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Women who are found to carry a BRCA1/2 pathogenic variant experience psychological distress due to an increased risk of breast and ovarian cancer. They may decide between different preventive options. In this secondary analysis of data collected alongside a larger randomized controlled trial, we are looking at 130 newly found BRCA1/2 pathogenic variant carriers and how their coping self-efficacy immediately after genetic test result disclosure is related to their psychological burden and status of preventive decision making. Participants received the Coping Self-Efficacy Scale, the Hospital Anxiety and Depression Scale, the Impact of Event Scale, the Decisional Conflict Scale, and the Stage of Decision-Making Scale after positive genetic test result disclosure. We found that women with higher coping self-efficacy showed fewer symptoms of anxiety or depression and were less affected by receiving the genetic test result in terms of post-traumatic stress. However, coping self-efficacy had no relationship with any decision-related criteria, such as decisional conflict or stage of decision making. This shows that despite its buffering capacity on psychological burden, possessing coping self-efficacy does not lead to more decisiveness in preference-sensitive decisions.

Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers, however the role of this pathway in cancers with wildtype KEAP1 remains poorly understood. To answer this question, we induced NRF2 via pharmacological inactivation of KEAP1 in a panel of 50+ non-small lung cancer cell lines. Unexpectedly, marked decreases in viability were observed in >13% of the cell lines—an effect that was completely rescued by NRF2 ablation. Genome-wide and targeted CRISPR screens revealed that NRF2 induces NADH-reductive stress, through the upregulation of the NAD+-consuming enzyme ALDH3A1. Leveraging these findings, we show that cells treated with KEAP1 inhibitors or those with endogenous KEAP1 mutations are selectively vulnerable to Complex I inhibition, which impairs NADH oxidation capacity and potentiates reductive stress. Thus, we identify reductive stress as a metabolic vulnerability in NRF2-activated lung cancers.

Acquired thrombotic thrombocytopenic purpura (TTP) is an uncommon microangiopathic disorder that can have variable presentations and can be precipitated by a multitude of stressors to the body, most commonly sepsis. TTP is caused by a deficiency of ADAMTS13 leading to intravascular clotting causing thrombocytopenia and microangiopathic hemolytic anemia. TTP can be associated with various other pathologic conditions. One such rare association has been reported with diabetic ketoacidosis (DKA). Here, we present an even less appreciated presentation in association with DKA. A 62-year-old African American male with previously diagnosed prediabetes presented with DKA and developed hemodynamically significant bleeding. He was confirmed to have TTP that responded to plasmapheresis. TTP is a life-threatening illness if not treated urgently with plasmapheresis with or without rituximab. As acquired TTP most commonly occurs during stress on the body, it is important to treat the underlying stressor. Early identification and initiation of appropriate interventions are crucial to reducing mortality associated with TTP. Furthermore, we need to appreciate less commonly associated conditions such as DKA among patients.

La luna ha sido considerada por mucho tiempo una fuerza determinante en los ritmos naturales y de los ciclos femeninos. Este cuerpo celeste se metamorfoseó en Diana, Luna y Lucina, las deidades greco-romanas del parto, en correspondencia con las fases y tiempos de la procreación. Estos, en relación con los diferentes aspectos de las diosas, la luna y su influencia, se analizan desde un punto de vista interdisciplinar en obras como el tratado legal Disputatio de vera humani partus naturalis et legitimi designatione de Alonso Carranza, el tratado médico Tratado sobre el uso de mujeres de Francisco Núñez, el tratado moral Ejemplos morales, humanos y divinos de Juan Pérez de Montalbán, obras de teatro y poesía, las cartas del emperador Leopoldo I, Juan Pérez de Moya, Fernando de Herrera y otras. Las antiguas diosas siguen presentes aún a comienzos de la España Moderna. Se caracterizan por su ambivalencia como expresión de la indeterminación acerca de la procreación, que el ser humano intenta entender y controlar. The moon has been considered to be the driving force of natural rhythms of reproduction, female life cycles and birth. The Greco-Roman lunar goddesses of birth Diana, Luna and Lucina, in correlation with the moon, represent different phases and times of procreation and are still present in Spanish Early Modern testimonies of time. Different aspects of the goddesses’ and the moon’s influence on procreation are presented from an interdisciplinary point of view by gathering and analyzing evidence in: Alonso Carranza’s legal treatise Disputatio de vera humani partus naturalis et legitimi designatione, the moral treatise of Juan Pérez de Montalbán Ejemplos morales, humanos y divinos, a medical treatise of doctor Francisco Núñez Tratado sobre el uso de mujeres, poetry and theater, letters of the Emperor Leopold I, Juan Pérez de Moya, Fernando de Herrera, and others. The goddesses’ ambiguity serves as an expression of indetermination about procreation, which mankind tries to determine.