Liver cirrhosis is a risk-factor for Pneumocystis jirovecii associated mortality.

Background: Pneumocystis jirovecci pneumonia (PCP) is a life threating disease in immunodeficient patients. Liver cirrhosis itself can lead to immunodefiency, however little is known if Pneumocystis jirovecci infection affects the outcome of patients with liver cirrhosis.

Aim: We aimed to assess the predictors for Pneumocystis jirovecci-associated mortality in patients with Pneumocystis jirovecci infection treated at intensive care units.

Subthalamic nucleus deep brain stimulation induces functional deficits in norepinephrinergic neurotransmission in a Parkinson's disease model.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a successful treatment option in Parkinson's disease (PD) for different motor and non-motor symptoms, but has been linked to postoperative cognitive impairment.

Aim: Since both dopaminergic and norepinephrinergic neurotransmissions play important roles in symptom development, we analysed STN-DBS effects on dopamine and norepinephrine availability in different brain regions and morphological alterations of catecholaminergic neurons in the 6-hydroxydopamine PD rat model.

Methods: We applied one week of continuous unilateral STN-DBS or sham stimulation, respectively, in groups of healthy and 6-hydroxydopamine-lesioned rats to quantify dopamine and norepinephrine contents in the striatum, olfactory bulb and dentate gyrus.

Adult-onset Still's disease with concurrent thrombotic microangiopathy: Observations from pooled analysis for an uncommon finding.

Background: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated.

Structural basis for the toxicity of Legionella pneumophila effector SidH.

Legionella pneumophila (LP) secretes more than 300 effectors into the host cytosol to facilitate intracellular replication. One of these effectors, SidH, 253 kDa in size with no sequence similarity to proteins of known function is toxic when overexpressed in host cells. SidH is regulated by the LP metaeffector LubX which targets SidH for degradation in a temporal manner during LP infection.

Hexasome-INO80 complex reveals structural basis of noncanonical nucleosome remodeling.

Loss of H2A-H2B histone dimers is a hallmark of actively transcribed genes, but how the cellular machinery functions in the context of noncanonical nucleosomal particles remains largely elusive. In this work, we report the structural mechanism for adenosine 5'-triphosphate-dependent chromatin remodeling of hexasomes by the INO80 complex. We show how INO80 recognizes noncanonical DNA and histone features of hexasomes that emerge from the loss of H2A-H2B.

Gastric peroral endoscopic pyloromyotomy (G-POEM) in patients with refractory gastroparesis: a review.

Gastric peroral endoscopic pyloromyotomy (G-POEM or POP) is an endoscopic therapeutic modality for treatment of refractory gastroparesis. Since the first case reported in 2013, there are more than 200 papers published on G-POEM. In this narrative review, we summarize the short-term and long-term outcomes and review other important studies.

Structural basis for guide RNA selection by the RESC1-RESC2 complex.

Kinetoplastid parasites, such as trypanosomes or leishmania, rely on RNA-templated RNA editing to mature mitochondrial cryptic pre-mRNAs into functional protein-coding transcripts. Processive pan-editing of multiple editing blocks within a single transcript is dependent on the 20-subunit RNA editing substrate binding complex (RESC) that serves as a platform to orchestrate the interactions between pre-mRNA, guide RNAs (gRNAs), the catalytic RNA editing complex (RECC), and a set of RNA helicases. Due to the lack of molecular structures and biochemical studies with purified components, neither the spacio-temporal interplay of these factors nor the selection mechanism for the different RNA components is understood.

Comparing the Toxicological Responses of Pulmonary Air-Liquid Interface Models upon Exposure to Differentially Treated Carbon Fibers.

In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air-liquid interface cell culture models of the human lung to CF.

Impact of the 2021 La Palma volcanic eruption on air quality: Insights from a multidisciplinary approach.

The La Palma 2021 volcanic eruption was the first subaerial eruption in a 50-year period in the Canary Islands (Spain), emitting ~1.8 Tg of sulphur dioxide (SO) into the troposphere over nearly 3 months (19 September-13 December 2021), exceeding the total anthropogenic SO emitted from the 27 European Union countries in 2019. We conducted a comprehensive evaluation of the impact of the 2021 volcanic eruption on air quality (SO, PM and PM concentrations) utilising a multidisciplinary approach, combining ground and satellite-based measurements with height-resolved aerosol and meteorological information.

Coronary plaque characterization assessed by delayed enhancement dual-layer spectral CT angiography and optical coherence tomography.

This study aimed to prospectively evaluate delayed enhancement imaging by spectral computed tomography using soluble iodine containing contrast media to improve the in vivo characterization of coronary plaque types based on the quantification of delayed iodine enhancement. Patients with known or suspected coronary artery disease (CAD) underwent spectral coronary CT-angiography (SCCTA). Absolute delayed iodine enhancement in all visible coronary plaques was assessed.

Structural basis for sequence-independent substrate selection by eukaryotic wobble base tRNA deaminase ADAT2/3.

The essential deamination of adenosine A to inosine at the wobble base is the individual tRNA modification with the greatest effects on mRNA decoding, empowering a single tRNA to translate three different codons. To date, many aspects of how eukaryotic deaminases specifically select their multiple substrates remain unclear. Here, using cryo-EM, we present the structure of a eukaryotic ADAT2/3 deaminase bound to a full-length tRNA, revealing that the enzyme distorts the anticodon loop, but in contrast to the bacterial enzymes, selects its substrate via sequence-independent contacts of eukaryote-acquired flexible or intrinsically unfolded motifs distal from the conserved catalytic core.

[Development of specific guidance for the safe opening and operation of recreational destinations under pandemic conditions].

Background: The SARS-CoV‑2 pandemic led to the closure of leisure and recreation facilities worldwide. As part of a model study funded by the Baden-Wuerttemberg Ministry of Social Affairs, Health and Integration, it was possible to demonstrate how a hygiene and safety concept can be successfully implemented in practice using the example of the opening and operation of an amusement park in Baden-Wuerttemberg (Germany) under scientific supervision.

Objective: The aim of the model project was, besides the verification of a possible infection event through a visit to the amusement park, to develop and review a recommended course of action for the safe opening and operation of leisure facilities under pandemic conditions, which can be transferred to other destinations.

Aerosol measurement identifies SARS-CoV 2 PCR positive adults compared with healthy controls.

Background: SARS-CoV-2 is spread primarily through droplets and aerosols. Exhaled aerosols are generated in the upper airways through shear stress and in the lung periphery by 'reopening of collapsed airways'. Aerosol measuring may detect highly contagious individuals ("super spreaders or super-emitters") and discriminate between SARS-CoV-2 infected and non-infected individuals.

Exhaled Aerosols in SARS-CoV-2 Polymerase Chain Reaction-Positive Children and Age-Matched-Negative Controls.

Background: Children and adolescents seem to be less affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease in terms of severity, especially until the increasing spread of the omicron variant in December 2021. Anatomical structures and lower number of exhaled aerosols may in part explain this phenomenon. In a cohort of healthy and SARS-CoV-2 infected children, we compared exhaled particle counts to gain further insights about the spreading of SARS-CoV-2.

Nanofluidic chips for cryo-EM structure determination from picoliter sample volumes.

Cryogenic electron microscopy has become an essential tool for structure determination of biological macromolecules. In practice, the difficulty to reliably prepare samples with uniform ice thickness still represents a barrier for routine high-resolution imaging and limits the current throughput of the technique. We show that a nanofluidic sample support with well-defined geometry can be used to prepare cryo-EM specimens with reproducible ice thickness from picoliter sample volumes.

Reducing indoor particle exposure using mobile air purifiers-Experimental and numerical analysis.

Aerosol particles are one of the main routes of transmission of COVID-19. Mobile air purifiers are used to reduce the risk of infection indoors. We focus on an air purifier that generates a defined volumetric air flow through a highly efficient filter material.

Structural basis of branch site recognition by the human spliceosome.

Recognition of the intron branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is a critical event during spliceosome assembly. In mammals, BS sequences are poorly conserved, and unambiguous intron recognition cannot be achieved solely through a base-pairing mechanism. We isolated human 17 U2 snRNP and reconstituted in vitro its adenosine 5´-triphosphate (ATP)–dependent remodeling and binding to the pre–messenger RNA substrate.

Structural basis for protein glutamylation by the Legionella pseudokinase SidJ.

Legionella pneumophila (LP) avoids phagocytosis by secreting nearly 300 effector proteins into the host cytosol. SidE family of effectors (SdeA, SdeB, SdeC and SidE) employ phosphoribosyl ubiquitination to target multiple host Rab GTPases and innate immune factors. To suppress the deleterious toxicity of SidE enzymes in a timely manner, LP employs a metaeffector named SidJ.

Early Bronchoscopy Improves Extubation Rates after Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Analysis.

Background: Patients suffering from out-of-hospital cardiac arrest (OHCA) frequently receive a bronchoscopy after being admitted to the ICU. We investigated the optimal timing and the outcome in these patients.

Methods: All patients who suffered from OHCA and were treated in our ICU from January 2013 to December 2018 were retrospectively analyzed.

Impact of Nanocomposite Combustion Aerosols on A549 Cells and a 3D Airway Model.

The use of nanomaterials incorporated into plastic products is increasing steadily. By using nano-scaled filling materials, thermoplastics, such as polyethylene (PE), take advantage of the unique properties of nanomaterials (NM). The life cycle of these so-called nanocomposites (NC) usually ends with energetic recovery.

Combining high throughput and high quality for cryo-electron microscopy data collection.

Cryo-electron microscopy (cryo-EM) can be used to elucidate the 3D structure of macromolecular complexes. Driven by technological breakthroughs in electron-microscope and electron-detector development, coupled with improved image-processing procedures, it is now possible to reach high resolution both in single-particle analysis and in cryo-electron tomography and subtomogram-averaging approaches. As a consequence, the way in which cryo-EM data are collected has changed and new challenges have arisen in terms of microscope alignment, aberration correction and imaging parameters.

Hybrid PET/MR imaging for the prediction of left ventricular recovery after percutaneous revascularisation of coronary chronic total occlusions.

Purpose: To evaluate myocardial viability assessment with hybrid 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging ([F]FDG-PET/MR) in predicting left ventricular (LV) wall motion recovery after percutaneous revascularisation of coronary chronic total occlusion (CTO).

Methods And Results: Forty-nine patients with CTO and corresponding wall motion abnormality (WMA) underwent [F]FDG-PET/MR imaging for viability assessment prior to percutaneous revascularisation. After 3-6 months, 23 patients underwent follow-up MR to evaluate wall motion recovery.

The structure of the cohesin ATPase elucidates the mechanism of SMC-kleisin ring opening.

Genome regulation requires control of chromosome organization by SMC-kleisin complexes. The cohesin complex contains the Smc1 and Smc3 subunits that associate with the kleisin Scc1 to form a ring-shaped complex that can topologically engage chromatin to regulate chromatin structure. Release from chromatin involves opening of the ring at the Smc3-Scc1 interface in a reaction that is controlled by acetylation and engagement of the Smc ATPase head domains.

Molecular insight into RNA polymerase I promoter recognition and promoter melting.

RNA polymerase I (Pol I) assembles with core factor (CF) and Rrn3 on the rDNA core promoter for transcription initiation. Here, we report cryo-EM structures of closed, intermediate and open Pol I initiation complexes from 2.7 to 3.