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86) between groups. Median survival was 29 months in those receiving AC within 45 days and was 28 months in those receiving AC at other timepoints. On multivariable analysis, delay in receipt of AC beyond 45 days was not associated with inferior survival. This was preserved when time to AC was analyzed as a continuous variable (HR 1.0, 95% CI 1.0-1.0). CONCLUSIONS Timing of initiation of AC following esophagectomy does not appear to impact survival. Given the highly variable post-operative course following esophagectomy, the decision to start AC should involve multidisciplinary discussion and be made on a patient-by-patient basis. NMDA receptors are widely expressed throughout the brain on many cell types, and loss of function of these receptors (ie NMDAr hypofunction) is a candidate mechanism explaining working memory impairment in schizophrenia. However, the cellular source driving the working memory deficits caused by NMDA hypofunction has not been explored. The aim of this study was to assess the contribution of NMDAr on pyramidal cells and parvalbumin (PV+) interneurons to impairments in working memory induced by NMDAr hypofunction. We excised GluN1 - the gene encoding the obligatory subunit of the NMDAr from PV + interneurons or CaMKII + pyramidal cells - using Cre-lox technology. Adult male PV GluN1 KO (n = 10) and CaMKIIα GluN1 KO mice (n = 9) and WT controls (n = 10 and n = 13) were trained to perform the Trial-Unique Nonmatching-to-Location (TUNL) task of working memory. Once trained, mice received the NMDA receptor antagonist MK-801 (0.1 and 0.3 mg/kg ip), and working memory assessed. Neither task acquisition nor working memory differed between the two transgenic lines and WT littermates. MK-801 dose-dependently decreased working memory accuracy in all strains (p less then 0.001). PV GluN1 KO mice were sensitised to the impairing effects of MK-801 (p = 0.04), whereas CaMKIIα GluN1 KO mice showed equivalent working memory deficits as WT. Developmental NMDAr hypofunction at either PV + interneurons or forebrain pyramidal cells is not sufficient to impair working memory, and neither of these cell types exclusively mediates working memory impairment caused by NMDA receptor antagonism. Reduced NMDAr signalling at PV + interneurons could predispose circuits to NMDAr hypofunction magnifying deficits in working memory. Aging is characterized by the deterioration of different cellular and organismal structures and functions. A typical hallmark of the aging process is the accumulation of dysfunctional mitochondria and excess iron, leading to a vicious cycle that promotes cell and tissue damage, which ultimately contribute to organismal aging. Accordingly, altered mitochondrial quality control pathways such as mitochondrial autophagy (mitophagy) as well as altered iron homeostasis, with consequent iron overload, can accelerate the aging process and the development and progression of different age-associated disorders. In this review we first briefly introduce the aging process and summarize molecular mechanisms regulating mitophagy and iron homeostasis. We then provide an overview on how dysfunction of these two processes impact on aging and age-associated neurodegenerative disorders with a focus on Alzheimer's disease, Parkinson's disease and Amyotrophic Lateral Sclerosis. Finally, we summarize some recent evidence showing mechanistic links between iron metabolism and mitophagy and speculate on how regulating the crosstalk between the two processes may provide protective effects against aging and age-associated neuronal pathologies. V.The diagnosis of Parkinson's disease (PD) is made relatively late in the pathological process, when already most of the dopaminergic synapses have died. The evidence showed that, at the time of the clinical diagnosis, which can be done only after motor symptoms' appearance, the pathogenetic process is too advanced for a potential neuroprotective agent to be efficacious. Thus, the identification of early markers of neurodegeneration would be essential in the fight again the disease. A growing body of literature reported that non-motor symptoms, including sleep disorders, are commonly the earliest manifestation of the disease (i.e. prodromal stage). Furthermore, evidence claimed that these disturbances may have an impact on the progression of the disease itself, possibly altering its phenotype and leading to the emergence of levodopa-induced dyskinesia (LID), a typical treatment-related complication. The early recognition of subjects at risk of developing PD would offer the opportunity to evaluate the efficacy of possible neuroprotective agents. Additionally, the early identification of sleep alterations, which could possibly be considered an indicator of aberrant brain plasticity and thus be helpful in predicting the emergence of LID, if confirmed, would offer a platform for testing possible sleep targeted therapies able to protect the patients from the development of this treatment-induced condition. In this review, new techniques for the study of sleep will be addressed, in order to investigate their possible role as diagnostic and prognostic tools in the evaluation of patients suffering from PD. V.The transition from a naïve to an effector T cell is an essential event that requires metabolic reprogramming. We have recently demonstrated that the rapid metabolic changes that occur following stimulation of naïve T cells require the translation of preexisting mRNAs. Here, we provide evidence that translation regulates the metabolic asset of effector T cells. By performing ribosome profiling in human CD4+ Th1 cells, we show that the metabolism of glucose, fatty acids and pentose phosphates is regulated at the translational level. In Th1 cells, each pathway has at least one enzyme regulated at the translational level and selected enzymes have high translational efficiencies. Bemnifosbuvir mRNA expression does not predict protein expression. For instance, PKM2 mRNA is equally present in naïve T and Th1 cells, but the protein is abundant only in Th1. 5'-untranslated regions (UTRs) may partly account for this regulation. Overall we suggest that immunometabolism is controlled by translation. Sarcoidosis is a relatively rare inflammatory condition which potentially carries high morbidity and substantial mortality. Due to the fact that it does not subject patients to ionizing radiation, has high temporal, spatial and contrast resolutions, cardiovascular magnetic resonance imaging (CMR) has become an important diagnostic and prognostic modality in the evaluation for cardiac involvement in this condition. This review provides relevant clinical and pathophysiological background on cardiac sarcoidosis, whilst detailing the role of CMR imaging in the diagnosis, and management of this condition. BACKGROUND Venom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity. METHODS This was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deprived SV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs. It is estimated that approximately 300 million people worldwide are affected by asthma, and the number of patients affected is growing exponentially-with potential for an additional 100 million people affected by the condition by 2025.1 With this increasing burden of disease, there is high motivation to discover effective prevention strategies. Strategies aimed at stalling the atopic progression, modifying the microbiome, preventing respiratory viral infections, and reducing the impact of toxin/pollutant exposure through dietary supplements have had limited success in the prevention of asthma. This is likely because asthma is heterogenous, and influenced by different genetic and environmental factors. Genes underlie a predisposition to asthma and allergic sensitization, while exposure to allergens, respiratory infections, and pollution may modify asthma pathogenesis and the variation in severity seen among individuals. Future advances in asthma prevention may include a more personalized approach genetic variations among susceptible individuals with distinct asthma phenotypes, or different biomarkers of disease may help individualize prevention strategies and render them more effective. In this article, we summarize interventions that have been studied for the prevention of asthma and identify some of the clinical trials that are actively underway in asthma prevention. Acute respiratory distress syndrome (ARDS) is a lethal form of acute respiratory failure, and as no specific treatments exist, supportive care remains the primary management strategy in these patients. Extracorporeal membrane oxygenation (ECMO) has emerged as an intervention in patients with severe ARDS to facilitate gas exchange and the delivery of more lung protective ventilation. Over the past 20 years, improvements in ECMO technology has increased its safety and transportability, making it far more available to this patient population globally. Deciding which patients with ARDS should be initiated on ECMO remains a challenging question. Numerous clinical and laboratory markers have been investigated, and multiple risk scores developed, to aid clinicians in this decision-making process. However, they are still imperfect, and the choice is often based on institutional guidelines and the clinical impression of the treating physician. Given the potential risks and resource implications for this intervention, patient selection is critical and it is important to provide ECMO only to patients who have a reasonable chance for recovery or bridge to transplantation. In ECMO patients where there is no potential for recovery or transplant, the only option may be withdrawal of ECMO and palliation. These patients may be awake and interactive, which is often a very challenging scenario for patients, families, and the clinical team. In this article, we present a more controversial case and a review of the literature regarding the selection of ARDS patients who should receive ECMO. BACKGROUND When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and for public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. We aimed to assess whether changes in case definitions affected inferences on the transmission dynamics of coronavirus disease 2019 (COVID-19) in China. METHODS We examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used exponential growth models to estimate how changes in the case definitions affected the number of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic. FINDINGS From Jan 15 to March 3, 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. We estimated that when the case definitions were changed, the proportion of infections being detected as cases increased by 7·1 times (95% credible interval [CrI] 4·8-10·9) from version 1 to 2, 2·8 times (1·9-4·2) from version 2 to 4, and 4·2 times (2·6-7·3) from version 4 to 5.
