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Abstract Background Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left–right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy. Case presentation We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left–right body axis. Conclusions Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.

Abstract Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

ObjectivesStandardized criteria for disease activity and end of treatment of systemic treatment of atopic dermatitis have not been established. The objective of this study is to explore the experience using upadacitinib retrospectively, to find clues to weaning from systemic treatment, and to determine the algorithm for setting treatment goals and terminating systemic treatment.MethodsFourteen patients treated with upadacitinib between 1 November 2021 and 31 December 2023 were enrolled in the study. Topical anti-inflammatory treatments were combined. Treatment outcomes were established according to the European Task Force of Atopic Dermatitis guidelines. To evaluate disease status and control, we adopted the Treat to target strategy. Changes in serum biomarkers (TARC and IgE) were also observed.ResultsAll patients achieved EASI 50 after 52 weeks. At 76 weeks, 80% and 30% of patients achieved EASI 75 and EASI 90, respectively. Four patients completed upadacitinib, five patients discontinued treatment, and five patients remained on treatment. Two patients achieved complete remission without topical anti-inflammatory treatment. Two patients discontinued due to adverse events. Patients with better treatment adherence, mainly topical treatment, tended to be able to withdraw from UPA. IgE increased from baseline in 11 patients (78.6%) and TARC increased in 14 patients (100%). These biomarkers decreased from the peak 24–48 weeks after initiating treatment, after the improvement of eczema.ConclusionCombining systemic and topical treatments effectively induces remission in AD patients. Transitioning off systemic treatment begins by achieving remission maintained solely with topical therapy, emphasizing the importance of adherence.

In this study, we focused on assessing the symmetry of shapes and quantifying an index of ‘order’ in three-dimensional shapes using curvature, which is important in product design. Specifically, the target three-dimensional shape was divided into two segments, and the Jensen–Shannon distance was calculated for the distribution of the Casorati curvatures in both segments to determine the similarity between them. This was proposed as an indicator of the ‘order’ exhibited by the shape. To validate the effectiveness of the proposed index, sensory evaluation experiments were conducted on three shapes: extruded, rotated, and vase. For the rotated shape, the coefficient of determination between the proposed index and the sensory evaluation value of ‘order’ on a 5-point Likert scale was found to be less than 0.1. The reason for the poor correlation coefficient of determination may be attributed to the bias in human perception, where individuals tend to perceive mirror symmetry with respect to the plane that includes the vertical axis when recognizing the mirror symmetry of an object. In contrast, for the extruded and vase shapes, the coefficients of determination were 0.36 and 0.66, respectively, supporting the validity of the proposed index. Nonetheless, the coefficient of determination decreased slightly for familiar extruded shapes and asymmetric vase shapes. In future research, our aim is to quantify ‘aesthetic preference’ by combining the ‘order’ and ‘complexity’ indexes.