The Development of Diabetes and Diabetic Ketoacidosis Following Immunotherapy Treatment: A Systematic Review of Case Reports.

As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available that target tumor cells in innovative ways. Immunotherapies (e.g., immune checkpoint inhibitors (ICI)) ramp up the immune system to target cancer cells, providing patients with more personalized and tumor cell-specific treatment options. This new age oncological treatment option has been found to provide a more meaningful and stronger alternative to traditional chemotherapy, resulting in longer periods of remission and milder side effects. However, because ICI heightens the immune system, resultant autoimmune conditions can occur. One of the most recently shown adverse effects of ICI are extreme hyperglycemia (i.e., type 1 diabetes) and diabetic ketoacidosis (DKA). To determine the incidence of immunotherapy-induced diabetes, a systematic literature review was performed using CINHAL, EBSCO, MEDLINE, and Web of Science. A total of 403 articles were initially screened, with a final 28 case reports included. The results show that checkpoint inhibitors were found to be most commonly associated with new-onset diabetes as opposed to traditional chemotherapy. Additionally, 41% of patients developed autoimmune diabetes and DKA after being placed on a single therapy of pembrolizumab (targets PD-1: programmed cell death protein 1). However, the pathological process underlying the development of endocrinopathies after treatment with ICI continues to be under investigation.

High-precision screening and sorting of double emulsion droplets.

Mounting evidence suggests that cell populations are extremely heterogeneous, with individual cells fulfilling different roles within the population. Flow cytometry (FC) is a high-throughput tool for single-cell analysis that works at high optical resolution. Sub-populations with unique properties can be screened, isolated and sorted through fluorescence-activated cell sorting (FACS), using intracellular fluorescent products or surface-tagged fluorescent products of interest. However, traditional FC and FACS methods cannot identify or isolate cells that secrete extracellular products of interest. Double emulsion (DE) droplets are an innovative approach to retaining these extracellular products so cells producing them can be identified and isolated with FC and FACS. The water-in-oil-in-water structure makes DE droplets compatible with the sheath flow of flow cytometry. Single cells can be encapsulated with other reagents into DEs, which act as pico-reactors. These droplets allow biological activities to take place while allowing for cell cultivation monitoring, rare mutant identification, and cellular events characterization. However, using DEs in FACS presents technical challenges, including rupture of DEs, poor accuracy and low sorting efficiency. This study presents high-performance sorting using fluorescent beads (as simulants for cells). This study aims to guide researchers in the use of DE-based flow cytometry, offering insights into how to resolve the technical difficulties associated with DE-based screening and sorting using FC.

The Impact of Modern Dietary Practices on Cancer Risk and Progression: A Systematic Review.

Cancer is a leading cause of mortality around the world, despite continued advancements in the management of cancer. Recent research efforts have shifted to evaluating the role that modifiable risk factors play in cancer risk and development, as diet and nutrition have been found to play a significant role in the onset and progression of cancer. As a result, there has been an increasing focus on the impact of dietary modifications on preventing the onset, progression, and reoccurrence of cancer. In this systematic review, data were collected on three common diets, the Mediterranean diet (MD), ketogenic diet (KD), and plant-based diet, to gain insight into the application of these three dietary modification approaches for risk prevention and limitation of cancer burden. Initially, 4,397 articles were identified from three databases (Ovid, Web of Science, and CINHAL). After removing studies based on the exclusion criteria, only 23 studies were eligible to be included in the systematic review of which 15 evaluated the MD, four assessed the ketogenic diet, and four evaluated the plant-based diet. Each article was considered for its methods, procedures, and findings. The findings indicate that dietary interventions may effectively reduce the odds of cancer development and the advancement of diagnosed cancers. With the introduction of the MD, KD, and plant-based diets, significant improvements in lowering cancer development, recurrence-free status, and limiting tumor growth were noted across numerous cancer types. Currently, the MD has been extensively studied in the literature, and amongst the widest variety of cancer types. Additional information and evaluation are required on the ketogenic and plant-based diets to fully understand their impact on the cancer burden across a wider subset of cancers. Clinicians should evaluate and recommend nutritional adaptations to their patients to limit the development of specific cancers and as an adjunctive therapy to traditional pharmacological treatment options for patients with diagnosed cancers.

Computed Tomography (CT) Calcium Scoring in Primary Prevention of Acute Coronary Syndrome and Future Cardiac Events in Patients With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex and chronic autoimmune disease that impacts multiple organ systems and presents with varying symptomatology that makes targeting treatment extremely difficult. The cardiovascular system and more specifically the coronary arteries are heavily affected by SLE causing increased atherosclerosis and subsequently increased acute coronary syndrome (ACS) and increased future cardiac events. ACS is a common occurrence in patients with SLE due to the premature development of atherosclerosis due to the dysregulation of pro-inflammatory cytokines. Calcium scoring has been effectively utilized to identify plaque burden in patients with coronary artery calcification (CAC). Calcium scoring is a score obtained from a computed tomography (CT) image using non-contrast imaging, which provides quantitative information regarding CAC and aids in assessing cardiovascular risk. A calcium score of zero Hounsfeild units can be obtained using CT calcium scoring which indicates no calcium is identified in the coronary arteries and is a strong negative risk predictor for coronary artery disease. Early screening of SLE patients with CT calcium scoring could aid in early detection and treatment subsequently leading to delay of premature coronary atherosclerosis and future cardiac events in this patient population. Multiple studies have used calcium scoring as a method to measure arterial calcification in SLE patients. The Society of Cardiovascular Imaging has now endorsed the idea of obtaining a baseline calcium artery score with a repeat progression scan in 3-5 years. Calcium scoring has also been identified as an effective initial tool for stratification and identification of possible ACS. The various advantages of early calcium scoring signify the further research needed to fully understand and implement the advantages calcium scoring has to offer patients with SLE.

Systematic analyses identify modes of action of ten clinically relevant biocides and antibiotic antagonism in Acinetobacter baumannii.

Concerns exist that widespread use of antiseptic or disinfectant biocides could contribute to the emergence and spread of multidrug-resistant bacteria. To investigate this, we performed transposon-directed insertion-site sequencing (TraDIS) on the multidrug-resistant pathogen, Acinetobacter baumannii, exposed to a panel of ten structurally diverse and clinically relevant biocides. Multiple gene targets encoding cell envelope or cytoplasmic proteins involved in processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, were identified to have effects on bacterial fitness upon biocide exposure, suggesting that these compounds may have intracellular targets in addition to their known effects on the cell envelope. As cell respiration genes are required for A. baumannii fitness in biocides, we confirmed that sub-inhibitory concentrations of the biocides that dissipate membrane potential can promote A. baumannii tolerance to antibiotics that act intracellularly. Our results support the concern that residual biocides might promote antibiotic resistance in pathogenic bacteria.

Oral Feeding Outcomes in Infants Born With Neonatal Abstinence Syndrome.

OBJECTIVE: Breastfeeding is the optimal source of nutrition for all infants, but there are limited data on feeding outcomes in infants with neonatal abstinence syndrome (NAS) who are admitted in the neonatal intensive care unit (NICU). METHODS: A retrospective cohort study was conducted at a level II/III NICU. Study sample consisted infants with a diagnosis of NAS and those diagnosed with respiratory distress syndrome. The primary outcome was attainment of independent oral feeds, defined as the number of days to transition from full-tube to full oral feeds. Secondary outcomes included length of hospital stay and method (breast or bottle) of oral feeds at the start, at attainment of independent oral feeds, and at hospital discharge. RESULTS: Infants with NAS took significantly longer to attain independent oral feeds than controls (P = .021) and received significantly fewer breastfeeds at the start of oral feeds, at independent oral feeds, and at hospital discharge (P = .000). There was no difference in length of hospital stay between groups. CONCLUSION: These results suggest that infants with NAS can experience difficulties achieving independent oral feeds and are less likely to receive breastfeeds. Additional support is required to enhance oral feeds in infants with NAS in the NICU.

Identification of a Novel Ciprofloxacin Tolerance Gene, aciT, Which Contributes to Filamentation in Acinetobacter baumannii.

Fluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms, including Acinetobacter baumannii We sought to investigate the transcriptomic and proteomic responses of the clinical A. baumannii strain AB5075-UW upon exposure to subinhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analyses found that the most highly expressed genes and proteins were components of the intact prophage phiOXA. The next most highly expressed gene (and its protein product) under ciprofloxacin stress was a hypothetical gene, ABUW_0098, named here the Acinetobacterciprofloxacin tolerance (aciT) gene. Disruption of this gene resulted in higher susceptibility to ciprofloxacin, and complementation of the mutant with a cloned aciT gene restored ciprofloxacin tolerance to parental strain levels. Microscopy studies revealed that aciT is essential for filamentation during ciprofloxacin stress in A. baumannii Sequence analysis of aciT indicates the encoded protein is likely to be localized to the cell membrane. Orthologs of aciT are found widely in the genomes of species from the Moraxellaceae family and are well conserved in Acinetobacter species, suggesting an important role. With these findings taken together, this study has identified a new gene conferring tolerance to ciprofloxacin, likely by enabling filamentation in response to the antibiotic.

Rapid microevolution of biofilm cells in response to antibiotics.

Infections caused by Acinetobacter baumannii are increasingly antibiotic resistant, generating a significant public health problem. Like many bacteria, A. baumannii adopts a biofilm lifestyle that enhances its antibiotic resistance and environmental resilience. Biofilms represent the predominant mode of microbial life, but research into antibiotic resistance has mainly focused on planktonic cells. We investigated the dynamics of A. baumannii biofilms in the presence of antibiotics. A 3-day exposure of A. baumannii biofilms to sub-inhibitory concentrations of antibiotics had a profound effect, increasing biofilm formation and antibiotic resistance in the majority of biofilm dispersal isolates. Cells dispersing from biofilms were genome sequenced to identify mutations accumulating in their genomes, and network analysis linked these mutations to their phenotypes. Transcriptomics of biofilms confirmed the network analysis results, revealing novel gene functions of relevance to both resistance and biofilm formation. This approach is a rapid and objective tool for investigating resistance dynamics of biofilms.