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Dupilumab, blocking IL‐4 and IL‐13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab‐treated patients with moderate‐to‐ severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate‐to‐severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty‐nine patients with moderate‐to‐severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL‐33 tear fluid levels and a significantly lower tear break‐up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management. [ABSTRACT FROM AUTHOR]

This article reports on two cases of successful treatment with tralokinumab in patients with atopic dermatitis (AD) and dupilumab-induced psoriasis. The first case involves a 75-year-old woman who experienced psoriatic lesions after receiving dupilumab treatment. Methotrexate was added to manage the psoriatic eruption, but it was discontinued due to side effects. Tralokinumab was then started, resulting in the resolution of both AD and psoriatic lesions. The second case involves an 18-year-old woman who also developed psoriasis while on dupilumab. Tralokinumab was started after topical steroids showed minimal improvement, leading to remission of the psoriatic lesions and maintenance of AD remission. The article suggests that tralokinumab may be a valid option for treating AD in patients with dupilumab-induced psoriasis. [Extracted from the article]

Background: Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients. Methods: We performed a retrospective cohort study of first‐time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10–20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator‐free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)‐III score. Results: We included 129 patients with median PRISM‐III score of 9 (interquartile range, IQR 7–15) and calculated Pediatric End‐stage Liver Disease score of 15 (IQR 2–23). A total of 37 patients (28.7%) had 10–20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18–2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10–1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74–0.97). There were no differences between groups in the likelihood of postoperative complications. Conclusions: In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes. [ABSTRACT FROM AUTHOR]

Summary: Identifying genes or genomic regions influencing carcass‐quality traits such as fatness (FTN) is essential to optimize the genetic selection processes in beef cattle. The aim of this study was to identify genomic regions associated with FTN in Nellore cattle as well as to elucidate the metabolic pathways related to the phenotypic expression. Ultrasound‐based measurements of FTN were collected in 11 750 animals, with 39 903 animals in the pedigree file. Additionally, 1440 animals were genotyped using the GGP‐indicus 35K SNP panel, which contained 33 623 SNPs after quality control. Twenty genes related to FTN were found on 11 chromosomes, explaining 12.96% of the total additive genetic variance. Gene ontology revealed seven genes: NR1L2, PKD2, GSK3β, EXT1, RAD51B, SORCS1 and DPH6, associated with important processes related to FTN. In addition, novel candidate genes (MAATS1, LYPD1, CDK5RAP2, RAD51B, c13H2Oorf96 and TRAPPC11) were detected and could provide further knowledge to uncover genetic regions associated to carcass fatness in beef cattle. [ABSTRACT FROM AUTHOR]

Introduction: One of the major difficulties with respect to molar incisor hypomineralization (MIH) is its classification and differentiation from other enamel development defects (EDDs). The aim of this study was to evaluate diagnostic accuracy in dental students to classify MIH as well as its differentiation from other EDDs by combining conventional theoretical classes and e-learning-assisted pre-clinical practices., Methods: In this one-group pre-test and post-test study, 59 second-year students assessed 115 validated photographs using the MIH Index on the Moodle learning platform. This index assesses the clinical features and extent of MIH, differentiating it from other EDDs. Students received automatic feedback after the pre-test. Two weeks later, students re-evaluated the same photographs. Both pairwise accuracy and overall diagnostic accuracy were estimated and compared for pre- and post-testing, with the area under the curve AUC, along with 95% confidence intervals (95% CI)., Results: The lowest diagnostic accuracy was for the ability to discriminate between white or cream-coloured demarcated opacities and hypomineralization-type defect that is not MIH. The overall pre-test accuracy was AUC = 0.83 and increased significantly post-test to AUC = 0.99 (p < .001). The overall accuracy to discriminate the extent of the lesion also increased significantly post-test (p < .001)., Conclusion: Diagnostic skills to classify MIH can be developed by combining conventional theoretical classes and e-learning-assisted pre-clinical practices., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate bleb morphology features of different glaucoma drainage devices (GDD) using magnetic resonance imaging (MRI)., Materials and Methods: Prospective cohort study of GDD and bleb morphology in consecutive glaucoma patients implanted with Ahmed Glaucoma Valve (AGV), Paul Glaucoma Implant (PGI), Baerveldt Glaucoma Implant (BGI) and Ahmed ClearPath (ACP) devices. Thirty-six eyes from 30 consecutive patients underwent standardized GDD implantation followed by MRI at least 1 month after surgery. Main outcomes included bleb volume and endplate position relative to the optic nerve. Secondary outcomes included intraocular pressure (IOP), medication and surgical complications during a 12-month follow-up., Results: Seven eyes were implanted with the AGV (19%), 5 with BGI (14%), 16 with PGI (44%) and 8 with ACP (22%). MRI scans were obtained 85 ± 66 days after surgery. Mean total bleb volume was 563 ± 390 mm 3 . This bleb volume was inversely correlated with early post-operative IOP (day 7; r s  = -0.3326, p = 0.0475) but positively correlated with IOP at 12 months (r s  = 0.3592, p = 0.0341). No significant difference in total bleb volume was found between GDD types (p = 0.1223). A double-layered bleb was observed in 34 eyes (94%). The inferior bleb volume was significantly larger in PGI devices versus other GDD types (380 ± 205 vs. 193 ± 161 mm 3 ; p = 0.0043). Distance from the endplate to the optic nerve was 9.5 ± 4.0 mm, similar across GDDs (p = 0.2519)., Conclusions: Double-layered blebs are a common finding with GDDs. Bleb volume showed different correlations with IOP at distinct timepoints and the PGI device formed larger blebs. A standardized GDD implantation technique ensures a safe distance from the GDD endplate to the optic nerve., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate the feasibility of developing visual diagnostic skills for detecting and assessing dental caries using e-learning assisted practice in preclinical dental education., Methods: A one-group before and after the study was conducted. After a theoretical lesson on cariology, 53 inexperienced second-year preclinical students assessed 78 clinical photographs using the Nyvad criteria; they received automated feedback upon completion of the test. After a week, all students reassessed the same set of photographs, which were randomly reordered. Differential diagnostic accuracy was analyzed category-pairwise, and overall accuracy measures were based on the receiver operator curve. Diagnostic accuracy in both attempts was evaluated and compared through estimation and pooling of individual student accuracies., Results: Pooled category-pairwise accuracy was lower for discriminating Sound surface from Non-cavitated-active caries, and for discriminating inactive caries (surface discontinuity) from intact surface inactive caries and Cavitated-active caries. Pooled overall accuracy, after the theoretical lesson, was 0.79 (95% confidence interval [CI] 0.77-0.81), and it increased to 0.99 (95% CI 0.98-0.99) after feedback. Between-student variability in accuracy was reduced from I 2  = 0.66 to 0.55., Conclusion: E-learning assisted practice is a feasible alternative to start developing visual diagnostic skills for detecting and assessing dental caries using the Nyvad criteria from preclinical dental education in cariology. However, further studies are required to evaluate its effectiveness in improving real-world practice knowledge and skills., (© 2022 American Dental Education Association.)

The position of the coronary ostia was investigated in 70 segments of the aorta from young adult crossbred horses. After fixation with a 4% buffered aqueous formaldehyde solution and cautious dissection of the aortic bulb, the morphometric relationships between the coronary ostium and the aortic valvar elements were digitally analysed with the support of Image-Pro Plus® software. In horses, the left coronary ostium was near to the right valvular commissure in all cases (100%) analysed in this study. The left coronary ostium was at the level of the intercommissural line in 57.1% and below it in 42.9%. The right coronary ostium was near to the left valvular commissure in 58.6% (2.14 ± 0.32 cm) and close to the right valvular commissure in 41.4% (2.27 ± 0.40 cm). Concerning the intercommissural line, the right coronary ostia was at its level in 24.3% and below it in 75.7%. Accessory coronary ostia were observed in 8.6% of the specimens. In view of the results, it was possible to assume that the positions of the coronary ostia in equines tend towards a standard morphological disposition. Thus, perfusion of the left coronary artery occurs partly more frequently in ventricular systole and complete perfusion occurs less frequently in ventricular diastole. For the right coronary artery, perfusion is mostly complete in diastole and partially in ventricular systole., (© 2022 Wiley-VCH GmbH.)

The aortic valve was investigated in 58 sheep and 60 swine without heart disease. After fixation in 4% formalin, the distance between the ostia and the elements of the right/left aortic sinuses was measured. For the left coronary ostium (LCO), it was found that in sheep 81% were below and 19% at the level of intercomissural line (IL). In pigs, 88.3% were below and 11.7% at the IL level. In sheep, the OCL was close to the right valve commissure (CVR) in 98.3% and close to the left valve commissure (CVV) in 1.7%. In pigs, it was close to RVC at 83.3% and close to LVC at 16.7%. Regarding to RCO, it was found that in sheep 69% was below, 1.7% was above and 29.3% at the IL level. In pigs, 20% were below, 15% above and 65% at the IL level. The distance of the RCO in relation to the valve commissures was 56.9% close to LVC and 43.1% close to RVC in sheep. In pigs, 81.7% were close to LVC and 18.3% close to RVC. The position of LCO was balanced between sheep and swine, while the RCO in swine was closer to CVE when compared with sheep. The accessory coronary ostium was observed in 18.6% of sheep and 10% of pigs. Thus, it is concluded that in sheep and swine the left coronary artery is perfused only in ventricular diastole. Perfusion of the right coronary artery occurs more frequently in diastole and less frequently in ventricular systole., (© 2022 Wiley-VCH GmbH.)

Astrocytes are key players in the regulation of brain development and function. They sense and respond to the surrounding activity by elevating their intracellular calcium (Ca 2+ ) levels. These astrocytic Ca 2+ elevations emerge from different sources and display complex spatio-temporal properties. Ca 2+ elevations are spatially distributed in global (soma and main processes) and/or focal regions (microdomains). The inositol 1,4,5-trisphosphate receptor type 2 knockout (IP 3 R2 KO) mouse model lacks global Ca 2+ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP 3 R2 during development may trigger compensating phenotypes, which could bias the results of experiments using developing or adult mice. To address this issue, we performed a detailed neurodevelopmental evaluation of male and female IP 3 R2 KO mice, during the first 21 days of life, as well as an evaluation of motor function, strength and neurological reflexes in adult mice. Our results show that male and female IP 3 R2 KO mice display a normal acquisition of developmental milestones, as compared with wild-type (WT) mice. We also show that IP 3 R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP 3 Rs, we quantified the relative mRNA levels of all 3 subtypes, in brain tissue. We found that, along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3. Overall, our results show that the IP 3 R2 KO mouse is a reliable model to study the functional impact of global IP 3 R2-dependent astrocytic Ca 2+ elevations., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Clinical and experimental studies suggest immunologic proteins contribute to hepatocellular carcinoma (HCC) development., Aim: To evaluate circulating immunologic markers and HCC risk., Methods: From a Taiwanese cohort of chronically hepatitis B virus (HBV)-infected individuals followed over time (REVEAL-HBV), we sampled 175 who developed HCC, 117 cirrhosis only, and 165 non-cirrhotic controls. From a similar Taiwanese cohort of chronically hepatitis C virus (HCV)-infected individuals (REVEAL-HCV), we included 94 individuals who developed HCC, 68 cirrhosis only and 100 non-cirrhotic controls. We compared pre-diagnostic plasma levels of 102 markers in HCC cases to non-cirrhotic and cirrhotic controls using polytomous logistic regression. A priori markers included insulin-like growth factor binding protein-3 (IGFBP-3), intercellular adhesion molecule 1 (ICAM-1) and interleukin 6 (IL-6). P-values for other markers were corrected for multiple testing (false discovery rate = 10%)., Results: In both REVEAL-HBV and REVEAL-HCV, increasing levels of ICAM-1 were associated with increased risk of HCC compared to non-cirrhotic controls (P-trend 0.02 and 0.001, respectively). In both REVEAL-HBV and REVEAL-HCV, two novel markers [C-X-C motif chemokine 11 (CXCL11) and hepatocyte growth factor (HGF)] were positively associated [strongest odds ratio quartile 4 versus 1 (OR) 4.55 for HGF in HCV], while two [complement factor H related 5 (CFHR5) and stem cell factor (SCF)] were negatively associated (strongest OR Q4vQ1 0.14 for SCF in HCV) with development of HCC compared to non-cirrhotic controls., Conclusions: We confirmed the association for ICAM-1 and identified 4 additional proteins associated with HBV- and HCV-related HCC. These findings highlight the importance of immunologic processes in HBV- and HCV-related HCC., (© 2021 Mayo Foundation for Medical Education and Research. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)