Bacteriophages (phages) likely play a critical role in modulating transmission dynamics of diarrheal pathogens. This study investigated the role of phages in modulating the prevalence and seasonal patterns of major diarrheal pathogens, Vibrio cholerae O1 (VCO1), enterotoxigenic Escherichia coli (ETEC), Shigella spp., and Salmonella spp. in diarrheal patients and environmental wastewater specimens collected from six different sites in Dhaka, Bangladesh, in 2024. VCO1, ETEC, Shigella, and Salmonella were detected in 10.1%, 7.8%, 1.7%, and 2.4% of diarrheal specimens, respectively. In contrast, phages targeting these pathogens were more frequently isolated, with detection rates of 20% for VCO1, 30% for ETEC, 57% for Shigella, and 9.2% for Salmonella-specific phages. Adults showed a significantly higher burden of VCO1 and corresponding phages compared with children <5 years (P < 0.001). Seasonal analysis revealed significant correlations between VCO1 (37.3%) and corresponding phages (57.6%) peaking in late September in both clinical (r = 0.53, P < 0.0001) and environmental wastewater specimens (r = 0.65, P < 0.001). The highest correlation (r = 0.68) was found between the increased rate of wastewater phages in the preceding week and a rise in cholera cases in the following week. ETEC and ETEC phages isolated from wastewater also showed strong correlations (r = 0.65, P < 0.001). Cross-specificity analysis demonstrated that VCO1 phages were highly specific to their targets, whereas ETEC and Shigella phages exhibited broader host ranges, with some Shigella phages capable of infecting ETEC and Salmonella spp. Overall, these findings support the hypothesis that Vibrio phages could serve as an alternative or complementary tool for cholera surveillance.IMPORTANCEUnderstanding the dynamics between phages and their bacterial hosts is critical for elucidating disease burden; however, their potential for surveillance remains underexplored. To our knowledge, this is the first study that longitudinally investigated major diarrheal pathogens and their phages in both clinical and environmental sources to assess the potential of bacteriophages as a tool to improve diarrheal surveillance. The high frequency of phages compared to the host bacterial counterparts suggests a valuable, yet underutilized, role for phages in surveillance systems. Strong seasonal alignment between V. cholerae O1 and its phages, both peaking in late September, suggests that phage dynamics may reflect pathogen transmission. These preliminary observations raise the possibility that wastewater-derived Vibrio phages could function as early indicators of cholera burden. Future research should aim to explore the complex and poorly understood interactions between phages and their bacterial hosts, particularly how these dynamics shape pathogen populations in endemic settings.
Publications by Year: 2026
2026
OBJECTIVES: In the United States, training for physicians who manage critically ill adult patients (intensivists) evolved through parallel subspecialty critical care medicine (CCM) pathways with significant commonality. The Society of Critical Care Medicine Adult Critical Care Physician Core Knowledge and Skills Task Force aimed to delineate the common core knowledge and skills required of all intensivists.
DESIGN: A master list of content areas and procedural skills was compiled from all CCM subspecialty program requirements and blueprints of the certification examinations. Using a modified Delphi approach, participants were asked to categorize the knowledge items as "advanced knowledge is essential," "general, but not advanced, knowledge is essential," or "knowledge is not essential." Procedures were categorized as "intensivist performs routinely," "intensivist only performs in an emergency," or "intensivist knows" about the procedure.
SETTING: Representatives from CCM stakeholder organizations, including accreditation and certification organizations, critical care societies, and program directors' societies, were invited to participate.
SUBJECTS: Members of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care Medicine.
INTERVENTIONS: For the first two rounds of the modified Delphi process, Research Electronic Data Capture was used. For the third and fourth rounds, the process was completed through online meetings with Zoom (Zoom Video Corporations, San Jose, CA) utilizing Zoom's polling feature.
MEASUREMENTS AND MAIN RESULTS: A total of 541 items were determined to be essential, with 145 requiring advanced knowledge and 323 requiring general knowledge. For 73 items, consensus regarding advanced vs. general could not be achieved, but they remained essential. Only eight items were felt to be nonessential. Of the 16 procedures, most were categorized as "intensivist performs."
CONCLUSIONS: The large number of items included in the list of essential knowledge and skills demonstrates the complexity of modern CCM. Utilization of a common framework across the subspecialties of CCM could lead to greater harmonization among the fellowship program requirements and certification examinations.
BACKGROUND/OBJECTIVES: Adverse events (AEs) are frequent in hospitalized children and may lead to unplanned transfers to intensive care units (ICUs). ICU transfers may occur following activation of nonemergent or emergent assessments by a rapid response team (RRT). We sought to measure and characterize AEs around RRT activations and ICU transfers and whether different RRT triage mechanisms were associated with differences in AE rates or characteristics.
METHODS: We performed a retrospective cohort study of hospitalized patients younger than 18 years with RRT evaluations for and transfers to ICUs. We measured AEs from hospital admission until RRT activation (pretransfer) and during the first 48 hours following ICU transfer (posttransfer). AEs identified on primary chart review underwent secondary review by 2 independent physicians who determined case classification, severity level, and preventability.
RESULTS: In total, 699 RRT activations were reviewed, and 407 AEs were recorded. Pretransfer AE rates were higher for patients triaged emergently vs nonemergently (0.68 vs 0.52 AE/RRT, P = .03). Most AEs pretransfer resulted in temporary harm (National Coordinating Council for Medication Error Reporting and Prevention level F, 69.7%). Most AEs were preventable pre- (53.4%) and post-ICU transfer (51.6%). The most common clinical types of AEs were related to medications/fluids (38.3%), procedures (24.8%), and diagnosis (17.4%).
CONCLUSIONS: We identified high rates of AEs among patients requiring ICU triage and transfer, especially among those triaged emergently. Activation of an RRT or ICU transfer is a very high-yield trigger for AE detection.
BACKGROUND AND OBJECTIVES: Sleep architecture, including spindles and slow oscillations, is disrupted in Alzheimer disease (AD). How changes in these sleep elements relate to cognitive decline is less clear. Our objectives were to examine changes in sleep macroarchitecture and microarchitecture in early clinical stages of AD compared with older adult controls (CTLs) and to investigate their associations with longitudinal cognitive change.
METHODS: This was both a cross-sectional and longitudinal study performed at Mass General Brigham Hospitals, where participants with early AD or CTLs underwent overnight ambulatory scalp EEG and longitudinal cognitive testing. We compared sleep microarchitectural features extracted from the EEG, including spindle activity, across the brain topography and between groups. We then performed longitudinal analyses using mixed-effects models to test the association of these sleep features with changes in cognition on the Montreal Cognitive Assessment (MoCA), collected annually for up to 7 years.
RESULTS: AD (n = 47, mean age 74.1 years, 66% female) and CTL (n = 43, mean age 72.6 years, 56% female) groups spent a similar proportion of sleep time in each stage of sleep. Sleep efficiency, however, was lower in the AD group (mean: CTL 75.1% vs AD 70.9%; p = 0.034). We found a significant reduction in spindle range power (11-16 Hz) in patients with AD compared with CTLs, particularly in the temporal regions (mean normalized power at EEG channels T3/T4: CTL 3.13 ± 1.13 vs AD 2.48 ± 1.01; p = 0.005). In participants with longitudinal MoCA scores (AD = 26, CTL = 25), reduced temporal lobe spindle density (β = 0.61, 95% CI 0.35-0.87; false discovery rate [FDR]-adjusted p < 0.001) and temporal lobe spindle power (β = 0.56, 95% CI 0.22-0.88; FDR-adjusted p = 0.005) were each associated with a faster rate of cognitive decline.
DISCUSSION: Temporal lobe sleep spindle activity is reduced in early clinical stages of AD and is associated with a faster rate of cognitive decline. Our results underscore the importance of including temporal lobe measurements when assessing sleep neurophysiology in AD, which is not standard in polysomnography. Future work examining the relationship between AD biomarkers and reduced spindle activity is needed to elucidate the potential mechanisms underlying these findings.
Patients who present with reduced FVC, yet show no further FVC decline, still face poor outcomes. This demonstrates how progression-based criteria can misclassify these “stable” cases and highlights the importance of flagging them early. https://bit.ly/4oAnTgw
Epigenetic macromolecular enzyme complexes tightly regulate gene expression at the chromatin level and have recently been found to colocalize with RNA splicing machinery during active transcription; however, the precise functional consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex (LSD1-HDAC1-CoREST) with components of the RNA splicing machinery and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM, we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex selective inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies. Moreover, these corin-induced splicing changes are shown to promote global effects on oncogenic and survival-associated splice variants, leading to a tumor-suppressive phenotype. Using machine learning models, MHC IP-MS, and ELISpot assays, we identify thousands of neopeptides derived from unannotated splice sites that generate corin-induced splice-neoantigens that are demonstrated to be immunogenic in vitro. Corin is further shown to reactivate the response to immune checkpoint blockade, effectively sensitizing tumors to anti-PD-1 immunotherapy. These data position CoREST complex inhibition as a unique therapeutic opportunity that perturbs oncogenic splicing programs while also creating tumor-associated neoantigens that enhance the immunogenicity of current therapeutics.
Obesity is a chronic, systemic disease that alters the function of tissues, organs, and overall health, requiring prompt recognition and treatment by qualified professionals. IFSO recognizes the need to provide a new methodology for developing IFSO position statements. All new official position statements should be developed using a GRADE-based methodology, systematically reviewing all available evidence relevant to Metabolic and Bariatric Surgery (MBS). The present Position Statement was developed using results coming from a systematic review and meta-analysis, reported herein, following the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Fourteen Randomized controlled trials (RCTs) were included in this meta-analysis, 13 and 1 of them assessing outcomes of OAGB in primary and revisional setting respectively, with a total of 1288 patients. In the short term, OAGB exhibited a significantly higher excess weight loss percentage (EWL%) compared to RYGB. Regarding weight loss and metabolic outcomes, OAGB was not reported to be inferior in terms of weight loss and T2DM resolution when compared to RYGB. Further RCTs comparing OAGB to other MBS procedures are needed to reach a definitive recommendation regarding OAGB in revisional surgery setting. Regarding safety profile, no statistically significant differences between OAGB and other MBS were reported. This position statement was issued by the IFSO OAGB task force and approved by IFSO Scientific Committee aims to provide evidence on the effectiveness of One Anastomosis Gastric Bypass in both primary and revisional settings.