Shared and distinct neural signatures in major depressive disorder and comorbid post-traumatic stress disorder: Insights from structural and functional imaging.

Evaluating cannabis substitution for alcohol within the context of a canadian managed alcohol program.

A high-fat diet disrupts neural tracts in apolipoprotein E mouse models.

The effects of combined structural and nonstructural measures in reducing urban flood damage in the Taehwa District, Jung-gu, Ulsan Metropolitan City, South Korea, were analyzed using the storm water management model (SWMM). Sixteen scenarios combining structural measures, such as drainage pump stations and high-altitude drainage tunnels, with nonstructural measures, including low impact development (LID) facilities (planter box, bioretention, permeable pavement, vegetative swale, infiltration channel, infiltration chamber) and detention facilities, were simulated using rainfall data from Typhoon Chaba in 2016. Analysis results revealed that scenarios incorporating structural measures significantly reduced inundation area and water levels, with some combinations reducing the flooded area by more than 50％. In contrast, the flood-reduction effects of LID measures alone were minimal, demonstrating virtually no impact during the extreme rainfall event. LID facilities contributed to improving water circulation by absorbing the initial rainfall into the subsurface. This study concluded that structural measures, such as drainage pump stations and high-altitude drainage tunnels, are essential for large-scale flood response, while the concurrent implementation of non-structural measures, such as LID facilities and detention basins, can provide additional flood reduction and water circulation improvement effects.

Aim. To determine the impact of porto-azygos dissection procedures with splenic artery ligation/splenectomy in patients with bleeding from esophageal varices against the background of liver cirrhosis on the development of thrombotic complications with a view to preventing them. Materials and methods. The results of treatment of 59 patients from 2012 to 2024 were retrospectively analyzed. A sample of patients who underwent surgical correction of bleeding from esophageal-gastric phlebectases was formed. Operative intervention involved portoazygous dissection, supplemented by splenic artery ligation to reduce splenic blood flow in n=17 (28.8%) or splenectomy in n=42 (71.7%) patients. Results. In all 59 (100%) patients, splenomegaly (171±25 mm), with a determined spleen volume index (1604±821 mm3) and hypersplenism with a platelet count of 63±21×109/l, were detected, respectively. In the first group, there was a slight increase in the number of PLT (158±6 × 109/l), a direct correlation of the average power (rP=0.39) with the indicator of the spleen volume index. In the second study group, a more than 10-fold increase in the PLT index (806.0±38 × 109/l) was noted, which showed a direct correlation of weak force (rP=0.28). The total frequency of thromboembolic complications in 59 operated patients was 5 (8.5%), namely, in the first experimental group – in 2 out of 17 (11.7%) patients, in the second experimental group – in 3 out of 42 (7.1%) of patients. Thrombotic complications occurred between the 6th and 11th day of the postoperative period. During anticoagulant therapy from 1.5 to 6 months (105 ±58,9 days) in the operated patients, no recurrence of upper gastroesophageal bleeding was observed. Conclusions. Postsplenectomy thrombocytosis should be considered a predictor of thrombotic complications in patients with cirrhosis of the liver, varices bleeding, and severe hypersplenism. Splenomegaly in patients with cirrhosis of the liver, bleeding esophageal varices and moderate manifestations of hypersplenism justifies indications for additional reduction of splenic blood flow, at the same time, no data were obtained regarding the reduction of the risk of thrombotic complications in the veins of the portal and caval systems in the postoperative period with the described volume of surgical treatment. Anticoagulant therapy can help prevent thrombotic complications. Convincing data have been obtained regarding the effectiveness of prescribing long-term anticoagulant therapy for 3-6 months to prevent the development of portal/caval vein thrombosis.

Nanoemulsions (NEs) offer a promising strategy for delivering lipophilic cannabidiol (CBD) to protect skin from particulate matter (PM)-induced damage. In this study, CBD-loaded oil-in-water NEs based on Brij® O10 (polyoxyethylene (10) oleyl ether) and olive oil were prepared by the phase inversion temperature (PIT) method and characterized. A 20% w/w Brij® O10 formulation (B20) remained clear and stable for 30 days. CBD solubility was markedly enhanced in Brij® O10 micelles and further increased in NEs, exceeding theoretical predictions and indicating synergistic solubilization in the oil–surfactant system. CBD incorporation lowered the PIT and induced nonlinear changes in droplet size with oil content. All formulations exhibited nanoscale droplets by dynamic light scattering and transmission electron microscopy, moderately low zeta potentials consistent with nonionic steric stabilization, and maintained physical stability despite increased turbidity at higher oil levels. In a full-thickness human ex vivo skin model exposed to PM, both blank and CBD-loaded NEs reduced interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) in PM-exposed skin, with CBD-loaded NEs providing additional reductions and uniquely restoring procollagen type I C-peptide (PIP) relative to their blanks. Overall, PIT-based CBD NEs enhance CBD solubilization and protect human ex vivo skin from PM-induced inflammation and extracellular matrix degradation.

Despite ongoing debates about cannabis regulation, little is known about how tax policy design influences cannabis use among U.S. adolescents and young adults (AYAs). With states adopting diverse taxation schemes based on weight, price, or product potency, evaluating how these approaches affect consumption is critical for evidence-based policymaking. This study uses a split sample volumetric choice experiment (VCE) to examine how variations in pretax prices, tax bases, tax rates, and THC levels influence both the amount of cannabis consumed and the overall intake of THC among US AYAs aged 15-20. We also estimate the own-price elasticities for four cannabis forms (legal flower, illegal flower, edibles, and cartridges) and cross-price elasticities between these products. We use a nationally representative sample of 1,100 AYA who reported current use or susceptibility to use and completed a set of hypothetical purchase tasks featuring choices among four product forms (legal flower, illegal flower, edibles, cartridges). Respondents were randomized to three tax bases: weight-, price-, or potency-based taxation, where pre-tax price levels, tax rates, and THC levels additionally vary. We estimated own- and cross-price elasticities and assessed how AYA current and susceptible users adjusted cannabis consumption in response to the varying attributes using zero-inflated negative binomial and fixed effects models. Higher pre-tax prices and elevated tax rates significantly reduce both purchase quantities and total THC intake among current and susceptible AYA users. Products with higher THC levels increased THC intake but did not affect quantity consumption, suggesting that these users continue to purchase similar quantities but opt for more potent products. Compared to weight-based taxation, potency-based taxes (i.e., THC) were associated with a 30%-32% increase in cannabis quantity consumption. The price elasticities of cannabis demand were -0.3, with edibles being complements to other forms and illegal flowers being substitutes for legal flowers and cartridges. Compared to weight-based taxes, THC-based taxes significantly reduce the impact of THCs in increasing THC consumption. Finally, the impact of taxes on reducing THC consumption from legal products may be completely offset by shifting from legal to illegal products. For AYAs who are using or susceptible to using cannabis, tax increases can effectively reduce the quantity and THC consumption, albeit a tax rate beyond 60% of pretax prices or equivalent generating no additional reductions. Compared to weight-based taxes, potency-based and price-based taxes reduce the consumption of high THC products, but potency-based taxes may also increase the consumption of low THC products. Given that higher prices on cartridges and edibles do not drive AYAs' substitution using flowers, tiered tax structures may have the advantage over potency or weight-based taxes in balancing the need for targeting THC while reducing the burden to administer potency taxes. Finally, given that illegal flowers are substitutes for both legal flowers and cartridges, policy impacts are offset by the availability of illegal products.

Background and Objectives: Sarcopenia and muscle wasting contribute significantly to functional decline in older adults, but differences in lower extremity muscle stiffness and gait variability between these groups are not yet fully understood. This study aimed to compare gait variability, and lower extremity muscle stiffness during contraction and relaxation in community-dwelling older adults classified as non-diseased, sarcopenic, and dynapenic. Materials and Methods: This cross-sectional study included 164 community-dwelling older adults classified as non-diseased, dynapenic, or sarcopenic, based on handgrip strength, 5-time sit-to-stand test, and skeletal muscle index. Spatiotemporal gait variability was measured at the participants’ preferred speed. Moreover, muscle thickness, as well as the contractile and relaxed stiffness, were measured for the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GAmed), and lateralis (GAlat). Results: In dynapenic and sarcopenic groups, gait variability increased across most parameters, but only the step width coefficient of variation differed significantly between the dynapenic and sarcopenic groups. Contractile stiffness of the RF, BF, and GAlat was lower in both groups, with additional GAmed stiffness reduction in the sarcopenic group. Relaxed stiffness of the BF and GAmed was significantly higher in the sarcopenic group than in the dynapenic group. Conclusions: This study identified differences in muscle thickness, stiffness, and gait variability among non-diseased, dynapenic, and sarcopenic older adults. Step width variability, GAmed contractile stiffness, and BF and GAmed relaxed stiffness emerged as potential early indicators for distinguishing dynapenia from sarcopenia. These findings highlight the importance of assessing muscle quality—including both mass and stiffness characteristics—to better characterize early stages of age-related muscle decline and to inform targeted intervention strategies.

Residual cardiovascular risk remains substantial in patients with atherosclerotic cardiovascular disease (ASCVD) despite high-intensity statin therapy. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies and small-interfering RNA agents, offer additional risk reduction, yet comparative evidence across individual regimens remains limited. We conducted a systematic review and network meta-analysis of randomized controlled trials evaluating approved PCSK9i dosages in patients with ASCVD. The primary outcome was major adverse cardiovascular events (MACE); the secondary outcomes included myocardial infarction, stroke, coronary revascularization, cardiovascular mortality, and all-cause death. A total of eight trials involving 49,847 patients were included. Evolocumab (140 mg every 2 weeks or 420 mg monthly) and alirocumab 150 mg every 2 weeks significantly reduced MACE compared with placebo (risk ratios (RR): 0.78, 95% confidence intervals (CI): 0.66-0.93 and RR: 0.47, 95% CI 0.25-0.86, respectively). Evolocumab was also associated with reductions in myocardial infarction, stroke, and revascularization. Alirocumab 150 mg demonstrated the most pronounced effect on revascularization and was superior to both evolocumab and the lower alirocumab dose in this outcome. No regimen significantly reduced cardiovascular or all-cause mortality. These findings suggest that PCSK9 inhibitors are effective in ASCVD, with generally similar efficacy across agents; however, regimens achieving lower and sustained low-density lipoprotein cholesterollevels may confer greater benefit, in line with the concept that "the lower, the better." PROSPERO identifier no. CRD420251022108.

A meta-analysis of the effects of nitrate supplementation on enteric methane emission, production performance, and blood methemoglobin in dairy cattle.

BackgroundData on the effects of sacubitril/valsartan combined with dapagliflozin in non-diabetic patients with advanced chronic kidney disease (CKD) are limited. In this study, we evaluated the efficacy and safety of sacubitril/valsartan plus dapagliflozin in non-diabetic patients with advanced CKD.MethodsA single-center, prospective cohort study was conducted in non-diabetic patients with advanced CKD who had not yet initiated renal replacement therapy. Group A included 65 patients who received combined sacubitril/valsartan and dapagliflozin therapy, while Group B consisted of 59 patients treated with sacubitril/valsartan alone. Estimated glomerular filtration rate (eGFR), proteinuria, blood pressure and serum potassium levels were assessed.ResultsBaseline eGFR was 36.35(31.00, 46.47) and 40.01(30.12, 45.86) mL/min/1.73m2 in the Group A and Group B, respectively. There was significant difference in eGFR between the two groups at month 6 [30.92(25.38, 35.38) vs. 25.42(21.58, 30.27)mL/min/1.73m2, p < 0.001]. The difference in the change in eGFR between the two groups was statistically significant (p < 0.001). Compared with sacubitril/valsartan alone, the combination of sacubitril/valsartan and dapagliflozin provided an additional significant reduction in blood pressure, attenuated the decline in eGFR, reduced proteinuria, and lowered the risk of hyperkalemia (p < 0.05).ConclusionIn non-diabetic patients suffering from advanced CKD, treatment with sacubitril/valsartan combined with dapagliflozin effectively controlled blood pressure, reduced proteinuria, slowed the progression of renal dysfunction, and did not increase the risk of adverse events, indicating a favorable safety profile.

The hit-to-lead phase of drug discovery is frequently bottlenecked by the time-consuming, iterative synthesis of analogs, especially when incorporating small C(sp3)-rich fragments such as methyl, cyclopropyl, or oxetanyl groups-moieties known to improve drug solubility, bioactivity, and metabolic stability. Conventional approaches like Suzuki or Negishi couplings make use of unstable reagents, high costs, and harsh reaction conditions, while many modern radical-based methods rely on exogenous redox agents or costly metal catalysts. To overcome these limitations, a toolbox of 15 sulfonyl hydrazide reagents is disclosed to facilitate redox-neutral, nickel-catalyzed radical cross-coupling of 14 distinct small fragments onto (hetero)arenes under mild conditions. These crystalline, bench-stable reagents are straightforward to synthesize from accessible precursors and require no additional oxidants, reductants, or precious metals, offering a modular and operationally simple platform. Demonstrated across a diverse set of over 60 (hetero)aryl halides, the method exhibits exceptional substrate scope and functional group tolerance, accommodating complex, medicinally relevant scaffolds. Comparative studies with existing techniques underscore its advantages, including a 51% yield for trideuteromethylation of a MET kinase inhibitor precursor (versus a precedented 14% via Kumada coupling) and a streamlined one-step cyclobutylation of an NLRP3 inhibitor intermediate at 41% yield (versus a known<5% over a four-step sequence).

Repeated full-spine radiography for scoliosis follow-up in children results in increased radiation exposure, especially to anteriorradiosensitive organs. Optimizing projection direction and beam filtration is essential for dose reduction. To quantitatively evaluate the age-dependent effects of anteroposterior (AP) and posteroanterior (PA) projections, with and without a0.1-mm copper filter, on organ and effective doses in pediatric full-spine radiography. Monte Carlo simulations were performed using the Particle and Heavy Ion Transport code System with 5-, 10-, and 15-year-oldfemale hybrid phantoms. Full-spine radiography from the first cervical vertebra to both femoral heads was modeled under AP and PAconditions, with or without copper filtration. Organ doses were calculated, with active bone marrow and bone surface evaluated usingthe "International Commission on Radiological Protection Publication 116" dose response functions. Percentage depth dose analysiswas performed to assess the effect of body thickness. PA projection markedly reduced doses to anterior radiosensitive organs, with maximum reductions of approximately 93% for thebreast (AP/PA ratio 14) and over 80% for the thyroid. Copper filtration provided additional reductions of 15-19% in AP and 5-6% inPA. In contrast, dose increases were observed in posterior and deep-seated organs such as the kidneys and active bone marrow.Effective dose was reduced by about half with PA and further decreased with copper filtration. PA projection and copper filtration are effective strategies for reducing radiation exposure to anterior radiosensitive organs andlowering effective dose in pediatric full-spine radiography. However, dose increases in deep-seated organs were also observed,highlighting the need for protocol optimization according to patient age and organ location.

This article investigates the influence of adding polyurethane with refined coal to high-strength mortar, evaluating its mechanical and physics. The tests conducted for this study included X-ray diffraction, compressive strength, elastic modulus, and tensile strength. Results showed that the compressive strength of the mortar decreased when refined coal was incorporated into the reference mortar, and the inclusion of polyurethane in this mixture led to a further reduction in compressive strength. Additionally, a decrease in the elastic modulus was observed with the addition of refined coal, and the inclusion of polyurethane in this mixture caused an additional reduction. The porosity of the mortar significantly increased with the addition of polyurethane to the mortar containing refined coal. In summary, adding polyurethane and refined coal to high-strength mortar compromises its mechanical properties, particularly through a re-duction in compressive strength, elastic modulus, tensile strength, and an increase in porosity. Although polyurethane contributes to flexibility and adhesion between particles, its interaction with refined coal creates a more porous structure, potentially impairing the material’s durability and strength.

Objectives: To evaluate the impact of patient-specific contrast volume adjustments on preoperative aortic computed tomography angiography (CTA) image quality after adjusting and reducing the total, injected contrast volume based on patients’ body surface area (BSA) and heart rate (HR) and after adapting the CT-scanner’s kilovoltage (kV).Methods: Prospective study included 80 surgery-naive patients. Three study groups were included: Group 1 (n = 56 patients): the injected contrast dose, calculated from BSA and HR, was reduced by 50%; Group 2 (n = 11 patients): the injected contrast dose, calculated from BSA and HR, was reduced by 50%, and an additional volume reduction was based on the kV values; Group 3 (n = 13 patients): the injected contrast dose, calculated from BSA and HR, was reduced by 50% and additionally diluted to 80% contrast and 20% saline. Image quality was evaluated by quantitative analysis (Hounsfield units) and qualitative analysis (five-point visual score).Results: The mean injected contrast dose was 46.1 ml, 28.3 ml, and 35.0 ml in Groups 1, 2, and 3, respectively, with a significant difference between Group 1 vs Group 2 (P < 0.001) and between Group 1 vs Group 3 (P < 0.001). A linear relationship between the Hounsfield units and the given contrast dose for all study groups was observed. The mean image quality score for Group 1 was 4.34/5. The mean image quality score for Group 2 was 2.8/5 and for Group 3 was 3.5/5.Conclusions: Significant contrast dose reduction, based on HR and BSA, in preoperative aortic CTA is associated with acceptable diagnostic quality.

Systemic and skeletal muscle metabolic signatures associated with early insulin resistance in just-weaned non-obese Goto-Kakizaki diabetic rats.

Rationale and design of the REMBRANDT trial: A phase 3 study to evaluate the effect of obicetrapib/ezetimibe on coronary plaque characteristics.

To enhance the effectiveness of sequential detection methods, we introduce a kernel smoothing moving average (KSMA) chart that places greater emphasis on recent observations. This new approach is benchmarked against established methods, including the finite moving average (MA), exponentially weighted moving average (EWMA), and CUSUM charts, evaluated in terms of the conditional average detection delay time (ADDT) for a given in-control average run length ( ARL 0 ) under persistent change. A tailored kernel function is proposed to maximize asymptotic efficiency across the signal strength spectrum while maintaining consistently high performance. The comparative study considers both fixed-mean and random-mean change models in multivariate settings. Our results indicate that for moderate signal strengths with fixed mean changes, the KSMA procedure outperforms the alternatives, whereas the EWMA procedure is superior when the signal strength is small. Overall, both the EWMA and KSMA procedures perform competitively and consistently surpass the other methods across fixed and random mean change scenarios. Applications to Dow Jones stock prices and EEG monitoring further illustrate the practical value of the proposed approach. Additional dimension reduction techniques for sparse signal detection are also briefly discussed.

The smallest worthwhile effects of strengthening exercise on pain intensity for people with knee osteoarthritis: A benefit-harm trade-off study.

This paper investigates the noise reduction mechanism of a three-element airfoil with a swept angle. It analyzes the impact of the swept angle on airfoil noise through numerical simulations validated by wind tunnel experiments. An in-house high-precision numerical scheme based on the lattice Boltzmann method combined with the parallel computing capabilities of graphics processing units is used to directly simulate the unsteady vortices around the airfoil. The study finds that the noise reduction effect of the swept angle is not solely attributed to the decrease in effective incoming flow velocity, the sweepback effect introduces a spanwise phase difference during vortex shedding, which weakens the spanwise coherence of the vortex structures. Meanwhile, the breakdown into smaller vortex structures leads to an increase in broadband noise which compensates exactly the additional reduction of the low frequency spectrum pressure level. Based on the Lamb vector ω×u in the vortex-acoustic theory and combined with the dynamic mode decomposition method, this paper conducts a study on the quantitative relationship between the evolution of vortex morphology and noise changes.