Search

Abstract Background Congenital portosystemic shunts (CPSS) are rare vascular malformations associated with the risk of life-threatening systemic conditions, which remain underdiagnosed and often are identified after considerable diagnostic delay. CPSS are characterized by multiple signs and symptoms, often masquerading as other conditions, progressing over time if the shunt remains patent. Which patients will benefit from shunt closure remains to be clarified, as does the timing and method of closure. In addition, the etiology and pathophysiology of CPSS are both unknowns. This rare disorder needs the strength of numbers to answer these questions, which is the purpose of the international registry of CPSS (IRCPSS). Method A retrospective and prospective registry was designed using secuTrial® by the ISO certified Clinical Research Unit. Given that a significant number of cases entered in the registry are retrospective, participants have the opportunity to use a semi-structured minimal or complete data set to facilitate data entry. In addition, the design allows subjects to be entered into the IRCPSS according to clinically relevant events. Emphasis is on longitudinal follow-up of signs and symptoms, which is paramount to garner clinically relevant information to eventually orient patient management. The IRCPSS includes also three specific forms to capture essential radiological, surgical, and cardiopulmonary data as many times as relevant, which are completed by the specialists themselves. Finally, connecting the clinical data registry with a safe image repository, using state-of-the-art pseudonymization software, was another major focus of development. Data quality and stewardship is ensured by a steering committee. All centers participating in the IRCPSS have signed a memorandum of understanding and obtained their own ethical approval. Conclusion Through state-of-the-art management of data and imaging, we have developed a practical, user-friendly, international registry to study CPSS in neonates, children, and adults. Via this multicenter and international effort, we will be ready to answer meaningful and urgent questions regarding the management of patients with CPSS, a condition often ridden with significant diagnostic delay contributing to a severe clinical course.

Objectives This study aimed to evaluate older people’s experience of a COVID-19 partial lockdown (16 March–11 May 2020) in Lausanne, Switzerland.Setting and participants Community-dwelling participants of the Lausanne cohort (Lc65+) in 2020, aged 71–86 years (n=2642).Design and outcome This cross-sectional study was nested within the Lc65+ longitudinal study. A specific COVID-19 questionnaire was sent on 17 April 2020 to evaluate participants’ experience of the lockdown (outcome). Multinomial logistic regression models were used to determine the sociodemographic, living environment, health and social factors associated.Results Out of 2642 participants, 67.8% described the lockdown as ‘somewhat’ difficult (reference group), 21.5% as ‘not at all’ difficult (positive) and 10.7% as ‘very or extremely’ difficult (negative). The relative risk of a positive experience was higher in participants living alone (relative risk ratio, RRR=1.93, 95% CI 1.52 to 2.46) or in a house (RRR=1.49, 1.03 to 2.16); lower in those who reported fear of falling (RRR=0.68, 0.54 to 0.86), functional difficulties (RRR=0.78, 0.61 to 0.99), feeling of loneliness (RRR=0.67, 0.49 to 0.91), unfamiliarity with communication technologies (RRR=0.69, 0.52 to 0.91), usual social support (RRR=0.71, 0.50 to 0.93), previous participation in group activities (RRR=0.74, 0.59 to 0.92) and among women (RRR=0.75, 0.59 to 0.95). The relative risk of a negative experience was higher in participants with fear of falling (RRR=1.52, 1.07 to 2.15), and lower in those who had a terrace/garden (RRR=0.66, 0.44 to 0.99) and owned a dog (RRR=0.32, 0.11 to 0.90).Conclusions Only one in 10 participants experienced the lockdown as very or extremely difficult. Specific interventions targeting vulnerability factors, such as fear of falling, could lessen the impact of any future similar situation.

Chemical protein synthesis enables access to proteins that would otherwise be difficult or impossible to obtain with traditional means such as recombinant expression. Chemoselective ligations provide the ability to join peptide segments prepared by solid‐phase peptide synthesis. While native chemical ligation (NCL) is widely used, it is limited by the need for C‐terminal thioesters with suitable reaction kinetics, properly placed native Cys or thiolated derivatives, and peptide segment solubility at low mM concentrations. Moreover, repetitive purifications to isolate ligated products are often yield‐sapping, hampering efficiency and progress. In this work, we demonstrate the use of Controlled Activation of Peptides for Templated NCL (CAPTN). This traceless multi‐segment templated NCL approach permits the one‐pot synthesis of proteins by harnessing selective thioester activation and orthogonal conjugation chemistries to favor formation of the full‐length ligated product while minimizing side reactions. Importantly, CAPTN provides kinetic enhancements allowing ligations at sterically hindered junctions and low peptide concentrations. Additionally, this one‐pot approach removes the need for intermediate purification. We report the synthesis of two E. coli ribosomal subunits S16 and S17 enabled by the chemical tools described herein. We anticipate that CAPTN will expedite the synthesis of valuable proteins and expand on templated approaches for chemical protein synthesis. [ABSTRACT FROM AUTHOR]

In the last decade, a large number of clinical trials have been deployed using Cardiac Magnetic Resonance (CMR) to evaluate cardioprotective strategies aiming at reducing the irreversible myocardial damage at the time of reperfusion. In these studies, segmentation and quantification of myocardial infarct lesion are often performed with a commercial software or an in-house closed-source code development thus creating a barrier for reproducible research. This paper introduces CMRSegTools: an open-source application software designed for the segmentation and quantification of myocardial infarct lesion enabling full access to state-of-the-art segmentation methods and parameters, easy integration of new algorithms and standardised results sharing. This post-processing tool has been implemented as a plug-in for the OsiriX/Horos DICOM viewer leveraging its database management functionalities and user interaction features to provide a bespoke tool for the analysis of cardiac MR images on large clinical cohorts. CMRSegTools includes, among others, user-assisted segmentation of the left-ventricle, semi- and automatic lesion segmentation methods, advanced statistical analysis and visualisation based on the American Heart Association 17-segment model. New segmentation methods can be integrated into the plug-in by developing components based on image processing and visualisation libraries such as ITK and VTK in C++ programming language. CMRSegTools allows the creation of training and testing data sets (labeled features such as lesion, microvascular obstruction and remote ROI) for supervised Machine Learning methods, and enables the comparative assessment of lesion segmentation methods via a single and integrated platform. The plug-in has been successfully used by several CMR imaging studies.

Objective This study examines potential risk and protective factors associated with going outdoors frequently among older persons, and whether these factors vary according to physical limitations.Design Cross-sectional analysis.Setting and participants Community-dwelling participants of the Lausanne cohort Lc65+ in 2016, aged 68–82 years (n=3419).Methods Associations between going outdoors frequently and physical limitations, sociodemographic, health, psychological and social variables were examined using logistic regression models. Subgroup analyses were performed according to the severity of physical limitations.Main outcome measures ‘Going outdoors frequently’ was defined as going out ≥5 days/week and not spending most of the time sitting or lying down.Results Three in four (73.9%) participants reported going outdoors frequently. Limitations in climbing stairs (adjusted OR (AdjOR) 0.61, 95% CI 0.47 to 0.80) and walking (AdjOR 0.24, 95% CI 0.18 to 0.31), as well as depressive symptoms (AdjOR 0.58, 95% CI 0.47 to 0.70), dyspnoea (AdjOR 0.60, 95% CI 0.48 to 0.75), age (AdjORolder age group 0.73, 95% CI 0.59 to 0.92) and fear of falling (AdjOR 0.75, 95% CI 0.62 to 0.91) reduced the odds of going outdoors frequently. In contrast, living alone (AdjOR 1.30, 95% CI 1.08 to 1.56), reporting a dense (AdjOR 1.57, 95% CI 1.26 to 1.96) and a high-quality (AdjOR 1.28, 95% CI 1.06 to 1.53) social network increased the odds of going outdoors frequently. Among participants with severe limitations, 44.6% still went outdoors frequently. Among this subgroup, a new emotional relationship (AdjOR 2.52, 95% CI 1.18 to 5.38) was associated with going outdoors, whereas cognitive complaints (AdjOR 0.66, 95% CI 0.47 to 0.93), urinary incontinence (AdjOR 0.67, 95% CI 0.46 to 0.97), dyspnea (AdjOR:0.67, 95%CI:0.48-0.93), and depressive symptoms (AdjOR 0.67, 95% CI 0.48 to 0.93) lowered the odds of going outdoors.Conclusion Physical limitations are associated with decreased odds of going outdoors frequently. However, social characteristics appear to mitigate this association, even among older persons with severe limitations. Further studies are needed to determine causality and help guide interventions to promote going outdoors as an important component of active ageing.

The septation initiation network (SIN) is a conserved signal transduction network, which is important for cytokinesis in Schizosaccharomyces pombe. The SIN component Etd1p is required for association of some SIN proteins with the spindle pole body (SPB) during anaphase and for contractile ring formation. We show that tethering of Cdc7p or Sid1p to the SIN scaffold Cdc11p at the SPB, rescues etd1-Δ. Analysis of a suppressor of the mutant etd1-M9 revealed that SIN signalling is influenced by the carbon source of the cell. Growth on a nonfermentable carbon source glycerol reduces the requirement for SIN signalling but does not bypass it. The decreased need for SINsignalling is mediated largely by reduction of protein kinase A activity, and it is phenocopied by deletion of pka1 on glucosemedium. We conclude that protein kinase A is an important regulator of the SIN, and that SIN signalling is regulated by the carbon source of the cell. [ABSTRACT FROM AUTHOR]

Abstract Background Even though reported cases of syphilis have been increasing, cases of tertiary syphilis remain extremely rare. The majority of our knowledge with regard to complications of syphilis such as aortitis was acquired before the advent of relatively modern technologies such as CT, MRI and PET. This case report presents a rare case of syphilitic aortitis associated with a renal infarct caused by a peripheral arterial embolism diagnosed by CT. Case presentation We present a young man with sudden abdominal pain and flank tenderness without fever. Blood tests showed acute kidney failure. Computed tomography showed a right renal infarct and a non-circular thickening of the descending thoracic aortic wall with intra-luminal thrombus. Serology confirmed the diagnosis of syphilis. Treatment with anticoagulant and penicillin resulted in a good outcome. Follow-up PET-MRI showed resolution of the thrombus with a metabolically inactive atheromatous plaque. Conclusion Technologies, such as CT, PET-CT and PET-MRI, that were not present during the pre-antibiotic era, can provide new insights into rare presentations of tertiary syphilis such as aortitis. These imaging modalities show promise for early radiological diagnosis of aortitis in syphilis and may be useful for determining the response to treatment in specific cases.

Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components) are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM) remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM) image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM), mosaicking and registration (ir-tools), and large slice viewers (MosaicBuilder, Viking) can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina), terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally, this framework provides a mechanism for parallelization of ssTEM imaging, volume assembly, and data analysis across an international user base, enhancing the productivity of a large cohort of electron microscopists.