Biomedical Research Institute

Government regulations can control the design features of tobacco products, including flavours. Understanding how cigarette and e-cigarette flavour availability affects purchasing behaviour among adults who smoke menthol cigarettes can help determine the impact of such policies. Conducted in Roanoke, Virginia, USA, this study investigated how restrictions on menthol cigarettes and non-tobacco e-cigarette flavours affect purchases in the Experimental Tobacco Marketplace (ETM), a simulated environment designed to mimic real-world tobacco purchasing behaviour. In a within-subject design, 25 individuals who smoke menthol cigarettes completed purchasing trials with increasing cigarette prices in the ETM under different scenarios: (1) cigarette flavour restricted and e-cigarette flavour restricted, (2) cigarette flavour unrestricted and e-cigarette flavour restricted, (3) cigarette flavour restricted and e-cigarette flavour unrestricted and (4) cigarette flavour unrestricted and e-cigarette flavour unrestricted. Menthol cigarette flavour restrictions significantly decreased cigarette purchases (p<0.001) and increased substitution with e-cigarettes (p<0.002). E-cigarette flavour restrictions were associated with increased purchasing of nicotine replacement therapy (NRT) products (p<0.001). These findings suggest differential impacts of flavour restrictions across product types, highlighting complex substitution patterns among individuals who smoke menthol. This study experimentally demonstrated that menthol cigarette bans reduce cigarette purchases. Additionally, flavour restrictions on cigarettes and e-cigarettes distinctly influence substitution patterns, with a menthol cigarette ban encouraging switching to e-cigarettes, while an e-cigarette flavour restriction increases NRT purchasing. As policymakers consider strategies to reduce tobacco-related harms, these findings highlight the need to carefully evaluate broader impacts of flavour restrictions on consumer behaviour.

Resurgence of sarin use in the Syrian conflict demonstrates that chemical weapons are a vivid threat. Like other organophosphate compounds, sarin inhibits acetylcholinesterase resulting in cholinergic crisis. The current antidote therapy includes atropine (a muscarinic cholinergic antagonist) + an oxime (e.g., pralidoxime) to reactivate the inhibited cholinesterases. Long-term sequelae reported in victims of the 1995 Tokyo subway sarin attack emphasize the need to improve neuroprotection and to delineate more precise biomarkers of intoxication severity. Previously, we proposed that brain oscillations could indicate exposure severity to a sublethal dose of a neurotoxic agent. In the present study, we evaluated the effects of atropine + pralidoxime in mice exposed to a sublethal dose of sarin (0.9 LD50) on changes in short-term recovery, brainwaves and behavioral patterns. We demonstrated the benefits of the antidotes on alleviation of the sarin-induced encephalopathy, stabilization of brain oscillations, and attenuation of anhedonia behavior. Nevertheless, mice exhibited work memory impairments associated with the disruption of theta oscillations during the task, the disruption of sleep architecture and the anxiety-like behavior when exposed to the non-convulsive sarin dose. These outcomes were not mitigated by atropine + pralidoxime administration. Our findings suggest that the currently recommended antidote for sarin poisoning provides only partial neuroprotection. Despite stabilizing brain waves in resting state, current antidote is not effective in preventing long-term neurobehavioral complications.

Novel bioimpedance analysis (BIA) devices may improve the precision of fluid overload assessment, potentially offering additional prognostic information beyond clinical parameters in patients with HF. This study aimed to evaluate the association between fluid overload indexes obtained with a novel bioelectrical impedance device (BioScan touch i8 IVF, MALTRON®) and the risk of cardiovascular events in ambulatory patients with HF. Volume excess was assessed using BioScan Touch i8 IVF (MALTRON), which differentiates fluid distribution across body compartments. Volume-excess variables (total, intravascular, and tissue) were analysed both as quartiles (Q) and as continuous measures. Their independent associations with the composite of all-cause death or worsening HF were adjusted for established prognostic markers, including a clinical congestion score (CCS) and N-terminal pro-B-type natriuretic peptide. Among 386 ambulatory patients with stage C chronic HF, median total, intravascular, and tissue fluid excess were 1.3 L (Q1-Q3: 0.5, 2.3), 0.1 L (Q1-Q3: -0.1, 0.4), and 1.9 L (Q1-Q3: 1.1, 2.8), respectively. Total and tissue fluid excess had the strongest correlation with the CCS (Total fluid excess rho = 0.31; P < .001, tissue fluid excess rho = 0.33; P < .001). In adjusted analyses, patients in the highest quartile had significantly higher risk of the composite outcome compared with Q1: total fluid excess hazard ratio (HR) 2.11 [95% confidence interval (CI) 1.21-4.05, P = .010], intravascular fluid excess HR 2.16 (1.19-3.90, P = .011), and tissue fluid excess HR 2.81 (1.49-5.32, P = .001). Compartment-specific estimates of fluid overload obtained with the BioScan Touch i8 IVF were independently associated with adverse outcomes in ambulatory patients with chronic HF, beyond NT-proBNP and clinical surrogates of congestion. These findings support the potential role of BIA-derived indexes, particularly tissue fluid excess, as complementary tools for risk stratification in this population.

Abstract Synaptic dysfunction arises early in Alzheimer’s disease (AD) and contributes to cognitive decline. Yet, plasma biomarkers to evaluate synaptic functioning remains underexplored. We developed a novel immunoassay to detect the synaptic marker SNAP25 in plasma, aiming to evaluate the association of plasma SNAP25 with AD progression. Participants who were cognitively unimpaired or had subjective cognitive decline (CU or SCD Aβ+/Aβ-), mild cognitive impairment (MCI Aβ+), and AD dementia were included from multiple cohorts (n=884). Plasma SNAP25 levels were higher in all Aβ+ groups (p&lt;0.01), from the CU/SCD stages onward, and levels increased more steeply over time in SCD Aβ+ than in SCD Aβ- individuals (βtime*amyloid status 0.08±0.02, p&lt;0.001). Among SCD, higher baseline and steeper increases in plasma SNAP25 were associated with cognitive decline (both βtime*SNAP25 –0.02±0.01, p&lt;0.001) and an increased risk of progression to MCI or dementia (HR 1.94 [95%CI 1.42–2.65], p&lt;0.001). Among Aβ-, baseline plasma SNAP25 predicted Aβ status conversion to Aβ+ over four years with AUC 0.71 [0.57–0.85]. In conclusion, plasma SNAP25 emerges as a promising blood-based synaptic biomarker for prognosis and progression in the preclinical AD stages.

BackgroundDysregulation of platelet function and coagulation has been implicated in Alzheimer's disease (AD) pathogenesis. Increased platelet activation is linked to vascular inflammation and cognitive decline. Elevated coagulation factors (fibrinogen, p‐selectin) exacerbate neurovascular dysfunction, while Factor V has shown a potential neuroprotective role. These findings suggest that platelet and coagulation biomarkers may serve as early indicators of dementia. Our objective is to assess the associations between plasma platelet concentration, anticoagulant drug use, and coagulation factors, with dementia risk.MethodThis study analyzed PREDIMED cohort data, a Spanish multicenter clinical trial on cardiovascular risk. Two study designs were used: 1) Sub‐cohort analysis (7,447 participants) to assess platelet levels, antiplatelet drug use with dementia risk; 2) Nested Case‐Control study (95 dementia cases, 158 controls) evaluating the association of thrombosis biomarkers (fibrinogen, p‐selectin, Factor V, VII, VIII, PAI‐1) with dementia risk. Cox proportional hazards and conditional logistic regression models were used, adjusting for age, sex, education, cardiovascular risk factors, and ApoE‐ε4 genotype.ResultsHigher platelet concentrations were associated with an increased risk of dementia (HR 1.24, 95% CI 0.99–1.55) as well as antiplatelet drug use (HR 1.46, 95% CI 1.02–2.09); Factor V was inversely associated with dementia risk (OR 0.48, 95% CI 0.28–0.83) and AD risk (OR 0.32, 95% CI 0.15–0.72), suggesting a neuroprotective effect whilst no significant associations were found for fibrinogen, p‐selectin, Factor VII, or VIII.ConclusionHigher platelet levels and antiplatelet drug use are associated with increased dementia risk, while Factor V may be protective. These findings highlight the importance of coagulation biomarkers in early dementia detection and potential therapeutic strategies.

Backgound: Pulmonary arterial hypertension (PAH), a rare and progressive subtype of pulmonary hypertension (PH), leads to right heart failure and, ultimately, death. PH is defined by a mean pulmonary arterial pressure greater than 20 mmHg at rest, assessed via right heart catheterization. Methods: We investigated BMP3 expression in lung tissues from multiple animal models of PAH (mice, rats, pigs) and in pulmonary vascular cells from PAH patients. Functional studies were conducted using hPASMCs and hPAECs from healthy individuals and PAH patients. BMP3 loss- and gain-of-function models were generated via genetic deletion and BMP3 overexpression (recombinant protein and AAV1-mediated gene transfer). Phenotypic effects were assessed using hemodynamics, MRI, and histological analyses. Results: BMP3 was primarily expressed in PASMCs and found to be downregulated in PAH. Loss of BMP3 in PASMC enhanced the proliferation and migration of hPAEC, whereas BMP3 overexpression in PASMC restored endothelial function. Both global and SMC-specific BMP3 knockout mice exhibited worsened pulmonary vascular remodeling and right ventricular dysfunction in response to PAH stimuli. Therapeutically, systemic BMP3 administration and lung-specific AAV1-BMP3 delivery inhibited PAH. Mechanistically, BMP3 activated the protective BMP/Smad1/5/8 signaling pathway while suppressing the pro-fibrotic TGF-β/Smad2/3 pathway. Conclusion: BMP3 is a critical modulator of pulmonary vascular and cardiac remodeling in PAH. Restoration of BMP3 signaling offers a promising therapeutic avenue by rebalancing BMP and TGF-β pathways through paracrine cell-cell interactions.