Intensive blood pressure (BP) reduction may reduce the risk of poor functional outcomes in patients with acute intracerebral hemorrhage (ICH). Whether these potential benefits apply similarly to lobar and deep ICH, 2 biologically and clinically distinct subtypes, remains uncertain. We tested the hypothesis that intensive BP reduction has differential effects on functional outcomes based on ICH location. We performed a stepwise meta-analysis, stratified by ICH location, of 3 landmark randomized clinical trials of intensive BP reduction: Acute Cerebral Hemorrhage (ATACH-2), Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), and INTERACT3. Step 1 pooled ATACH-2 and INTERACT2 (3-month outcomes; intensive BP lowering only). Step 2 added INTERACT3 (6-month outcomes; care bundle protocol with intensive BP lowering plus glucose management, antipyresis, and anticoagulant reversal). For ATACH-2, we used pooled results from individual patient data (adjusted for age, Glasgow Coma Scale score, and presence of intraventricular hemorrhage), whereas for INTERACT2 and INTERACT3, we used their pooled, publicly available results. Our exposure of interest contrasted intensive systolic BP targets <140 mm Hg vs standard care 140-180 mm Hg. Our outcome of interest was poor functional outcome, defined as a modified Rankin Scale score of 4-6 in ATACH-2 and INTERACT3 and of 3-6 in INTERACT2. Step 1 included a total of 2,983 patients with deep and 537 patients with lobar ICH (mean age 63 y/o, 37% female). Intensive BP reduction was not associated with a significant difference in poor functional outcome for either deep (odds ratio [OR] 0.89; 95% CI 0.40-1.98; I2 = 0%) or lobar (OR 0.92; 95% CI 0.73-1.17; I2 = 0%) ICH. Step 2 included a total of 7,917 patients with deep and 1,105 patients with lobar ICH (mean age 63 y/o, 37% female). Similarly, intensive BP reduction was not associated with a significant difference in poor outcome in both deep (OR 0.82; 95% CI 0.57-1.18; I2 = 60%) and lobar (OR 0.97; 95% CI 0.76-1.24; I2 = 0%) ICH. In this stepwise meta-analysis of 3 landmark ICH trials, intensive BP reduction did not demonstrate a significant benefit in either deep or lobar ICH. Although our estimates did not reach statistical significance, the direction of effect in deep ICH and the substantial heterogeneity across trials, particularly with the inclusion of INTERACT3, limit firm conclusions. Given these uncertainties and the biological distinctions between deep and lobar ICH, future well-powered studies specifically designed to test whether intensive BP reduction has differential effects by hematoma location are warranted.

Catastrophizing contributes to the association between posttraumatic stress symptoms and pain outcomes in individuals with chronic low back pain: Differential effects as a function of sex.

Analysis of gut microbiota and intestinal secondary bile acids metabolism in rats after short-term antibiotic treatment.

Δ9-tetrahydrocannabinol (THC) has been studied for its neuroprotective benefits in disease and its ability to improve HIV-1-related symptoms in clinical and preclinical models. Chronic THC administration may cause reduced sensitivity to antinociceptive, hypothermic, and anxiolytic effects following acute THC administration, and HIV status may further influence these effects. Thus, the present study investigated the effects of an acute THC challenge after chronic THC exposure on behavioral and neuroinflammatory measures using the HIV-1 Tg26 neuroHIV mouse model. HIV-1 Tg26 transgenic [Tg26(+/-), n=32(16f)] mice and their control littermates [Tg26(-/-), n=31(16f)] received subcutaneous injections of vehicle solution or THC (3mg/kg), once a day, 5days per week, for 90days. After a 7-day drug-free period, all mice were given a high dose of THC (10mg/kg; intraperitoneally), and their body temperature, antinociception, locomotor activity, and elevated plus maze data were collected. To assess inflammation, cytokine/chemokine levels were assessed via Bio-Plex, and microglial quantification and microglial CCL3/MIP-1α were assessed via immunohistochemistry in various brain regions. THC metabolite levels in the plasma were also collected. A chronic THC history resulted in minor behavioral/physiological changes (e.g., increase in body temperature but no effects on antinociception or locomotor activity) but overall decreases in proinflammatory and anti-inflammatory cytokines/chemokines in various brain regions of female mice. Importantly, across behavioral measures, a chronic THC history attenuated the efficacy of the acute high THC challenge dose, resulting in reduced THC-induced hypothermia, antinociception, and hypolocomotion, especially in females, and occasionally in a genotype-dependent manner. In the elevated plus maze, the acute THC challenge increased anxiety-like behavior in female mice with a chronic THC history compared to chronic vehicle history females, whereas no effects were noted in males. Further, regardless of microglial quantity, Tg26(+/-) mice showed high microglial-CCL3/MIP-1α co-occurrence in a sex- and brain-region dependent manner (e.g., basolateral nucleus of the amygdala in females & dorsal striatum in males). The data suggest that female mice may develop reduced sensitivity to THC's hypothermic, antinociceptive, and anxiolytic effects, and that this insensitivity development may depend on HIV genotype. The sex and genotype effects seen in the behavioral assays may be elucidated by differential effects in the inflammatory measures.

Lymph Node Harvest and Survival Among Patients With Locally Advanced Appendiceal Adenocarcinoma.

Environmental aroma exposure for subthreshold depression: Differential psychophysiological effects of essential oils with distinct chemical profiles

Inhibition effect-involved colorimetric sensor array based on Ln-Ru dual-site nanozymes for thiol discrimination.

Hippocampal energy metabolism reprogramming underlies individual differences in paroxetine-facilitated contextual fear extinction.

Effects of fluoride chemical forms of sodium fluoride and monofluorophosphate on microbial viability and diversity in saliva-derived biofilms.

The improving effect of airflow on thermal comfort in moderately hot environment: a comparative study based on populations with different exercise backgrounds.

Differential effects of osmotic fluid dynamics on intestinal drug absorption between juvenile and adult rats: potential impact on drug interaction with hyperosmotic beverages.

Differential Effects of T-Cell Inhibitors and Antimetabolites on Graft Survival in High-Risk Penetrating Keratoplasty: A Tertiary Center Experience.

Warming altered the variational effects of microplastics and leachate from biodegradable mulch films on organic carbon transformation in riparian zones.

Differential effects of the microbial metabolite acetate on murine microglia in in vitro sepsis and trauma models.

Hierarchic redox micro-zones shape multipath nitrogen and phosphorus removal with distinct thermal responses

Statins are widely prescribed to those with atherosclerosis to lower cholesterol and reduce cardiovascular risk, but their influence on plaque calcification remains unclear. While clinical data associate statin use with increased calcium scores and reduced cardiovascular events, their effect on rupture-prone microcalcifications has not been clinically assessed due to imaging limitations. In vitro studies report conflicting outcomes on statin-induced calcification in various cell types. To address this gap, we investigated the impact of atorvastatin on calcification across multiple plaque-relevant cell types using both monolayer cultures and a tissue-engineered 3D plaque model. Human mesenchymal stromal cells (MSCs) were isolated from iliac crest bone chips and differentiated into smooth muscle (mSMCs) cells using TGF-β1, while human vena saphena cells (HVSCs) were obtained from bypass surgery material. Monolayer cultures of MSCs, mSMCs, and HVSCs were exposed to calcifying medium with or without atorvastatin (0.1-1 μM) for 2 weeks. For the 3D model, cells were embedded in fibrin gels, cultured to form a collagenous matrix for 2 weeks, then calcified for an additional 2 weeks with or without atorvastatin (1-10 μM). In both monolayer and the 3D model, atorvastatin inhibited calcification in MSCs, while it induced calcification in mSMCs. For HVSCs, atorvastatin reduced calcification in 2D monolayer cultures, while it had no visible effect in 3D. This study highlights the cell type-specific effects of atorvastatin on calcification, underscoring the need to consider cellular heterogeneity when evaluating its impact on plaque stability.

Differential effects of student and parental mobile phone use on academic procrastination trajectories: Machine learning evidence

Differential Effects of Cardiometabolic Risk Factors on All-Cause Mortality in United States Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Sex-specific influences of prenatal inflammation on offspring psychological symptoms in late midlife.

Effects of plastispheres and pristine microplastics on sediment microbial communities and nitrogen cycling under global warming.