Despite metabolic dysfunction–associated steatohepatitis (MASH) being a significant global health concern, there are few effective ways to prevent or treat MASH. Evidence from preclinical and clinical studies suggests that inflammatory polarization of Kupffer cells (KCs) and infiltration of monocyte-derived macrophages (MDMs) in liver macrophages play an essential role in the initiation and progression of MASH. Herein, we reported a liposomal nanoparticle (NP-OMg) that targets suppressive oligodeoxynucleotide (sODN) and magnesium ions (Mg2+) to KCs and MDMs. sODN acted as a potent inhibitor of multiple pattern recognition receptors (PRRs), while Mg2+ was chosen for its anti-oxidative and anti-pyroptotic effects, and its capability of coordinating with sODN in NP-OMg. Intravenously administrated NP-OMg was primarily engulfed by both KCs and MDMs in mouse liver. Therapeutically, NP-OMg mitigated hepatic steatosis, inflammation and fibrosis, and restored liver functions in mouse models of metabolic dysfunction–associated steatotic liver disease (MASLD)/MASH. Mechanistically, RNA-sequencing analysis revealed that NP-OMg largely reversed the aberrant gene expression and signaling pathways involved in the pathogenesis of MASLD/MASH. Through comprehensive targeting of inflammatory pathways in liver macrophages, NP-OMg treatment significantly reduced production of inflammatory cytokines/chemokines and decreased the liver recruitment of Ly6chigh inflammatory MDMs. These findings demonstrate the potential of a new liver macrophage-targeted nanomedicine strategy for the treatment of MASH.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer. J Natl Compr Canc Netw 2026;24(3):101-126 doi:10.6004/jnccn.2026.0011
Despite invasive methods are the gold standard for intracranial pressure (ICP) measurement, several non-invasive techniques (nICP) have been proposed as surrogate, although their use remains insufficiently recognized in clinical practice. These include transcranial Doppler blood flow velocity assessment (arterial or venous), optic nerve sheath diameter (ONSD), automated pupillometry, measurement of skull expansion and compliance, brain imaging, double-depth ophthalmic artery blood flow velocity, and ultrasound time-of-flight. The main limitations of all indirect methods are calibration and zeroing, which constrain the absolute accuracy of non-invasive ICP monitoring. For transcranial Doppler-based methods, the 95
The mainstay of surgical management for male stress urinary incontinence (SUI) for many years has been the male urethral sling and the artificial urinary sphincter. However, patients with pelvic radiation history are at increased risk for poorer outcomes. This review examines the surgical options for radiated men with SUI, how this history may affect outcomes, and surgical modifications which may optimize results. Male urethral slings demonstrate diminished success but may be considered in carefully selected radiated patients. The artificial urinary sphincter remains the gold-standard for radiated men though with increased risk of complications. Key technical modifications include conservative cuff sizing, selective transcorporal placement, and consideration of lower-pressure pressure-regulating balloons. Ongoing technological innovations may address the challenges in this patient population. Successful SUI management in radiated patients requires careful patient selection, consideration of technical modifications, and thorough patient counseling regarding anticipated risks and realistic expectations.
Intentional failure to pay workers their full wage for completed work—either by not paying at all or paying less than promised—is a widespread form of workplace abuse that disproportionately affects low-wage immigrant workers. Latino day laborers (LDLs) frequently experience this mistreatment, which can undermine their financial stability and mental health. In this study, we examined associations between being denied earned wages (not paid at all or paid less than promised) and select indicators of psychological distress (depression, state anxiety, and perceived stress). We also explored the influence of perceived powerlessness on these associations. A cross-sectional survey was conducted with 300 LDLs at 18 day-labor hiring sites. Participants reported the number of times in the past month they had (1) not been paid at all and (2) been paid less than promised for a completed job. Perceived powerlessness, depression, anxiety, and stress were assessed using validated measures. Linear regression was used to estimate associations between each wage denial exposure and each psychological distress indicator, adjusted for sociodemographic characteristics. Path analyses were conducted to evaluate whether powerlessness accounted for associations between wage denial and psychological distress. Regressions revealed that being paid less than promised was associated with greater depression, anxiety, and stress. Furthermore, path analyses indicated that powerlessness may partially account for 36.1
