Blood-Pressure Reduction Is Associated With Worsening In Renal Function But Does Not Prevent Successful Decongestion In Patients Treated For Acute Decompensated Heart Failure

Background: Reductions in blood pressure are common during the treatment of acute decompensated heart failure (ADHF) and strongly associated with worsening renal function (WRF). However, it is unclear whether a decline in systolic blood pressure (SBP), and the associated deterioration in renal function, might limit successful diuresis. Methods: We analyzed consecutive admissions with a primary discharge diagnosis of ADHF (n=657). Metrics of diuresis were assessed for their association with a decline in SBP from admission to discharge in addition to the use or titration of guideline recommended heart failure therapies (GDMT). SBP-reduction was defined as a relative reduction in SBP greater than the median value (\u3e9.9%). Results: Overall 77.6% of the population had a discharge SBP lower than the admission value. SBP-reduction resulted in significantly higher rates of WRF (OR= 1.9, p=0.004). Despite the negative impact on renal function, SBP-reduction was not associated with worse diuretic efficiency (p=0.274). Furthermore, the rate of hemoconcentration, net fluid loss, weight loss, adjuvant thiazide diuretic use, and loop diuretic infusion use was not different for patients with an SBP-reduction (p≤0.293for all). GDMT such as ACE-Is and beta blockers were associated with SBP-reduction but not with metrics of decongestion. Conclusion: Despite apparent negative effects on renal function, a reduction in blood pressure or titration of GDMT did not appear to limit successful decongestion

The Evolution of Molecular Compatibility between Bacteriophage ΦX174 and its Host

Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture. Engineered to include codons with a lesser usage and/or tRNA abundance within the host, three different attenuated strains of the bacterial virus ФX174 were created and propagated via serial transfers. Molecular sequence data indicate that biosynthetic compatibility was recovered rapidly. Extensive computational simulations were performed to assess the role of mutational biases as well as selection for translational efficiency in the engineered phage. Using bacteriophage as a model system, we can begin to unravel the evolutionary processes shaping codon compatibility between viruses and their host

The Impact of Increased Awareness of Acute Kidney Injury in the Neonatal Intensive Care Unit on Acute Kidney Injury Incidence and Reporting: Results of a Retrospective Cohort Study

Objective: To evaluate the impact of nephrology integration in the NICU on acute kidney injury (AKI) incidence, provider reporting, and nephrology referral. Study design: Cohort study in a single-center NICU from January 2012 to December 2017 (n = 1464). We assessed the impact of clinical practice changes including neonatal-nephrology rounds on the incidence of AKI. Results: AKI occurred in 318 neonates (22%). AKI occurred less frequently in those admitted after clinical practice changes (P < 0.001). After multivariable adjustment, clinical practice changes were associated with reduced odds of AKI (adjusted odds ratio, 0.31; 95% CI 0.22-0.44, P < 0.001). Provider reporting of AKI improved (P < 0.001) and more neonates were referred for nephrology follow-up (P < 0.001). Conclusions: Increased nephrology integration in the NICU was associated with decreased AKI incidence. While recognition of AKI improved, AKI remained poorly reported and nephrology AKI follow-up did not routinely occur. This study supports the importance of increased nephrology involvement in the NICU

Frailty and bone health in European men

© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health.Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre.Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05).Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Experimental Evolution of Specialism in a Wild Virus

A pathogen\u27s ability to successfully replicate and persist within a new host population is fraught with obstacles. While an expanded host-range allows for a greater chance at successful replication, such generalists are typically outcompeted by species which have specialized and adapted host-specific features. Although the most ubiquitous species on earth, very few bacteria-infecting viral species (bacteriophages) with truly broad host-ranges have been identified; this is partially due to the fact that only a small fraction of bacteria (and thus likely hosts) are amenable to laboratory conditions. Nevertheless, the processes of expanding as well as narrowing host-range are not well understood despite their profound importance for furthering our understanding of viral pathogens, be it bacteriophages or viral species impacting human health. Following the successful isolation of novel bacteriophage named ФHabibi, we identified this generalist species\u27 broad host-range, including several Enterobacteriaceae. In order to examine the cost of generalism, we propagated 30 lines of ФHabibi: 10 lines were exposed only to naïve E. coli C cells, 10 lines were exposed only to naïve P. aeruginosa, and 10 alternated every 16 generations between naïve populations of the two (serving as a control). While no reduction in fitness was observed on either host population for the control lines, this was not the case for either of the experimental conditions. Lines propagated through E. coli C cultures were more fit in E. coli C. Likewise, lines propagated through P. aeruginosa cultures were more fit in P. aeruginosa. Moreover, specialization as well as changes in phage development, from lytic to lysogenic and pseudolysogenic, were observed as a result of restricting host diversity thus providing insight into the cost and consequences of host-range

Experimental Investigations of Spatial Eco-Evolutionary Dynamics in Laboratory Saccharomyces cerevisiae

The study of eco-evolutionary dynamics has expanded in recent years due to the increasing recognition that evolution can occur much more quickly than previously thought. Eco-Evolutionary dynamics is a complex field of study with two main components: ecological processes and evolutionary responses. Eco-evolutionary dynamics examines how ecological and evolutionary processes interact with each other. By understanding ecological processes and evolutionary responses and how these two processes interact, we can better understand how populations will respond to environmental changes. Laboratory experiments provide an opportunity to explore the complex nature of eco-evolutionary dynamics while isolating for specific factors. Some factors that can impact eco-evolutionary dynamics are resource availability, competition, diffusion, and environmental stress. To further expand knowledge of coevolutionary dynamics, Saccharomyces cerevisiae, commonly known as baker's yeast, was used as a model organism to set up laboratory experiments. The first examination was to determine if populations could establish coexistence and if that coexistence would be maintained over time. The second examination was how resource distribution and population diffusion impact total population abundance. The third examination was an empirical study on whether a resident population in a deteriorating environment can adapt in time to stave off an invading population. The research of eco-evolutionary dynamics can be used to help understand how populations evolve and can adapt to environmental conditions

Editorial: The relevance of molecular mechanisms in HIV-1 latency and reactivation from latency

SCOPUS: ed.jinfo:eu-repo/semantics/publishe