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1.
GMS J Med Educ ; 40(4): Doc50, 2023.
Article in English | MEDLINE | ID: mdl-37560040

ABSTRACT

Objectives: In the early phase of their studies, students are confronted with a number of teaching and learning methods they are usually not familiar with. Beyond, learning in a university environment requires a high degree of self-organization. Thus, the transition from learning in a school environment to university can be challenging for students and associated with adjustment difficulties. We hypothesized that synchronous online lecturing might be able to serve as a thematic superstructure and a curricular guide that can positively influence course perception, motivation and exam outcome. Methods: We investigated this hypothesis in a retrospective approach by comparing results from histology exams (2020 n=411, 2021 n= 423) and questionnaires for course evaluation received from medical and dentistry second semester students of the RWTH Aachen University, Germany, in 2020 (n=113 questionnaire participants) and 2021 (n=106 questionnaire participants). While in 2020, due to the Corona Pandemic, no synchronous online lectures were held, these were reintroduced in 2021. Results: Our results show several differences in between the two study cohorts. Most important findings include a significantly (p<0.001) lower number of students that failed to pass or withdrew from the exam in 2021, an increased motivation to deal with the learning content (p<0.001) and a higher perceived quality of the study materials (p<0.001) in 2021. Conclusion: Our study indicates that synchronous online lectures can be an important tool to help students to accustom to new learning environments and to structure private study. Further studies will now have to show whether live (online) lectures can have the same significance during clinical training.


Subject(s)
Learning , Students , Humans , Retrospective Studies , Surveys and Questionnaires , Perception
2.
Int J Mol Sci ; 24(10)2023 May 12.
Article in English | MEDLINE | ID: mdl-37240031

ABSTRACT

Spinal cord injury (SCI) results in the production of proinflammatory cytokines due to inflammasome activation. Lipocalin 2 (LCN2) is a small secretory glycoprotein upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 secretion is induced by infection, injury, and metabolic disorders. In contrast, LCN2 has been implicated as an anti-inflammatory regulator. However, the role of LCN2 in inflammasome activation during SCI remains unknown. This study examined the role of Lcn2 deficiency in the NLRP3 inflammasome-dependent neuroinflammation in SCI. Lcn2-/- and wild-type (WT) mice were subjected to SCI, and locomotor function, formation of the inflammasome complex, and neuroinflammation were assessed. Our findings demonstrated that significant activation of the HMGB1/PYCARD/caspase-1 inflammatory axis was accompanied by the overexpression of LCN2 7 days after SCI in WT mice. This signal transduction results in the cleaving of the pyroptosis-inducing protein gasdermin D (GSDMD) and the maturation of the proinflammatory cytokine IL-1ß. Furthermore, Lcn2-/- mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1ß production, pore formation, and improved locomotor function compared with WT. Our data suggest that LCN2 may play a role as a putative molecule for the induction of inflammasome-related neuroinflammation in SCI.


Subject(s)
HMGB1 Protein , Spinal Cord Injuries , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Lipocalin-2/genetics , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Neuroinflammatory Diseases , Spinal Cord Injuries/metabolism , Cytokines/metabolism , Caspases/metabolism , Pyroptosis/physiology
3.
J Neuroinflammation ; 19(1): 134, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35668451

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) induces a multitude of deleterious processes, including neuroinflammation and oxidative stress (OS) which contributed to neuronal damage and demyelination. Recent studies have suggested that increased formation of reactive oxygen species (ROS) and the consequent OS are critical events associated with SCI. However, there is still little information regarding the impact of these events on SCI. Astrocytes are key regulators of oxidative homeostasis in the CNS and astrocytic antioxidant responses promote the clearance of oxidants produced by neurons. Therefore, dysregulation of astrocyte physiology might largely contribute to oxidative damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the main transcriptional regulator of cellular anti-oxidative stress responses. METHODS: In the current study, we hypothesized that astrocytic activation of Nrf2 protects the spinal cord post injury via suppression of neuroinflammation. Thus, using mice line with a GFAP-specific kelch-like ECH-associated protein 1 (Keap1)-deletion, we induced a hyperactivation of Nrf2 in astrocytes and further its effects on SCI outcomes. SCI-induction was performed in mice using the Infinite Horizon Spinal Cord Impactor with a force of 60 kdyn. To assess the quantitative pattern of Nrf2/ARE-activation, we included transgenic ARE-Luc mice. Data were analyzed with GraphPad Prism 8 (GraphPad Software Inc., San Diego, CA, USA). Brown-Forsythe test was performed to test for equal variances and normal distribution was tested with Shapiro-Wilk. RESULTS: In ARE-Luc mice, a significant induction of luciferase-activity was observed as early as 1 day post-injury, indicating a functional role of Nrf2-activity at the epicenter of SCI. Furthermore, SCI induced loss of neurons and oligodendrocytes, demyelination and inflammation in wild type mice. The loss of myelin and oligodendrocytes was clearly reduced in Keap1 KO mice. In addition, Keap-1 KO mice showed a significantly better locomotor function and lower neuroinflammation responses compared to wild type mice. CONCLUSIONS: In summary, our in vivo bioluminescence data showed Nrf2-ARE activation during primary phase of SCI. Furthermore, we found that cell specific hyperactivation of Nrf2 was sufficient to protect the spinal cord against injury which indicate a promising therapeutic approach for SCI-treatment.


Subject(s)
Demyelinating Diseases , Spinal Cord Injuries , Animals , Male , Mice , Astrocytes/metabolism , Demyelinating Diseases/metabolism , Disease Models, Animal , Inflammation/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Spinal Cord/metabolism , Spinal Cord Injuries/metabolism
4.
Life Sci ; 304: 120726, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35750202

ABSTRACT

AIMS: Spinal cord injury (SCI) is a debilitating neurological condition often associated with chronic neuroinflammation and redox imbalance. Oxidative stress is one of the main hallmark of secondary injury of SCI which is tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. In this study, we aimed at investigating the interplay between inflammation-related miRNAs and the Nrf2 pathway in animal model of SCI. MATERIALS AND METHODS: The expression of selected four validated miRNA-target pairs (miRNA223-3p, miRNA155-5p, miRNA145-5p, and miRNA124-3p) was examined at different time points (6 h, 12 h, 1 day, 3 day and 7 day) after SCI. Further, using GFAP-specific kelch-like ECH-associated protein 1 deletion (Keap1-/-) and whole-body Nrf2-/- knockout mice, we investigated the potential interplay between each miRNA and the Keap1/Nrf2 signaling system. KEY FINDINGS: The expression of all miRNAs except miRNA155-5p significantly increased 24 h after SCI and decreased after 7 days. Interestingly, Keap1-/- mice only showed significant increase in the miRNA145-5p after 24 h SCI compared to the WT group. In addition, Keap1-/- mice showed significant decrease in CXCL10/12 (CXCL12 increased in Nrf2-/- mice), and TNF-α, and an increase in Mn-SOD and NQO-1 (Mn-SOD and NQO-1 decreased in Nrf2-/- mice) compared to WT mice. SIGNIFICANCE: Our results suggest that astrocytic hyperactivation of Nrf2 exert neuroprotective effects at least in part through the upregulation of miRNA145-5p, a negative regulator of astrocyte proliferation, and induction of ARE in early phase of SCI. Further studies are needed to investigate the potential interplay between Nrf2 and miRNA145-5p in neuroinflammatory condition.


Subject(s)
MicroRNAs , Neuroprotective Agents , Spinal Cord Injuries , Animals , Antioxidant Response Elements/genetics , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Mice , MicroRNAs/metabolism , NF-E2-Related Factor 2/metabolism , Neuroprotective Agents/pharmacology , Oxidative Stress , Signal Transduction , Spinal Cord Injuries/genetics , Spinal Cord Injuries/metabolism , Superoxide Dismutase/metabolism
5.
Eur J Dermatol ; 32(6): 750-755, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36856395

ABSTRACT

Background: Local recurrence of lentigo maligna melanoma (LMM) and lentigo maligna (LM) continue to be challenging following surgical treatment and aftercare. Objectives: To investigate haematoxylin-eosin staining and immunohistochemistry of the tumour margins of LM and LMM and evaluate the impact of these data on local recurrence. Materials & Methods: In total, 489 tumours were included in this retrospective single-centre study, among them 199 (40.7%) LMs and 290 (59.3%) LMMs. All tumours were excised using micrographiccontrolled surgery. Additional immunohistochemistry staining of the tumour margins was performed in 35 specimens (7.2%). Results: Based on haematoxylin-eosin staining alone, 82/454 tumours (18.1%) were shown to develop local recurrence compared to 3/35 tumours (8.6%) when additional immunohistochemistry was performed. Conclusion: Following micrographic-controlled surgery, the additional use of immunohistochemistry of tumour margins of LM/LMM reduced the risk of local recurrence, although this was not statistically significant.


Subject(s)
Hutchinson's Melanotic Freckle , Skin Neoplasms , Humans , Eosine Yellowish-(YS) , Immunohistochemistry , Retrospective Studies , Staining and Labeling
6.
Cells ; 10(11)2021 11 12.
Article in English | MEDLINE | ID: mdl-34831370

ABSTRACT

Omega-3 polyunsaturated fatty acids (PUFA n3) ameliorate inflammation in different diseases and potentially improve neurological function after neuronal injury. Following spinal cord injury (SCI), inflammatory events result in caspase-1 mediated activation of interleukin-1 beta (IL-1b) and 18. We aim to evaluate the neuroprotective potency of PUFA n3 in suppressing the formation and activation of inflammasomes following SCI. Male Wistar rats were divided into four groups: control, SCI, SCI+PUFA n3, and SCI+Lipofundin MCT (medium-chain triglyceride; vehicle). PUFA n3 or vehicle was intravenously administered immediately after SCI and every 24 h for the next three days. We analyzed the expression of NLRP3, NLRP1, ASC, caspase-1, IL-1b, and 18 in the spinal cord. The distribution of microglia, oligodendrocytes, and astrocytes was assessed by immunohistochemistry analysis. Behavioral testing showed significantly improved locomotor recovery in PUFA n3-treated animals and the SCI-induced upregulation of inflammasome components was reduced. Histopathological evaluation confirmed the suppression of microgliosis, increased numbers of oligodendrocytes, and the prevention of demyelination by PUFA n3. Our data support the neuroprotective role of PUFA n3 by targeting the NLRP3 inflammasome. These findings provide evidence that PUFA n3 has therapeutic effects which potentially attenuate neuronal damage in SCI and possibly also in other neuronal injuries.


Subject(s)
Fatty Acids, Omega-3/therapeutic use , Inflammasomes/metabolism , Spinal Cord Injuries/drug therapy , Animals , Astrocytes/metabolism , Astrocytes/pathology , Blood-Brain Barrier/pathology , Cytokines/blood , Disease Models, Animal , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-3/pharmacology , Inflammation Mediators/blood , Male , Neuroglia/metabolism , Neuroglia/pathology , Rats, Wistar , Recovery of Function , Remyelination , Spinal Cord Injuries/blood , Spinal Cord Injuries/physiopathology
7.
Mol Neurobiol ; 58(11): 5907-5919, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34417948

ABSTRACT

Lipocalin 2 (LCN2), an immunomodulator, regulates various cellular processes such as iron transport and defense against bacterial infection. Under pathological conditions, LCN2 promotes neuroinflammation via the recruitment and activation of immune cells and glia, particularly microglia and astrocytes. Although it seems to have a negative influence on the functional outcome in spinal cord injury (SCI), the extent of its involvement in SCI and the underlying mechanisms are not yet fully known. In this study, using a SCI contusion mouse model, we first investigated the expression pattern of Lcn2 in different parts of the CNS (spinal cord and brain) and in the liver and its concentration in blood serum. Interestingly, we could note a significant increase in LCN2 throughout the whole spinal cord, in the brain, liver, and blood serum. This demonstrates the diversity of its possible sites of action in SCI. Furthermore, genetic deficiency of Lcn2 (Lcn2-/-) significantly reduced certain aspects of gliosis in the SCI-mice. Taken together, our studies provide first valuable hints, suggesting that LCN2 is involved in the local and systemic effects post SCI, and might modulate the impairment of different peripheral organs after injury.


Subject(s)
Lipocalin-2/physiology , Neuroinflammatory Diseases/metabolism , Spinal Cord Injuries/metabolism , Spinal Cord/metabolism , Animals , Apoptosis Regulatory Proteins/metabolism , Astrocytes/metabolism , Brain/metabolism , Gene Expression Regulation , Gliosis/metabolism , Lipocalin-2/blood , Lipocalin-2/deficiency , Lipocalin-2/genetics , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Tissue Proteins/metabolism , Organ Specificity , Paraplegia/etiology , Paraplegia/physiopathology , RNA, Messenger/biosynthesis
8.
J Oral Maxillofac Surg ; 76(7): 1587-1593, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29494804

ABSTRACT

PURPOSE: Computed tomographic angiography (CTA) is reported to give insight into patient-specific anatomy of the flap pedicle preoperatively. We compared information available from standard CTA (s-CTA) with that gained by modifying the conventional CTA technique (modified CTA [m-CTA]). Dissected cadavers served as the control group. MATERIALS AND METHODS: We evaluated 16 s-CTA scans (32 deep circumflex iliac arteries [DCIAs]) and 12 m-CTA scans (17 DCIAs) using 3-dimensional software (Vesalius; ps-medtech, Amsterdam, The Netherlands). We dissected 17 cadavers (n = 34 DCIAs) to serve as the control group. The positions of 4 landmarks (anterior superior iliac spine, origin of DCIA, origin of ascending branch, and crossing of horizontal branch and iliac crest) were defined in a 3-dimensional coordinate system. RESULTS: We found significant differences concerning the distances from the origin of the DCIA to the femoral bifurcation (P < .05) and the anterior superior iliac spine to the crossing point of the horizontal branch with the iliac crest (P < .05) between CTA scans and cadaveric studies. The imaging quality of the m-CTA scans was shown to be more consistent than and superior to that of the s-CTA scans. The visible length of the DCIA was longer on m-CTA scans (mean, 134.32 mm) than on s-CTA scans (mean, 73.62 mm). We could evaluate the branching off of perforators and the relation of the pedicle to the surrounding bone and soft tissue in more detail on m-CTA scans. Standard CTA allowed the bilateral evaluation of the pedicle, whereas m-CTA allowed the evaluation of the injected side only. CONCLUSIONS: The quality and quantity of information available from CTA could be improved by modifying the s-CTA examination by injection as close as possible to the target vessel. Standard CTA delivered information about both sides, whereas m-CTA may need an additional injection for contralateral-side imaging.


Subject(s)
Computed Tomography Angiography , Iliac Artery/anatomy & histology , Iliac Artery/diagnostic imaging , Surgical Flaps/blood supply , Adult , Aged , Aged, 80 and over , Anatomic Landmarks , Cadaver , Contrast Media , Female , Humans , Iohexol/analogs & derivatives , Male , Middle Aged , Preoperative Care
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