Otsuka Holdings Co., Ltd.

Resveratrol is an antioxidant polyphenolic compound found in grape skins and red wine. It has been suggested that resveratrol mediates sirtuin 1 (SIRT1) activation, leading to anti-aging, life extension, and anti-cancer effects as demonstrated primarily in model organisms. Additionally, resveratrol inhibits cyclooxygenase-2 (COX-2), resulting in anti-inflammatory effects in atopic dermatitis and psoriasis as well as suppression of carcinogenesis. Thus, resveratrol is a pharmacologically multifunctional compound. However, it suffers from low oral bioavailability and a short half-life. Carbostyril (2-quinolinone, 2-quinolone) has been adopted as a structural scaffold in natural products as well as in pharmaceutical agents and physiologically active substances. The carbostyril scaffold is recognized for its biological stability and lack of toxicity. Consequently, replacing parts of lead or model compounds with carbostyril scaffolds as bioisosteres may generate promising pharmaceutical agents with reduced toxicity. In this study, we synthesized and biologically evaluated resveratrol-like carbostyril derivatives as SIRT1 modulators or COX inhibitors.

The VALFASS study evaluated the SPF-10, a new 10-item patient-reported outcome measure developed with direct patient involvement to assess self-perceived functioning in schizophrenia. Covering autonomy, relationships, occupation, independence, and everyday capabilities, the SPF-10 was designed to address limitations of existing instruments, including limited patient input, reduced feasibility for routine use, and incomplete capture of the patient perspective. This cross-sectional, multicenter study included 155 participants: 44 recently exacerbated patients with schizophrenia, 55 clinically stable patients, and 56 healthy controls. The SPF-10 showed excellent feasibility, with a 100% item response rate and a median completion time of 5 min. Exploratory factor analysis supported a two-dimensional structure, Personal and Social Relationships and Self-Care and Capabilities, explaining 57.7% of the variance. The total SPF-10 score discriminated well between patients and controls (AUC = 0.888) and between patients with moderate-to-severe functional impairment and those with mild or no impairment (AUC = 0.851). A cut-off score of ≤32 yielded 80.8% sensitivity, 84.4% specificity, and 82.6% overall correct classification. Correlations with clinician-rated functioning measures were moderate (PSP r = 0.559; GAF r = 0.521), supporting its complementary value, and internal consistency was good in both patients and controls (Cronbach's α = 0.868 and 0.838, respectively). Overall, the SPF-10 showed adequate psychometric performance and high clinical applicability. Its brief format, patient-centered development, and ability to capture aspects of functioning not fully reflected by clinician-rated instruments support its potential value as a complementary tool for person-centered assessment and care planning in schizophrenia.

Ultrasound renal sympathetic denervation (uRDN) reduces blood pressure (BP) in the absence and presence of antihypertensive treatment at 2 months. Beyond 3 years, there is a lack of follow-up data. This study investigated the long-term safety and efficacy of uRDN.

This prospective observational study recruited patients previously included in the international multicenter ACHIEVE study, with office systolic blood pressure (SBP) ≥160 mmHg, 24 h ambulatory SBP ≥130 mmHg, ≥3 antihypertensive drugs and estimated Glomerular Filtration Rate (eGFR) ≥45 ml/min/1.73m 2 undergoing uRDN. The primary efficacy outcome was 24 h ambulatory SBP, adjusted for the number of defined daily dosages (DDD) of antihypertensive drugs. Statistical analyses were performed using linear mixed-effects models and inverse probability weighting.

A total of 27 out of the initially enrolled 96 patients underwent prospective follow-up at a median of 8.2 [7.6−8.9] years. Mean age was 62.6±9.3 years (37.0% female). Preprocedural 24 h ambulatory BP was 151.9/84.1±11.5/11.1 mmHg and the median number of DDDs was 5.0 [4.3−7.0]. At 8 years after uRDN, the change in 24 h ambulatory SBP was −19.5 [95%CI −26.7,−12.4] mmHg ( p <0.001). The 8-year change in the number of DDDs was −1.7 [−2.8,−0.6] ( p = 0.003). The 8-year decline in eGFR was −8.9 [−13.2,−4.7] ml/min/1.73m 2 ( p <0.001). Clinical event data were available for all 96 patients (median follow-up 3.5 [1.0–8.0] years). Renal failure occurred in one patient and no cases of renal artery stenosis were detected.

A significant BP reduction was observed up until 8 years following uRDN in parallel to a decrease in drug burden over time, in the absence of procedure-related adverse events.