for lung transplantation has steadily risen over the last few decades, the availability of donor grafts is limited, which have resulted in progressively longer waiting lists. In the early years of lung transplantation, only the ‘ideal’ donor grafts are considered for transplantation. Due to the donor shortages, there is ongoing discussion about the safe use of ‘suboptimal’ grafts to expand the donor pool. In this review, we will discuss the considerations around donor selection, donor-recipient matching, graft preparation and graft optimisation.

NETosis is a type of regulated cell death dependent on the formation of neutrophil extracellular traps (NET), where net-like structures of decondensed chromatin and proteases are produced by polymorphonuclear (PMN) granulocytes. These structures immobilise pathogens and restrict them with antimicrobial molecules, thus preventing their spread. Whilst NETs possess a fundamental anti-microbial function within the innate immune system under physiological circumstances, increasing evidence also indicates that NETosis occurs in the pathogenic process of other disease type, including but not limited to atherosclerosis, airway inflammation, Alzheimer's and stroke. Here, we reviewed the role of NETosis in the development of organ injury, including injury to the brain, lung, heart, kidney, musculoskeletal system, gut and reproductive system, whilst therapeutic agents in blocking injuries induced by NETosis in its primitive stages were also discussed. This review provides novel insights into the involvement of NETosis in different organ injuries, and whilst potential therapeutic measures targeting NETosis remain a largely unexplored area, these warrant further investigation.

NETosis is a type of regulated cell death dependent on the formation of neutrophil extracellular traps (NET), where net-like structures of decondensed chromatin and proteases are produced by polymorphonuclear (PMN) granulocytes. These structures immobilise pathogens and restrict them with antimicrobial molecules, thus preventing their spread. Whilst NETs possess a fundamental anti-microbial function within the innate immune system under physiological circumstances, increasing evidence also indicates that NETosis occurs in the pathogenic process of other disease type, including but not limited to atherosclerosis, airway inflammation, Alzheimer’s and stroke. Here, we reviewed the role of NETosis in the development of organ injury, including injury to the brain, lung, heart, kidney, musculoskeletal system, gut and reproductive system, whilst therapeutic agents in blocking injuries induced by NETosis in its primitive stages were also discussed. This review provides novel insights into the involvement of NETosis in different organ injuries, and whilst potential therapeutic measures targeting NETosis remain a largely unexplored area, these warrant further investigation.

Postoperative sleep disturbance is a common occurrence with significant adverse effects on patients including delayed recovery, impairment of cognitive function, pain sensitivity and cardiovascular events. The development of postoperative sleep disturbance is multifactorial and involves the surgical inflammatory response, the severity of surgical trauma, pain, anxiety, the use of anesthetics and environmental factors such as nocturnal noise and light levels. Many of these factors can be managed perioperatively to minimize the deleterious impact on sleep. Pharmacological and non-pharmacological treatment strategies for postoperative sleep disturbance include dexmedetomidine, zolpidem, melatonin, enhanced recovery after surgery (ERAS) protocol and controlling of environmental noise and light levels. It is likely that a combination of pharmacological and non-pharmacological therapies will have the greatest impact; however, further research is required before their use can be routinely recommended.

The COVID-19 pandemic has precipitated the worst global recession in decades. Academic institutions inevitably have been affected through cuts to funding. The charity sector, a significant source of research funding, has particularly suffered from loss of income. National lockdowns and social distancing measures implemented by laboratories have had a detrimental impact on laboratory research, with researchers being forced to temporarily abandon biological experiments.