Sterile kidney tissue injury induces neutrophil swarming in lung alveolar capillaries.

Sterile tissue injury, such as by acute kidney injury, is common in the clinic and frequently associated with respiratory compromise and hypoxemia. We previously described signaling components released by the injured kidney that drive a remote inflammatory response in the lung. How this caused the resultant hypoxemia remained unclear. Here, we report that sterile kidney tissue injury induces rapid intravascular "neutrophil train" formation in lung capillaries, a novel form of neutrophil swarming. Rapid swarming is enhanced by decreased deformability of circulating neutrophils that impedes their lung capillary passage. Classical lung monocytes are required for neutrophil train formation and release CXCL2 to attract and retain stiffened neutrophils in lung capillaries which reduces capillary perfusion. We thus discovered a novel feature of kidney-lung crosstalk after sterile kidney tissue injury, capillary perfusion deficits that lead to reduced oxygenation despite proper alveolar function and ventilation, unlike in infectious inflammatory lung processes, such as bacterial pneumonia.

CD30+ lymphoproliferative disorder masquerading as an atypical melanocytic proliferation.

Heuristics are cognitive strategies used to facilitate decision-making. They can be helpful tools for expediting pathologic diagnoses, however, they can also affect judgment and lead to biases that guide the pathologist astray. We report the case of a 52-year-old female who presented with two unusual pigmented lesions on the wrist and thigh that clinically and histopathologically resembled an atypical melanocytic proliferation. A biopsy of the thigh revealed a broad proliferation of large, atypical cells forming nests within a heavily pigmented epidermis. The lesion was initially misdiagnosed as melanoma in situ, despite equivocal staining for melanocytic markers, likely due to anchoring and adjustment as well as availability biases, which restricted the differential diagnosis and limited the selection of immunohistochemical stains. It was later discovered through chart review that the patient had a prior history of a cutaneous CD30+ lymphoproliferative disorder, which eventually led to the appropriate diagnosis in this case. Herein, we highlight a rare and unusual presentation of a pigmented epidermotropic CD30+ lymphoproliferative disorder, along with the biases leading to its misdiagnosis and the steps leading to the revelation of the actual diagnosis.

Psychedelics reopen the social reward learning critical period.

Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness1,2. These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies3-9. Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the 'open state' versus the 'closed state' provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.