Determination of bactericidal activity against 3HC-2-Tre-labelled Mycobacterium abscessus (Mycobacteroides abscessus) by automated fluorescence microscopy.

The minimum bactericidal concentration (MBC) of antibiotics is an important parameter for the potency of a drug in eradicating a bacterium as well as an important measure of the potential of a drug candidate in research and development. We have established a fluorescence-based microscopy method for the determination of MBCs against the non-tuberculous mycobacterium Mycobacterium abscessus (Mycobacteroides abscessus) to simplify and accelerate the performance of MBC determination compared to counting colony forming units on agar. Bacteria are labelled with the trehalose-coupled dye 3HC-2-Tre and analysed in a 96-well plate.

Broad-Spectrum In Vitro Activity of α-Aroyl--Aryl-Phenylalanine Amides against Non-Tuberculous Mycobacteria and Comparative Analysis of RNA Polymerases.

This study investigates the in vitro activity of α-aroyl--aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the complex, complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays.

Dynamic neuroreceptor positron emission tomography in non-anesthetized rats using point source based motion correction: A feasibility study with [C]ABP688.

To prevent motion artifacts in small animal positron emission tomography (PET), animals are routinely scanned under anesthesia or physical restraint. Both may potentially alter metabolism and neurochemistry. This study investigates the feasibility of fully awake acquisition and subsequent absolute quantification of dynamic brain PET data via pharmacokinetic modelling in moving rats using the glutamate 5 receptor radioligand [C]ABP688 and point source based motion correction.

Nα-Aroyl-N-Aryl-Phenylalanine Amides: A Promising Class of Antimycobacterial Agents Targeting the RNA Polymerase.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of death from a bacterium in the world. The global prevalence of clinically relevant infections with opportunistically pathogenic non-tuberculous mycobacteria (NTM) has also been on the rise. Pharmacological treatment of both TB and NTM infections usually requires prolonged regimens of drug combinations, and is often challenging because of developed or inherent resistance to common antibiotic drugs.

Radiosynthesis and In Vitro Evaluation of [C]tozadenant as Adenosine A Receptor Radioligand.

Tozadenant (4-hydroxy--(4-methoxy-7-morpholinobenzo[]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A receptor (AR) antagonist and a promising lead structure for the development of AR-selective positron emission tomography (PET) probes. Although several F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with F-labelling, they could also reflect inherent properties of the parent compound.

Synthesis and in vitro Metabolic Stability of Sterically Shielded Antimycobacterial Phenylalanine Amides.

Nα-aroyl-N-aryl-phenylalanine amides (AAPs) are RNA polymerase inhibitors with activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria. We observed that AAPs rapidly degrade in microsomal suspensions, suggesting that avoiding hepatic metabolism is critical for their effectiveness in vivo. As both amide bonds are potential metabolic weak points of the molecule, we synthesized 16 novel AAP analogs in which the amide bonds are shielded by methyl or fluoro substituents in close proximity.

Streaming the beautiful game: exploring big tech's growing presence in the soccer industry.

This study investigates the evolving role of major technology corporations-namely, Amazon, Apple, Microsoft, Facebook, Netflix, and Google-in the sports industry, with a specific focus on soccer. By employing a qualitative content analysis of media reports, scientific literature, and annual reports from 2000 to 2021, the research scrutinizes the varying approaches and investments of these tech giants in the domain of sports. The findings classify these companies into three distinct categories: (1) those actively securing broadcast rights for major competitions and leagues (Google, Facebook, Amazon); (2) those primarily producing and disseminating soccer documentaries (Netflix); and (3) those not directly engaging in media rights but advancing the technological aspects of clubs and leagues (Apple and Microsoft).

Talent concentration and competitive imbalance in European soccer.

Introduction: While most of the available literature on competitive balance analyses its impact on ticket sales and TV audiences, less empirical research is available that examines the observable variation in competitive balance across leagues and over time. This paper studies the concentration of player talent and end-of-season league points to empirically assess whether leagues with a more equal distribution of player talent produce a more balanced competition than leagues with less equal distribution.

Methods: The longitudinal data we use to estimate our empirical model comes from professional soccer leagues in twelve Western European countries from 2005/06 thru 2020/21, yielding 5,299 club-season observations.

Synthesis and Characterization of Phenylalanine Amides Active against and Other Mycobacteria.

α-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide [MMV688845, Pathogen Box; Medicines for Malaria Venture; IUPAC: (2)--(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide)] is a hit compound, which shows activity against (MIC 6.25-12.5 μM) and other mycobacteria.

Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus.

In a library screen of tuberculosis-active compounds for anti-Mycobacterium abscessus activity, we previously identified the synthetic phenylalanine amide MMV688845. In Mycobacterium tuberculosis, this class was shown to target the RpoB subunit of RNA polymerase, engaging a binding site distinct from that of the rifamycins. Due to its bactericidal activity, rifampicin is a key drug for the treatment of tuberculosis (TB).

mGluR and GABA receptor-specific parametric PET atlas construction-PET/MR data processing pipeline, validation, and application.

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR and GABA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies.

mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [C]ABP688 PET/MR-EEG.

Currently, the metabotropic glutamate receptor 5 (mGluR5) is the subject of several lines of research in the context of neurology and is of high interest as a target for positron-emission tomography (PET). Here, we assessed the feasibility of using [C]ABP688, a specific antagonist radiotracer for an allosteric site on the mGluR5, to evaluate changes in glutamatergic neurotransmission through a mismatch-negativity (MMN) task as a part of a simultaneous and synchronized multimodal PET/MR-EEG study. We analyzed the effect of MMN by comparing the changes in nondisplaceable binding potential (BP) prior to (baseline) and during the task in 17 healthy subjects by applying a bolus/infusion protocol.

Racemization-free synthesis of Nα-2-thiophenoyl-phenylalanine-2-morpholinoanilide enantiomers and their antimycobacterial activity.

Nα-2-thiophenoyl-D-phenylalanine-2-morpholinoanilide (MMV688845, IUPAC: N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide) from the Pathogen Box library (Medicines for Malaria Ventures, MMV) is a promising lead compound for antimycobacterial drug development. Two straightforward synthetic routes to the title compound starting from phenylalanine or its Boc-protected derivative are reported. Employing Boc-phenylalanine as starting material and the T3P and PyBOP amide coupling reagents enables racemization-free synthesis, avoiding the need for subsequent separation of the enantiomers.

Excitatory-inhibitory balance within EEG microstates and resting-state fMRI networks: assessed via simultaneous trimodal PET-MR-EEG imaging.

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and γ-aminobutyric acid (GABA) and the receptor availability (RA) of GABA and mGluR5, remains unexplored. This research investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data.

Can mandatory monitoring in rental apartments effectively prevent legionellosis? A retrospective analysis of data from Regensburg with a review of the literature.

can cause severe, often fatal, pneumonia in humans. Mandatory water sampling in commercially used buildings (mainly rental apartments) as regulated in the Drinking Water Ordinance () aim to protect the population against infection with Legionella. However, no data exist to date that could prove the effectiveness of the measures.

Bolus infusion scheme for the adjustment of steady state [C]Flumazenil levels in the grey matter and in the blood plasma for neuroreceptor imaging.

The use of hybrid PET/MR imaging facilitates the simultaneous investigation of challenge-related changes in ligand binding to neuroreceptors using PET, while concurrently measuring neuroactivation or blood flow with MRI. Having attained a steady state of the PET radiotracer using a bolus-infusion protocol, it is possible to observe alterations in ligand neuroreceptor binding through changes in distribution volumes. Here, we present an iterative procedure for establishing an administration scheme to obtain steady state [C]flumazenil concentrations in grey matter in the human brain.

Management of a measles outbreak in a reception facility for asylum seekers in Regensburg, Germany.

In July/August 2018, a measles outbreak occurred in a reception facility for asylum seekers in Regensburg, Bavaria, Germany. A five-year-old child and an 18-year-old man from Moldova were affected. At the time of the report, 491 people were accommodated at the facility.

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D R binding and reduces striatal D R binding in male hemiparkinsonian rats.

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7).

Preliminary Evidence Assessing Social-Emotional Competences in Deaf and Hard of Hearing Infants and Toddlers Using a New Parent Questionnaire.

Social-emotional competences are an important developmental domain for deaf and hard of hearing (DHH) children and early diagnosis of problems is needed to ensure that DHH children receive appropriate support in this domain. In order to explore the usefulness of an instrument, which was recently developed for very young children, two studies in DHH infants and toddlers were conducted from Germany using the Social-Emotional Assessment/Evaluation Measure (Squires et al. (2013).

[Social-Emotional Competence in Young Children with Hearing, Visual or Intellectual Impairments - an Explorative Study with the ITSEA].

Social-Emotional Competence in Young Children with Hearing, Visual or Intellectual Impairments - an Explorative Study with the ITSEA Early emotional and social competence is considered as an important requirement for social participation in family and child care settings. We report on a study exploring the usefulness of the competence scales as a part of the "Infant-Toddler Social and Emotional Assessment" (ITSEA) for one- to three-year old children in a sample of 253 toddlers with hearing, visual or intellectual impairments. Internal consistency of the six scales is good (alpha > .

[Risk factors for self-injurious, aggressive, and stereotypic behavior in children and youths with visual impairments].

Objective: To increase the limited knowledge concerning the form and risk factors of self-injurious, aggressive, and stereotypic behavior in children and youths with visual impairments.

Method: Parents of 83 children and youths with visual impairments report on the characteristics of visual impairment, the social-communicative competence of their children, and the frequency and severity of self-injurious, aggressive, and stereotypic behaviors.

Results: Stereotypic behaviors are reported more often than the other behavioral abnormalities.

[Social-emotional competences in deaf and hard-of-hearing toddlers – results from an empirical study with two current parent questionnaires].

Objective: Hearing loss in the deaf and hard of hearing (DHH) is associated with an elevated risk of problems in socio-emotional development. Early assessment is necessary to start timely interventions. The present study tested two parent questionnaires that allow evaluation of the socio-emotional development of toddlers from a competence perspective.

What are the factors that influence the delivery of smoking cessation advice in critical care?

Background: The world's leading cause of preventable deaths, diseases and disabilities is smoking. Hospitalization can provide an opportunity for smokers to quit. Previous research found that smokers make up a high percentage of patients admitted to intensive care.