The proteome of the infectious bronchitis virus Beau-R Virion

Infectious bronchitis is a highly contagious respiratory disease of poultry caused by the coronavirus IBV. It was thought that coronavirus virions were composed of three major viral structural proteins, until investigations of other coronaviruses showed that coronavirus virions also include viral non-structural and group specific proteins as well as host cell proteins. To study the proteome of IBV virions, virus was grown in embryonated chicken eggs and purified by sucrose gradient ultracentrifugation and analysed by mass spectrometry proteomic. Analysis of three preparations of purified IBV yielded the three expected structural proteins plus thirty-five additional virion-associated host proteins. Virion-associated host proteins had a diverse range of functional attributions, being involved in cytoskeleton formation, RNA binding and protein folding pathways. Some of these proteins were unique to this study, whilst others were found to be orthologous to proteins identified in SARS-CoV virions, and also virions from a number of other RNA and DNA viruses. Together these results demonstrate that coronaviruses have the capacity to incorporate a substantial variety of host protein, which may have implications for the disease process

Increasing incidence of spondylodiscitis in England: an analysis of the national health service (NHS) hospital episode statistics from 2012 to 2021

Background Spondylodiscitis is a potentially life-threatening infection of the intervertebral disk and adjacent vertebral bodies, with a mortality rate of 2–20%. Given the aging population, the increase in immunosuppression, and intravenous drug use in England, the incidence of spondylodiscitis is postulated to be increasing; however, the exact epidemiological trend in England remains unknown. Objective The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise the annual activity and longitudinal change of spondylodiscitis in England. Methods The HES database was interrogated for all cases of spondylodiscitis between 2012 and 2019. Data for the length of stay, waiting time, age-stratified admissions, and ‘Finished Consultant Episodes’ (FCEs), which correspond to a patient's hospital care under a lead clinician, were analysed. Results In total, 43135 FCEs for spondylodiscitis were identified between 2012 and 2022, of which 97.1% were adults. Overall admissions for spondylodiscitis have risen from 3 per 100,000 population in 2012/13 to 4.4 per 100,000 population in 2020/21. Similarly, FCEs have increased from 5.8 to 10.3 per 100,000 population, in 2012–2013 and 2020/21 respectively. The highest increase in admissions from 2012 to 2021 was recorded for those aged 70–74 (117% increase) and aged 75-59 (133% increase), among those of working age for those aged 60–64 years (91% increase). Conclusion Population-adjusted admissions for spondylodiscitis in England have risen by 44% between 2012 and 2021. Healthcare policymakers and providers must acknowledge the increasing burden of spondylodiscitis and make spondylodiscitis a research priority

Conservative or surgical treatment of pyogenic spinal infection: a retrospective multicenter binational retrospective cohort study [Abstract]

Spinal Tumors / Infections (Spine Parallel Session v.3), September 27, 2023, 8:30 AM - 10:00 AM Background: The optimal treatment of patients with spinal infections remains a controversial topic. While there is some consensus regarding the indication for surgical intervention in infections with neurologic deficit, significant deformity or progressive disease, other situations remain controversial. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis. Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit. Results: A total of 392 patients were included in the analysis (155 females and 237 males with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). Most of conservatively treated patients were treated in the United Kingdom (CoT 81/ SuT 7), while most of the surgically treated cases were treated in Germany (CoT 14/ SuT 290). There was no significant difference (p<0.01) related to patient’s disease characteristics: Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (CoT 20/, SuT 71, p=0.57), renal failure (CoT 19/ SuT 60, p= 0.97), hepatopathy (CoT 4/ SuT 26, p= 0.15), malignoma (CoT 9/ SuT 38, p=0.39) or i.v. drug abuse (CoT 5/, SuT 15, p=0.93) did also not differ between the groups. The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92). Conclusions: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen

Conservative versus early surgical treatment in the management of pyogenic spondylodiscitis: a systematic review and meta-analysis [Abstract]

Oral e-Poster Presentations - Booth 2: Spine 1 (Trauma&Misc), September 25, 2023, 10:00 AM - 10:40 AM Background: Spondylodiscitis is a prevalent type of spinal infection, with pyogenic spondylodiscitis being the most common subtype. While antibiotic therapy is the standard treatment, some argue that early surgery can aid in infection clearance, improve survival rates, and prevent long-term complications such as deformities. However, others view early surgery as excessively risky. Due to the high mortality rate of up to 20%, it is crucial to determine the most effective treatment. Methods: The primary objective of this study was to compare the mortality rate, relapse rate, and length of hospital stay for conservative and early surgical treatments of pyogenic spondylodiscitis, including determinants of outcomes. The study was registered on PROSPERO with the registration number CRD42022312573. The databases MEDLINE, Embase, Scopus, PubMed, and JSTOR were searched for original studies comparing conservative and early surgical treatments of pyogenic spondylodiscitis. The included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using meta-analyses, influence, and regression analyses. Results: The systematic review included 31 studies. The meta-analysis, which had a pooled sample size of 10,954 patients from 21 studies, found that the pooled mortality rate among patients treated with early surgery was 8%, while the rate was 13% for patients treated conservatively. The mean proportion of relapse/failure was 15% for patients treated with early surgery and 21% for those treated conservatively. Furthermore, the analysis concluded that early surgical treatment is associated with a 40% and 39% risk reduction in relapse/failure and mortality rates, respectively, when compared to conservative management. Additionally, early surgical treatment resulted in a 7.75-day reduction in length of hospital stay per patient (p<0.01). The most highly significant predictors of treatment outcome were found to be intravenous drug use, diabetes, the presence of an epidural abscess, positive cultures, location of infection, and age (p<0.001). Conclusions: Overall, early surgical management was found to be consistently significantly more effective than conservative management in terms of relapse/failure and mortality rates when treating pyogenic spondylodiscitis, particularly for non-spinal epidural abscess spondylodiscitis

Dementias show differential physiological responses to salient sounds.

Abnormal responsiveness to salient sensory signals is often a prominent feature of dementia diseases, particularly the frontotemporal lobar degenerations, but has been little studied. Here we assessed processing of one important class of salient signals, looming sounds, in canonical dementia syndromes. We manipulated tones using intensity cues to create percepts of salient approaching ("looming") or less salient withdrawing sounds. Pupil dilatation responses and behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent aphasia, n = 12; amnestic Alzheimer's disease, n = 10) and a cohort of 26 healthy age-matched individuals. Approaching sounds were rated as more salient than withdrawing sounds by healthy older individuals but this behavioral response to salience did not differentiate healthy individuals from patients with dementia syndromes. Pupil responses to approaching sounds were greater than responses to withdrawing sounds in healthy older individuals and in patients with semantic dementia: this differential pupil response was reduced in patients with progressive nonfluent aphasia and Alzheimer's disease relative both to the healthy control and semantic dementia groups, and did not correlate with nonverbal auditory semantic function. Autonomic responses to auditory salience are differentially affected by dementias and may constitute a novel biomarker of these diseases

Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex

The Tim50 subunit of the mitochondrial TIM23 complex contains a presequence-binding domain that is essential for viability and precursor transport across the inner membrane

Electricity Spot Market Design 2030-2050

Driven by the climate conference in Paris in December 2015 countries worldwide are confronted with the question of how to shape their power system and how to establish alternative technologies to reduce harmful CO2 emissions. The German government plans that even before the year 2050, all electricity generated and consumed in Germany should be greenhouse gas neutral [1]. To successfully integrate renewable energies, a future energy system must be able to handle the intermittent nature of renewable energy sources such as wind and solar. One important means to address such electricity production variability is demand-side flexibility. Here, industry plays a major role in responding to variable electricity supply with adequate flexibility. This is where the Kopernikus project SynErgie comes in with more than 80 project partners from academia, industry, governmental, and non-governmental organizations as well as energy suppliers and network operators. The Kopernikus project SynErgie investigates how to best leverage demand-side flexibility in the German industry. The current electricity market design in Germany is not well suited to deal with increasing levels of renewable energy, and it does not embrace demand-side flexibility. Almost 6GW of curtailed power in 2019 provide evidence that changes are needed with respect to the rules governing electricity markets. These rules were designed at a time when electricity generation was concentrated on a few large and dispatchable conventional power plants and demand was considered inelastic. The SynErgie Cluster IV investigates how a future-proof electricity market design should be organized. The corresponding Work Package IV.3.1 more specifically deals with analyzing and designing allocation and pricing rules on electricity spot markets. The resulting design must be well suited to accommodate demand-side flexibility and address the intermittent nature of important renewable energy sources. This whitepaper is the result of a fruitful collaboration among the partners involved in SynErgie Cluster IV which include Germany’s leading research organizations and practitioners in the field. The collaboration led to an expert workshop in October 2020 with participation from a number of international energy market experts such as Mette Bjørndal (NHH), Endre Bjørndal (NHH), Peter Cramton (University of Maryland and University of Cologne), and Raphael Heffron (University of Dundee). The whitepaper details the key recommendations from this workshop. In particular, the whitepaper recommends a move to a locational, marginal price-based system together with new bidding formats allowing to better express flexibility. We argue in favor of a one-step introduction of locational, marginal prices instead of repeatedly splitting existing zones. Frequent zone splitting involves recurring political debates as well as short- and long-run instabilities affecting the basis for financial contracts, for example. Importantly, the definition of stable prize zones is very challenging with increasing levels of distributed and renewable energy sources. The recommendation is the outcome of an intense debate about advantages and downsides of different policy alternatives. However, such a transition to locational, marginal prices is not without challenges, and it is a call to arms for the research community, policymakers, and practitioners to develop concepts on how to best facilitate the transition and ensure a reliable and efficient electricity market of the future

Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics

This review is a summary of factors affecting the drug pharmacokinetics (PK) of dogs versus humans. Identifying these interspecies differences can facilitate canine-human PK extrapolations while providing mechanistic insights into species-specific drug in vivo behavior. Such a cross-cutting perspective can be particularly useful when developing therapeutics targeting diseases shared between the two species such as cancer, diabetes, cognitive dysfunction, and inflammatory bowel disease. Furthermore, recognizing these differences also supports a reverse PK extrapolations from humans to dogs. To appreciate the canine-human differences that can affect drug absorption, distribution, metabolism, and elimination, this review provides a comparison of the physiology, drug transporter/enzyme location, abundance, activity, and specificity between dogs and humans. Supplemental material provides an in-depth discussion of certain topics, offering additional critical points to consider. Based upon an assessment of available state-of-the-art information, data gaps were identified. The hope is that this manuscript will encourage the research needed to support an understanding of similarities and differences in human versus canine drug PK.This article is published as Martinez, Marilyn N., Jonathan P. Mochel, Sibylle Neuhoff, and Devendra Pade. "Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics." The AAPS Journal 23 (2021): 59. DOI: 10.1208/s12248-021-00590-0.</p