医学最新文献

Maternal services and policies are initiated, envisioned and established under a colonial premise. Cheko Gǫįtì (gift of the child) is an effort to analyze and document how maternal care programs and policies affect maternal child services in 4 communities of the Northwest Territories (NT). Two frameworks were adapted, 2-eyed seeing and analyzing public policies. These frameworks guided the research process (community engagement, data collection and analysis and knowledge mobilization). The findings are grouped under the policy dimensions of effectiveness, unintended effects, equity, cost, feasibility and acceptability. What we learned informed our recommendations towards decolonizing the predominant westernized system.

Commensal bacteria have been a centerpiece for understanding interkingdom impacts on viral replication. Multiple groups have investigated the roles commensal bacteria played in regulating enteric virus infection and it has been found that the mechanisms through which this regulation occurs varies between the viruses and bacteria explored. For noroviruses, commensal bacteria enhance or suppress viral infection in a region-dependent manner. Recently, it was found that the extracellular vesicles (EVs) produced by commensal bacteria can suppress norovirus infection. In this study, we used murine norovirus (MNV) to probe the immunological mechanisms induced by bacterial EVs. Global analysis of gene expression pointed to induction of cytosolic DNA pathways; thus, we evaluate the DNA content packaged within the bacterial EVs and DNA-sensing pathways that activate type I interferons (IFN), including STING and TLR9. Our results showed that loss of sting or tlr9, significantly decreased IFNβ production and recovered MNV replication in the presence of bEVs. Collectively, these data demonstrated bEVs of certain gram-negative bacteria can initiate antiviral DNA-mediated type I IFN production pathways and that these pathways are involved in the suppression of MNV replication. These findings expose novel mechanisms through which the native microbiota aids the host in controlling an enteric viral infection and offers a fresh perspective on interkingdom host‒microbiota interactions.

Heart failure (HF) is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. Globally, the morbidity and mortality of HF are still on the rise, especially in elderly individuals, and the low 5-year survival rate of HF is a major social and health management problem. The pathogenesis of heart failure involves genetic factors and persistent cardiac inflammation. Genetic factors typically increase a patient's susceptibility to specific diseases. Notably, persistent cardiac inflammation is also a significant contributor to heart failure. Whether it is spontaneous aseptic inflammation of the heart or inflammation caused by infection, both can lead to excessive activation of the immune system, thereby triggering adverse cardiac remodeling. This review focuses on describing the inflammatory/immune activation mechanisms involved in heart failure and explores targeted drugs for inflammatory/immune activation. Additionally, we focused on the NLRP3 inflammasome (a cellular signaling protein complex), whose excessive activation produces large number of inflammatory factors, including IL-1β and IL-18, ultimately leading to persistent inflammation and excessive immune activation in the myocardium, which in turn triggers myocardial cell death and adverse remodeling. We have revealed the pathogenic role of NLRP3 in heart failure, providing a theoretical basis for further research into heart failure.

Objective: This study aimed to investigate the mechanism of the involvement of USP33 in autophagic ferroptosis in endometriosis (EMs).

Methods: Endometrial stromal cells (ESCs) were isolated from 15 healthy controls and 30 patients with EMs, which were designated NESCs and EESCs, respectively. Real-time PCR and Western blotting were utilized to determine USP33 expression as well as GPX4, LC3II/LC3I, NCOA4, FTH1, LAST1, p-LAST1, YAP, and p-YAP levels. Immunofluorescence was used to detect the colocalization of ferritin and LAMP2, as well as that of LC3 and ferritin. The levels of ROS, Fe²⁺, MDA, and GSH were measured to assess ferroptosis. An LDH assay was performed to evaluate cell death. A co-IP assay was implemented to identify the interaction between USP33 and LAST1 and detect the level of LAST1 ubiquitination. The stability of the protein was also detected via a cycloheximide (CHX) assay.

Results: USP33 was underexpressed in EMs patients. Loss of USP33 conferred resistance to ferroptosis in EESCs, as evidenced by increased proliferation; decreased levels of ROS, Fe²⁺, and MDA; elevated levels of GPX4 and GSH; and reduced cell death. In addition, USP33, which is localized in autophagosomes, was suggested to promote the degradation of ferritin in autophagosomes. Furthermore, USP33 repressed the Hippo-YAP pathway by suppressing LATS1 ubiquitination, thereby contributing to the reduced resistance of EESCs to ferroptosis.

Conclusion: USP33 impedes the ubiquitination of LAST1 and represses the Hippo/YAP pathway, thus facilitating ferritinophagy and ferroptosis in EMs.

The unregulated use of highly purified arachidonic acid (AA) supplements among Chinese fitness enthusiasts raises concerns about cardiovascular safety. To evaluate these risks, we integrated population-based, genetic, and experimental evidence. Cross-sectional analysis of NHANES data demonstrated a higher risk of hypertension in individuals within the highest AA intake quartile (OR = 1.262, 95% CI: 1.109-1.438, P < 0.001). Two-sample Mendelian randomization confirmed causal effects of AA metabolites, including thromboxane (OR = 1.006, P < 0.001), eicosanoid C20H28O4 (OR = 1.305, P = 0.009), and 20-HETE-related C20H32O3 (OR = 1.290, P = 0.043). Single-cell transcriptomic profiling revealed increased renal expression of CYP4A11 in hypertensive patients, supporting a mechanistic link between AA metabolism and blood pressure regulation. In vivo, Wistar-Kyoto and spontaneously hypertensive rats fed a high-dose AA diet for six weeks exhibited significant elevations in systolic, diastolic, and mean arterial pressure, accompanied by increased renal vascular resistance. Mechanistic analyses showed that AA upregulated CYP4A1 expression and enhanced 20-HETE production without altering thromboxane synthase activity. Histological assessments revealed glomerular edema, tubular injury, and marked cardiac and renal fibrosis in AA-treated animals. Together, these convergent findings indicate that chronic high-dose AA intake promotes hypertension and multiorgan fibrosis via CYP4A/20-HETE activation. These results highlight the translational importance of AA metabolism in cardiovascular disease and underscore the need for regulatory oversight of AA supplements and therapeutic targeting of this pathway.

Background/objective: This study investigates factors associated with long-term posttraumatic stress following later termination of pregnancy due to fetal anomaly.

Methods: N = 159 women undergoing later termination of pregnancy were assessed at four time points: pre-termination (T0), at four months (T1, N = 115), one year (T2, N = 99), and four years post-termination (T3, N = 90). Participants answered a questionnaire containing questions about posttraumatic stress (IES), optimism (LOT-R), social support (F-SozU) and several sociodemographic as well as pregnancy related variables. To assess changes in posttraumatic stress over time and possible predictors, generalized estimating equations were calculated.

Results: Average posttraumatic stress declined significantly from T1 (52.3% above average) to T2 (20.0%) and T3 (17.8%). Optimism at T0 was a significant predictor for lower overall posttraumatic stress, avoidance and intrusion. Having previous children and higher gestational age were significant predictors for higher intrusion scores.

Conclusions: Findings align with research indicating that most women recover from the initial distress, though some experience prolonged symptoms and should thus receive adequate psychological support. Lower optimism, having previous children and higher gestational age may be risk factors for higher posttraumatic stress levels. Further research should examine the sources of posttraumatic stress among people seeking abortion later in pregnancy due to fetal anomaly.

Over the past century, Brazil has become a hub of excellence in public health research, biomedical sciences and health technology policymaking. However, the Zika outbreak (2016) and the COVID-19 pandemic (2020) exposed critical weaknesses in its healthcare innovation system, particularly regarding the rapid production and delivery of essential technologies. This article examines the interconnected factors shaping vaccine research and development (R&D) and production capacity for neglected and re-emerging diseases in Brazil. The study is based on semi-structured interviews with 22 participants, including university professors, laboratory leaders, scientific staff, innovation managers and policymakers. Thematic analysis identified four interconnected factors: (1) the resilience of science and technology policies (S&TPs); (2) the quality of health technology programs and initiatives (HTP&I); (3) the catalytic role of health emergencies in mobilizing funding and fostering R&D capacity; and (4) the ability of data-intensive local health R&D actors to establish international collaborations. The findings reveal how Brazil's vaccine R&D and production capacity are shaped by the interaction of policy resilience, institutional capability-building and the health system. The accumulation of technological capabilities remains influenced by discontinuous funding cycles, fragmented governance and a reactive policy mode centered on crisis response rather than long-term efforts to align S&TPs and HTP&I.

Objective: The purpose of this systematic review and meta-analysis is to assess the association of handgrip strength (HGS) in subjects with high-normal or mildly elevated and low-normal serum uric acid (SUA) reported by quartiles.

Methods: The research protocol was registered at PROSPERO (CRD420251050351). We searched four databases to obtain relevant articles reporting HGS by SUA quartiles in subjects without gout. Outcomes were compared by combining the third and fourth SUA (higher) quartiles versus the first and second (low) quartiles. The risk of bias was assessed using the Newcastle‒Ottawa Scale, and heterogeneity with the I² test. The results are reported as the mean difference (MD), standardized MD (SMD), or odds ratio (OR).

Results: Seven cross-sectional studies, including 18,765 adult subjects with higher SUA quartiles showed significant higher HGS (SMD: 0.21, 95% confidence interval [CI]: 0.03, 0.39), body mass index (MD: 1.02 kg/m², 95% CI: 0.48, 1.55), total cholesterol (SMD: 0.14, 95% CI: 0.05, 0.24), LDL-cholesterol SMD: 0.13, 95% CI: 0.09, 0.17), and triglycerides (SMD: 0.26, 95% CI: 0.11, 0.41) than those with lower SUA quartiles. HDL-cholesterol was significantly reduced in subjects with higher SUA (SMD: -0.13, 95% CI: -0.20, -0.07). High SUA levels were associated with a drinking history (OR: 1.21, 95% CI: 1.10, 1.34) and hypertension (OR: 1.51, 95% CI: 1.15, 1.99).

Conclusions: Subjects with higher normal SUA levels showed higher HGS compared to those with lower normal levels.

Alterations in the gut microbiota, known as gut dysbiosis, are associated with inflammatory bowel disease (IBD). There is a need for model systems that can recapitulate the IBD gut microbiome to better understand the mechanistic impact of differences in microbiota composition and its functional consequences in a controlled laboratory setting. To this end, we introduced fecal samples from patients with Crohn's disease (CD) and ulcerative colitis (UC), as well as from healthy control subjects, to miniature bioreactor arrays (MBRAs) and analyzed the microbial communities over time. We then performed two functional assessments. First, we evaluated the colitogenic potential of the CD microbiotas in genetically susceptible germ-free IL-10-deficient mice and found that colitogenic capacity was preserved in a bioreactor-cultivated CD microbiota. Second, we tested impaired colonization resistance against Clostridioides difficile in UC microbiotas using the MBRA system and found that UC microbiotas were innately susceptible to C. difficile colonization while healthy microbiotas were resistant, consistent with what is seen clinically. Overall, our results demonstrate that IBD microbiotas perform comparably to healthy donor microbiotas in the MBRA system, successfully recapitulating microbial structure while preserving IBD-specific functional characteristics. These findings establish a foundation for further mechanistic research into the IBD microbiota using MBRAs.