Search Results (36)

The interdisciplinary nature of science, technology, engineering, and mathematics (STEM) offers the opportunity to implement educational approaches to biotechnology and process engineering issues. The focus should be on the promotion of scientific literacy in contexts relevant to research, industry, and society. This article specifically shows the development of suitable low-level experiments to provide a milestone for the implementation of biotechnological and process engineering issues in STEM education. The experiments show the successful transfer of inquiry-based bioprocess engineering experiments with a Do-It-Yourself (DIY) bioreactor and low-cost sensors. It was possible to achieve comparable trends of process-relevant state variables like mixing time and volumetric mass transfer coefficient (k_La) for the DIY bioreactor in comparison to established commercial systems. Furthermore, microalga Microchloropsis gaditana could be successfully cultivated under different cultivation conditions in the DIY system, and the respective growth curves could be observed. The DIY system is well suited for experimental application in schools and provides a scientifically substantiated basis for data interpretation. The scientific outreach approach and cooperation in a multiprofessional team for the transfer of process engineering questions to education can be evaluated as enriching. Experiments involving educational concepts offer a variety of connecting elements in the curriculum and opportunities to foster scientific literacy. Full article

Background/Objectives: The oral delivery of large-molecule drugs remains challenging due to poor solubility, perdemeability, and stability in the gastrointestinal tract, resulting in low bioavailability. In this study, hot melt extrusion (HME) was investigated as a solvent-free manufacturing technique for mucoadhesive bilayer films to improve drug absorption. Methods: Polyvinyl alcohol (PVA) and polyethylene oxide (PEO) were evaluated as mucoadhesive film-forming polymers, in conjunction with Eudragit^® RS as a water-insoluble backing layer. Paracetamol and lactase were utilized as small and large molecule APIs, respectively. The resulting films were assembled into bilayer film samples and examined for mechanical properties, mucoadhesion, and dissolution behavior. A novel dissolution model was developed to evaluate unidirectional drug transport. Results: The results showed that bilayer films could be successfully fabricated using HME, with different mechanical properties depending on the polymer and drug content. Tests with the newly developed dissolution model showed a unidirectional drug release. The model also confirmed the need for biorelevant dissolution test systems because of a better differentiation between polymers compared to standard test methods such as the paddle-over-disk method. Furthermore, the investigation revealed that the activity of enzymes was retained after extrusion, thus indicating the feasibility of processing biologics. Conclusions: This study highlights the potential of HME to produce bilayer films as an innovative drug delivery platform offering improved bioavailability for both small and large molecules. Full article

Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing syndrome in patients with liver cirrhosis, often triggered by bacterial infections. Piperacillin/Tazobactam is a key antibiotic in this setting, and therapeutic drug monitoring (TDM) helps optimize its dosing. This study evaluates the impact of an interprofessional TDM strategy for Piperacillin/Tazobactam in ACLF patients in the ICU. Methods: This retrospective ICU study evaluated an interprofessional TDM approach for optimizing Piperacillin/Tazobactam dosing in critically ill ACLF patients. The team, consisting of physicians, clinical pharmacists, and staff nurses, engaged in shared decision making, collaboratively interpreting TDM results and adjusting the dosing accordingly. This study included 26 patients with ACLF who underwent initial TDM and 7 who received follow-up TDM. Piperacillin/Tazobactam dosing was modified based on TDM recommendations, with serum concentrations measured weekly. Adherence to and the implementation of interprofessional dosing recommendations were systematically analyzed to assess the impact of this approach. Results: The initial TDM showed that 30.8% of patients had Piperacillin/Tazobactam levels within the target range, while 53.8% were above and 15.4% below. The interprofessional team recommended dose reductions in seven patients, increases in three, and no change in eleven, with five requiring antibiotic modifications. At the first follow-up TDM, 20.0% reached target levels, while 80.0% remained above, with no subtherapeutic cases. The team recommended one further dose reduction and maintained dosing in four patients. All recommendations were fully implemented, demonstrating strong adherence to the collaborative protocol. Conclusions: The interprofessional TDM strategy optimized Piperacillin/Tazobactam dosing in ACLF patients with full adherence to the recommendations. This collaborative approach improves outcomes and supports global efforts to curb antibiotic resistance. Full article

Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50–5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68–4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83–1.58) or metachronous (Median 1.83, IQR 1.29–3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19–3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = −0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions. Full article

Background/Objectives In recent years, the national Gender Identity Service for individuals under 18 years of age in Denmark has seen a considerable increase in referrals of youngsters during puberty. Given this development, it is important to deepen our understanding of the characteristics of contemporary youngsters seeking help for gender incongruence. This understanding can serve as the foundation for improving current treatment regimens by ensuring optimal individual assessment and care. In this study, we aim to describe the sociodemographic characteristics, health profiles, and treatment trajectories in detail, as well as any changes in these characteristics, of all transgender and gender-diverse youngsters referred to the Gender Identity Service in Denmark from 2016 through 2022. Methods: This is a retrospective observational study of a national cohort comprising all individuals under 18 years of age referred to the Danish Gender Identity Service from 1 January 2016 to 1 January 2023. We will use data from medical records obtained at routine visits from the first assessment through repeated visits. Data on demographics, physical and mental health profiles, and information regarding gender identity will be collected and analyzed. The characteristics of those individuals who progressed to hormone therapy will be compared to those who did not. Results: This study aims to enhance our understanding of the characteristics and needs of contemporary youngsters with gender identity issues. Conclusions: The scientific evidence for the assessment and treatment of gender incongruence in youngsters is limited. The characteristics of youngsters seeking healthcare for gender incongruence today may differ from earlier. Full article

The aim of this study was to assess the mental health situation of children and adolescents during a period of less strict COVID-19-pandemic-related measures after the first pandemic wave. This cross-sectional study was conducted in July 2021 by carrying out an online survey among children and adolescents (aged 10–18 years) from Halle (Saale), Germany (n = 233). The questionnaire measured important aspects of mental health among young people, namely health-related quality of life (HRQoL, using the self-report version of the KIDSCREEN-10), mental health problems in general (using the SDQ), depressive symptoms (using the CES-DC), and psychosomatic complaints (using the HBSC symptom checklist). In addition, other important health issues such as sleep behavior and related difficulties, disordered eating, and any positive consequences of the pandemic were addressed. The results were analyzed using descriptive statistics. A total of 223 children participated in the survey. About 69.7% of the participating children and adolescents had a high HRQoL, while 10.5% displayed abnormal results on the SDQ. There were indications of emotional problems in 16.5% of the participants based on the SDQ subscales. Almost 44% of the participants were screened as positive for depressive symptoms on the CES-DC, with girls and older adolescents being more likely to be affected. This also applied for psychosomatic complaints. Here, irritability was experienced at least once a week or more frequently by 58.9% of the children and adolescents. Although we had a small sample size, this study showed a high prevalence of mental health problems regarding the SDQ and HRQoL. However, our study population showed a better mental health than comparable studies conducted earlier in the pandemic. Depressive symptoms were still substantially higher than those in pre-pandemic data. We hypothesize that this might reflect the fact that there were a few COVID-19-related restrictions at the time when our survey took place. Based on these findings, we assume that the mental health of children and adolescents differed between different phases in the pandemic. Full article

Risk prediction prior to oncologic esophagectomy is crucial for assisting surgeons and patients in their joint informed decision making. Recently, a new risk prediction model for 90-day mortality after esophagectomy using the International Esodata Study Group (IESG) database was proposed, allowing for the preoperative assignment of patients into different risk categories. However, given the non-linear dependencies between patient- and tumor-related risk factors contributing to cumulative surgical risk, machine learning (ML) may evolve as a novel and more integrated approach for mortality prediction. We evaluated the IESG risk model and compared its performance to ML models. Multiple classifiers were trained and validated on 552 patients from two independent centers undergoing oncologic esophagectomies. The discrimination performance of each model was assessed utilizing the area under the receiver operating characteristics curve (AUROC), the area under the precision–recall curve (AUPRC), and the Matthews correlation coefficient (MCC). The 90-day mortality rate was 5.8%. We found that IESG categorization allowed for adequate group-based risk prediction. However, ML models provided better discrimination performance, reaching superior AUROCs (0.64 [0.63–0.65] vs. 0.44 [0.32–0.56]), AUPRCs (0.25 [0.24–0.27] vs. 0.11 [0.05–0.21]), and MCCs (0.27 ([0.25–0.28] vs. 0.15 [0.03–0.27]). Conclusively, ML shows promising potential to identify patients at risk prior to surgery, surpassing conventional statistics. Still, larger datasets are needed to achieve higher discrimination performances for large-scale clinical implementation in the future. Full article

Background: The NOL^® system (PMD-200™ Nociception Level Monitor; Medasense Ltd., Ramat Gan, Israel) is used for the real-time detection of physiological nociception in anesthetized patients by assessing the parameters indicative of sympathetic activity, such as photoplethysmography, skin conductance, peripheral temperature, and accelerometry, which are quantified into the NOL^®-Index. This index is more sensitive than traditional clinical parameters in estimating pain and stress responses. While its effectiveness in general anesthesia is well documented, its efficacy in epidural anesthesia needs further investigation. Methods: This retrospective study analyzed NOL^®-Index dynamics compared to conventional parameters after epidural administration of bupivacaine. Following ethics committee approval, 119 NOL^® measurements were retrospectively analyzed after thoracic epidural catheter administration in 40 patients undergoing abdominal and urological surgery. The NOL-Index^® was assessed at 0, 1, 3, and 5 min post application and compared to heart rate, blood pressure, and bispectral index dynamics. Results: This study showed a significant decrease in the NOL^®-Index post-local-anesthetic administration with better sensitivity than classical clinical parameters (0 min = 38 ± 11; 1 min = 22 ± 13*; 3 min = 17 ± 11*; 5 min = 12 ± 10*). Higher doses of local anesthetics led to a significant, dose-dependent decrease in NOL^®-Index (low dose, 5 min = 15 ± 10*; high dose, 5 min = 8 ± 8*). Conclusions: This study is the first to demonstrate the effectiveness of the NOL^®-Index in measuring nociceptive effects following epidural administration, highlighting its potential superiority over conventional parameters and its sensitivity to dose variations. Full article

The field of regenerative medicine is increasingly in need of effective and biocompatible materials for tissue engineering. Human acellular dermal matrix (hADM)-derived collagen matrices stand out as a particularly promising candidate. Their ability to preserve structural integrity, coupled with exceptional biocompatibility, positions them as a viable choice for tissue replacement. However, their clinical application has been largely confined to serving as scaffolds. This study aims to expand the horizon of clinical uses for collagen sheets by exploring the diverse cutting-edge clinical demands. This review illustrates the clinical utilizations of collagen sheets beyond traditional roles, such as covering skin defects or acting solely as scaffolds. In particular, the potential of Epiflex^®, a commercially available and immediately clinically usable allogeneic membrane, will be evaluated. Collagen sheets have demonstrated efficacy in bone reconstruction, where they can substitute the induced Masquelet membrane in a single-stage procedure, proving to be clinically effective and safe. The application of these membranes allow the reconstruction of substantial tissue defects, without requiring extensive plastic reconstructive surgery. Additionally, they are found to be apt for addressing osteochondritis dissecans lesions and for ligament reconstruction in the carpus. The compelling clinical examples showcased in this study affirm that the applications of human ADM extend significantly beyond its initial use for skin defect treatments. hADM has proven to be highly successful and well-tolerated in managing various etiologies of bone and soft tissue defects, enhancing patient care outcomes. In particular, the application from the shelf reduces the need for additional surgery or donor site defects. Full article

MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC. Full article

(1) Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing disease in patients with liver cirrhosis. Meropenem is crucial for treating severe infections. Therapeutic drug monitoring (TDM) offers an effective means to control drug dosages, especially vital for bactericidal antibiotics like meropenem. We aimed to assess the outcomes of implementing TDM for meropenem using an innovative interprofessional approach in ACLF patients on a medical intensive care unit (ICU). (2) Methods: The retrospective study was conducted on a medical ICU. The outcomes of an interprofessional approach comprising physicians, hospital pharmacists, and staff nurses to TDM for meropenem in critically ill patients with ACLF were examined in 25 patients. Meropenem was administered continuously via an infusion pump after the application of an initial loading dose. TDM was performed weekly using high-performance liquid chromatography (HPLC). Meropenem serum levels, implementation of the recommendations of the interprofessional team, and meropenem consumption were analyzed. (3) Results: Initial TDM for meropenem showed a mean meropenem serum concentration of 20.9 ± 9.6 mg/L in the 25 analyzed patients. Of note, in the initial TDM, only 16.0% of the patients had meropenem serum concentrations within the respective target range, while 84.0% exceeded this range. Follow-up TDM showed serum concentrations of 15.2 ± 5.7 mg/L (9.0–24.6) in Week 2 and 11.9 ± 2.3 mg/L (10.2–13.5) in Week 3. In Week 2, 41.7% of the patients had meropenem serum concentrations that were within the respective target range, while 58.3% of the patients were above this range. In Week 3, 50% of the analyzed serum concentrations of meropenem were within the targeted range, and 50% were above the range. In total, 100% of the advice given by the interprofessional team regarding meropenem dosing or a change in antibiotic therapy was implemented. During the intervention period, the meropenem application density was 37.9 recommended daily doses (RDD)/100 patient days (PD), compared to 42.1 RDD/100 PD in the control period, representing a 10.0% decrease. (4) Conclusions: Our interprofessional approach to TDM significantly reduced meropenem dosing, with all the team’s recommendations being implemented. This method not only improved patient safety but also considerably decreased the application density of meropenem. Full article

Bleeding and thromboembolic (TE) complications in neurosurgical diseases have a detrimental impact on clinical outcomes. The aim of this study is to provide a scoping review of the available literature and address challenges and knowledge gaps in the management of coagulation disorders in neurosurgical diseases. Additionally, we introduce a novel research project that seeks to reduce coagulation disorder-associated complications in neurosurgical patients. The risk of bleeding after elective craniotomy is about 3%, and higher (14–33%) in other indications, such as trauma and intracranial hemorrhage. In spinal surgery, the incidence of postoperative clinically relevant bleeding is approximately 0.5–1.4%. The risk for TE complications in intracranial pathologies ranges from 3 to 20%, whereas in spinal surgery it is around 7%. These findings highlight a relevant problem in neurosurgical diseases and current guidelines do not adequately address individual circumstances. The multidisciplinary COagulation MAnagement in Neurosurgical Diseases (COMAND) project has been developed to tackle this challenge by devising an individualized coagulation management strategy for patients with neurosurgical diseases. Importantly, this project is designed to ensure that these management strategies can be readily implemented into healthcare practices of different types and with sustainable integration. Full article

Olive mill wastewater (OMW) management is an economic and environmental challenge for olive oil-producing countries. The recovery of components with high added value, such as antioxidants, is a highly researched approach that could help refinance performant wastewater treatment systems. Anaerobic (co-)digestion is a suitable process to valorize the energetic and nutritional content of OMW and OMW-derived waste streams from resource recovery processes. Issues of process stability, operation, and yields discourage industrial application. Deepening the understanding of biomethane potential, continuous anaerobic digester operational parameters, and co-substrates is key to large-scale implementation. The biomethane potential of different OMW-derived samples and organic solid market waste as co-substrate was 106–350 NL methane per kg volatile solids (VS). The highest yields were obtained with the co-substrate and depolyphenolized OMW mixed with retentate from an ultrafiltration pretreatment. Over 150 days, an anaerobic fixed-bed 300 L digester was operated with different OMW-derived substrates, including OMW with selectively reduced polyphenol concentrations. Different combinations of organic loading rate and hydraulic retention time were set. The biogas yields ranged from 0.97 to 0.99 L of biogas per g of volatile solids (VS) eliminated, with an average methane content in the produced biogas of 64%. Potential inhibition of the process due to high polyphenol concentrations or over-acidification through volatile fatty acids was avoided in the continuous process through process and substrate manipulation. High concentrations of potassium and low concentrations of nitrogen and phosphate end up in the digestate. Sulfate reduction results in high H₂S concentrations in the biogas. The digestate was tested for phytotoxic properties via the germination index. Diluted digestate samples improved germination by up to 50%. Full article

Vestibular schwannoma (VS) are benign cranial nerve sheath tumors of the vestibulocochlear nerve. Their incidence is mostly sporadic, but they can also be associated with NF2-related schwannomatosis (NF2), a hereditary tumor syndrome. Metastasis associated in colon cancer 1 (MACC1) is known to contribute to angiogenesis, cell growth, invasiveness, cell motility and metastasis of solid malignant cancers. In addition, MACC1 may be associated with nonsyndromic hearing impairment. Therefore, we evaluated whether MACC1 may be involved in the pathogenesis of VS. Sporadic VS, recurrent sporadic VS, NF2-associated VS, recurrent NF2-associated VS and healthy vestibular nerves were analyzed for MACC1 mRNA and protein expression by quantitative polymerase chain reaction and immunohistochemistry. MACC1 expression levels were correlated with the patients’ clinical course and symptoms. MACC1 mRNA expression was significantly higher in sporadic VS compared to NF2-associated VS (p < 0.001). The latter expressed similar MACC1 concentrations as healthy vestibular nerves. Recurrent tumors resembled the MACC1 expression of the primary tumors. MACC1 mRNA expression was significantly correlated with deafness in sporadic VS patients (p = 0.034). Therefore, MACC1 might be a new molecular marker involved in VS pathogenesis. Full article

The mechanical properties in laser-based powder bed fusion (PBF-LB/M) manufactured parts are anisotropic in nature due to the layer-wise build-up but also change due to different solidification conditions in dependence on the process strategy and the geometry. In this work, the latter effect is examined by means of simulating the thermal history on a part scale (macro temperature) and correlating the critical temperature and holding time with the local hardness and microstructure. A macro temperature model is introduced and validated with vector-based thermal simulations and thermo couple measurements from the build-up process. Two cone-shaped geometries are investigated, namely, an upright and an inverted cone. The examinations are performed and validated with Inconel 718. An outlook to further investigations and more complex, real-life applicable geometries is given. Full article