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Acute and Long-Term Healthcare Utilization and Expenditures for Serious Bacterial Infections among Newborns in US Hospitals
No full textIntroduction: Serious bacterial infections among newborns are associated with significant morbidity, mortality, and economic costs. While most newborns fully recover following the acute phase of illness, some develop long-term complications that require medical care. The objective of this real-world study was to estimate acute and long-term healthcare utilization and expenditures among US newborns with bacterial meningitis or sepsis during their birth hospitalization.
Methods: A retrospective matched-cohort design and a US healthcare claims database were employed. Study population comprised newborns who, during their birth hospitalization, had evidence of meningitis or sepsis due to a bacterial pathogen and matched comparison newborns. Study measures included all-cause healthcare utilization and expenditures during the birth hospitalization as well as the 1-year period following discharge.
Results: Among newborns with bacterial meningitis (N = 678), 61% were born prematurely, 27% had low birthweight, and 56% had ≥ 1 high-risk condition; among those with bacterial sepsis (N = 33,478), corresponding values were 48%, 20%, and 33%. During the birth hospitalization, utilization and expenditures were higher (versus comparators) among newborns with meningitis (hospital days, 37 versus 23; intensive care unit [ICU], 97% versus 64%; expenditures, US 168,861) and sepsis (hospital days, 18 versus 14; ICU, 93% versus 52%; expenditures, 78,549). Mean levels during the 1-year follow-up period were also markedly higher (versus comparators) among newborns with meningitis (expenditures: by 39,259).
Conclusions: Serious bacterial infections among newborns place a substantial burden on the US healthcare system for the treatment of acute illness as well as long-term complications. Interventions targeting the prevention of newborn bacterial infections have the potential to yield significant resource utilization and cost offsets
Indiana Emergency Medical Services Workforce Student Data Report 2024-2025
No full textThis report consolidates data from six survey periods (October 2023–September 2025) of the Indiana EMS Student Pulse Check. Across all periods, students were predominantly White and male, with EMT programs enrolling the largest share. Paramedic programs consistently reported the highest training costs, while EMR programs reported the lowest. Most students had no prior ambulance experience and commonly learned about EMS careers through personal connections. Students generally expressed high comfort with responding to accidents and caring for patients with suspected COVID‑19.
Employment intentions were stable across periods, with many students seeking EMS roles in fire departments or hospital ambulance services. Health insurance, paid time off, and retirement benefits were the most valued job benefits, and cost of living and commute time were key community considerations. Few students reported recruitment outreach from EMS agencies. Geographic data indicated that many students trained within their home counties. Overall, the survey reflects consistent patterns in demographics, training experiences, and employment preferences over time
P-387. Evaluation of Treatment Satisfaction and Experiences Among People With HIV When Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide From Cabotegravir + Rilpivirine: Results From the Phase 4 EMPOWER Study
No full textBackground:
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a guideline-recommended treatment for HIV that has shown high levels of efficacy. EMPOWER assessed experiences with and reasons for switching to daily oral B/F/TAF from bimonthly injectable cabotegravir + rilpivirine (CAB + RPV) among people with HIV (PWH).
Methods:
This Phase 4, single-arm, open-label multicenter study (NCT06104306) assessed switching to B/F/TAF in virologically suppressed PWH unable to continue on CAB + RPV or who expressed a preference to switch to oral therapy. Participants were aged ≥ 18 years, had received ≥ 1 (and no missed) doses of CAB + RPV, and had documented HIV-1 RNA < 50 copies/mL for ≥ 6 months prior to screening. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire: status version (HIVTSQs) at baseline (BL), Week (W)12, and W24. Satisfaction with treatment change was assessed using the HIVTSQ: change version (HIVTSQc) at W4. A study-specific questionnaire on reasons for decision to switch therapies was completed at BL and W4. W12 interim analyses were completed using descriptive statistics.
Results:
29 participants from North America were included (Table 1). Of those with available data, 21 (84.0%) had ≥ 95% adherence up to W12. All participants achieved HIV-1 RNA < 50 copies/mL at W4 and W12 (missing = excluded). After switching to B/F/TAF, improvements from BL in treatment satisfaction (HIVTSQs) were reported at W12 (Figure 1). At W4, participants (n = 28) reported a mean (SD) increase in treatment satisfaction (HIVTSQc) of 28 (6.8) points . Improvements were seen in all aspects of treatment satisfaction (Figure 2).The most common reason for switching from CAB + RPV was due to side effects (Table 2): 16/28 (57.1%) reported that side effects of CAB + RPV affected their ability to do daily activities. All participants reported feeling hopeful or very hopeful about successfully treating their HIV with B/F/TAF. No grade 3/4 treatment-related adverse events were reported with B/F/TAF.
Conclusion:
Participants choosing to discontinue CAB + RPV and start B/F/TAF reported a meaningful increase in treatment satisfaction and fewer side effects. B/F/TAF is an option for PWH wanting to switch from CAB + RPV to a daily oral regimen
BRD4 Phosphorylation Regulates the Structure of Chromatin Nanodomains
No full textThe interplay between chromatin structure and phase-separating proteins is an emerging topic in cell biology with implications for understanding disease states. Here, we investigate the functional relationship between bromodomain protein 4 (BRD4) and chromatin architecture. By combining molecular dynamics simulations with live-cell imaging, we demonstrate that BRD4, when mutated at specific N-terminus sites, significantly impacts the organization and dynamics of chromatin nanodomains, known as nucleosome clutches. Our findings reveal that a constitutively phosphorylated mutant of BRD4 condenses nucleosome clutches, while treatment with (+)-JQ1 increases the diffusion dynamics of single nucleosomes and decondenses nucleosome clutches. Simultaneously, we demonstrate that BRD4 mutations can alter localization of BRD4 to chromatin as well as modify single nucleosome dynamics. These results suggest that both chromatin binding and phase separation of BRD4 could co-regulate the nanoscale chromatin architecture and the chromatin microenvironment. Our observations shed light on the nuanced regulation of chromatin structure by BRD4, offering insights into its role in maintaining the nuclear architecture and transcriptional activity
Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis
No full textNF2 (neurofibromatosis type 2)-related schwannomatosis (NF2-SWN) is a cancer predisposition syndrome characterized by the development of bilateral vestibular (VS) and spinal schwannomas. While benign, these tumors can cause substantial morbidity, and effective pharmacological treatments remain limited. Here, we demonstrate that genetic ablation of focal adhesion kinase (Fak/Ptk2) impairs tumor formation and preserves hearing in a murine model of NF2. Mechanistically, we show that Fak deletion decreases macrophage infiltration, attenuates nucleotide-binding oligomerization domain-containing protein 2-, leucine rich repeats (LRR)- and pyrin domain-containing protein 3 inflammasome activation, and suppresses the hepatocyte growth factor-MET axis. Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN
Evaluation of ASC as a therapeutic target for Alzheimer's disease
No full textNeuroinflammation is increasingly recognized as a central contributor to the pathogenesis and progression of Alzheimer's disease (AD). The apoptosis-associated speck-like protein containing a CARD (ASC), encoded by the PYCARD gene, plays a critical role in the formation of multiple inflammasomes, including NLRP3, a key mediator of inflammation signaling. Beyond its role in inflammasome formation, extracellular ASC specks have been shown to promote amyloid-β aggregation, showing a potential link between inflammation and plaque formation. In this review, we examine the role of ASC in AD pathology and highlight emerging tools to study ASC biology and strategies for ASC targeted drug discovery
Diagnostic sequencing identifies high-risk markers and mechanisms of resistance to guide immunotherapy selection
No full textHere, we present the case for next-generation sequencing of samples from patients with multiple myeloma (MM), not only identify high-risk markers but also mutations and deletions relating to immunomodulatory drugs (IMiD), and more importantly to guide the sequencing of immunotherapy regimens in response to intrinsic antigen escape as a means of treatment resistance and relapse. This is a single-center study of CD138+ selected (n = 134) bone marrow aspirate samples from patients with smoldering MM (n = 11) and MM (newly diagnosed, n = 38; relapsed, n = 79). Samples were sequenced using a targeted panel in a clinical diagnostics laboratory. Data were analyzed for high-risk markers, treatment-related resistance mechanisms, and precision medicine targets to guide the future treatment of patients in the clinic. High-risk markers, including t(4;14), t(14;16), t(14;20), gain or amplification 1q, deletion of CDKN2C, and deletion or mutation of TP53, were identified in 15% samples from patients with newly diagnosed. At relapse, alterations in the cereblon degradation pathway were found in 24.3% of IMiD-treated patients. Deletions of 4p (CD38) were also enriched in patients who received anti-CD38 treatment (P = .03), which were mostly monoallelic. Deletions and mutations were detected in TNFRSF17-encoding B-cell maturation antigen (BCMA) in patients treated with anti-BCMA regimens, and the information was used to change the treatment of the patients. Targeted sequencing of diagnostic samples of patients with MM can be used for risk stratification and to monitor and adjust treatments as resistance mechanisms evolve
Nucleosome Clustering as a Biomarker and Mechanistic Switch for Reprogramming Cells
No full textChromatin architecture is highly dynamic, undergoing nanoscale rearrangements throughout the cell cycle and in response to environmental cues. In this study, we employed high-resolution stochastic optical reconstruction microscopy (STORM) to visualize chromatin organization and cellular plasticity at the nanoscale in two osteosarcoma cell lines, U2OS and MG63. To promote a tumor-suppressive bone microenvironment, we applied three biophysical modalities, namely mechanical vibration, electrical stimulation, and optical pulses, each previously linked to altered tumor behavior by reprogramming cells and generating induced tumor-suppressing (iTS) cells. These stimuli enlarged nuclear size and disrupted nuclear envelope integrity, as revealed by increased surface roughness. Critically, all three modalities transiently scattered nucleosome clusters, indicating chromatin decondensation as a hallmark of iTS cell generation. iTS cells exhibited elevated expression of histone demethylases lysine demethylase 3A (KDM3A) and lysine demethylase 4 (KDM4), accompanied by reduced levels of trimethylated histone H3 lysine 9 (H3K9me3). Consistently, pharmacological agents-Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor-induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment
Ultra-processed food intake is associated with improved nutrient profile but not associated with metabolic syndrome in US children
No full textBackground: Studies have linked the consumption of ultra-processed foods (UPF) to metabolic syndrome (MetSyn). It is not known if UPF consumption is associated with MetSyn in US children
Objective: The objective of this study was to investigate the association between the consumption of UPF and MetSyn in US children utilizing the data from the nationally representative sample surveys.
Methods: We used two cycles of National Health and Nutrition Examination surveys, 2003-2004 and 2005-2006. The study sample consisted of 5515 children aged ˂19 years old. MetSyn was defined according to the ATP III criteria. Multivariate regression models were used to determine the association between UPF consumption and MetSyn