Patients with classical dermal lesions were younger (P  less then  0.0001) and had a smaller number of lesions (P  less then  0.05) than those without the lesions. The lesion(s) resolved in 24 of the 44 untreated cases within 1 week to 19 months. Refractory or recurrent lesion(s) were seen in four of 21 treated cases and in four of 44 untreated cases. Because subcutaneous granuloma annulare lesions often resolve spontaneously without treatment, invasive treatments should be avoided. © 2020 Japanese Dermatological Association.Immune checkpoints are cell surface molecules that initiate regulatory pathways which have powerful control of CD8+ cytolytic T cell activity. Antagonistic and agonistic antibodies engaging these molecules have demonstrated profound impact on immune activation and have entered clinical use for the treatment of a variety of diseases. Over the past decade, antagonistic antibodies known as immune checkpoint inhibitors have become a new pillar of cancer treatment and have reshaped the therapeutic landscape in oncology. These agents differ in their mechanism of action and toxicity profiles compared to more traditional systemic cancer treatments such as chemo- and targeted therapies. This article reviews the pharmacology of these new class of agents. This article is protected by copyright. All rights reserved.BACKGROUND Warmblood Fragile Foal Syndrome (WFFS) is a lethal condition detected in Warmblood horses. Its origin and association with performance traits and fertility among horse populations is unknown. OBJECTIVES To validate the previously identified WFFS type 1 (WFFST1)-associated missense variant PLOD1c.2032G>A and to investigate its distribution among various horses with particular focus on Hanoverian breed, as well as its pathomorphologic picture. The study aimed at identifying the origin of the mutant allele and its correlation with performance and fertility traits in Warmblood horses. STUDY DESIGN Retrospective case-control and association study. METHODS WFFST1 variant was validated using whole genome sequencing (WGS) in 78 equids. In an affected foal with a homozygous mutant genotype, necropsy was performed. Skin samples were examined using histology and transmission electron microscopy. Pathway analysis was performed to trace back 81 genetic carriers to the most common recent ancestor. Furthermore, gFFST1 variant and traces it back to its potential origin. This article is protected by copyright. All rights reserved.Infantile hemangiomas are the most common benign vascular tumors in childhood. Propranolol is the first-line treatment for infantile hemangiomas, but failures may occur. Sirolimus, an mTOR inhibitor, is a promising drug for the treatment of vascular malformations and vascular tumors. We present the case of a child with multiple infantile hemangiomasthat was successfully treated with sirolimus and propranolol after failure of combined propranolol and prednisolone treatment. © 2020 Wiley Periodicals LLC.Hypertension and coronary events are becoming more prevalent in aging societies, and myocardial infarction usually occurs in calcium channel blocker (CCB)-treated hypertensive patients. We herein compared the effects of cilnidipine, an L/N-type CCB and amlodipine, an L-type CCB, on post-infarct left ventricular (LV) remodeling in spontaneously hypertensive rats (SHRs). Male SHRs were subjected to 30 minutes of left coronary artery occlusion followed by reperfusion (MI group). The administration of cilnidipine (10 mg/kg/day; MI+Cil group) or amlodipine (10 mg/kg/day; MI+Aml group) was initiated one week before surgery and continued for five weeks. Both CCBs decreased blood pressure. Four weeks after surgery, cilnidipine, but not amlodipine, attenuated LV dilatation, fractional shortening impairments, end-diastolic pressure elevations, and tau elongation. In the non-infarct region, myocyte hypertrophy and brain natriuretic peptide (BNP) mRNA levels were similarly attenuated by both CCBs. On the other hand, interstitial fibrosis, the mRNA expression of collagen type III and TGF β and immunohistological TGF β protein expression in the non-infarct region were reduced more in the MI+Cil group than in the MI+Aml group. Additionally, elevated angiotensin-converting enzyme activity and interstitial norepinephrine concentrations in the non-infarct region were reduced by cilnidipine. These results suggest that cilnidipine reduced cardiac norepinephrine concentrations and inhibited the renin-angiotensin system, which attenuated post-infarct remodeling more than amlodipine in hypertensive rats. This article is protected by copyright. All rights reserved.Cadmium (Cd) is an environmental pollutant that causes health hazard to living organisms. Melatonin (MT) has emerged as a ubiquitous pleiotropic molecule capable of coordinating heavy metal (HM) stresses in plants. However, it remains unclear how melatonin mediates Cd homeostasis and detoxification at transcriptional and/or post- transcriptional levels in radish. Herein, the activities of five key antioxidant enzymes were increased, while root and shoot Cd content were dramatically decreased by melatonin. A combined small RNA and transcriptome sequencing analysis showed that 14 differentially expressed microRNAs (DEMs) and 966 differentially expressed genes (DEGs) were shared between the Cd and Cd+MT conditions. In all, 23 and ten correlated miRNA-DEG pairs were identified in Con vs. Cd and Con vs. Cd+MT comparisons, respectively. Several DEGs encoding yellow stripe 1-like (YSL), heavy metal ATPases (HMA), and ATP-binding cassette (ABC) transporters were involved in Cd transportation and sequestration in radish. Root exposure to Cd2+ induced several specific signaling molecules, which consequently trigger some HM chelators, transporters and antioxidants to achieve reactive oxygen species (ROS) scavenging and detoxification and eliminate Cd toxicity in radish plants. Notably, transgenic analysis revealed that over-expression of the RsMT1 (Metallothionein 1) gene could enhance Cd tolerance of tobacco plants, indicating that the exogenous melatonin confers Cd tolerance, which might be attributable to melatonin-mediated up-regulation of RsMT1 gene in radish plants. These results could contribute to dissecting the molecular basis governing melatonin-mediated Cd stress response in plants, and pave the way for high-efficient genetically engineering low-Cd-content cultivars in radish breeding programs. This article is protected by copyright. Bovine Serum Albumin chemical structure All rights reserved.