Electric shock causes fear-like persistent behavioral response in the nematode Caenorhabditis elegans

Electricity is widely utilized as environmental stimulus to sense the world by many animal species. Despite its importance, however, molecular and physiological mechanisms for responding to electrical stimulus have been far less understood compared to other sensory stimuli. Here we report novel behavioral responses to electrical stimulus of the nematode C. elegans. When the animals on food are stimulated by alternating current, their movement speed suddenly increases more than 2-fold, which persists for a few minutes even after the electrical stimulation is terminated. Genetic analyses reveal that voltage-gated channels are required for the response, possibly as the sensors, and neuropeptide signaling suppresses the persistent response. Additional behavioral analysis reveals that, in addition to the persistence, the animal's response to electrical shock is scalable and has a negative valence, which are recently regarded as emotion primitives, suggesting that the response may reflect a primitive form of "fear" of animals.

Persistent Response and Prolonged Survival Following Pembrolizumab Discontinuation Due to Long-Lasting Autoimmune Colitis in Advanced NSCLC: A Case Report

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies including non-small-cell lung cancer (NSCLC). Immune-mediated colitis is a known adverse effect of pembrolizumab which can lead to the treatment interruption, although not compromising the control of the oncological disease. Herein, we report the case of a 59-year-old woman on pembrolizumab for advanced NSCLC which developed a severe and persistent colitis treated with infliximab for several months following anti-PD-1 antibody discontinuation. This strategy resulted in an improvement but not complete recovery of the gastrointestinal toxicity despite revealed sustained response and control of the oncological disease with prolonged survival over 24 months.

Effective treatment of alopecia universalis with oral tofacitinib: A case report

Alopecia areata is a common autoimmune disease presenting itself with patches of hair loss on the scalp, eyebrows, eyelashes, or any part of the body. It may manifest itself as a single patch, involving the entire scalp (alopecia totalis), or affecting the entire body, thus the name alopecia universalis. Multiple lines of treatment may be employed, but no single most effective treatment exists, especially if the condition is generalized and, thus, becomes more difficult to treat. Herein, we report a case of alopecia universalis treated with oral tofacitinib with an excellent and persistent response one year after.

CDK6 coordinates JAK2V617F mutant MPN via NF-κB and apoptotic networks

Over 80% of patients with myeloproliferative neoplasms (MPNs) harbor the acquired somatic JAK2V617F mutation. JAK inhibition is not curative and fails to induce a persistent response in most patients, illustrating the need for the development of novel therapeutic approaches. We describe a critical role for CDK6 in MPN evolution. The absence of Cdk6 ameliorates clinical symptoms and prolongs survival. The CDK6 protein interferes with 3 hallmarks of disease: besides regulating malignant stem cell quiescence, it promotes nuclear factor κB (NF-κB) signaling and contributes to cytokine production while inhibiting apoptosis. The effects are not mirrored by palbociclib, showing that the functions of CDK6 in MPN pathogenesis are largely kinase independent. Our findings thus provide a rationale for targeting CDK6 in MPN.

Acute renal insufficiency and pancreatitis in a child with atypical Henoch–Schönlein purpura: efficacy of a single dose of cyclophosphamide

A 9-year-old boy with petechiae on the legs and abdominal pain was unsuccessfully treated with steroids. He was admitted to our hospital for the onset of fever, ecchymosis, and arthralgia. Skin lesions suggested vasculitis, but they were not typical of Henoch–Schönlein purpura. He showed ecchymosis of the scrotal bursa, diffusion of petechiae to the trunk and arms, vomiting, severe abdominal pain, oliguria with hyponatremia, hypoalbuminemia, low C3 levels, high levels of creatinine, blood urea nitrogen, and tubular enzymes, proteinuria, and glycosuria. The urinary sediment showed macrohaematuria, and hyaline and cellular casts. Ultrasound showed polyserositis. He was treated with intravenous furosemide, albumin, and methylprednisolone. He underwent colonoscopy and gastroscopy because of development of acute pancreatitis and severe anaemia. Typical lesions of Henoch–Schönlein purpura were observed in the small intestine and colon mucosa. He received three high doses of methylprednisolone, followed by intravenous cyclophosphamide. A dramatic and persistent response was observed after these doses. A single high dose of cyclophosphamide is appropriate in Henoch–Schönlein purpura with acute renal failure and severe pancreatitis that are non-responsive to high-dose steroids.