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In comparison to the stable ones, 12 patients who experienced clinical end point had significantly higher baseline SUVRV/SUVLV ratio (1.21 (IQR 0.87-1.95) vs 0.53 (0.24-1.08), p=0.01) and lower RV ejection fraction (RVEF) (37.9±5.2 vs 46.8±5.7, p=0.03). Cox regression revealed that SUVRV/SUVLV ratio was significantly associated with the time to clinical end point. Kaplan-Meier analysis showed that combination of RVEF from MRI and SUVRV/SUVLV assessment may help to predict prognosis. Conclusions Increased RV glucose uptake in PET and decreased RVEF identify patients with PAH with worse prognosis. Combining parameters from PET and MRI may help to identify patients at higher risk who potentially benefit from therapy escalation, but this hypothesis requires prospective validation.Some jurisdictions have instituted limits on electronic cigarette (ECIG) liquid nicotine concentration, in an effort to control ECIG nicotine yield, and others are considering following suit. Because ECIG nicotine yield is proportional to the product of liquid nicotine concentration (milligram per millilitre) and device power (watts) regulations that limit liquid nicotine concentration may drive users to adopt higher wattage devices to obtain a desired nicotine yield. In this study we investigated, under various hypothetical regulatory limits on ECIG liquid nicotine concentration, a scenario in which a user of a common ECIG device (SMOK TF-N2) seeks to obtain in 15 puffs the nicotine emissions equivalent to one combustible cigarette (ie, 1.8 mg). We measured total aerosol and carbonyl compound (CC) yields in 15 puffs as a function of power (15-80 W) while all else was held constant. The estimated nicotine concentration needed to achieve combustible cigarette-like nicotine yield at each power level was then computed based on the measured liquid consumption. We found that for a constant nicotine yield of 1.8 mg, reducing the liquid nicotine concentration resulted in greater amount of liquid aerosolised (p less then 0.01) and greater CC emissions (p less then 0.05). Thus, if users seek a given nicotine yield, regulatory limits on nicotine concentration may have the unintended consequence of increasing exposure to aerosol and respiratory toxicants. This outcome demonstrates that attempting to control ECIG nicotine yield by regulating one factor at a time may have unintended health effects and highlights the need to consider multiple factors and outcomes simultaneously when designing regulations.Pseudomonas aeruginosa exhibits a high requirement for iron which it can acquire via several mechanisms including the acquisition and utilization of heme. The P. aeruginosa genome encodes two heme uptake systems, the heme assimilation system (Has) and the Pseudomonas heme utilization (Phu) system. Extracellular heme is sensed via the Has system, which encodes an extra cytoplasmic function (ECF) σ factor system. SEL120-34A mouse Previous studies have shown that transfer of heme from the extracellular hemophore HasAp to the outer membrane receptor HasR is required for activation of the σ factor HasI and up-regulation of has operon expression. Herein, employing site-directed mutagenesis, allelic exchange, quantitative PCR analyses, immunoblotting and 13C-heme uptake experiments, we delineated the differential contributions of the extracellular FRAP/PNPNL loop residue His-624 in HasR and of His-221 in its N-terminal plug domain required for heme capture to heme transport and signaling, respectively. Specifically, we show that substitution of the N-terminal plug His-221 disrupts both signaling and transport, leading to dysregulation of both the Has and Phu uptake systems. link2 Our results are consistent with a model wherein heme release from HasAp to the N-terminal plug of HasR is required to initiate signaling, whereas His-624 is required for simultaneously closing off the heme transport channel from the extracellular medium and triggering heme transport. Our results provide critical insight into heme release, signaling, and transport in P. aeruginosa and suggest a possible functional link between the ECF s factor and Phu heme uptake system.In this analysis we discuss the change in criteria for triage of patients during three different phases of a pandemic like COVID-19, seen from the critical care point of view. Availability of critical care beds has become a hot topic, and in many countries, we have seen a huge increase in the provision of temporary intensive care bed capacity. However, there is a limit where the hospitals may run out of resources to provide critical care, which is heavily dependent on trained staff, just-in-time supply chains for clinical consumables and drugs and advanced equipment. In the first (good) phase, we can still do clinical prioritisation and decision-making as usual, based on the need for intensive care and prognostication what are the odds for a good result with regard to survival and quality of life. In the next (bad phase), the resources are mostly available, but the system is stressed by many patients arriving over a short time period and auxiliary beds in different places in the hospital being used. We may have to abandon admittance of patients with doubtful prognosis. In the last (ugly) phase, usual medical triage and priority setting may not be sufficient to decrease inflow and there may not be enough intensive care unit beds available. In this phase different criteria must be applied using a utilitarian approach for triage. We argue that this is an important transition where society, and not physicians, must provide guidance to support triage that is no longer based on medical priorities alone.Key ethical challenges for healthcare workers arising from the COVID-19 pandemic are identified isolation and social distancing, duty of care and fair access to treatment. The paper argues for a relational approach to ethics which includes solidarity, relational autonomy, duty, equity, trust and reciprocity as core values. The needs of the poor and socially disadvantaged are highlighted. Relational autonomy and solidarity are explored in relation to isolation and social distancing. Reciprocity is discussed with reference to healthcare workers' duty of care and its limits. link3 Priority setting and access to treatment raise ethical issues of utility and equity. Difficult ethical dilemmas around triage, do not resuscitate decisions, and withholding and withdrawing treatment are discussed in the light of recently published guidelines. The paper concludes with the hope for a wider discussion of relational ethics and a glimpse of a future after the pandemic has subsided.The COVID-19 pandemic crisis has necessitated widespread adaptation of revised treatment regimens for both urgent and routine medical problems in patients with and without COVID-19. Some of these alternative treatments maybe second-best. Treatments that are known to be superior might not be appropriate to deliver during a pandemic when consideration must be given to distributive justice and protection of patients and their medical teams as well the importance given to individual benefit and autonomy. What is required of the doctor discussing these alternative, potentially inferior treatments and seeking consent to proceed? Should doctors share information about unavailable but standard treatment alternatives when seeking consent? There are arguments in defence of non-disclosure; information about unavailable treatments may not aid a patient to weigh up options that are available to them. There might be justified concern about distress for patients who are informed that they are receiving second-best therapies. However, we argue that doctors should tailor information according to the needs of the individual patient. For most patients that will include a nuanced discussion about treatments that would be considered in other times but currently unavailable. That will sometimes be a difficult conversation, and require clinicians to be frank about limited resources and necessary rationing. However, transparency and honesty will usually be the best policy.Objective To test a scalable health system intervention to improve long term adherence to secondary prevention treatments among patients who have had a recent myocardial infarction. Design Three arm, pragmatic randomised controlled trial with blinded outcome assessment. Setting Nine cardiac centres in Ontario, Canada. Participants 2632 patients with obstructive coronary artery disease after a myocardial infarction, identified from a centralised cardiac registry. Interventions Participants were randomised 111 to receive usual care, five mail-outs developed through a user centred design process, or mail-outs plus phone calls. The phone calls were delivered first by an interactive automated system to screen for non-adherence to treatment. Trained lay health workers followed up as necessary. Interventions were coordinated centrally but delivered from each patient's hospital site. Main outcome measures Co-primary outcomes were completion of cardiac rehabilitation and adherence to recommended medication. Data were phone can increase completion of cardiac rehabilitation after myocardial infarction but not adherence to medication. More intensive interventions should be tested to improve adherence to medication and to evaluate the association between attendance at cardiac rehabilitation and adherence to medication. Trial registration ClinicalTrials.gov NCT02382731, registered 9 March 2015 before any patient enrolment.Objective To evaluate potential risk factors that may make patients susceptible to nephrotoxicity in those concomitantly receiving vancomycin in the hospital. Methods This was a single-centre retrospective analysis of patients treated with vancomycin for gram-positive or mixed infections in the Renmin Hospital of Wuhan University from January 2017 to May 2018. All of them were treated for ≥48 hours and had no kidney disease. Nephrotoxicity refers to acute kidney diseases and disorders after the use of vancomycin, and includes acute kidney injury. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with nephrotoxicity. Results Of the 790 patients treated with vancomycin, only 257 patients met the inclusion criteria, and 40 (15.6%) subjects developed nephrotoxicity. Significant differences (p less then 0.05) were seen in the number of combined antimicrobials (p=0.012), dose adjustment (p less then 0.001), more than three antimicrobials (p=0.015), monitoring trough concentrations (p=0.001), furosemide (p less then 0.001), torasemide (p less then 0.001), cefoperazone sodium tazobactam sodium (p=0.039), voriconazole (p=0.012) and ganciclovir (p=0.008). Regression analysis further indicated that furosemide (OR 7.983, p less then 0.001) and torasemide (OR 3.496, p less then 0.001) were risk factors for vancomycin nephrotoxicity. Diabetes mellitus (OR 3.062, p=0.035), voriconazole (OR 3.515, p=0.020) and fluconazole (OR 3.326, p=0.018) might be also risk factors. Conclusion Fluconazole and voriconazole might be potential risk factors for vancomycin nephrotoxicity, besides furosemide and torasemide. It is not recommended to use imipenem cilastatin sodium and vancomycin at the same time. If necessary, meropenem may be safer. Appropriate combination drugs, cautious initial dose or timely dose adjustment might reduce the occurrence of nephrotoxicity when using vancomycin.

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