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Genotyping of European Toxoplasma gondii strains by a new high-resolution next-generation sequencing-based method.
PURPOSE
A new high-resolution next-generation sequencing (NGS)-based method was established to type closely related European type II Toxoplasma gondii strains.
METHODS
T. gondii field isolates were collected from different parts of Europe and assessed by whole genome sequencing (WGS). In comparison to ME49 (a type II reference strain), highly polymorphic regions (HPRs) were identified, showing a considerable number of single nucleotide polymorphisms (SNPs). After confirmation by Sanger sequencing, 18 HPRs were used to design a primer panel for multiplex PCR to establish a multilocus Ion AmpliSeq typing method. Toxoplasma gondii isolates and T. gondii present in clinical samples were typed with the new method. The sensitivity of the method was tested with serially diluted reference DNA samples.
RESULTS
Among type II specimens, the method could differentiate the same number of haplotypes as the reference standard, microsatellite (MS) typing. Passages of the same isolates and specimens originating from abortion outbreaks were identified as identical. In addition, seven different genotypes, two atypical and two recombinant specimens were clearly distinguished from each other by the method. Furthermore, almost all SNPs detected by the Ion AmpliSeq method corresponded to those expected based on WGS. By testing serially diluted DNA samples, the method exhibited a similar analytical sensitivity as MS typing.
CONCLUSION
The new method can distinguish different T. gondii genotypes and detect intra-genotype variability among European type II T. gondii strains. Furthermore, with WGS data additional target regions can be added to the method to potentially increase typing resolution
Abrupt climate fluctuations in Tibet as imprints of multiple meltwater events during the early to mid-Holocene.
Understanding the impact of meltwater discharge during the final stage of the Laurentide Ice Sheet (LIS) has important implications for predicting sea level rise and climate change. Here we present a high-resolution ice-core isotopic record from the central Tibetan Plateau (TP), where the climate is sensitive to the meltwater forcing, and explore possible signals of the climate response to potential LIS meltwater discharges in the early to mid-Holocene. The record shows four abrupt large fluctuations during the 7-9 ka BP (kiloannum before present), reflecting large shifts of the mid-latitude westerlies and the Indian summer monsoon (ISM) over this period, and they corresponded to possible LIS freshwater events documented in other paleoclimate records. Our study suggests that multiple rapid meltwater discharge events might have occurred during the final stage of LIS. The finding implies the possibility of rapid sea level rise and unstable climate in the transition zone between the mid-latitude westerlies and the ISM due to fast polar ice retreat under the anthropogenic global warming
Die Situation von LGBTQ+ Jugendlichen in Deutschschweizer Schulen. Forschungsbericht des Projektes SOGUS – Sexuelle Orientierung, Geschlecht und Schule.
Patient-reported symptomatology and its course in spontaneous intracranial hypotension - Beware of a chameleon.
OBJECTIVE
Although orthostatic headache is the hallmark symptom of spontaneous intracranial hypotension (SIH), patients can present with a wide range of different complaints and thereby pose a diagnostic challenge for clinicians. Our aim was to describe and group the different symptoms associated with SIH and their course over time.
METHODS
We retrospectively surveyed consecutive patients diagnosed and treated for SIH at our institution from January 2013 to May 2020 with a specifically designed questionnaire to find out about their symptomatology and its course.
RESULTS
Of 112 eligible patients, 79 (70.5%) returned the questionnaire and were included in the analysis. Of those, 67 (84.8%) reported initial orthostatic headaches, whereas 12 (15.2%) denied having this initial symptom. All except one (98.7%) patients reported additional symptoms: most frequently cephalic pressure (69.6%), neck pain (68.4%), auditory disturbances (59.5%), nausea (57%), visual disturbances (40.5%), gait disturbance (20.3%), confusion (10.1%) or sensorimotor deficits (21.5%). Fifty-seven (72.2%) patients reported a development of the initial symptoms predominantly in the first three months after symptom onset. Age and sex were not associated with the symptomatology or its course (p > 0.1).
CONCLUSION
Although characteristic of SIH, a relevant amount of patients present without orthostatic headaches. In addition, SIH can manifest with non-orthostatic headaches at disease onset or during the course of the disease. Most patients report a wide range of associated complaints. A high degree of suspicion is crucial for an early diagnosis and targeted treatment
Two-year clinical outcomes of Resorbable Magnesium Scaffold versus conventional drug-eluting stents in ST-segment Elevation Myocardial Infarction: a propensity score matching analysis.
Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.
Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes
Safety and Efficacy of Balloon-Expandable Transcatheter Aortic Valve Implantation in Patients with Extreme Horizontal Aorta.
Anatomical risk assessment based on pre-procedural multidetector computed tomography (MDCT) is key to preprocedural planning in patients undergoing transcatheter aortic valve implantation (TAVI). Horizontal aorta, is a challenging anatomical feature for device delivery and proper prosthesis positioning. Previous studies have suggested that the use of balloon-expandable valve (BEV) is preferred in patients with horizontal aorta1,2. However, few studies have adequately included patients with extreme horizontal aorta (≥70°), for which manufacturers have issued a warning2,3. Thus, we sought to investigate the impact of extreme horizontal aorta on procedural outcomes in patients undergoing TAVI with BEV
Is the time right for a new initiative in mathematical modeling of the lower urinary tract? ICI-RS 2023.
INTRODUCTION
A session at the 2023 International Consultation on Incontinence - Research Society (ICI-RS) held in Bristol, UK, focused on the question: Is the time right for a new initiative in mathematical modeling of the lower urinary tract (LUT)? The LUT is a complex system, comprising various synergetic components (i.e., bladder, urethra, neural control), each with its own dynamic functioning and high interindividual variability. This has led to a variety of different types of models for different purposes, each with advantages and disadvantages.
METHODS
When addressing the LUT, the modeling approach should be selected and sized according to the specific purpose, the targeted level of detail, and the available computational resources. Four areas were selected as examples to discuss: utility of nomograms in clinical use, value of fluid mechanical modeling, applications of models to simplify urodynamics, and utility of statistical models.
RESULTS
A brief literature review is provided along with discussion of the merits of different types of models for different applications. Remaining research questions are provided.
CONCLUSIONS
Inadequacies in current (outdated) models of the LUT as well as recent advances in computing power (e.g., quantum computing) and methods (e.g., artificial intelligence/machine learning), would dictate that the answer is an emphatic "Yes, the time is right for a new initiative in mathematical modeling of the LUT.