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[This corrects the article DOI: 10.14309/crj.0000000000001299.].

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Cutaneous metastatic disease from primary gastric cancer is quite scarce, often going unrecognized. In this case, the patient presented with an expanding rash that was biopsied, with findings concerning for metastatic adenocarcinoma from a suspected luminal upper gastrointestinal origin. Subsequent biopsies during an esophagogastroduodenoscopy confirmed poorly differentiated adenocarcinoma with signet ring cell features, most likely from an upper gastrointestinal primary (gastric vs gastroesophageal junction). We review this case to help providers identify signet cell type cutaneous metastases of gastric cancer quickly to improve patient outcomes.

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OBJECTIVES: To determine the clinical course of children with initial negative polysomnography (PSG) tests. METHODS: A retrospective chart review was performed on pediatric patients seen by an otolaryngologist who underwent a PSG between October 2012 and March 2019 for obstructive sleep apnea at a single, academic, tertiary-care center. Data including demographics, follow-up PSG tests, and surgeries were collected. RESULTS: A total of 2018 pediatric patients underwent PSG during the timeframe. About 535/2018 (26.5%) patients were negative for obstructive sleep apnea by PSG and had no prior adenotonsillectomy. About 408/535 (76.3%) did not obtain follow-up testing or surgeries; 69/535 (12.9%) underwent subsequent adenotonsillectomy for worsening symptoms without repeat PSG; and 58/535 (10.8%) obtained 1 or multiple follow-up PSG tests. Of the 58 who obtained repeat PSG, 25 (43.1%) were subsequently positive, with 17 of those 25 (29.3% of 58) undergoing adenotonsillectomy. Taken together, 94/535 (17.6%) of patients with initial negative PSG had worsening sleep disordered breathing. CONCLUSION: A significant minority of children who initially tested negative for pediatric obstructive sleep apnea met criteria for diagnosis on follow up PSG. Additionally, other children with initial negative PSG underwent adenotonsillectomy for worsening symptoms in lieu of repeat testing. Patients should be educated that snoring in children could persist or worsen over time, even in the setting of a initial negative PSG.

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Angiotensin-I-converting enzyme (ACE) inhibitors have been very effective in treating cardiac hypertension since their clinical inception over four decades ago. Since then, it has been established that angiotensin II, the product of ACE, has oncogenic and pro-proliferative qualities, which begs the question as to whether ACE inhibitors may have oncolytic characteristics. In fact, scattered reports suggest that ACE inhibitors are oncolytic and oncopreventive, but the available literature has yet to be thoroughly examined. In the present review, we examine the available literature and determine that ACE inhibitors would have great utility in the prevention and treatment of cancer. At the same time, they would augment the efficacy of chemo- and radiotherapy as well as mitigating damage to healthy tissue by standard chemotherapeutic regimens. We review some of the mounting clinical evidence and show that ACE inhibitors have oncolytic activity in multiple types of cancer and discuss the ability of ACE inhibitors to prevent cardiotoxicity of multiple chemotherapies. Our analysis demonstrates that the actions of ACE inhibitors converge on vascular endolthelial growth factor to reduce its levels in tumors and prevent construction of blood vessels to masses, leaving them nutrient-depleted and subsequently hindering their growth. Given that ACE inhibitors are approved by the Federal Drug Administration and the therapeutic dose for hypertension treatment also slows the growth of multiple cancers types, ACE inhibitors are in a perfect position to be repurposed as oncolytic agents, that would widely increase their utility in the clinic.

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Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing. Sexually naïve females received bilateral Me injections of an adeno-associated virus carrying an inhibitory DREADD. Females were later ovariectomized, treated with ovarian hormones, and given behavioral tests following intraperitoneal injections of saline or clozapine-N-oxide (CNO; which hyperpolarizes infected Me neurons). CNO attenuated females' preference to investigate male vs. female urinary odors. Repeated CNO treatment also slowed the increase in lordosis otherwise seen in females given saline. However, when saline was given to females previously treated with CNO, their lordosis quotients were as high as other females repeatedly given saline. No disruptive behavioral effects of CNO were seen in estrous females lacking DREADD infections of the Me. Finally, CNO attenuated the ability of male pheromones to stimulate Fos expression in the Me of DREADD-infected mice but not in non-infected females. Our results affirm the importance of Me signaling in females' chemosensory preferences and in the acute expression of lordosis. However, they provide no indication that Me signaling is required for the increase in receptivity normally seen after repeated hormone priming and testing with a male.

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Previous research has shown that repeated testing with a stimulus male is required for ovariectomized, hormone-primed female mice to become sexually receptive (show maximal lordosis quotients; LQs) and that drug-induced, epigenetic enhancement of estradiol receptor function accelerated the improvement in LQs otherwise shown by estrous females with repeated testing. We asked whether pre-exposure to male pheromones ('pheromone priming') would also accelerate the improvement in LQs with repeated tests and whether optogenetic inhibition of accessory olfactory bulb (AOB) projection neurons could inhibit lordosis in sexually experienced estrous female mice. In Experiment 1, repeated priming with soiled male bedding failed to accelerate the progressive improvement in LQs shown by estrous female mice across 5 tests, although the duration of each lordosis response and females' investigation of male body parts during the first test was augmented by such priming. In Experiment 2, acute optogenetic inhibition of AOB inputs to the forebrain during freely moving behavioral tests significantly reduced LQs, suggesting that continued AOB signaling to the forebrain during mating is required for maximal lordotic responsiveness even in sexually experienced females. Our results also suggest that pheromonal stimulation, by itself, cannot substitute for the full complement of sensory stimulation received by estrous females from mounting males that normally leads to the progressive improvement in their LQs with repeated testing.

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