Menin serves both tumor suppressor and promoter roles in a highly tumor-specific manner. In colorectal cancer (CRC) menin is over-expressed and plays a critical role in regulating transcription of SKP2, and combined treatment with a menin inhibitor (MI) and small molecule EGFR inhibitor (EGFRi) leads to synergistic killing of CRC cells. However, the full spectrum of menin function in CRC remains uncertain. Herein, we demonstrate that menin inhibition increases glycolysis in CRC cells. This MI-induced increase in glycolysis occurs in an mTOR-independent manner and enhances the sensitivity of CRC cells to EGFRis. Additionally, we show that EGFRis induce autophagy in CRC cells, which is important for cell survival in the setting of combined treatment with an EGFRi and MI. Inhibition of autophagy with chloroquine further sensitizes CRCs to treatment with the combination of an EGFRi and MI. Together these findings uncover a novel role for menin in CRC as a repressor of glycolysis and demonstrate that MI-induced increases in glycolysis sensitize CRC to EGFRis. Additionally, these findings illustrate the importance of autophagy as a protective mechanism against EGFRis, especially in the presence of menin inhibition. Ultimately this data opens the possibility of using menin-mediated regulation of glycolysis to potentially improve treatment modalities for CRC.Acute myeloid leukemia (AML) is the most common and aggressive blood cancer in adults. In particular, significant unmet medical needs exist for effective treatment strategies for acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) AML subtypes. Antibody-drug conjugates (ADC) are a promising drug class for AML therapy, as demonstrated by the FDA-approved anti-CD33 ADC, gemtuzumab ozogamicin (Mylotarg). However, CD33 is expressed in normal hematopoietic stem cells, highlighting the critical need to identify AML-specific targets to minimize the risk of potential adverse effects. We have demonstrated that the leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) is expressed at significantly higher levels on monocytic M4 and M5 AML cells than on normal counterparts. Here, we test whether LILRB4 is a promising ADC target to kill monocytic AML cells while sparing healthy counterparts. To this end, we generated ADCs from a humanized anti-LILRB4 mAb and the antimitotic payload, monomethyl auristatin F. The conjugates constructed were characterized and evaluated for LILRB4-specific cell killing potency, toxicity to progenitor cells, pharmacokinetics, and therapeutic efficacy. Our ADC linker technology platform efficiently generated homogeneous anti-LILRB4 ADCs with defined drug-to-antibody ratios. The homogeneous anti-LILRB4 ADCs demonstrated the capacity for LILRB4-mediated internalization, suitable physicochemical properties, and high cell killing potency against LILRB4-positive AML cells. Importantly, our data indicate that these ADCs spare normal progenitor cells. One of our homogeneous conjugates exerted a remarkable therapeutic effect and no significant toxicity in a xenograft mouse model of disseminated human AML. Our findings highlight the clinical potential of anti-LILRB4 ADCs in monocytic AML therapy.As we approach the end of 2020, the Year of the Nurse and Nurse Midwife, it is a good time to reflect on our evidence-based practice (EBP) competencies through a review of a recent study by Melnyk and colleagues. Before describing these competencies, our progress in achieving EBP competency, and the effect competency status has on health care quality, safety, and patient outcomes, this column reviews the definition of EBP and provides a high-level overview of the steps of EBP as defined in Melnyk and Fineout-Overholt.Cytomegalovirus (CMV) was first identified in the 1950s and noted to cause newborn disease in the 1960s. It is now known to be the most common cause of congenital infection in the world, leading to various central nervous system sequelae, the most common being hearing loss.  https://www.selleckchem.com/products/fluoxetine.html  Cytomegalovirus is a ubiquitous pathogen that affects nearly 30,000 infants annually in the United States, leading to 3,000-4,000 cases of hearing loss. Prevention through vaccination has proved unreliable, as has the use of immune globulin. Prevention through education has been shown to be the most effective method of minimizing infection. Antiviral therapy is effective at reducing the impact of infection on newborns. Continued global efforts will hopefully provide more solutions for this opportunistic infection.
  We report findings from an institutional ethnography (IE) of nurses' work of feeding infants within an increasingly technical organization of NICUs.
 
  Five primary informants; 18 secondary informants.
 
  The institutional ethnographic approach included field observations, interviews, and phone and e-mail conversations. Our analysis followed accounts of what actually happened within the textual organization of nurses' work.
 
  Nurses' feeding practices are directed by protocols that arise within multiple documentation systems and clinical technologies. These systems produce barriers to nurses' efforts to skillfully feed infants.
 
  Prioritization of quality and safety perspectives can obscure and constrain the ordinary yet critical clinical reasoning neonatal nurses employ during feeding work. Clinical technologies that have been developed to improve safety can paradoxically disrupt the ability of nurses to respond in the moment to neonatal feeding cues. This finding provides nurses, leaders, and policymakers with insight into why policies and procedures may not be followed as expected.
 Prioritization of quality and safety perspectives can obscure and constrain the ordinary yet critical clinical reasoning neonatal nurses employ during feeding work. Clinical technologies that have been developed to improve safety can paradoxically disrupt the ability of nurses to respond in the moment to neonatal feeding cues. This finding provides nurses, leaders, and policymakers with insight into why policies and procedures may not be followed as expected.Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy worldwide, is an insufficient amount of the G6PD enzyme, which is vital to the protection of the erythrocyte. Deficient enzyme levels lead to oxidative damage, hemolysis, and resultant severe hyperbilirubinemia. If not promptly recognized and treated, G6PD deficiency can potentially lead to bilirubin-induced neurologic dysfunction, acute bilirubin encephalopathy, and kernicterus. Glucose-6-phosphate dehydrogenase deficiency is one of the three most common causes for pathologic hyperbilirubinemia. A change in migration patterns and intercultural marriages have created an increased incidence of G6PD deficiency in the United States. Currently, there is no universally mandated metabolic screening or clinical risk assessment tool for G6PD deficiency in the United States. Mandatory universal screening for G6PD deficiency, which includes surveillance and hospital-based risk assessment tools, can identify the at-risk infant and foster early identification, diagnosis, and treatment to eliminate neurotoxicity.