Search

ABSTRACT Host-bacterial interactions over the course of aging are understudied due to complexities of the human microbiome and challenges of collecting samples that span a lifetime. To investigate the role of host-microbial interactions in aging, we performed transcriptomics using wild-type Caenorhabditis elegans (N2) and three long-lived mutants (daf-2, eat-2, and asm-3) fed Escherichia coli OP50 and sampled at days 5, 7.5, and 10 of adulthood. We found host age is a better predictor of the E. coli expression profiles than host genotype. Specifically, host age was associated with clustering (permutational multivariate analysis of variance [PERMANOVA], P = 0.001) and variation (Adonis, P = 0.001, R2 = 11.5%) among E. coli expression profiles, whereas host genotype was not (PERMANOVA, P > 0.05; Adonis, P > 0.05, R2 = 5.9%). Differential analysis of the E. coli transcriptome yielded 22 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 100 KEGG genes enriched when samples were grouped by time point [LDA, linear discriminant analysis; log(LDA), ≥2; P ≤ 0.05], including several involved in biofilm formation. Coexpression analysis of host and bacterial genes yielded six modules of C. elegans genes that were coexpressed with one bacterial regulator gene over time. The three most significant bacterial regulators included genes relating to biofilm formation, lipopolysaccharide production, and thiamine biosynthesis. Age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, building on a growing literature of host-microbial interactions. IMPORTANCE Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans, including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans. The manuscript represents the first study, to our knowledge, to perform temporal host-microbial transcriptomics in the model organism C. elegans. Understanding changes to the microbial transcriptome over time is an important step toward elucidating host-microbial interactions and their potential relationship to aging. We found that age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, which contributes to our growing knowledge about host-microbial interactions.

Urban tree canopy (UTC) coverage, or area, is an important metric for monitoring changes in UTC over large areas within a municipality. Several methods have been used to obtain these data, but remote sensing image classification is one of the fastest and most reliable over large areas. However, most studies have tested only one or two classification methods to accomplish this while using costly satellite imagery or LiDAR data. This study seeks to compare three urban tree canopy cover classifiers by testing a deep learning U-Net convolutional neural network (CNN), support vector machine learning classifier (SVM) and a random forests machine learning classifier (RF) on cost-free 2012 aerial imagery over a small southern USA city and midsize, growing southern USA city. The results of the experiment are then used to decide the best classifier and apply it to more recent aerial imagery to determine canopy changes over a 10-year period. The changes are subsequently compared visually and statistically with recent urban heat maps derived from thermal Landsat 9 satellite data to compare the means of temperatures within areas of UTC loss and no change. The U-Net CNN classifier proved to provide the best overall accuracy for both cities (89.8% and 91.4%), while also requiring the most training and classification time. When compared spatially with city heat maps, city periphery regions were most impacted by substantial changes in UTC area as cities grow and the outer regions get warmer. Furthermore, areas of UTC loss had higher temperatures than those areas with no canopy change. The broader impacts of this study reach the urban forestry managers at the local, state/province, and national levels as they seek to provide data-driven decisions for policy makers.

John Dickinson commenced the discourse, as "He wished to know what was meant by the 'testimony of two witnesses;' whether they were to be witnesses to the same overt act, or to different overt acts."[11] Dickinson expressed a strong preference that the two witness the same overt act, and the Convention generally concurred. Treason is the only criminal offense defined in the Constitution, and as such, allegations of the crime are sparsely levied. 71 Chapin, "Colonial and Revolutionary Origins of the American Law of Treason", 10. 72 The following statutes included two-witness standards: An Act to punish Treasons and disaffected Persons, and for the Security of the Government (1777) in Delaware. New Jersey in 1668 and the New Plymouth Colony in 1671 mandated two or three witnesses in any case concerning taking away a man's life.[61] In 1676, New Jersey extended the reach of the witness requisite to all matters, mandating "at least" two witnesses.[62] The Massachusetts Bay Colony utilized the requirement for treason charges in 1678 in a fashion heavily reflecting the British tradition, though without specifying treasonous acts as did 25 Edw. [Extracted from the article]

Abstract Background Placebo-controlled surgical trials are recognised as the gold standard way to test the efficacy of a surgical procedure. Despite a rise in arthroscopic subacromial decompression (ASD) surgeries for the treatment of shoulder pain, only two placebo-controlled surgical trials have been conducted. These trials encountered significant recruitment challenges, threatening the external validity of findings. Difficulties with recruitment are common in clinical trials and likely to be amplified in placebo-controlled surgical trials. This mixed method feasibility trial aims to address the following questions: (i) Feasibility: What proportion of patients who have consented to undergo ASD report that they would be willing to enrol in a placebo-controlled trial for this procedure? (ii) Optimisation: Can patients’ willingness to enrol in, or understanding of, such a trial be improved by supplementing written consent materials with a brief visual animation that outlines the details of the trial? And (iii) exploration: What factors influence patients stated willingness to enrol in such a trial, and how do they believe the recruitment process could be improved? Methods This study aims to recruit 80 patients on the waiting list for ASD. Participants will be randomised (1:1) to either view a brief video animation explaining the hypothetical placebo-controlled trial in addition to written information or to written information only. Participants in both groups will be required to state if they would be willing to opt-in to the hypothetical ASD trial after immediately being presented with the consent material and again 1 week after completion of the consent process. Patients in both groups will also be required to complete a measure of trial literacy. Twenty participants will be purposively sampled to take part in an embedded qualitative study exploring understanding of trial concepts and factors contributing to willingness to opt-in. Discussion This feasibility study will provide evidence for optimising participant recruitment into a placebo-controlled trial of ASD by consenting patients using animated trial information in addition to written information. This pilot and feasibility data may also be relevant to placebo-controlled surgical trials more broadly, which are characterised by recruitment challenges. Trial registration ANZCTR, ACTRN12620001132932 , date October 30, 2020

Plain English summary Involving consumers and community members in the research process is an important step towards developing and delivering effective, person-centered health care. The National Health and Medical Research Council have provided recommendations for involving consumers and community members in research; however, definitive actions to implement these are not well defined. To address this, an established research centre in Melbourne, Australia, has developed a consumer and community involvement framework to incorporate the national recommendations into their research program. This paper describes the framework the research centre has employed, in the hope that other researchers can adapt this approach and learnings to their own research practices. The framework described in this paper aims to foster partnerships between consumers, community members and researchers, and in doing so, encourages consumers to be actively involved in research to help improve future outcomes for those living with musculoskeletal conditions. Simultaneously, the framework encourages researchers to value the consumer voice in their research to ensure they yield meaningful research outcomes for those living with musculoskeletal conditions. Abstract Background The value of involving consumers and community members in every stage of the research process is gaining recognition as an important consideration in the wider research landscape. The National Health and Medical Research Council (NHMRC) has provided general recommendations for involving consumers and community members in research, although the translation of these recommendations into tangible actions has not yet been well defined. In light of these recommendations, many research institutions are now seeking to incorporate the voices of consumers and community members in their research practices. Methods The consumer and community involvement framework described in this paper incorporates the NHMRC’s recommendations to produce a four-tiered model where consumer participants nominate their level of involvement depending on their research interests and preferred level of commitment. In ascending order, the tiers are: Consumer Subscriber, Document Reviewer, Research Buddy and Consumer Advocate. The success of this framework depends upon the implementation of effective governance and access to appropriate infrastructure. A Consumer and Community Advisory Group and a designated Consumer and Community Liaison Officer will take responsibility for ensuring appropriate interactions between consumers, researchers, and the research center’s executive team. The framework aims to apply suitable support structures in place to manage expectations and minimize barriers to effective involvement, whilst ensuring that consumer contributions are appropriately valued and incorporated in the research. Discussion Involving consumers and community members in the research process is an important step towards developing and delivering effective, person-centered health care. While consumer and community involvement offer researchers invaluable perspectives on their research program, it provides an opportunity for consumers and community members to be actively involved in health research and improve the health and wellbeing for those living with health conditions.

Purpose The St Vincent’s Melbourne Arthroplasty Outcomes (SMART) Registry is an institutional clinical registry housed at a tertiary referral hospital in Australia. The SMART Registry is a pragmatic prospective database, which was established to capture a broad range of longitudinal clinical and patient-reported outcome data to facilitate collaborative research that will improve policy and practice relevant to arthroplasty surgery for people with advanced arthritis of the hip or knee. The purpose of this cohort profile paper is to describe the rationale for the SMART Registry’s creation, its methods, baseline data and future plans for the Registry. A full compilation of the data is provided as a reference point for future collaborators.Participants The SMART Registry cohort comprises over 13 000 consecutive arthroplasty procedures in more than 10 000 patients who underwent their procedure at St Vincent’s Hospital Melbourne, since January 1998. Participant recruitment, data collection and follow-up is ongoing and currently includes up to 20 years follow-up data.Findings to date SMART Registry data are used for clinical audit and feedback, as well as for a broad range of research including epidemiological studies, predictive statistical modelling and health economic evaluations. At the time of writing, there were 46 publications from SMART Registry data, with contributions from more than 67 coauthors.Future plans With the recent linking of the SMART Registry with Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data through the Australian Institute of Health and Welfare, research into prescribing patterns and health system utilisation is currently underway. The SMART Registry is also being updated with the Clavien-Dindo classification of surgical complications.

Single-photon emission computerized tomography (SPECT) is a tool which can be used to image perfusion in the brain. Clinicians can use such images to help diagnose dementias such as Alzheimer's disease. Due to the intrinsic stochasticity in the photon imaging system, some form of statistical comparison of an individual image with a 'normal' patient database gives a clinician additional confidence in interpreting the image. Due to the variations between SPECT camera systems, ideally a normal patient database is required for each individual system. However, cost or ethical considerations often prohibit the collection of such a database for each new camera system. Some method of adapting existing normal patient databases to new camera systems would be beneficial. This paper introduces a method which may be regarded as a 'first-pass' attempt based on 2-norm regularization and a codebook of discrete spatially stationary convolutional kernels. Some preliminary illustrative results are presented, together with discussion on limitations and possible improvements. [ABSTRACT FROM AUTHOR]

Over the past two decades, there has been a sharp rise in the use of prescription opioids. In several countries, most notably the United States, opioid-related harm has been deemed a public health crisis. As surgeons are among the most prolific prescribers of opioids, growing attention is now being paid to the role that opioids play in surgical care. While opioids may sometimes be necessary to provide patients with adequate relief from acute pain after major surgery, the impact of opioids on the quality and safety of surgical care calls for greater scrutiny. This narrative review summarizes the available evidence on rates of persistent postsurgical opioid use and highlights the need to target known risk factors for persistent postoperative use before patients present for surgery. We draw attention to the mounting evidence that preoperative opioid exposure places patients at risk of persistent postoperative use, while also contributing to an increased risk of several other adverse clinical outcomes. By discussing the prevalence of excess opioid prescribing following surgery and highlighting significant variations in prescribing practices between countries, we note that there is a pressing need to optimize postoperative prescribing practices. Guided by the available evidence, we call for specific actions to be taken to address important research gaps and alleviate the harms associated with opioid use among surgical patients.

Inherited coagulopathies are reported in a number of dog breeds. However, to date, there is no report of Weimaraners suffering factor VIII deficiency (haemophilia A). We report the discovery of haemophilia A in both males from a single litter of Weimaraners. Haemophilia A in human beings often results from a de novo stochastic mutation. We found no evidence using currently available screening tests of haemophilia A in relatives as far back as three generations making a stochastic mutation possible in this litter. [ABSTRACT FROM AUTHOR]

Abstract Background Precise identification of bacterial pathogens at the strain level is essential for epidemiological purposes. In Streptococcus pneumoniae, the existence of 90 different serotypes makes the typing particularly difficult and requires the use of highly informative tools. Available methods are relatively expensive and cannot be used for large-scale or routine typing of any new isolate. We explore here the potential of MLVA (Multiple Loci VNTR Analysis; VNTR, Variable Number of Tandem Repeats), a method of growing importance in the field of molecular epidemiology, for genotyping of Streptococcus pneumoniae. Results Available genome sequences were searched for polymorphic tandem repeats. The loci identified were typed across a collection of 56 diverse isolates and including a group of serotype 1 isolates from Africa. Eventually a set of 16 VNTRs was proposed for MLVA-typing of S. pneumoniae. These robust markers were sufficient to discriminate 49 genotypes and to aggregate strains on the basis of the serotype and geographical origin, although some exceptions were found. Such exceptions may reflect serotype switching or horizontal transfer of genetic material. Conclusion We describe a simple PCR-based MLVA genotyping scheme for S. pneumoniae which may prove to be a powerful complement to existing tools for epidemiological studies. Using this technique we uncovered a clonal population of strains, responsible for infections in Burkina Faso. We believe that the proposed MLVA typing scheme can become a standard for epidemiological studies of S. pneumoniae.

The introduction of smaller footprint, more sensitive Cadmium-Zinc-Telluride (CZT)-based detectors with improved spatial and energy resolution has enabled the design of innovative full-ring 360° CZT SPECT/CT systems (e.g., VERITON ® and StarGuide™). With this transformative technology now aiming to become mainstream in clinical practice, several critical questions need to be addressed. This EANM position paper provides practical recommendations on how to use these devices for routine bone SPECT/CT studies, facilitating the transition from traditional planar whole-body imaging and conventional SPECT/CT to these novel systems. In particular, initial guidance is provided on imaging acquisition and reporting workflows, image reconstruction, and CT acquisition parameters. Given the emerging nature of this technology, the available evidence base is still limited, and the proposed adaptations in workflows and scan protocols will likely evolve before being integrated into definitive guidelines. In the meantime, this EANM position paper serves as a comprehensive guide for integrating these advanced hybrid SPECT/CT imaging systems into clinical practice and outlining areas for further study., Competing Interests: Declarations. Competing interests: RG has received honoraria from GE Healthcare. The department LI is associated with is a Spectrum Dynamics reference site for the Veriton SPECT/CT. All other authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a common cause of dementia characterized by the presence of two proteinaceous deposits in the brain. These pathologies may be a consequence of complex interactions between neurons and glia before the onset of cognitive impairments. Curcumin, a bioactive compound found in turmeric, is a promising candidate for AD because it alleviates neuropathologies in mouse models of the disease. Although its clinical efficacy has been hindered by low oral bioavailability, the development of new formulations may overcome this limitation. The purpose of this study was to determine the effects of a bioavailable curcumin formulation in a mouse model of AD. The formulation was administered to mice in drinking water after encapsulation into micelles using a previously validated method. A neuropathological assessment was performed to determine if it slows or alters the course of the disease. Cognitive performance was not included because it had already been assessed by a previous study. The bioavailable curcumin formulation was unable to alter the size or number of amyloid plaques in a transgenic mouse model. In addition, mechanisms that regulate amyloid beta production were unchanged, suggesting that the disease had not been altered. The number of reactive astrocytes in the hippocampus and dentate gyrus was not altered by curcumin. However, protein levels of glial fibrillary acidic protein were increased overall in the brain, suggesting that it may have aggravated neuroinflammation. Therefore, a higher dosage, despite its enhanced oral bioavailability, may have a potential risk for neuroinflammation., Competing Interests: The authors, Larisa Bobrovskaya, the Editorial Member, and Xin‐Fu Zhou, the Editor‐in‐Chief of Ibrain, were both excluded from all decisions. Editorial decision‐making is handled independently by Editor‐in‐Chief, Professor Ting‐Hua Wang to minimize bias. Xin‐Fu Zhou is a named inventor of the curcumin formulation used in this study, Chinese patent 201610267974.5. The remaining authors declare no conflicts of interest., (© 2024 The Author(s). Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

Introduction: Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar-capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions., Methods: Sixty trained male triathletes (age 39 ± 9 years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar-capillary membrane diffusing capacity for carbon monoxide (DM CO ). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV 1 ), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DM CO /alveolar volume) were compared with those without these dysfunctions., Results: The race lasted 14 h 20 min ± 1 h 26 min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E', which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328 mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (- 26 ± 13 versus - 15 ± 9%, P = 0.001) and positively correlated with DM CO /alveolar volume reduction., Conclusion: After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar-capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise., (© 2024. The Author(s).)

The early transition to Alzheimer's disease is characterized by a period of accelerated brain atrophy that exceeds normal ageing. Identifying the molecular basis of this atrophy could facilitate the discovery of novel drug targets. The precursor of brain-derived neurotrophic factor, a well characterized neurotrophin, is increased in the hippocampus of aged rodents, while its mature isoform is relatively stable. This imbalance could increase the risk of Alzheimer's disease by precipitating its pathological hallmarks. However, less is known about how relative levels of these isoforms change in middle-aged mice. In addition, the underlying mechanisms that might cause an imbalance are unknown. The main aim of this study was to determine how precursor brain-derived neurotrophic factor changes relative to its mature isoform with normal brain ageing in wild type mice. A secondary aim was to determine if signaling through the neurotrophin receptor, p75 influences this ratio. An increasing ratio was identified in several brain regions, except the hippocampus, suggesting a neurotrophic imbalance occurs as early as middle age. Some changes in receptors that mediate the isoforms effects were also identified, but these did not correspond with trends in the isoforms. Relative amounts of precursor brain-derived neurotrophic factor were mostly unchanged in mutant p75 mice. The lack of changes suggested that signaling through the receptor had no influence on the ratio., (© 2023. The Author(s).)

This guideline must be read in conjunction with the British Nuclear Medicine Society (BNMS) Generic guidelines. The purpose of this guideline is to assist specialists in Nuclear Medicine and Radionuclide Radiology in recommending, performing, interpreting and reporting the results of bone scintigraphy studies. This guideline could also be used to help individual departments formulate their own local protocols. This does not aim to be prescriptive regarding technical aspects of individual camera acquisitions, which should be developed in conjunction with the local medical physics expert., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: SARS-CoV-2 infection can induce cardiac damage. Therefore, in the absence of clear data, a cardiac evaluation was recommended for athletes before returning to play after recent SARS-CoV-2 infection., Aim: To assess the proportion of anomalies detected by this cardiac screening., Methods: We reviewed the medical files of elite athletes referred for cardiac evaluation before returning to play after a non-hospitalized SARS-CoV-2 infection (based on a positive polymerase chain reaction or antigen test) from March 2020 to July 2021 in 12 French centres., Results: A total of 554 elite athletes (professional or national level) were included (median age 22 years, 72.0% male). An electrocardiogram (ECG), echocardiogram and exercise test were performed in 551 (99.5%), 497 (89.7%) and 293 (52.9%) athletes, respectively. We found anomalies with a potential link with SARS-CoV-2 infection in four ECGs (0.7%), three echocardiograms (0.6%) and three exercise tests (1.0%). Cardiac magnetic resonance imaging was performed in 34 athletes (6.1%), mostly due to abnormal first-line examinations, and was abnormal in one (2.9%). The rates of those abnormalities were not higher among athletes with cardiac symptoms or more severe forms of non-hospitalized SARS-CoV-2 infection. Only one athlete had a possible SARS-CoV-2 myocarditis and sport was temporally contraindicated. None had a major cardiac event declared during the follow-up., Conclusion: The proportion of cardiac involvement after non-hospitalized forms of SARS-CoV-2 infection in athletes are very low. Systematic cardiac screening before returning to play seems to be unnecessary., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID)., Objectives: The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes., Methods: 950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR)., Results: 285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+) prevalent ); 206 (28.3%) during follow-up (COVID(+) incident )]. 2.6% COVID(+) athletes had abnormal ECGs, while 0.4% had an abnormal echocardiogram. During stress testing (following 7-day rest), COVID(+) athletes had a functional capacity of 12.8 ± 2.7 METS with only stress-induced premature ventricular ectopy in 10 (4.3%). Prevalence of CMR scar was comparable between COVID(+) athletes and controls [COVID(+) vs. COVID(-); 1/102 (1.0%) vs 1/28 (3.6%)]. During 289 ± 56 days follow-up, one athlete had ventricular tachycardia, with no obvious link with a SARS-CoV-2 infection. The proportion with troponin I and CRP values above the upper-limit threshold was comparable between pre- and post-infection (5.9% vs 5.9%, and 5.6% vs 8.7%, respectively). The proportion with D-Dimer values above the upper-limit threshold increased when comparing pre- and post-infection (7.9% vs 17.3%, P = 0.01)., Conclusion: The absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503)., (© 2022. The Author(s).)

Alzheimer's disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer's disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer's disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease's progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer's disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer's disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer's disease., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Aims: To explore whether the novel 360° gamma camera design of VERITON-CT adversely affects the rate of scan non-completion due to claustrophobia or other patient experience factors, when compared to a standard dual-headed gamma camera. Methods: Single centre prospective study of all nuclear medicine studies on either of two gamma cameras; the VERITON-CT (Spectrum Dynamics Medical) and Discovery NM/CT 670 (GE Healthcare). It was recorded whether the patient had completed the scan as protocoled or, due to claustrophobia, had a shortened scan or no scan. The patients were also offered a patient experience questionnaire, with domains of comfort, scan time, scan noise and claustrophobia assessed using a five-point Likert scale. Results: Over a four-month period, there were 296 patients scanned on the Discovery scanner and 274 patients scanned on the VERITON-CT scanner. There was a scan non-completion rate, due to claustrophobia, of 1.35 % for the Discovery and 1.46 % for the VERITON-CT scanner. 354/570 (62%) of all patients involved returned their questionnaires. There was no statistical difference between the responses for comfort, scan time, scan noise and feelings of claustrophobia. Conclusion: The study provides evidence that the novel 360° gamma camera design of VERITON-CT does not lead to a significantly increased scan failure rate due to claustrophobia and there is no change in the subjective experience for patients., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objective: Afibrinogenaemic haemorrhage was previously reported in a Maine Coon cat. Two littermates subsequently died from surgical non-haemostasis, suggesting a hereditable coagulopathy., Methods: We prospectively recruited cats which were: a) Maine Coons with pathological haemorrhage (group 1, n=8), b) healthy familial relatives of group 1 (group 2, n=13) and c) healthy Maine Coons unrelated to groups 1 and 2 (group 3, n=12). Coagulation tests: prothrombin time, activated partial thromboplastin time and thrombin clotting time (TCT) were performed on citrated plasma along with quantification of fibrinogen. Routine haematological examination was performed on EDTA-anticoagulated blood collected contemporaneously., Results: Thirty-three blood samples were analysed. Fibrinogen concentrations were significantly reduced in groups 1 (P<0.01) and 2 (P<0.01) compared with group 3. Similarly, TCT was found to be significantly extended in group 1 (P<0.01) and group 2 (P=0.02) with respect to group 3., Conclusions: Dysfibrinogenaemia was identified in clinical cases and their healthy relatives, suggesting that this may represent a hereditary condition of Maine Coon cats. Clinicians should be aware of the increased potential for non-haemostasis in this cat breed and consider assessing clotting function before (elective) surgery., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Electronic waste (E-waste) recycling is a rapidly growing occupation in the USA with the potential for elevated exposure to flame retardants and metals associated with electronic devices. We previously measured polybrominated diphenyl ethers (PBDEs) in plasma from E-waste workers and found them similar to non-E-waste workers. This study focused on structurally related PBDE derivatives, the hydroxylated (OH-PBDEs) and methoxylated (MeO-PBDEs) forms along with metals known to occur in E-waste. Humans can metabolize PBDEs and some MeO-PBDEs into OH-PBDEs, which is a concern due to greater health risks associated with OH-PBDEs. We measured 32 different OH-PBDEs and MeO-PBDEs in plasma samples provided by 113 volunteers living in the greater Puget Sound region of Washington State, USA. We measured 14 metals in a subset of 10 E-waste and 10 non-E-waste volunteers. Volunteers were selected based on occupational and dietary habits: work outdoors and consume above average amounts of seafood (outdoor), electronic waste recycling (E-waste) or non-specific indoor occupations (indoor). A two-week food consumption diary was obtained from each volunteer prior to blood sampling. OH-PBDEs were detected in all volunteers varying between 0.27 and 102 ng/g/g-lipid. The MeO-PBDEs were detected in most, but not all volunteers varying between n.d. - 60.4 ng/g/g-lipid. E-waste recyclers had OH-PBDE and MeO-PBDE plasma levels that were similar to the indoor group. The outdoor group had significantly higher levels of MeO-PBDEs, but not OH-PBDEs. Comparison of plasma concentrations of BDE-47 with its known hydroxylated metabolites suggested OH-PBDE levels were likely determined by biotransformation and at least two subpopulations identified differing in their apparent rates of OH-PBDE formation. The metals analysis indicated no significant differences between E-waste workers and non-E-waste workers. Our results indicate E-waste workers do not have elevated plasma levels of these contaminants relative to non-E-waste workers., Competing Interests: Declaration of competing interest The other authors declare they have no actual or potential competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: This audit investigated hepatobiliary function imaging in UK hospitals, reviewing protocol differences in acquisition and processing parameters and the effect on calculated gallbladder ejection fraction (GBEF)., Participants and Methods: Two dynamic data sets were available: one continuous dynamic data set, and the other with a 5-min break to administer the fatty stimulus. Participants used a set of 12 anonymized patient data sets most similar to their standard protocol calculating GBEF using their routine method., Results: Fifty-two UK centres responded. Across all centres for all data sets, there was large variability in GBEF quoted, mostly owing to variations in the calculation method, motion correction and imaging type/times. The largest contributor to GBEF variation was time acquired after stimulus which varied from 20 to 70 min. Only 48.1% centres acquired for 60 min after stimulus, which is the acquisition time stated in normal range references. Overall, 13.5% participating centres administered fatty stimuli that fell below the recommended 10 g. Widespread variations were found in GBEF normal ranges and fatty stimulus administration. Motion correction has a large effect on GBEF; in one data set, motion correction alone changed GBEF from 44 to 9%, but 25% of the participants stated motion correction was not used., Conclusion: The authors proposed gold standard is fat content of the stimulus should be at least 10 g; and images should be acquired for 60 min after stimulus. If GBEF is quoted, motion correction should be used, and if compared with a normal range, the stimulus used must fit with the reference.

Aims: Percutaneous left atrial appendage (LAA) occlusion is occasionally incomplete, with residual permeability of the LAA on cardiac computed tomography. The cause for this is unclear. Our objective was to determine if residual permeability was related to incomplete endothelialization., Methods: A total of 35 consecutive patients contraindicated for anticoagulant therapy admitted for LAA occlusion were included; 12 patients received a Watchman device (Boston Scientific) and 23 patients received an Amplatzer Cardiac Plug (St. Jude Medical). Incomplete endothelialization was defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography at follow-up., Results: Five patients did not receive cardiac computed tomography. After 10 ± 6 months of follow-up, residual permeability of the LAA (at least partial) was recorded on cardiac computed tomography in 21 of 30 patients (70%). Seven of 30 patients presented with a peridevice leak on transesophageal echocardiography. Among the remaining 23 patients, 14 (61%) presented with incomplete endothelialization and 9 (39%) presented with complete endothelialization. There was no statistical difference between the patients presenting with complete vs incomplete endothelialization., Conclusion: We found that incomplete endothelialization, defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography, occurred in 61% of the patients after 10 ± 6 months of percutaneous LAA closure. Predisposing factors and appropriate monitoring of LAA patients remain to be determined in larger cohorts.

Background: Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI)., Aim: The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard)., Patients and Methods: A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment., Results: I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02)., Conclusion: In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to construct in silico experiments using an intuitive graphical 'strategy' approach. The current release of the database integrates microbial census data with sample details for nearly 14 000 samples originating from human, animal and environmental sources, including over 9000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The gut microbiome is a novel frontier in xenobiotic metabolism. Polybrominated diphenyl ethers (PBDEs), especially BDE-47 (2, 2', 4, 4'-tetrabromodiphenyl ether) and BDE-99 (2, 2', 4, 4',5-pentabromodiphenyl ether), are among the most abundant and persistent environmental contaminants that produce a variety of toxicities. Little is known about how the gut microbiome affects the hepatic metabolism of PBDEs and the PBDE-mediated regulation of drug-processing genes (DPGs) in vivo. The goal of this study was to determine the role of gut microbiome in modulating the hepatic biotransformation of PBDEs. Nine-week-old male C57BL/6J conventional (CV) or germ-free (GF) mice were treated with vehicle, BDE-47 or BDE-99 (100 μ mol/kg) for 4 days. Following BDE-47 treatment, GF mice had higher levels of 5-OH-BDE-47 but lower levels of four other metabolites in liver than CV mice; whereas following BDE-99 treatment GF mice had lower levels of four minor metabolites in liver than CV mice. RNA sequencing demonstrated that the hepatic expression of DPGs was regulated by both PBDEs and enterotypes. Under basal conditions, the lack of gut microbiome upregulated the Cyp2c subfamily but downregulated the Cyp3a subfamily. Following PBDE exposure, certain DPGs were differentially regulated by PBDEs in a gut microbiome-dependent manner. Interestingly, the lack of gut microbiome augmented PBDE-mediated upregulation of many DPGs, such as Cyp1a2 and Cyp3a11 in mouse liver, which was further confirmed by targeted metabolomics. The lack of gut microbiome also augmented the Cyp3a enzyme activity in liver. In conclusion, our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs., (Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context., Aims: To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI)., Methods: All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization., Results: Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P=0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03mg/L vs 21.86mg/L, respectively; P=0.36), even after adjustment for type of culprit artery (26.99 vs 24.99mg/L, respectively; P=0.79)., Conclusion: In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts. To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. EuPathDB is updated with numerous new analysis tools, features, data sets and data types. New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host-pathogen interactions., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Cardiac biomarkers including troponins are the cornerstone of the biological definition of acute myocardial infarction. New high-sensitivity cardiac assays determining troponin T (hs-cTnT) as well as I ((hs-cTnI) from Abbott and s-cTnI from Siemens) raise concerns because of their unclear kinetics following the peak., Aims: This study aims to compare kinetics of creatine kinases, hs-cTnT, hs-cTnI and s-cTnI in patients with ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention., Methods: We prospectively studied 106 consecutive patients admitted in our institution for STEMI and treated by percutaneous coronary intervention. We evaluated for all the patients simultaneously kinetics of creatine kinases, hs-cTnT (Roche) and two different cTnIs (hs-cTnI from Abbott and s-cTnI from Siemens). Modelling of kinetics was realized using mixed effects with cubic splines., Results: Kinetics of markers showed a first peak at 10.7h (8.0-12.0) for creatine kinases, 11.8h (10.4-13.3) for hs-cTnT (Roche); 11.8h (10.7-11.8) for hs-cTnI from Abbott and 10.2h (8.7-11.6) for s-cTnI from Siemens, respectively. This peak was followed by a nearly log linear decrease for hs-cTnI/s-cTnI and creatine kinases in contrast to hs-cTnT, which appeared with a biphasic shape curve marked by a second peak at 76.9h (69.5-82.8). The analysis of the decrease in percentage of the peak value at 77h showed that hs-cTnT follows a twice lower decrease than other markers., Conclusion: Kinetics of hs-cTnT, hs-cTnI and s-cTnI differ significantly with a linear decrease regarding both cTnI assays contrasting with a biphasic shape curve for hs-cTnT. This is of importance for clinical management of patients in routine settings especially in follow-up after STEMI including the suspicion of reinfarction., (© The European Society of Cardiology 2015.)

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Background: Cardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI)., Methods: We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines., Results: Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9-12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1-99.9) vs. cTnI by 86.8% (76.6-92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9-42.9) when compared with CK that fell by 79.5% (64.3-90.7)., Conclusions: Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.

Background: Several trials investigating erythropoietin as a novel cytoprotective agent in myocardial infarction (MI) failed to translate promising preclinical results into the clinical setting. These trials could have missed crucial events occurring in the first few minutes of reperfusion. Our study differs by earlier intracoronary administration of a longer-acting erythropoietin analogue at the onset of reperfusion., Aim: To evaluate the ability of intracoronary administration of darbepoetin-alpha (DA) at the very onset of the reperfusion, to decrease infarct size (IS)., Methods: We randomly assigned 56 patients with acute ST-segment elevation MI to receive an intracoronary bolus of DA 150 μg (DA group) or normal saline (control group) at the onset of reflow obtained by primary percutaneous coronary intervention (PCI). IS and area at risk (AAR) were evaluated by biomarkers, cardiac magnetic resonance (CMR) and validated angiographical scores., Results: There was no difference between groups regarding duration of ischemia, Thrombolysis in Myocardial Infarction flow grade at admission and after PCI, AAR size and extent of the collateral circulation, which are the main determinants of IS. The release of creatine kinase was not significantly different between the two groups even when adjusted to AAR size. Between 3-7 days and at 3 months, the area of hyperenhancement on CMR expressed as a percentage of the left ventricular myocardium was not significantly reduced in the DA group even when adjusted to AAR size., Conclusion: Early intracoronary administration of a longer-acting erythropoietin analogue in patients with acute MI at the time of reperfusion does not significantly reduce IS., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)