Male Subfertility Induced by Heterozygous Expression of Catalytically Inactive Glutathione Peroxidase 4 Is Rescued in Vivo by Systemic Inactivation of the Alox15 Gene.

Glutathione peroxidase 4 (GPX4) and arachidonic acid 15-lipoxygenase (ALOX15) are antagonizing enzymes in the metabolism of hydroperoxy lipids. In spermatoid cells and/or in the male reproductive system both enzymes are apparently expressed, and GPX4 serves as anti-oxidative enzyme but also as a structural protein. In this study we explored whether germ line inactivation of the Alox15 gene might rescue male subfertility induced by heterozygous expression of catalytically silent Gpx4. To address this question we employed Gpx4 knock-in mice expressing the Sec46Ala-Gpx4 mutant, in which the catalytic selenocysteine was replaced by a redox inactive alanine. Because homozygous Gpx4 knock-in mice (Sec46Ala-Gpx4+/+) are not viable we created heterozygous animals (Sec46Ala-Gpx4+/-) and crossed them with Alox15 knock-out mice (Alox15-/-). Male Sec46Ala-Gpx4+/- mice, but not their female littermates, were subfertile. Sperm extracted from the epididymal cauda showed strongly impaired motility characteristics and severe structural midpiece alterations (swollen mitochondria, intramitochondrial vacuoles, disordered mitochondrial capsule). Despite these structural alterations, they exhibited similar respiration characteristics than wild-type sperm. When Sec46Ala-Gpx4+/- mice were crossed with Alox15-deficient animals, the resulting males (Sec46Ala-Gpx4+/-+Alox15-/-) showed normalized fertility, and sperm motility was reimproved to wild-type levels. Taken together these data suggest that systemic inactivation of the Alox15 gene normalizes the reduced fertility of male Sec46Ala-Gpx4+/- mice by improving the motility of their sperm. If these data can be confirmed in humans, ALOX15 inhibitors might counteract male infertility related to GPX4 deficiency.

Comparison of artery diameters in the Aachen minipig serving as a human intracranial in vivo model.

Minipigs are used as in vivo endovascular models, particularly in stroke and aneurysm research. However, detailed knowledge of the diameters of forelimb arteries that are commonly used as surrogates for human brain-supplying arteries are lacking. This study aimed to determine the diameters of forelimb and neck arteries in Aachen minipigs and to compare those to the diameters of human cerebral brain-supplying arteries in order to assess the validity of the Aachen minipig as a human intracranial in vivo model. We measured the diameters in the external carotid artery and eight different branches of the subclavian artery in 12 Aachen minipigs using angiographic imaging. Analysed arteries comprised the external carotid artery, axillary artery, brachial artery, subscapular artery first segment, subscapular artery second segment, external thoracic artery, caudal circumflex humeral artery, suprascapular artery and thoracodorsal artery. We compared these diameters to diameters of the following human brain-supplying arteries: terminal internal carotid artery (carotid-T and petrous segment), M1 segment of the middle cerebral artery, M2 segments of the middle cerebral artery, anterior cerebral artery, vertebral artery and basilar artery. Median diameters of porcine forelimb arteries ranged from 1.8 to 4.9 mm, and human brain supplying arteries ranged in diameter from 1.4 to 4.3 mm. Depending on the intended use, this allows porcine forelimb arteries to be selected which are statistically comparable to human brain-supplying vessels. In conclusion, we identified several equivalent arteries of the porcine subclavian branches that are comparable to human brain-supplying arteries. This may help to validate the minipig as a suitable in vivo model for neurovascular experiments.

Bacterial Contamination of Syringes and Fluids in Diagnostic and Interventional Neuroangiography.

(1) Background: Bacterial contamination has been shown to occur during angiographies, although data on its frequency and relevance are sparse. Our aim was to evaluate the incidence of bacterial contamination of syringes used under sterile conditions during neuroangiographies. We sought to differentiate between contamination of the outside of the syringes and the inside and to detect the frequency, extent and germ spectrum of bacterial contamination. (2) Methods: We prospectively collected 600 samples from 100 neuroangiographies. Per angiography, fluid samples from the three routinely used syringes as well as the syringes themselves were analyzed. We analyzed the frequency and extent of contamination and determined the germ spectrum. (3) Results: The majority of samples (56.9%) were contaminated. There was no angiography that showed no contamination (0%). The outer surfaces of the syringes were contaminated significantly more frequently and to a higher extent than the inner surfaces. Both the frequency and extent of contamination of the samples increased with longer duration of angiographic procedures. Most of the bacterial species were environmental or skin germs (87.7%). (4) Conclusions: Bacterial contamination is a frequent finding during neuroangiographies, although its clinical significance is believed to be small. Bacterial contamination increases with longer duration of angiographic procedures.

Platelet function testing using the Multiplate analyzer after administration of aspirin in Aachen minipigs.

Knowledge of platelet function in pigs and the effectiveness of antiplatelet therapy is important to ensure proper transferability from animal studies to humans. Our aim was to (1) characterize baseline platelet function of Aachen minipigs using the bedside Multiplate analyzer, (2) compare baseline platelet function with Göttingen minipigs, and (3) characterize platelet inhibition within the first 5 minutes after intravenous administration of acetylsalicylic acid (ASA). We characterized the baseline platelet function and hematological parameters in 9 Aachen minipigs. Historical data of 8 unmedicated Göttingen minipigs were used for comparison of baseline values. Platelet inhibition in Aachen minipigs was tested 1-5 minutes after intravenous administration of 500 mg ASA. Multiplate examinations included the following tests: ASPI test (to assess the effect of ASA), adenosine-diphosphate-test (ADP test) and thrombin receptor activating peptide test (TRAP test). Median values and interquartile range (IQR) of the Multiplate baseline tests in Aachen minipigs were as follows: ASPI: 39 U (IQR = 21-71), ADP: 70 U (IQR = 48-73), and TRAP: 8 U (IQR = 6-9), whereas the values in Göttingen minipigs were as follows: ASPI: 70.5 U (IQR = 60-78), ADP: 51 U (IQR = 45-66), and TRAP: 6.5 U (IQR = 4-8). ASPI values of Göttingen minipigs were significantly higher than those of Aachen minipigs (p = 0.046). Intravenous administration of ASA in Aachen minipigs resulted in significant platelet inhibition after 1 minute, which remained stable over a period of 5 minutes (p≤0.038). Aachen minipigs appeared to have a high variance in arachidonic acid-mediated platelet aggregation. In Aachen minipigs, intravenous ASA administration resulted in immediate platelet inhibition.

Is the detectability of the spot sign on CT angiography depending on slice thickness and reconstruction type?

OBJECTIVE: The spot sign is a validated imaging marker widely used in CT angiography (CTA) to detect active bleeding and a higher risk of hematoma expansion in patients with intracerebral hemorrhage (ICH). The aim of this study was to investigate the detectability of spot signs on thin multiplanar projection reconstruction (MPR) images compared to thicker maximum intensity projection (MIP) images. METHODS: In this retrospective analysis, we assessed imaging data of 146 patients with primary hypertensive/microangiopathic ICH who received emergency non-contrast computed tomography (NCCT) and CTA. Two experienced radiologists, blinded to each other, evaluated images of thin (1 mm) MPR images and thick (3 mm) MIP images on the presence of spot signs and performed a consensus reading. Kappa tests were used for data comparison. RESULTS: In total, spot signs were observed in 27 cases (=18.5 %) in both thin MPR and thick MIP slices. Detectability of the spot sign did not differ in 1 mm MPR images and 3 mm MIP images (Cohen's kappa, 1.0; p = 0.00). Also, when the readings of the two radiologists were analyzed separately, results for MPR and MIP slices were similar (MPR: Cohen's kappa, 0.81, p = 0.00; MIP: Cohen's kappa, 0.74; p = 0.00). CONCLUSION: No significant difference in the detectability of the spot sign could be demonstrated when comparing 1 mm MPR images with 3 mm MIP images.

Seeing faces, when faces can't be seen: Wearing portrait photos has a positive effect on how patients perceive medical staff when face masks have to be worn.

INTRODUCTION: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, wearing surgical face masks has become mandatory for healthcare staff in many countries when interacting with patients. Recently, it has been shown that wearing face masks impairs social interaction by diminishing a person's ability to read the emotion of their counterparts, an essential prerequisite to respond adequately in social situations. It is easily conceivable that this may have a tangible negative influence on the communication and relationship between patients and healthcare personnel. We therefore investigated whether it has an effect on how patients perceive healthcare professionals when physicians and nursing staff wear portrait photos with their smiling faces in addition to face masks. METHODS: During the study period of 16 days, the medical staff of our Department wore surgical face masks at all times during any kind of interaction with patients. In a pseudorandomized order, all members of our staff additionally affixed their portrait photos to their work clothes on 8 of the 16 days. After completion of their visit, 226 patients were interviewed anonymously in a cross-sectional study design using a questionnaire in which they rated the following three items: friendliness of staff, medical quality of treatment, and how well they felt taken care of during treatment in our Department. RESULTS: On days, on which staff wore photos, mean scores of the questionnaires were significantly higher than on non-photo days (p = 0.013; mean ± standard deviation = 92.8 ± 11.3 vs. 91.0 ± 12.6; median (range) = 97 (98) vs. 96 (76)). When analyzed separately, the increased scores were only significant for the item friendliness of staff (p = 0.009; mean ± standard deviation = 95.8 ± 6.3 vs. 92.2 ± 11.5; median (range) = 98 (39) vs. 97 (54)). CONCLUSION: Our study suggests that the use of portrait photos with smiling faces has a positive effect on how patients perceive healthcare staff.