Inflammatory Signaling via PEIZO1 Engages and Enhances the LPS-Mediated Apoptosis during Clinical Mastitis.

Bovine clinical mastitis is characterized by inflammation and immune responses, with apoptosis of mammary epithelial cells as a cellular reaction to infection. PIEZO1, identified as a mechanotransduction effector channel in nonruminant animals and sensitive to both mechanical stimuli or inflammatory signals like lipopolysaccharide (LPS). However, its role in inflammatory processes in cattle has not been well-documented. The aim of this study was to elucidate the in situ expression of PIEZO1 in bovine mammary gland and its potential involvement in clinical mastitis. We observed widespread distribution and upregulation of PIEZO1 in mammary epithelial cells in clinical mastitis cows and LPS-induced mouse models, indicating a conserved role across species. In vitro studies using mammary epithelial cells (MAC-T) revealed that LPS upregulates PIEZO1. Notably, the effects of PIEZO1 artificial activator Yoda1 increased apoptosis and NLRP3 expression, effects mitigated by PIEZO1 silencing or NLRP3 inhibition. In conclusion, the activation of the PIEZO1-NLRP3 pathway induces abnormal apoptosis in mammary epithelial cells, potentially serving as a regulatory mechanism to combat inflammatory responses to abnormal stimuli.

Fixational eye movements and their associated evoked potentials during natural vision are altered in schizophrenia.

Background: Visual exploration is abnormal in schizophrenia; however, few studies have investigated the physiological responses during selecting objectives in more ecological scenarios. This study aimed to demonstrate that people with schizophrenia have difficulties observing the prominent elements of an image due to a deficit mechanism of sensory modulation (active sensing) during natural vision. Methods: An electroencephalogram recording with eye tracking data was collected on 18 healthy individuals and 18 people affected by schizophrenia while looking at natural images. These had a prominent color element and blinking produced by changes in image luminance. Results: We found fewer fixations when all images were scanned, late focus on prominent image areas, decreased amplitude in the eye-fixation-related potential, and decreased intertrial coherence in the SCZ group. Conclusions: The decrease in the visual attention response evoked by the prominence of visual stimuli in patients affected by schizophrenia is generated by a reduction in endogenous attention mechanisms to initiate and maintain visual exploration. Further work is required to explain the relationship of this decrease with clinical indicators.

Vascularized Femoral Myo-Periosteal Graft for Congenital Pseudarthrosis of the Tibia: A Case Report.

Pure vascularized periosteal transplants have been shown to be extremely effective at achieving rapid bone healing in children with biologically complex non-union. Free tibial and fibular periosteal transplants are generally indicated when large periosteal flaps are necessary. We report using a vascularized femoral myo-periosteal graft (VFMPG) to treat distal tibial osteotomy non-union in a six-year-old boy with congenital pseudarthrosis of the tibia. The graft consisted of a 9 cm myo-periosteal flap (after 50% of elastic retraction) that incorporated the vastus intermedius muscle and diaphyseal femoral periosteum nourished by the descending branch of the lateral circumflex femoral vessels. Plantaris medialis was used as a recipient vessel. Healing occurred 10 weeks after surgery. The patient resumed gait and sports activity without orthosis. No donor or recipient site complications occurred 17 months after surgery. Employing a VFMPG might be an alternative to other free or large vascularized periosteal flaps currently in use for complex pediatric non-unions.

Differences in toxicology reports and hospital emergency care for patients suspected of experiencing drug-facilitated crimes: an analysis according to gender. / Atención de pacientes con sospecha de sumisión química en un servicio de urgencias hospitalario y resultados del análisis toxicológico: diferencias según el sexo.

OBJECTIVE: To analyze gender-related differences in patient and care characteristics and in toxicology findings in suspected cases of drug facilitated crime (DFC). METHODS: Observational cross-sectional study of all patients in suspected DFC cases attended in the emergency department of Hospital Clínico San Carlos and of their blood or urine samples analyzed by the National institute of Toxicology and Forensics in Madrid between March 1, 2015, and March 1, 2023. We analyzed variables from patient records and the toxicology reports according to gender. RESULTS: A total of 514 suspected DFC episodes were studied; 101 (19.6%) were proactive crimes, 61 (11.9%) opportunistic, and 352 (68.5%) mixed. The median (interquartile range) age was 25 years (21-34 years), and 370 (72%) were women. Eighty-three percent of the patients had amnesia, and 48% of the cases involved sexual assault or robbery. Toxicology identified substances in 78% of the patients (alcohol, 53%; street drugs, 37%; and/or psychopharmaceuticals or opioids, 23%). Independent variables associated with female gender in the multivariate analysis, according to adjusted odds ratio (aORs) were age less than 25 years (aOR, 2.73; 95% CI, 1.75 4.24; P < .001); physician-referred emergency (aOR, 1.77; 95% CI, 1.12-2.80; P = .03); robbery (aOR, 0.25; 95% CI, 0.15-0.41; P < .001); alcohol-positive test result (aOR, 1.91; 95% CI, 1.21-3.00; P = .01); and a drug-positive result (aOR, 0.43; 95% CI, 0.28-0.64; P < .001). Police and a forensic physician intervened in 13% of the cases, and in such cases the victim was more likely to be female (aOR, 3.97; 95% CI, 1.41-11.13; P < .001). Toxicology identified the presence of an unknown substance in 39%, and a woman was less likely to be involved in such cases (aOR, 0.43; 95% CI, 0.28-0.67; P < .001). CONCLUSIONS: The majority of victims of DFCs were female, and the crimes were mixed, involving involve alcohol, psychopharmaceuticals or street drugs. Female victims were more likely to be under the age of 25 years, be referred to the emergency service by a physician, be attended by a forensic physician for sexual assault, and have an alcoholpositive toxicology report. Women were also less likely to report a robbery or have a toxicology report identifying drugs or an unknown substance.

OBJETIVO: Analizar las diferencias en las características de los pacientes atendidos por sospecha de sumisión química (SQ) y en los resultados del análisis toxicológico (AT) en función del sexo. METODO: Estudio observacional transversal retrospectivo que incluyó a todos los casos con SQ atendidos en el servicio de urgencias del Hospital Clínico San Carlos y las muestras (sangre o orina) para el AT en el Instituto Nacional de Toxicología y Ciencias Forenses de Madrid entre el 1 de marzo de 2015 y el 1 de marzo de 2023. Se analizan variables de la historia clínica y del AT según el sexo. RESULTADOS: Se incluyeron 514 episodios con sospecha de SQ [101 (19,6%) proactiva, 61 (11,9%) oportunista y 352 (68,5%) mixta] en pacientes con una mediana de 25 años (RIC: 21-34), 370 (72%) de sexo femenino. El 83% presentó amnesia y el 48% asoció agresión sexual o robo. En el 78% se identificó alguna sustancia en el AT (53% alcohol etílico, 37% drogas y/o 23% psicofármaco u opiáceos). En el análisis multivariado las variables que se asociaron de manera independiente con el sexo femenino fueron la edad menor de 25 años con ORa de 2,73 (IC 95%: 1,75-4,24; p < 0,001), con médico deriva a urgencias con ORa de 1,77 (IC 95%: 1,12-2,80; p = 0,03), delito de robo con de ORa 0,25 (IC 95%: 0,15-0,41; p < 0,001), alcohol etílico en el AT con ORa 1,91 (IC 95%: 1,21-3,00; p = 0,01) y alguna droga en el AT con ORa 0,43 (IC 95%: 0,28-0,64; p < 0,001). En el 13% de casos hubo intervención policial y médico-forense y fue más probable que fuera a una mujer, con ORa 3,97 (IC 95%: 1,41-11,13; p < 0,001). En el 39% de AT se identificó alguna sustancia desconocida y fue menos probable que fuera mujer, con ORa de 0,43 (IC 95%: 0,28-0,67; p < 0,001). CONCLUSIONES: La mayoría de casos registrados fueron mujeres con sospecha de SQ mixta por alcohol, psicofármacos o drogas de abuso. Las mujeres presentaron mayor probabilidad de tener menos de 25 años, ser derivada a urgencias por un médico, de intervención médico-forense por agresión sexual y encontrar alcohol etílico en el AT.

Silicon nanowire aqueous dispersions for processing into macroscopic network materials.

Nanowires and other high aspect ratio nanoparticles are building blocks to form network materials in formats such as films, sheets, fibres and electrodes that thus bridge the nano and macro scales. The assembly of nanowire network materials is enabled by a new floating catalyst chemical vapour deposition synthesis method that produces crystalline silicon nanowires (SiNW) on a scale of grams per day. Here, we produce SiNW dispersions in water by sonication through steric and electrostatic stabilisation of the negatively charged particles in basic pH or with cationic surfactants. Negative charge arises from the 1.3 nm-thin native oxide layer. Some permanent aggregates are found as a consequence of cross-links between the thin oxide at the surface of adjacent SiNWs. Removing them by centrifugation yields SiNW dispersions of 52 µg mL-1. Processing into macroscopic materials is demonstrated as transparent films and as freestanding sheets. In the sheets, the SiNWs are predominately aligned parallel to the sheet thickness, as a paper-like SiNW solid with tensile strength above 10 MPa, modulus above 1 GPa and toughness of 0.5 J g-1.

Epidemiological, Phylogenetic, and Resistance Heterogeneity Among Acinetobacter baumannii in a Large U.S. Deep South Healthcare system.

Background: Acinetobacter baumannii (Ab) disease in the United States is commonly attributed to outbreaks of 1 or 2 monophyletic carbapenem resistance (CR) Ab lineages that vary by region. However, there is limited knowledge regarding CRAb epidemiology and population structures in the U.S. Deep South, and few studies compare contemporary CR and carbapenem-susceptible (Cs) Ab, despite relative prevalence of the latter. Methods: We performed a multiyear analysis of 2462 Ab cases in a large healthcare system in Birmingham, AL, and 89 post-2021 Ab isolates were sequenced and phenotyped by antibiotic susceptibility tests. Results: Although the cumulative CR rate was 17.7% in our cohort, rates regularly increased in winter months as result of seasonal changes in case incidence of CsAb, specifically. Genotyped CRAb belonged to clonal group (CG) 1, CG2, CG108, CG250, or CG499, with local clones of CG108, CG250, and CG499 persisting over multiple months. There was no clonal expansion of any CsAb lineage. Among CRAb isolates, levels of ß-lactam antibiotic resistance and the repertoire of related genetic resistance determinants, which included the novel CR-conferring FtsI A515V polymorphism, differed according to CG. CG108 and CG499 isolates displayed specific heteroresistance to sulbactam and trimethoprim/sulfamethoxazole, respectively, which resulted in discrepant susceptibility results in microbroth versus agar-based antibiotic susceptibility tests modalities. Conclusions: We report an unusually high degree of CRAb phylogenetic diversity principally driven by emergent U.S. lineages harboring novel resistance elements that must be incorporated into diagnostic, surveillance, and preclinical research efforts.

A Hybrid Control Framework for Chemical Processes with Long Time Delay: Theory and Experiments.

This paper proposes a hybrid control framework based on internal model concepts, sliding mode control methodology, and fractional-order calculus theory. As a result, a modified Smith predictor (SP) is proposed for nonlinear systems with significant delays. The particular predictive approach enhances the sliding mode control (SMC) controller's transient responses for dead-time processes, and the SMC gives the predictive structure robustness for model mismatches by combining the previous methods with fractional order concepts; the result is a dynamical sliding mode controller. A numerical example is considered to evaluate the performance of the proposed approach, where a step change, external disturbance, and parametric uncertainty test are performed. A real application in the TCLab Arduino kit is presented; the proposed method presented good performance with a little amount of chattering, and in the disturbance rejection case, the overshoot increased with an aggressive response; in both cases, better tuning parameters can improve the process response and the controller action.

Epigallocatechin-3-gallate protects bovine ruminal epithelial cells against lipopolysaccharide-induced inflammatory damage by activating autophagy.

BACKGROUND: Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown. RESULTS: In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS. CONCLUSIONS: Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.

Acute Kidney Injury and Its Association With Dementia and Specific Dementia Types: Findings From a Population-Based Study in Sweden.

BACKGROUND AND OBJECTIVES: Preclinical studies suggest that acute kidney injury (AKI) results in biochemical and pathologic changes in the brain. We aimed to explore the association between experiencing AKI and subsequent risks of developing dementia. METHODS: We conducted a study involving individuals aged 65 years and older in Stockholm from 2006 to 2019, who were free from dementia diagnosis and had data on kidney function. The exposure was an episode of AKI (time varying), ascertained by issued clinical diagnoses and transient creatinine elevations according to Kidney Disease Improving Global Outcomes criteria. The outcome was all-cause dementia and specific types of dementia, ascertained by clinically confirmed cases in the Swedish registry of cognitive/dementia disorders, the presence of 2 issued dementia diagnoses in outpatient care, or initiation of specific antidementia medications. We investigated associations with dementia through Cox proportional hazard regression by AKI, severity levels of AKI, AKI recurrence, and setting (community-acquired or hospital-acquired AKI). RESULTS: We included 305,122 individuals with a median age of 75 ± 8 years (56.6% women). During a median follow-up of 12.3 (interquartile range 8.7-13.3) years, there were 79,888 individuals (26%) suffering from at least 1 episode of AKI and 47,938 incident cases (16%) of dementia. The rate of dementia cases was 37.0 per 1,000 person-years (95% CI 36.2-37.8) after developing AKI, which was approximately 2 times higher than the rate observed during the periods before AKI (17.3, 95% CI 17.2-17.5). After multivariable adjustment, developing AKI was associated with a 49% higher rate of subsequent dementia (adjusted hazard ratio hazard ratio [HR] 1.49, 95% CI 1.45-1.53). This pattern was consistent across dementia types, with HRs of 1.88 (95% CI 1.53-2.32), 1.47 (1.38-1.56), and 1.31 (1.25-1.38) for dementia with Lewy bodies and Parkinson disease with dementia, vascular dementia, and Alzheimer dementia, respectively. Risk associations were stronger in magnitude across more severe AKIs and in hospital-acquired vs community-acquired AKI. DISCUSSION: Individuals who experienced an AKI were at increased risk of receiving a diagnosis of dementia.

The intestinal microbiome of infants with cow's milk-induced FPIES is enriched in taxa and genes of enterobacteria.

OBJECTIVES: Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis. METHODS: Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology. RESULTS: A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors. CONCLUSION: These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.

Hypothermic oxygenated machine perfusion influences the immunogenicity of donor livers in humans.

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion-injury (IRI)-related complications following liver transplantation (LT). In animal models HOPE can also decrease alloimmune responses post-transplantation, but this remains to be evaluated in humans. Our study, involving 27 LT patients enrolled in 2 randomised controlled trials comparing static cold storage (SCS) with HOPE (14 HOPE- and 13 SCS-treated), delves into the impact of HOPE on the molecular profile of liver allografts and on the immune responses elicited post-transplantation. Following HOPE treatment, fewer intra-hepatic immune cells were observed in liver perfusates compared to SCS. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks post-transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells (Tregs) (p<0.01), which corresponded to a higher frequency of donor specific Tregs (p<0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months post-transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver IRI and to modulate effector and regulatory donor-specific T cell responses post-transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts.

Revisiting morphology of xiphoid process of the sternum in human: a comprehensive anatomical study.

BACKGROUND: The xiphoid process (XP) in animals such as sheep and rats are well known to have cartilage called xiphoidal cartilage (XC). In humans, the cartilage in the xiphoid process is considered an anatomical variant and is not well understood. The aim of this study was to investigate the morphology of the XP. METHODS: A total of twenty embalmed European descendant cadaveric sterna (aged 52 to 98 years) were used. Transilluminated XPs and midsagittal sections of XPs were used to examine the bone and cartilage. Subsequently, a sagittally-sectioned XP was harvested for histology and stained with Masson's trichrome. The results of the transillumination and histological examinations were compared qualitatively. RESULTS: The dark area visible in transilluminated XPs was consistent with the bony part in the midsagittal XP sections, which contained bone marrow; the bright area was consistent with the cartilage part in the midsagittal XP sections. This was all demonstrated histologically. Most of the XPs (85%) had some portion of cartilage. The XP was classified into four types based on its proportions of bone and cartilage: Type I, no ossification (< 1/3 ossification) 45%; Type II, minor ossification (1/3 - 1/2 ossification) 20%; Type III, major ossification (1/2-2/3 ossification) 20%; Type IV, complete ossification (> 2/3 ossification) 15%. Most of the XPs (85%) had bone and cartilage, which could have been overlooked in studies using skeletons or CT. CONCLUSION: Previous studies probably underestimated or overestimated the size of the XP. The XC needs to be considered as normal anatomy.

Unforeseen plant phenotypic diversity in a dry and grazed world.

Earth harbours an extraordinary plant phenotypic diversity1 that is at risk from ongoing global changes2,3. However, it remains unknown how increasing aridity and livestock grazing pressure-two major drivers of global change4-6-shape the trait covariation that underlies plant phenotypic diversity1,7. Here we assessed how covariation among 20 chemical and morphological traits responds to aridity and grazing pressure within global drylands. Our analysis involved 133,769 trait measurements spanning 1,347 observations of 301 perennial plant species surveyed across 326 plots from 6 continents. Crossing an aridity threshold of approximately 0.7 (close to the transition between semi-arid and arid zones) led to an unexpected 88% increase in trait diversity. This threshold appeared in the presence of grazers, and moved toward lower aridity levels with increasing grazing pressure. Moreover, 57% of observed trait diversity occurred only in the most arid and grazed drylands, highlighting the phenotypic uniqueness of these extreme environments. Our work indicates that drylands act as a global reservoir of plant phenotypic diversity and challenge the pervasive view that harsh environmental conditions reduce plant trait diversity8-10. They also highlight that many alternative strategies may enable plants to cope with increases in environmental stress induced by climate change and land-use intensification.

Disruptions in the food supply chain: A literature review.

Disruptions in the food supply chain are events that affect the flow of products and can be caused by extreme weather, natural disasters, conflicts, pandemics, and political situations, among others. These events can significantly impact food products' availability, quality, and cost, creating risks to the well-being of local populations and livelihoods. The specific literature on food supply chains needs to address other approaches to risk categorisation, which allow for establishing reference frameworks focused on the general classification of types of disruption and parameters related to solution methods. In this paper, we present a literature review to analyse the disruptions in the food supply chain. We classified 74 papers according to the types of disruptions, stakeholders, response level, supply chain echelon, solution methods, goals, and related considerations. The review results showed that the most common disruptions in the food supply chain are climatic, biological and environmental, logistics and infrastructure, and supply. The results of this review allow us to suggest some new research directions.

Optimised phycoerythrin extraction method from Porphyridium sp. combining imidazolium-based ionic liquids.

Phycoerythrin (PE) extraction from Porphyridium sp. was studied employing ultrasound-assisted extraction combined with aqueous mixtures of two imidazolium-based ionic liquids (ILs) simultaneously, marking a significant novelty. A face-centred central composite design and response surface optimised PE yield (EPE), considering the effects of ionic liquid concentration (IL), [Emim][EtSO4]/[Bmim][EtSO4] mass ratio (E/B), biomass concentration (BM), and time (t). Improvements in EPE by 300 % and 115 % were achieved compared to a phosphate buffer solution and the freeze-thaw method, respectively. Temperature and pH effects were examined independently, leading to the determination of optimal operating conditions: BM = 10 mg mL-1, IL = 18.6 wt%, E/B = 0.78/0.22, t = 10 min, T = 35 °C, and pH = 7.5. Results indicated the potential for reusing the ILs for at least five consecutive extraction cycles, maintaining an EPE of 94.2 % compared to fresh ones. This underscores the success and innovation of the developed technology in enhancing PE extraction from Porphyridium sp.

Prescription Patterns for Sodium-Glucose Cotransporter 2 Inhibitors in U.S. Health Systems.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure (HF) hospitalizations, recurrent cardiovascular events, and chronic kidney disease (CKD) progression, and thus constitute a Class 1a recommendation in people with diabetes and atherosclerotic cardiovascular disease, HF, or CKD and in people with severe albuminuria or HF, regardless of diabetes status. OBJECTIVES: The purpose of this study was to comprehensibly characterize the rate of SGLT2 inhibitor prescriptions among people with a Class 1a recommendation for SGLT2 inhibitor use. METHODS: Among 3,189,827 adults from 28 U.S. health systems within Optum Labs Data Warehouse between April 1, 2022, and March 31, 2023, we assessed SGLT2 inhibitor prescription rates, stratified by presence of diabetes and Class 1a recommendation. RESULTS: Among 716,387 adults with diabetes, 63.4% had a Class 1a recommendation for SGLT2 inhibitor therapy. There was little difference by Class 1a recommendation status (present: 11.9%; 95% CI: 11.9%-12.0% vs absent: 11.4%; 95% CI: 11.3%-11.6%; standardized mean difference: 1.3%). Among 2,473,440 adults without diabetes, 6.2% had a Class 1a recommendation for SGLT2 inhibitor therapy, and 3.1% (3.0%-3.2%) of those received a prescription. Internists/family practitioners initiated SGLT2 inhibitor prescriptions most commonly among people with diabetes, whereas specialists initiated SGLT2 inhibitor prescriptions most commonly among people without diabetes. No health system had >25% SGLT2 inhibitor prescription rate among people with a Class 1a recommendation. Health systems with higher proportions of patients with commercial insurance and lower proportions with Medicare had higher SGLT2 inhibitor prescription rates. CONCLUSIONS: In this analysis of U.S. data from 2022 to 2023, SGLT2 inhibitor prescription among people with a Class 1a recommendation is low. Interventions are needed to increase uptake of guideline-recommended SGLT2 inhibitor use.