Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavir (Paxlovid) in Patients Treated for COVID-19: Results from a Prospective Multicenter Observational Study.

Background: Paxlovid is a combination of the antiviral agents nirmatrelvir and ritonavir indicated for the oral treatment of high-risk, symptomatic patients with coronavirus disease 2019 (COVID-19). As real-world data on the plasma concentrations of nirmatrelvir/ritonavir (Paxlovid) are limited, the aim of this study was to investigate nirmatrelvir/ritonavir plasma trough levels in a clinical setting using therapeutic drug monitoring.

Methods: A prospective, noninterventional, multicenter, observational clinical study was conducted in which the plasma trough levels of nirmatrelvir/ritonavir were simultaneously determined by using liquid chromatography tandem mass spectrometry in patients with symptomatic COVID-19.

One-pot hydroaminomethylation of an alkene under formation of primary amines by combining hydroformylation at elevated syngas pressure and biocatalytic transamination in water.

We report a novel one-pot chemoenzymatic synthesis of primary amines in water, combining rhodium-catalysed hydroformylation of styrene with a biocatalytic transamination. This process is starting from styrene at 50 mM substrate loading on a 10 mL preparative scale. Combined towards a one-pot process with both steps running concurrently, this chemoenzymatic synthesis involves a 6-DPPon/rhodium-catalysed hydroformylation of styrene at 20 bar of syngas, forming the - and -aldehydes and an enzymatic transamination of the -formed aldehydes to the corresponding primary amines catalysed by the amine transaminase from , yielding the desired primary amines with 99% conversion.

Association between white matter microstructural changes and aggressiveness. A case-control diffusion tensor imaging study.

Research has focused on identifying neurobiological risk factors associated with aggressive behavior in order to improve prevention and treatment efforts. This study aimed to characterize microstructural differences in white matter (WM) integrity in individuals prone to aggression. We hypothesized that altered cerebral WM microstructure may underlie normal individual variability in aggression and tested this using a case-control design in healthy individuals.

The MARVIN Hypothesis: Linking Unhealthy Lifestyles to Intracranial Aneurysm Rupture Risk and Clinical Prognosis.

: The rising incidence of modifiable lifestyle risk factors and cardiovascular diseases, driven by poor diet, inactivity, excessive alcohol use, and smoking, may influence the development and rupture of intracranial aneurysms (IA). This study aimed to examine the impact of lifestyle-related and cardiovascular risk factors on IA rupture and patient outcomes. : We developed the "MARVIN" (Metabolic and Adverse Risk Factors and Vices Influencing Intracranial Aneurysms) model and conducted a retrospective analysis of 303 patients with 517 IAs, treated between 2007 and 2020.

The Correlation Between Effort-Reward Imbalance at Work and the Risk of Burnout Among Nursing Staff Working in an Emergency Department-A Pilot Study.

: Nurses in emergency rooms face high levels of psychological stress during their work, which is why they have an increased risk of burnout. The aim of this pilot study was to determine the extent to which effort-reward imbalance (ERI) at work is connected to the risk of burnout among emergency nurses. : Thirty-five nurses from the central emergency department of a maximum care provider, aged 35.

Risk of Postoperative Hemorrhage After Glioma Surgery in Patients with Preoperative Acetylsalicylic Acid.

Background/objectives: Patients with gliomas show an increased risk of spontaneous hemorrhages throughout the disease. Simultaneously, the number of patients taking acetylsalicylic acid (ASA) for primary and secondary prophylaxis is rising in daily clinical practice, and interrupting ASA intake before elective or emergency intracranial surgery is not always feasible. This study aims to evaluate the risks associated with continuing ASA use perioperatively while focusing on hemorrhage and potential thromboembolic events that may arise from discontinuing ASA, particularly in multimorbid patients undergoing glioma surgery.

Risk factors for substantial weight retention at 1 year postpartum: evidence from a German birth cohort study (KUNO-Kids).

Purpose: Postpartum weight retention (PPWR) increases the risk of overweight and obesity. This study aims to identify risk factors for substantial weight retention (≥ 5 kg) at 1 year postpartum.

Methods: Data were obtained from N = 747 mothers participating in the KUNO-Kids birth cohort study.

Anatomical Characteristics of Cervicomedullary Compression on MRI Scans in Children with Achondroplasia.

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.

Surveillance in Children and Adolescents with von Hippel-Lindau (VHL)-Related Pheochromocytomas and Paragangliomas: A Survey of MET and Freiburg-VHL Registries in Germany.

Early identification of patients at risk with von Hippel-Lindau (VHL) syndrome-related pheochromocytoma and paraganglioma (PPGL) is crucial to prevent morbidity. We investigated the current surveillance recommendations in VHL-related PPGL in children and adolescents. German Pediatric Oncology and Hematology-Malignant Endocrine Tumor registry (GPOH-MET) and Freiburg-VHL registry (1996-2022).

Development and Assessment of a High-Fidelity Simulator for the Microsurgical Dissection of the Sylvian Fissure.

Background: The dissection of the Sylvian fissure (SF) is a crucial technique requiring considerable expertise and skills traditionally acquired through years of experience. The continuous decline in surgical case-load necessitates the development of efficient alternative training opportunities. However, building a realistic and effective training simulator for the microsurgical dissection of the SF as an integral part of the neurosurgical curriculum remains a challenging endeavor.

Archaeometallurgical investigation of the Nebra Sky Disc.

The world heritage object Nebra Sky Disc is one of the best investigated archaeological objects. The origin of the raw materials it is made of is well known. However, its manufacturing process was not completely clear.

Psychological interventions to prevent the onset of major depression in adults: a systematic review and individual participant data meta-analysis.

Background: Psychological interventions are increasingly discussed as a method to prevent major depressive disorder (MDD) in adults who already experience subthreshold depressive symptoms. In this individual participant data meta-analysis, we quantify the effect of preventive interventions against control on MDD onset in this population, and explore effect modifiers.

Methods: In this systematic review and individual participant data meta-analysis, we screened full-texts of eligible studies within the Metapsy research domain for articles on psychological interventions for depression, from database inception to May 1, 2023, published in English, German, Spanish, and Dutch.

Rasopathy-Associated Mutation Ptpn11 has Age-Dependent Effect on Synaptic Vesicle Recycling.

Rasopathies are genetic disorders often associated with developmental delay and intellectual disability. Noonan syndrome (NS) is one of the most common Rasopathies, caused by mutations in PTPN11 in more than 50% of cases. In mammalian neurons, PTPN11 controls the trafficking of postsynaptic glutamate receptors.

Proteome-wide CETSA reveals new step in apoptosis control.

Apoptosis, a well-established program of cell death, is fundamental to all multicellular organisms. Recent studies of apoptosis initiation events using proteome-wide cellular thermal shift assay (CETSA) have revealed a novel regulatory mechanism involving the cleavage of nuclear substrates. This finding suggests a previously unrecognized amplification step in apoptosis occurring within the nucleus.