Multi-State Gene Cluster Switches Determine the Adaptive Mitochondrial And Metabolic Landscape of Breast Cancer.

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states.

The employment of art therapy to develop empathy and foster wellbeing for junior doctors in a palliative medicine rotation - a qualitative exploratory study on acceptability.

BACKGROUND: The interdisciplinary realm of medical humanities explores narratives and experiences that can enhance medical education for physicians through perspective-taking and reflective practice. However, there is a gap in comprehension regarding its appropriateness at the postgraduate level, especially when utilising art therapists as faculty. This study aims to assess the acceptability of an innovative art therapy-focused educational initiative among junior doctors during a palliative care rotation, with the goal of cultivating empathy and promoting well-being. METHODS: A qualitative research project was conducted at the Division of Supportive and Palliative Care (DSPC) in the National Cancer Centre Singapore (NCCS). The study involved the recruitment of junior doctors who had successfully completed a three-month palliative care rotation program, spanning from January 2020 to April 2021. In a single small-group session lasting 1.5 h, with 3 to 4 participants each time, the individuals participated in activities such as collage making, group reflection, and sharing of artistic creations. These sessions were facilitated by an accredited art therapist and a clinical psychologist, focusing on themes related to empathy and wellbeing. To assess the acceptability of the program, two individual interviews were conducted three months apart with each participant. An independent research assistant utilised a semi-structured question guide that considered affective attitude, burden, perceived effectiveness, coherence, and self-efficacy. Thematic analysis of the transcribed data was then employed to scrutinise the participants' experiences. RESULTS: A total of 20 individual interviews were completed with 11 participants. The three themes identified were lack of pre-existing knowledge of the humanities, promotors, and barriers to program acceptability. CONCLUSIONS: The participants have mixed perceptions of the program's acceptability. While all completed the program in its entirety, the acceptability of the program is impeded by wider systemic factors such as service and manpower needs. It is vital to address these structural limitations as failing to do so risks skewing current ambivalence towards outright rejection of future endeavours to integrate humanities programs into medical education.

Substituting Generic Lamivudine for Emtricitabine in Virologically Suppressed HIV-Infected Patients.

This study evaluated the effectiveness of formulary substitution from products or regimens containing name brand emtricitabine to alternative regimens containing generic lamivudine among virologically suppressed HIV-infected patients in a correctional managed health care system. Results of this retrospective cohort study showed that 94.9% of patients switched from emtricitabine to lamivudine ( n = 447) and 93.0% of emtricitabine control patients ( n = 449) had an undetectable viral load at last available test over a 2-year period. The two groups also showed similar values for CD4 counts, compliance, discontinuation, and M184V mutation; however, a slightly greater proportion of lamivudine patients experienced respiratory symptoms. Nonetheless, this study demonstrates that switching virologically suppressed HIV-infected patients from name brand emtricitabine-containing regimens to generic lamivudine-based regimens may reduce costs without compromising safety or effectiveness in correctional managed health care systems with directly observed therapy.

Cost variability of suggested generic treatment alternatives under the Medicare Part D benefit.

BACKGROUND: The substitution of generic treatment alternatives for brand-name drugs is a strategy that can help lower Medicare beneficiary out-of-pocket costs. Beginning in 2011, Medicare beneficiaries reaching the coverage gap received a 50% discount on the full drug cost of brand-name medications and a 7% discount on generic medications filled during the gap. This discount will increase until 2020, when beneficiaries will be responsible for 25% of total drug costs during the coverage gap. OBJECTIVE: To examine the cost variability of brand and generic drugs within 4 therapeutic classes before and during the coverage gap for each 2011 California stand-alone prescription drug plan (PDP) and prospective coverage gap costs in 2020 to determine the effects on beneficiary out-of-pocket drug costs. METHODS: Equivalent doses of brand and generic drugs in the following 4 pharmacological classes were examined: angiotensin II receptor blockers (ARBs), bisphosphonates, HMG-CoA reductase inhibitors (statins), and proton pump inhibitors (PPIs). The full drug cost and patient copay/coinsurance amounts during initial coverage and the coverage gap of each drug was recorded based on information retrieved from the Medicare website. These drug cost data were recorded for 28 California PDPs. RESULTS: The highest cost difference between a brand medication and a Centers for Medicare Medicaid Services (CMS)-suggested generic treatment alternative varied between $110.53 and $195.49 at full cost and between $51.37 and $82.35 in the coverage gap. The lowest cost difference varied between $38.45 and $76.93 at full cost and between -$4.11 and $18.52 during the gap. CONCLUSION: Medicare beneficiaries can realize significant out-of-pocket cost savings for their drugs by taking CMS-suggested generic treatment alternatives. However, due to larger discounts on brand medications made available through recent changes reducing the coverage gap, the potential dollar savings by taking suggested generic treatment alternatives during the gap is less compelling and will decrease as subsidies increase.

Antimicrobial drug resistance in Escherichia coli from humans and food animals, United States, 1950-2002.

We conducted a retrospective study of Escherichia coli isolates recovered from human and food animal samples during 1950-2002 to assess historical changes in antimicrobial drug resistance. A total of 1,729 E. coli isolates (983 from humans, 323 from cattle, 138 from chickens, and 285 from pigs) were tested for susceptibility to 15 antimicrobial drugs. A significant upward trend in resistance was observed for ampicillin (p<0.001), sulfonamide (p<0.001), and tetracycline (p<0.001). Animal strains showed increased resistance to 11/15 antimicrobial agents, including ampicillin (p<0.001), sulfonamide (p<0.01), and gentamicin (p<0.001). Multidrug resistance (≥3 antimicrobial drug classes) in E. coli increased from 7.2% during the 1950s to 63.6% during the 2000s. The most frequent co-resistant phenotype observed was to tetracycline and streptomycin (29.7%), followed by tetracycline and sulfonamide (29.0%). These data describe the evolution of resistance after introduction of new antimicrobial agents into clinical medicine and help explain the range of resistance in modern E. coli isolates.