RepoMed (Medizinische Hochschule Hannover)
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Workflow optimization in acute stroke therapy using a mobile application: a pilot study
Full text linkMittelfristige klinische und radiologische Ergebnisse nach dorsoventraler Stabilisierung von Wirbelkörperfrakturen des thorakolumbalen Übergangs
Full text linkData BDIX SD Carprofen Refinement
No full textData concerning the following project/manuscript: Perioperative dose intake and plasma concentrations achieved with pain therapy based on voluntary carprofen intake depend on rat strain and surgical procedure Aylina Glasenapp, Alina Ottlewski, Marcel Oelerich, Mesbah Alam, Christine Häger, Heike Bähre, Kerstin Schwabe, Marion Bankstahl Introduction: Surgical interventions in rats require appropriate pain relief. Based on previous species-specific pharmacokinetic and safety evaluations, this study investigated refined carprofen-based multimodal analgesic regimens for surgical interventions in two rat strains. Methods: Male rats (BDIX, n=14; Sprague Dawley (SD), n=6) underwent subcutaneous (s.c.) transmitter implantation (TM) and up to two consecutive neurosurgeries (tumor cell injection, BDIX; intracerebral 6-OHDA injection and electrode implantation, SD). Analgesia was based on voluntary intake of carprofen-medicated water (10 mg/kg/24 h) starting either after (regimen 1) or before (regimen 2) surgery and continuing for three days post intervention. This was combined with a single s.c. injection of carprofen (5 mg/kg) before (regimen 1, BDIX) or after (regimen 2, BDIX, SD) surgery as well as intraoperative local anesthesia. At expected critical time points (12, 24, 36 h post surgery), plasma concentrations were measured. Water intake, body weight, and clinical scores were recorded daily. Results: Analgesic regimen 1 did not achieve the desired plasma levels in most individuals due to reduced water intake and consequent failure of target dose intake. With regimen 2, carprofen-medicated water intake before surgery was reduced in BDIX but increased in SD rats. Following s.c. TM and frontal tumor cell injection in BDIX, as well as after intracerebral 6-OHDA injection in SD rats, plasma levels reflected transiently decreased water intake. Still, regimen 2 resulted in anticipated plasma levels for up to 36 h post surgery, depending on the intervention type. Bodyweight was marginally reduced after all surgery types in BDIX and increased after transmitter implantation in SD rats. Clinical score values increased in several SD rats after 6-OHDA injection, reflecting the loss of nigrostriatal dopamine, as well as after electrode implantation. Discussion: Voluntary oral carprofen intake was influenced both by rat strain and surgery type. When oral treatment started in the pre-operative phase target plasma levels were generally achieved even at critical time points, particularly after TM. As water consumption might be reduced early after interventions, monitoring fluid intake is recommended for non-invasive carprofen treatment. Should fluid intake be distinctly reduced, an additional carprofen injection on day 2 post surgery may be beneficial
A database to initiate methodological advances in the evaluation of transitivity assumption in network meta-analysis: qualitative features and limitations of the tracenma R package.
Full text linkBackground Transitivity assumption underlies the network meta-analysis framework and states that treatment comparisons are similar regarding the distribution of important characteristics that act as effect modifiers. Currently, there is a lack of methods to assess transitivity quantitatively. The methodological gap in assessing the transitivity assumption motivated the development of the tracenma database, aspiring to initiate methodological advances in transitivity assessment using empirical data. Methods We used the nmadb R package to build a database of connected networks and consulted the relevant literature to determine the necessary characteristics comprising potential effect modifiers. We referred to the systematic review report and supplementary material for each eligible network to retrieve at least four extractable characteristics. The extracted information comprised the studies, corresponding treatment comparisons, and aggregated characteristics at the study level. We classified the characteristics into three types (clinical, demographic and methodological) and ten subtypes (participants, treatments, outcomes, age, sex, ethnicity, study design, study setting, risk of bias and withdrawals). We summarised the distribution of the characteristics and missing data across all datasets by type and subtype. Results Of the 453 networks in the nmadb database, 217 (48%) were eligible for the tracenma database, with each network comprising a dataset. The extracted characteristics ranged from 4 to 35 (median: 11), with the middle half comprising 8 to 15 characteristics. In most datasets, some characteristics were transformed for being reported inconsistently across the studies concerning the measure scale and summary statistics. Methodological characteristics dominated all datasets and were less prone to missing data. The study design was ubiquitous among the methodological subtypes, while withdrawals were hardly reported. Clinical characteristics were present in most datasets and were subject to most missing data; their characteristic subtypes received uneven attention, with participant characteristics reported more frequently. Demographic characteristics were the least frequently reported. Seventy per cent of the datasets included all types; however, the characteristic subtypes varied substantially in frequency. Conclusions Tracenma is the first database built to motivate the development and empirical evaluation of novel methods for assessing transitivity. The database is hosted in the tracenma R package with functions that facilitate data access
PAM-interacting domain turn-helix 51 motifs can improve Cas9–SpRY activity
Full text linkCas9-SpRY is an engineered variant of the Streptococcus pyogenes Cas9 with relaxed PAM recognition, which can technically be utilized at any target in the genome but some targets are addressed with low efficiency. Here, we show that a previously unexplored motif at the turn and beginning of α-helix 51 (TH51) can be engineered to improve both nuclease and prime-editing activity of Cas9-SpRY. Interaction of the lysine-rich PID loop 2 (PL2) with the target DNA downstream of the PAM (post-PAM) mediates initiation of R-loop formation and subsequent cleavage yet it was unclear if other regions of the PID engage with post-PAM as well. To this end, the NAAN-PAM-targeting iSpyMac hybrid nuclease, which lacks all lysine residues in PL2, was compared with Cas9-SpRY at identical targets using molecular dynamics simulation and in cell culture models, uncovering four crucial post-PAM-interacting lysines in TH51 and TH53 of iSpyMac. Ectopic insertion of a lysine-rich PL2 into iSpyMac boosted its nuclease and prime-editing activities and, in turn, Cas9-SpRY benefited from certain lysine-rich TH51 motifs. Specifically, TH51 from an uncultured Abiotrophia Cas9 species boosted overall Cas9-SpRY activity. Together, this study demonstrates that engineering of post-PAM interacting motifs opens new avenues for the design of advanced CRISPR enzymes
Postoperative neurologische und neuropsychiatrische Komplikationen: prospektive Erhebung in einem herzchirurgischen und kardiologischen Kollektiv
Full text linkAssoziations- und Genexpressionsanalysen zur Validierung von GWAS-Signalen bei zervikalen Dysplasien und Karzinomen
Full text linkIlf2 is a regulator of stress resilience and plasticity in kidney epithelial cells
No full textThe submitted research data consist of two main components: (1) processed RNA sequencing datasets (including bulk RNA-Seq, and single-cell RNA-Seq) derived from mouse kidney, and (2) microscopy images from accompanying cellular experiments such as immunofluorescence staining.RNA sequencing was performed using a [Illumina NovaSeq 6000] platform. The data were processed using standard bioinformatics tools such as [STAR, DESeq2, Seurat], and include normalized expression values (TPM and normalized counts). Microscopy images were acquired using a confocal microscope. Data collection and analysis were conducted between October 2023 and March 2025 at the Institute of Nephrology, Hannover Medical School (MHH). A complete list of references is included in the associated manuscript and can be checked after publishing