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One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked reduction in glycolytic and TCA cycle metabolites in M-I-treated cells. M-I treatment significantly downregulated mRNA and protein expression of essential enzymes involved in de novo lipogenesis, including ACLY, ACC1, FASN, SREBP1, and SCD1. Using shotgun lipidomics, we found a significant increase in lysophosphatidylcholine and phosphatidylcholine loss in M-I treated cells. Subsequently, we observed dysregulation of mitochondrial membrane potential and significant reduction of mitochondrial oxygen consumption after M-I treatment. We further observed M-I treatment induced autophagy, activated AMPK and inhibited mTOR and Akt signaling pathways and leading to apoptosis. However, blocking autophagy did not rescue the M-I-mediated alterations in lipogenesis, suggesting an independent mechanism of action. M-I treated mouse HNC MOC2 cell tumors displayed reduced Hk1, Pdk3, Fasn, and Acly expression. In conclusion, our study revealed that M-I inhibits glycolysis, lipid metabolism, induces autophagy in HNC cells and reduces tumor volume in mice. Therefore, M-I-mediated metabolic reprogramming of HNC has the potential for important therapeutic implications., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Researchers who work on course-based undergraduate research experiences (CUREs) and issues related to science, technology, engineering, and math (STEM) retention have begun exploring changes in student thinking about what it means to be a scientist. To support this effort, we developed rubrics to score answers to three open-response prompts: What does it mean to think like a scientist? What does it mean to do science? and Did you do real research in your coursename labs? The rubric development process was iterative and was based on input from the literature, experienced researchers, and early-career undergraduates. A post hoc analysis showed that the rubric elements map to 27 of 31 statements in the Culture of Scientific Research (CSR) framework, suggesting that scored responses to the three prompts can assess how well students understand what being a science professional entails. Scores on responses from over 400 students who were starting an introductory biology course for majors furnish baseline data from the rubrics and suggest that (i) undergraduates at this level have, as expected, a novice-level understanding of CSR, and (ii) level of understanding in novice students does not vary as a function of demography or academic preparation. Researchers and instructors are encouraged to add CSR to their list of learning objectives for CUREs and consider assessing it using the rubrics provided here., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wachtell et al.)

We developed labs on the evolution of antibiotic resistance to assess the costs and benefits of replacing traditional laboratory exercises in an introductory biology course for majors with a course-based undergraduate research experience (CURE). To assess whether participating in the CURE imposed a cost in terms of exam performance, we implemented a quasi-experiment in which four lab sections in the same term of the same course did the CURE labs, while all other students did traditional labs. To assess whether participating in the CURE impacted other aspects of student learning, we implemented a second quasi-experiment in which all students either did traditional labs over a two-quarter sequence or did CURE labs over a two-quarter sequence. Data from the first experiment showed minimal impact on CURE students' exam scores, while data from the second experiment showed that CURE students demonstrated a better understanding of the culture of scientific research and a more expert-like understanding of evolution by natural selection. We did not find disproportionate costs or benefits for CURE students from groups that are minoritized in science, technology, engineering, and mathematics.

The Royal College of Anaesthetists was commissioned by the United Kingdom Health Quality Partnership to conduct the National Emergency Laparotomy Audit of England and Wales (NELA), to compare outcomes of patients undergoing emergency laparotomy in order to promote quality improvement. Prior to 2016 there were minimal data for emergency laparotomy patients in Australia. The aim of this cohort study was to assess the utility and applicability of the NELA model in a tertiary centre in Western Australia. NELA-related data of patients who underwent emergency laparotomy, between June 2018 and May 2020, were merged with other administrative databases and clinical records. The discriminative ability and calibration of the model were assessed by the area under the receiver operating characteristic (AUROC) curve and calibration plot, respectively. Cox proportional hazards regression was used to assess whether the NELA-predicted risks were an independent predictor of hospital mortality. Of the 502 patients included, 168 (33.5%) patients had a NELA-predicted risk >10%, and of these, 93 (55.4%) were admitted to a critical care unit in a planned fashion immediately after surgery. The NELA model had a good ability to discriminate between survivors and non-survivors (AUROC 0.892, 95% confidence intervals 0.854 to 0.93, P <0.001). However, the model was not perfectly calibrated, with the predicted risks tending to overestimate the observed risks of mortality, especially when the predicted risks were >50%. A high NELA-predicted risk remained significantly associated with mortality after adjusting for other covariates, including sepsis and plasma lactate concentration, suggesting that it is a reliable screening tool for identifying high-risk patients requiring emergency laparotomy.

The objective of this paper is to describe the development of a minimally invasive cochlear implant surgery (MICIS) electrode array insertion tool concept to enable clinical translation. First, analysis of the geometric parameters of potential MICIS patients (N = 97) was performed to inform tool design, inform MICIS phantom model design, and provide further insight into MICIS candidacy. Design changes were made to the insertion tool based on clinical requirements and parameter analysis results. A MICIS phantom testing model was built to evaluate insertion force profiles in a clinically realistic manner, and the new tool design was evaluated in the model and in cadavers to test clinical viability. Finally, after regulatory approval, the tool was used for the first time in a clinical case. Results of this work included first, in the parameter analysis, approximately 20% of the population was not considered viable MICIS candidates. Additionally, one 3D printed tool could accommodate all viable candidates with polyimide sheath length adjustments accounting for interpatient variation. The insertion tool design was miniaturized out of clinical necessity and a disassembly method, necessary for removal around the cochlear implant, was developed and tested. Phantom model testing revealed that the force profile of the insertion tool was similar to that of traditional forceps insertion. Cadaver testing demonstrated that all clinical requirements (including complete disassembly) were achieved with the tool, and the new tool enabled 15% deeper insertions compared to the forceps approach. Finally, and most importantly, the tool helped achieve a full insertion in its first MICIS clinical case. In conclusion, the new insertion tool provides a clinically viable solution to one of the most difficult aspects of MICIS., (Copyright © 2021 by ASME.)

Some new guidelines have been published by European (2010) and American (2011) Societies of Cardiology regarding to the management of atrial fibrillation, the most frequent arrhythmia affecting from 1 to 2% of the global population. In this article we summarize and analyse the new aspects of these guidelines in which the different types of atrial fibrillation are redefined, as well as new criterias for the indication of oral anticoagulation and bleeding risk. New antiarrhythmic and anticoagulant molecules also appear in these guidelines, and there is growing evidence for the use of catheter ablation.

This article discusses the challenging issues faced by women who are diagnosed as being medically obese (i.e., body mass index > or = 30 kg/m). Recently cited as the new national epidemic by some healthcare professionals, obesity can lead to other medical comorbidities, including chronic heart problems, joint deterioration, sleep apnea, depression, and lower self-esteem. On the basis of medical records released by Methodist Hospital in Houston, TX, most patients who seek medical or surgical health options to control obesity are women between 25 and 40 years of age. This article discusses bariatric surgery as a weight loss option and applies the Health Belief Model to explain why patients are choosing this option to help them change eating behaviors. Interventions for nurses and other healthcare professionals are addressed.

A 60-year-old man without any history of cardiac disease was admitted for fulminant hepatic failure (FHF) with coma which revealed severe dilated cardiomyopathy. The patient improved with an adapted medical treatment and was finally discharged from the hospital. Congestive heart failure is a rare cause of FHF, but an important differential diagnosis because it has a specific and potentially efficient treatment.