Hennepin County

Objectives: Erhuang Quzhi Formula (EQF) has been used for the treatment of non-alcoholic fatty liver disease (NAFLD). However, its active components and mechanistic basis remain unclear. This study aims to systematically identify the therapeutic material basis of EQF and to elucidate its potential mechanisms of action against NAFLD through an integrated multi-omics strategy. Methods: An integrated strategy combining UPLC-Q-TOF-MS and network pharmacology was applied to characterize serum components of EQF and construct a compound–target network. Core targets were screened and validated by molecular docking. A NAFLD model was established in C57BL/6 mice through high-fat diet feeding. To evaluate the therapeutic effects, mice were treated with EQF and assessed by measurements of serum biochemical parameters, liver histopathology, and glucose tolerance. UPLC-Q-TOF-based lipidomic and metabolomic analyses of liver tissue were conducted to clarify EQF’s regulatory effects on global lipid profiles and endogenous metabolites. Key genes and proteins involved in relevant signaling pathways were verified by RT-qPCR and Western blot. Results: A total of thirty-one prototype compounds were identified in the EQF-containing serum. Network pharmacology analysis predicted that EQF may alleviate NAFLD by acting on core targets such as TNF, JUN, and STAT3. In vivo experiments demonstrated that EQF administration significantly improved liver function, attenuated dyslipidemia, and reduced inflammation in model mice. Furthermore, metabolomic and lipidomic analyses indicated that EQF effectively reversed abnormal glycerophospholipid and sphingolipid levels and restored their metabolic homeostasis. Conclusions: EQF exerts therapeutic effects in a NAFLD mouse model through multi-component, multi-target, and multi-pathway mechanisms, primarily associated with the regulation of lipid metabolism, improvement of liver function, and suppression of inflammatory responses. This study provides mechanistic insights and a pharmacodynamic basis for the future clinical investigation of EQF.

ABSTRACTBrucellosis, a zoonotic bacterial infection often characterized by nonspecific symptoms including fever, night sweats, and weight loss, has a prolonged and recurrent course, often leading to chronic symptoms if inadequately treated. Hepatic involvement is well-documented with manifestations ranging from mild hepatitis to hepatic abscesses and granulomas. However, the association of brucellosis with biliary dysplasia or ampullary adenocarcinoma has not been previously reported in medical literature. We present a 68-year-old man with hepatic granulomatosis due to chronic brucellosis complicated by numerous episodes of ascending cholangitis secondary to choledocholithiasis and common bile duct strictures, with high-grade dysplasia and development of ampullary adenocarcinoma.

ABSTRACTBackgroundDelirium is an acute cognitive disturbance that is linked to increased healthcare costs, extended hospitalization, and a greater incidence of adverse outcomes, including cognitive decline. Despite its clinical importance, existing strategies for predicting and managing delirium remain inadequate. This study, therefore, sought to investigate the potential relationship between cerebrospinal fluid proteins and delirium via Mendelian randomization (MR) and to identify potential therapeutic targets.MethodsGenetic data related to delirium were obtained from the 11th iteration of the FinnGen Biobank, which includes a total of 431,880 individuals of Finnish ancestry consisting of 3827 cases and 428,053 controls. Data on 910 cerebrospinal fluid proteins from 970 samples were collected via the ONTIME platform (https://ontime.wustl.edu/hg38/). MR analysis was used to evaluate genetic associations between cerebrospinal fluid proteins and delirium. Additionally, enrichment analysis was performed on cerebrospinal fluid proteins with genetic associations to identify potential cellular pathways and therapeutic targets.ResultsWe identified 46 cerebrospinal fluid proteins associated with the occurrence of delirium. Among these, insulin (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.07–1.70, p = 0.01), interleukin‐7 (OR: 0.56, 95% CI: 0.37–0.85, p = 0.01), and B‐cell lymphoma/leukemia 2‐like protein 1 (OR: 0.63, 95% CI: 0.45–0.88, p = 0.01) were identified as key proteins. Horizontal pleiotropy had a minimal impact on establishing causal relationships, with p values of 0.08, 0.26, and 0.32, respectively. Additionally, no evidence of heterogeneity in genetic variation was found between these three cerebrospinal fluid proteins and delirium, with p values of 0.07, 0.45, and 0.96, respectively. Leave‐one‐out analysis further confirmed the stability and robustness of these associations. The enrichment analysis indicated that the cytokine‐mediated signaling pathway plays a significant role in the pathogenesis of delirium.ConclusionOur study identified a genetic causal relationship between specific cerebrospinal fluid proteins and delirium, with insulin being a key factor. We also found that cytokine‐mediated signaling pathways may contribute to the pathophysiology of delirium. Future research should focus on the roles of peripheral and central glucose metabolism, as well as cellular immunity, in the pathological processes of delirium.

Was ist zu diesem Thema bereits bekannt? Seit 2021 gilt das Soteria-Konzept laut WHO als „Good Clinical Practice“ zur Förderung personenzentrierter und rechtebasierter Ansätze. Wie wird eine neue Perspektive eingebracht? Im vorliegenden Artikel wird die Umsetzung des Soteria-Konzepts in einer akutpsychiatrischen Station mit Versorgungsauftrag dargestellt. Was sind die Auswirkungen für die Praxis? Soteria leistet als komplexes Interventionsprogramm einen Beitrag zur Reduktion von Zwang und Gewalt in der Psychiatrie, fördert die Zufriedenheit der Nutzenden und der Mitarbeitenden.

The rapid adoption of electric vehicles (EVs) and other electrification trends, such as heat pumps and electric water heaters, is driving unprecedented growth in electricity demand. Unlike historical load increases, EV charging contributes significantly to higher peak loads and sustained energy consumption, placing considerable strain on secondary service transformers. This study leverages readily available utility meter data to evaluate the impact of EV penetration on service transformers with a focus on thermal stress and insulation life loss. Using a one-year dataset from a local feeder, this analysis provides a practical and cost-effective approach to assess transformer health and highlights the need for utilities to adapt planning practices to address evolving load profiles.

ABSTRACT OBJECTIVES Clinical management of traumatic brain injury (TBI) focuses on preventing secondary injury from cerebral edema and ongoing anoxic injury. Consensus guidelines recommend maintaining systolic blood pressure (SBP) > 110 mmHg. A recent prehospital study suggested lowest adjusted mortality from 130 mmHg to 180 mmHg, suggesting the ideal pressure may be higher. This study aims to explore and externally validate the association between lowest out of hospital SBP and mortality in a nationwide database. METHODS Retrospective observational study of nationwide data from the ESO© (Austin, TX) prehospital electronic health record. Inclusion criteria were an ICD-10 code for TBI, age >10 years, admission to the hospital, abbreviated injury severity head/neck sub-score ≥ 3. Data were split into 70% training and 30% test sets. Unadjusted and adjusted generalized additive models with splines for the continuous variables of SBP and age were created to assess the relationship between lowest SBP and mortality. Adjusted model covariates included age, sex, injury severity score, mechanism, polytrauma, trauma center transport (level 1, 2, or 3), hypoxia and airway management. To evaluate the independent association of lowest SBP with mortality, the adjusted marginal means for predicted probability of death at any fixed value of SBP were estimated and an optimized SBP range was identified. Age and injury severity were evaluated as possibly relevant interaction terms with SBP. RESULTS From 2018 to 2022, 44,360 encounters with ICD-10 codes for TBI were screened and 9,449 met final inclusion criteria, with 2,005 meeting the primary outcome (21.2%). Both unadjusted and adjusted analysis identified lowest prehospital SBP as a significant predictor (p < 0.001). Based on adjusted marginal means, the optimized SBP for mortality was 132 mmHg (range 110-158 mmHg). The interaction between SBP and age was significant with a higher optimized SBP of 133 mmHg (range 125-145 mmHg) for patients aged 65 and older. CONCLUSIONS Out of hospital SBP is a significant predictor of mortality in subjects with severe TBI. These results suggest an optimized SBP range 110-158 mmHg, consistent with current consensus guidelines of SBP > 110 mmHg but may suggest benefit for higher SBP targets in older patients.

Refugees, immigrants and migrants often have barriers to travel medicine. Community Advisory Boards (CAB) are a vital but underutilized tool for understanding and meeting healthcare needs and challenges, providing communities with a voice, and finding solutions. The paper discusses a malaria prevention community-based participatory research project informed by a CAB.

We build a scenario for inflation in the United States in the years to come. Following Gao, Kulish, and Nicolini (2021), we use the quantity theory of money as a conceptual framework and confront the theory with evidence from both the United States and other OECD countries. We argue that a) the quantity theory of money works very well in the medium term, which we define to be close to four years; b) deviations from the inflation rate predicted by the quantity theory tend to disappear in the medium term; c) the burst in inflation that started in 2012 in the United States is a deviation from the inflation rate predicted by the quantity theory; and d) if the policy framework does not change, we expect inflation to be back close to its 2% target no later than 2025.