Background and objective
The COVID‐19 pandemic has caused disruption to health, social interaction, travel and economies worldwide. In New Zealand, the government closed the border to non‐residents ...and required all arrivals to quarantine for 14 days. They also implemented a strict contact‐restriction system to eliminate COVID‐19 from the community. These measures also reduced the circulation of other respiratory viruses such as influenza and respiratory syncytial virus. We assessed the impact of these measures on hospital admissions for respiratory and cardiac diseases.
Methods
National data on hospital admissions for each week of 2020 were compared to admissions for the previous 5 years. Analyses were curtailed after week 33, when a COVID‐19 outbreak in Auckland led to different levels of pandemic restrictions making national data difficult to interpret.
Results
The numbers of acute infectious respiratory admissions were similar to previous years before the introduction of COVID‐19 restrictions, but then fell lower and remained low after the pandemic restrictions were eased. The usual winter peak in respiratory admissions was not seen in 2020. Other than small reductions during the period of the strictest contact restrictions, non‐infectious respiratory and cardiac admissions were similar to previous years and the usual winter peak in heart failure admissions was observed.
Conclusion
The observed patterns of hospital admissions in 2020 are compatible with the hypothesis that circulating respiratory viruses drive the normal seasonal trends in respiratory admissions. By contrast, these findings suggest that respiratory viruses do not drive the winter peak in heart failure.
COVID‐19 pandemic restrictions in New Zealand led to marked reductions in circulating respiratory viruses and winter infectious respiratory admissions. There was little change in cardiac admissions, suggesting that respiratory viruses play a central role in seasonal respiratory admissions but not the winter peak in heart failure.
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BackgroundNon-invasive ventilation (NIV), although effective in treating hypercapnic respiratory failure, has not demonstrated the same efficacy in treating acute hypoxaemic respiratory failure. We ...aimed to examine the effect of NIV use on ventilator-free days in patients with acute hypoxaemic respiratory failure admitted to the intensive care unit (ICU).MethodsWe conducted a retrospective study of patients admitted to the ICU with acute hypoxaemic respiratory failure at Waikato Hospital, New Zealand, from 1 January 2009 to 31 December 2018. Patients treated with NIV as the initial oxygenation strategy were compared with controls treated with early intubation. The two groups were matched using a propensity score based on baseline characteristics. The primary outcome was the number of ventilator-free days at day 28. The secondary outcomes were ICU and hospital length of stay and in-hospital mortality.ResultsOut of 175 eligible patients, 79 each out of the NIV and early intubation groups were matched using a propensity score. Early NIV was associated with significantly higher median ventilator-free days than early intubation (17 days vs 23 days, p=0.013). There was no significant difference in median ICU length of stay (112.5 hours vs 117.7 hours), hospital length of stay (14 days vs 14 days) or in-hospital mortality (31.6% vs 37.9%) between the NIV and the early intubation group.ConclusionCompared with early intubation, NIV use was associated with more ventilator-free days in patients with hypoxaemic respiratory failure. However, this did not translate into a shorter length of stay or reduced mortality based on our single-centre experience.
COPD patients often have cardiac comorbidities. Cardiac involvement at the time of a COPD exacerbation is associated with a high short-term mortality, but whether this influences long-term outcomes ...is unknown. We explored whether biomarkers of cardiac dysfunction at the time of a COPD exacerbation predict long-term outcomes.
Two prospective cohorts of patients admitted to Waikato Hospital for exacerbations of COPD were recruited during 2006-2007 and 2012-2013. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured on admission and were used to indicate cardiac stretch and myocardial injury, respectively. 5-year survival after discharge and subsequent admissions for cardiac disease and COPD exacerbations were analysed using Kaplan-Meier and Cox proportional hazards tests.
The overall 5-year mortality was 61%. Patients with high NT-proBNP on admission had higher mortality than those with normal cardiac biomarkers (adjusted hazard ratio (aHR) 1.76, 95% CI 1.18-2.62). High NT-proBNP was also associated with a higher risk of future cardiac admissions (aHR 1.75, 95% CI 1.2-2.55). Troponin T levels were not associated with long-term survival (aHR 0.86, 95% CI 0.40-1.83) or future cardiac admissions (aHR 0.74, 95% CI 0.34-1.57). Neither biomarker predicted future COPD exacerbations.
The long-term prognosis following a hospitalisation for an exacerbation of COPD is poor with less than half of patients surviving for 5 years. Elevated NT-proBNP at the time of a COPD exacerbation is associated with higher long-term mortality and a greater likelihood of future cardiac admissions, but not future COPD exacerbations.
Mitochondrial Ca2+ Uniporter (MCU)-dependent mitochondrial Ca2+ uptake is the primary mechanism for increasing matrix Ca2+ in most cell types. However, a limited understanding of the MCU complex ...assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1) have severely impaired Ca2+m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca2+-dependent mitochondrial metabolism.
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•MCUR1 binds to MCU and EMRE and functions as a scaffold factor•The coiled-coil domains of both MCU and MCUR1 are essential for MCU complex assembly•Genetic deletion of MCUR1 severely impairs Ca2+m uptake and IMCU current•MCUR1 deletion impairs bioenergetics and cell migration and elicits autophagy
Tomar et al. show that genetic ablation of the MCU complex component MCUR1 perturbs MCU heterooligomeric complex and impairs mitochondrial Ca2+ uptake. MCUR1 binds to MCU and EMRE and functions as a scaffold factor that is necessary for proper Ca2+-dependent mitochondrial bioenergetics.
To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and ...96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments. Additional analyses showed that early transfusion (within 3 days of hospital admission) of higher titer plasma is associated with lower patient mortality. These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized patients with COVID-19.
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Agents that inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS) have anti-cancer activity and our prior studies have investigated the structure-function relationship for a ...family of isoprenoid triazole bisphosphonates as GGDPS inhibitors. To further explore this structure-function relationship, a series of novel α-modified triazole phosphonates was prepared and evaluated for activity as GGDPS inhibitors in enzyme and cell-based assays. These studies revealed flexibility at the α position of the bisphosphonate derivatives with respect to being able to accommodate a variety of substituents without significantly affecting potency compared to the parent unsubstituted inhibitor. However, the monophosphonate derivatives lacked activity. These studies further our understanding of the structure-function relationship of the triazole-based GGDPS inhibitors and lay the foundation for future studies evaluating the impact of α-modifications on in vivo activity.
We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists ...of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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