Travoprost/Timolol Maleate

We aimed to investigate the association between time to first cigarette after waking (TTFC) and incident heart failure (HF) in a large prospective cohort.

This study included 229 391 participants from the UK Biobank. Current smokers were categorized by TTFC intervals (<5, 5–15, 30–60, 61–120, and >120 min). Multivariable Cox proportional hazards models were employed to assess the relationship between TTFC and HF. Joint analyses evaluated the combined associations of TTFC with daily cigarette amount and smoking duration. Subgroup and interaction analyses were conducted by age, sex, BMI, education, and alcohol consumption.

During a median follow-up of 15.5 years, 6912 (3.01%) incident HF cases occurred among 229 391 participants. The cohort included 203 653 (88.77%) non-smokers (age 55.9 ± 8.1 years, 41.4% female, 91.5% White ethnicity, 2.7% incident HF cases) and 25 738 (11.23%) current smokers (age 54.5 ± 8.1 years, 49.0% female, 89.1% White ethnicity, 5.7% incident HF cases). A significant dose-dependent relationship was observed between shorter TTFC and HF risk (P for trend <.001). Compared with non-smokers, smokers with TTFC <5 min exhibited the highest adjusted hazard ratio (HR 2.22, 95% CI 1.58–3.10; P < .001), corresponding to an absolute risk difference of 4.03%. Joint analyses showed that among individuals smoking ≤median cigarettes/day, HF risk increased from HR 1.61 (95% CI: 1.35–1.92; P < .001) to 2.25 (1.86–2.72; P < .001) across decreasing TTFC categories; among those smoking >median cigarettes/day, the corresponding HRs ranged from 1.95 (1.41–2.69; P < .001) to 2.17 (1.74–2.69; P < .001). Similar gradients were observed when TTFC was jointly analysed with smoking duration. Subgroup analyses indicated stronger associations in participants aged <60 years (HR 1.98, 95% CI 1.56–2.51; P < .001 for TTFC <15 min) than in those ≥60 years (HR 1.55, 95% CI 1.25–1.91; P < .001), both compared with non-smokers (P for interaction <.001).

Shorter TTFC is independently and dose-dependently associated with a higher risk of incident HF, even after accounting for smoking burden and comorbidities. TTFC assessment may improve HF risk stratification, particularly in younger individuals.

Bacterial vaccines using recombinant antigens displayed on the bacterial surface represent a major advancement in vaccine development. This approach leverages bacteria's natural ability to induce immune responses while improving vaccine targeting and efficacy. Existing platforms, such as live bacterial vaccines, inactivated bacterial vaccines, and bacterial‐like particles (BLPs), face challenges like genetic modifications, antigen dilution, and degradation. To address these limitations, a novel system called coated bacterial vaccine (CBV) is proposed, combining the properties of inactivated bacterial vaccines and BLPs technology. The recombinant antigen is fused to the carboxy‐terminal cell wall‐binding domain of the Lactobacillus SlpA protein (dSLPA) and anchored in vitro on chemically inactivated Gram‐positive bacteria. To validate this system, CBVs were created using inactivated B. subtilis 15245 and the TTFC antigen, a fragment of tetanus toxin (TeTx) fused with dSLPA. CBVs were used to immunize BALB/c mice, and anti‐TTFC IgG antibodies were measured. Mice were then challenged with TeTx to assess the protective effects of CBVs. Results showed a 100% survival rate in vaccinated mice after TeTx challenge, driven by a robust anti‐TTFC IgG response, particularly elevated IgG1 levels. Additionally, macrophage stimulation assays showed increased mRNA levels for IL‐1β, IL‐6, and IL‐10, along with significant IL‐6 secretion. These findings demonstrate that CBVs based on B. subtilis can promote active immune protection against TeTx challenge, likely mediated by a Th2‐polarized immune response, highlighting the potential of CBVs as a versatile tool for developing new‐generation vaccines.