University of Basel

Depression and anxiety are common during pregnancy, but the prevalence of antidepressant use during pregnancy in Switzerland is not well documented. We explored antidepressant use before, during, and after pregnancy in Switzerland. We conducted a descriptive study using a Swiss health care insurance claims database (Helsana) between 2015 and 2021. We included pregnancies resulting in birth of women who were continuously insured during three 270-day periods: preconceptional, pregnancy, and postpartum. In these periods, we quantified the exposure prevalence to antidepressants overall and stratified by region and use of co-medication. Antidepressants of interest included selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors, Hyperici herba and others. Additionally, we assessed prevalence of antidepressant discontinuation during pregnancy. We included 34,584 pregnancies of whom 1386 (4.0%) were exposed (≥1 claim) to antidepressants preconceptionally, 788 (2.3%) during pregnancy, and 1273 (3.7%) postpartum. Of 1386 women with preconceptional use, 60% had no antidepressant claim during pregnancy. Antidepressant use decreased from 1.6% in trimester one to 1.1% in trimester three. The most frequently dispensed antidepressants during pregnancy were SSRIs (75.0%). Exposure to antidepressants was two-fold higher in the French-speaking region (2.6%) than in Central Switzerland (1.3%). About one-third of women continuing antidepressant treatment during pregnancy also used benzodiazepines (co-medication) at least once during this time. 4 of 100 women in Switzerland took antidepressants before pregnancy, but 60% discontinued treatment when they became pregnant. Since untreated depression in pregnancy may lead to severe long-term consequences for mother and child, this might be of concern.

Incorporation of the nephelauxetic effect into ligand design enabled red-shifting of spin-flip transitions of CrIII and MnIV complexes into the near-infrared region. Using carbazolide complexes as a model, we present a strategy for tuning the ratio of ligand field strength to the Racah parameter B by combining a covalent carbazolide core with variable σ-donor ligand "side arms." Substitution of pyridine, as in [Cr(Lpy)2]+ ([Lpy]- = 3,6-di-tert-butyl-1,8-di(pyridin-2-yl)carbazol-9-ide), with stronger σ-donors such as N-heterocyclic or mesoionic carbenes in [Cr(LNHC)2]+ or [Cr(LMIC)2]+ ([LNHC]- = 3,6-di-tert-butyl-1,8-bis(imidazolin-2-yliden-1-yl)carbazolide and [LMIC]- = 3,6-di-tert-butyl-1,8-bis(4,5,6,7-tetrahydro-2H-[1,2,3]triazolo[1,5-a]pyridin-2-yl)-carbazol-9-ide) increased the ligand field strength from 17 500 to 24 400 cm-1, with only a modest rise in B from 550 to 600 cm-1. This balance favors near-infrared spin-flip transitions while extending their excited-state lifetimes. Despite these advances, carbazolide-based ligands exhibit also drawbacks, including low-lying charge-transfer states and geometric distortions, which limit lifetimes and prevent emission, contrasting with other near-infrared-emissive CrIII systems. Additionally, we demonstrate an approach for estimating energies of dark, low-energy spin-flip states in CrIII complexes via photoinduced electron transfer and Rehm-Weller analysis. Our results offer guidance on balancing ligand field strength and metal-ligand bond covalency to optimize the photophysical and photochemical properties of first-row transition metal complexes.

Perioperative antibiotic prophylaxis is crucial in improving outcomes after colorectal surgery. Although guidelines in elective procedures are well established, evidence in emergency settings remains limited. This study evaluated the association between antibiotic timing before incision and 30-day mortality as well as surgical site infections (SSIs) in emergency colorectal surgery. This nationwide retrospective cohort study analyzed colorectal operations recorded in the Swiss National Infection Surveillance Program. Demographics, antibiotic regimens, and surgical characteristics of consecutive cases were compared between elective and emergency procedures. Independent predictors of 30-day mortality and SSIs were identified using multivariable logistic regression adjusted for patient and surgical factors. Timing of antibiotic administration was modeled using natural cubic splines to assess nonlinear effects. Among 63,945 patients, 16,939 (26.5%) underwent emergency procedures. In the fully adjusted model, antibiotic timing was significantly associated with 30-day mortality (p < 0.001) in both elective and emergency operations. A U-shaped pattern was observed, with the lowest predicted 30-day mortality when antibiotics were administered 48 minutes before incision in elective operations (mean 1.28%, 95% CI 1.15 to 1.40) and 51 minutes before incision in emergency procedures (mean 10.50%, 95% CI 9.71 to 11.20). In contrast, antibiotic timing was not significantly associated with SSIs (p = 0.229). In both elective and emergency colorectal operations, early or late administration of antibiotics relative to the incision was associated with increased 30-day mortality. The lowest risk occurred when antibiotics were administered approximately 50 minutes before incision. These findings support optimizing perioperative antibiotic timing to improve postoperative outcomes in emergency colorectal surgery.

Interindividual variability in analgesic responsiveness often results in therapy failure (TF) or adverse drug reactions (ADR) and poses a major challenge in chronic pain management, as it is influenced by multiple factors. This exploratory study investigated whether pharmacogenetic (PGx) testing could identify drug-gene interactions (DGIs) explaining variability in drug response. In addition, we explored whether genetic predispositions in CYP2D6 and COMT , indicating increased pain sensitivity, are linked to TF. We analyzed data from chronic pain patients who underwent pharmacogenotyping due to suspected TF or ADR. PGx panel testing was carried out by a commercial provider. Additional genotyping of COMT rs6269, rs4633, and rs4818 was performed using PCR, RFLP, and Sanger sequencing. PGx panel testing confirmed at least one relevant genetic variant in 45% of the suspected DGIs. Notably, 41% involved the pharmacogenes CYP2D6 , CYP2C19 , and CYP2C9 . Subgroup analyses revealed that patients carrying the COMT high pain sensitivity (HPS) allele, COMT high pain phenotype, or CYP2D6 intermediate metabolizer (IM) phenotype were significantly more likely to experience TF. Logistic regression confirmed both phenotypes as significant predictors of TF. Our findings support the relevance of CYP2D6 , CYP2C19 , and CYP2C9 as key pharmacogenes for PGx testing in chronic pain management. The results suggest that a genetic predisposition in CYP2D6 and COMT , associated with increased pain sensitivity, may contribute to insufficient analgesia and subsequent TF. These insights indicate the potential value of incorporating CYP2D6 and COMT as pain-modulating genetic markers into the broader framework of PGx testing.

A deeper understanding of how tissue-localized immune cells arise and function is critical for developing mucosal vaccines. Currently, there are no murine models that specifically target tissue T cells while leaving their lymphoid counterparts untouched. Here, we leverage the observation that during influenza infection, HIF-1α regulatory activity is higher in the lung compared with lymph node CD4+ T cells. Inducible deletion of Hif1a in CD4+ T cells, at the onset of its activity in the lung, reduces the tissue-resident T cell compartment with minimal impact on peripheral immunity. HIF-1α-active CD4+ T cells occupy the border of tertiary lymphoid structures, where they coordinate an interleukin 21 (IL-21)-dependent network of spatially colocalized immune cells including macrophages, natural killer (NK) cells, and immunoglobulin A-positive (IgA+) B cells. A similar HIF-1α-dependent network is engaged in a lung adenocarcinoma model, highlighting a broader role for HIF-1α+ CD4+ T cells in integrating protective immunity during infection and cancer.

Lymphatic vessels play an important role in pathologies, such as cardiovascular diseases or metastasizing cancers. However, mechanisms involved in cancer metastasis through lymphatic vessels remain largely unknown. In this study, we engineer 3D lymphatic microvessels by co-culturing human lymphatic endothelial cells (hLECs) with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) in synthetic and fully defined enzymatically crosslinked poly(ethylene glycol) (TG-PEG) hydrogels. By tuning the stiffness of the TG-PEG scaffolds, varying seeding densities of hLECs and hBM-MSCs, and stimulation with lymphangiogenic factors, we identify suitable culture conditions for lymphatic network formation. Immunocytochemistry-based evaluations reveal the formation of lymphatic structures consisting of hLECs that are ensheathed with basement membrane extracellular matrix components and hBM-MSCs, which express perivascular-specific markers. Finally, the addition of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells to the forming lymphatic structures shows a clear negative influence of cancer cells on the length of lymphatic networks. Moreover, we observe a closer association of invasive than of non-invasive cancer cells with the lymphatic networks, which can be inhibited by blocking of CCL21. Our findings present a promising approach to investigate the cancer microenvironment, as our model can serve as a tool to study physiological lymphangiogenesis and pathological phenomena in vitro.

SummarySecreted mucins are the major component of the mucus layer that protects intestinal epithelial surfaces by blocking excessive interactions with the microbiota. Mucins are complex glycoproteins decorated with over 100 differentO-glycans. Some bacteria can utilize mucins and excessive degradation has been associated with disruption of the mucus barrier and inflammation. Despite the importance of mucins, a detailed enzymatic pathway by which gut bacteria degrade colonic mucinO-glycans and the impact of this process on gut colonization are unknown. Here, we identified >100 genes that are expressed by the symbiontBacteroides thetaiotaomicronduring growth on differentO-glycan substrates, revealing effects of glycan structure on gene expression. The characterization of 33 glycoside hydrolase enzymes revealed the pathway for colonicO-glycan degradation by this bacterium.In vivocompetition experiments show that multiple exo-acting enzymes targeting mucin capping structures are central to gut colonization and may provide targets to inhibit bacterial mucin degradation.

Acute myeloid leukemia (AML) remains challenging to treat due to extensive genetic heterogeneity, high relapse rates, and treatment-related toxicity. Although drug combinations offer therapeutic promise, their selection is often empirical. Here, we introduce Combinatorial Proteome Integral Solubility/Stability Alteration analysis (CoPISA), a high-throughput proteomics workflow that captures protein solubility/stability alterations uniquely induced by drug combinations. We applied CoPISA to two rationally designed AML drug pairs, LY3009120-sapanisertib (LS) and ruxolitinib-ulixertinib (RU), previously identified as the most effective and least toxic combinations among many candidates and validated in AML cell lines, patient-derived samples and zebrafish xenograft models. We uncovered an emergent mechanism termed "conjunctional targeting", in which combinatorial drug action induces combination-exclusive protein targets consistent with an AND-gate logic model. LS-specific converged on SUMOylation, chromatin condensation, and VEGF-linked adhesion, while RU-specific targets disrupted DNA-damage checkpoints, mitochondrial bioenergetics, and RNA-splicing. Post-translational modification analysis revealed combination-induced acetylation, methylation, and phosphorylation of key AML proteins, including NPM1. Network analysis demonstrated that a substantial fraction of AML-associated proteins targeted by CoPISA are unique to combinations, including DNMT3A, NPM1, and TP53. By uncovering a mechanistic layer beyond classical synergy, CoPISA provides a robust framework for the precision-guided design of combinatorial therapies in heterogeneous cancers.

The S2K guideline, organized by the German Respiratory Society, is aimed at physicians in Germany, Switzerland, and Austria who perform outpatient or inpatient diagnostic flexible bronchoscopy in adult patients. Its goal is to standardize the procedure, minimize complications, and improve diagnostic safety. The guideline specifically addresses specialists in pulmonology, thoracic surgery, and hospital hygiene, as well as nursing and technical staff. It provides evidence- and consensus-based recommendations on indications, preparation, execution, hygiene measures, and aftercare. Additionally, it serves as an information resource for physicians from other specialties, payers, professional societies, and can support quality management. It applies to medical care in Germany, Austria, and Switzerland and incorporates the latest scientific findings up to the date of publication.