Chronic Obstructive Pulmonary Disease (COPD) is a major chronic respiratory disease affecting human health worldwide. However, there is still a lack of effective drugs for treating COPD. This study is intended to explore the function and molecular mechanism of ARHGAP18 and miR-613 in COPD pathogenesis.

We initially identified the marker gene closely related to epithelial dysfunction in COPD by integrating bioinformatic analyses. ARHGAP18 expression in CSE-induced bronchial epithelial cells (BEAS-2B) was detected by qRT-PCR. Besides, ARHGAP18 levels were modulated by lentivirus-mediated overexpression. Thereafter, cell variability, apoptosis, and migration were detected by CCK8, flow cytometry, and wound healing assay. IL-1β and TNF-α levels were examined by qRT-PCR. Epithelial-mesenchymal transition (EMT)-associated proteins were determined by Western blotting. The function of miR-613 in COPD was further detected. Functional rescue experiments were performed to determine the mechanism of ARHGAP18 in COPD.

Our study identified ARHGAP18 as the key gene associated with epithelial dysfunction in COPD. ARHGAP18 was downregulated in CSE-induced BEAS-2B cells. Overexpression of ARHGAP18 inhibited cell apoptosis of BEAS-2B cells and enhanced their proliferation and migration. Besides, ARHGAP18 overexpression reduced IL-1 β and TNF-α levels, enhanced E-cadherin expression, and suppressed Vimentin and N-cadherin expression. In contrast, miR-613 mimics exerted opposite effects. Furthermore, downregulation of ARHGAP1, mediated by miR-613 inhibitor promoted cell apoptosis and EMT of CSE-induced BEAS-2B cells, suggesting a regulatory role of miR-613 in COPD pathogenesis.

These findings highlight miR-613/ARHGAP18 axis as a critical regulator of epithelial dysfunction in COPD, offering a potential therapeutic target to counteract apoptosis, inflammation, and airway remodeling.

The COVID-19 pandemic exposed profound weaknesses in global and national capacities for pandemic preparedness, emphasizing the urgent need for robust public health policies. This manuscript examines Indonesia's 2024 presidential election, where leading candidates largely neglected pandemic prevention and preparedness despite the enduring socio-economic and health impacts of COVID-19. This work highlights the critical need to embed pandemic preparedness into electoral platforms, national policies, and global health agendas. Kingdon's three streams framework (problem-policy-politics) illustrates how elections shape the prioritization of preparedness through shifts in political will. Therefore, public health advocates must strategically influence electoral agendas by forming unified policy proposals, developing tools like candidate scorecards, and mobilizing community education. Making pandemic preparedness a central electoral issue ensures readiness for future health crises and strengthens systemic resilience.

The lungs are constantly exposed to airborne pathogens and depend on robust innate immune surveillance for protection. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, a core component of the innate immune system, plays a pivotal role in defending against respiratory infections caused by viruses, bacteria, and mycobacteria, including Mycobacterium tuberculosis. Dysregulation of this pathway has been linked to several chronic lung diseases, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and asthma. Upon sensing cytoplasmic DNA, cGAS activates the STING pathway, producing type I interferons and pro-inflammatory cytokines that drive host immune response. However, many pathogens have developed strategies to evade detection or surpass cGAS-STING signaling. This systematic review highlights the molecular mechanisms governing cGAS-STING activation, its interaction with lung pathogens, and its potential as a therapeutic agent in respiratory diseases.

Olfactory disorders have been a hallmark of COVID-19. Since the emergence of Omicron, the prevalence of anosmia has dropped, reducing interest for Omicron pathophysiology in the nasal cavity. Using the hamster model, we show that despite a lower impact than early variants of SARS-CoV-2 (D614G), Omicron BA.1 infection leads to hyposmia as early as 2 days postinfection (dpi). While the olfactory epithelium was mostly spared from Omicron infection at 2 dpi, the respiratory epithelium was strongly infected with increased presence of inflammation markers, epithelial damage, and cellular debris in the lumen of the nasal cavity. The hyposmia caused by the early SARS-CoV-2 variant and Omicron BA.1 infection was similar at 4 and 8 dpi. At 4 dpi, Omicron successfully infected the olfactory epithelium although to a lesser extent than D614G. The BA.1 infection led to innate immune cell invasion and desquamation of the olfactory epithelium similarly as the D614G variant, with persistent inflammatory markers in the olfactory turbinates at 8 dpi despite clearance of the virus. Overall, our results indicate that Omicron successfully infects the nasal epithelium including the olfactory epithelium, but with a delay and to a lesser extent than previous SARS-CoV-2 variants. These results are consistent with Omicron pathophysiology in humans showing a decreased olfactory threshold sensitivity that may be caused, as at the early stage in hamsters, by cellular debris filling the lumen of the olfactory cleft following epithelial damage.

Pertussis, also known as whooping cough, is a highly contagious acute respiratory infection primarily caused by Bordetella pertussis. Although this disease can occur at any age, infants and young children remain the most vulnerable to severe illness and mortality. Moreover, epidemiological trends indicate a notable shift in the incidence of pertussis over time, with an increasing number of reported cases in adolescents and adults. During the 1950s, the widespread implementation of whole-cell pertussis (wP) vaccines significantly reduced the incidence and mortality associated with pertussis. Despite their effectiveness, the frequent adverse reactions linked to wP vaccines prompted a shift towards the utilization of acellular pertussis (aP) vaccines, which have a lower reactogenicity. However, over the past two decades, several countries with a high coverage of aP vaccines have experienced a notable rise in the incidence of pertussis, a phenomenon called pertussis resurgence. The causes of this resurgence are multifactorial and highly complex. Notably, the peak incidence of pertussis has shifted from the infant population to adolescents and adults, who now serve as the primary sources of infection in infants. Such a shift raises critical concerns regarding the current and future control of pertussis. The lack of comprehensive understanding of its pathogenesis is a significant contributing factor to this public health challenge. Although extensive research on the pathogenesis of pertussis has been conducted, it remains an issue without appropriate animal models that effectively replicate the symptomatology commonly observed in human cases. This review provides an overview of B. pertussis epidemiology and recent pathogenesis advances. It further analyzes the potential causes and contributing elements responsible for the resurgence of pertussis. Lastly, the review proposes evidence-based strategies aimed at enhancing public awareness and implementing effective measures to prevent the risk of unexpected outbreaks.

This article discusses considerations on how visualization can be best positioned to help respond to future pandemics. We examine visualization, along with the corresponding and necessary enabling technologies and platforms, as a tool to facilitate a rapid and effective response to a forthcoming pandemic. We consider challenges in terms of an infrastructure supporting world-wide response, corresponding training and stakeholder engagement, integration of future technologies, and appraisal of such systems. Finally, we discuss how addressing these challenges also helps emergency response beyond infectious diseases.

Cerebral small vessel disease (CSVD) is a leading cause of cognitive and functional deficits. Retinal vasculature abnormalities may be an early indicator of CSVD. The aim of this study was to investigate the associations between retinal signs in midlife and imaging markers of CSVD 18 years later.

This study included participants from the Atherosclerosis Risk in Communities Study, a prospective community-based cohort, who had retinal imaging at visit 3 (1993-1995) and 3T brain MRI at visit 5 (2011-2013). MRI scans were reviewed centrally and rated for white matter hyperintensities (WMHs), lacunes (present vs absent), cerebral microbleeds (present vs absent), brain volumes (total, lobar, temporoparietal meta region of interest, deep gray subcortical structure), global fractional anisotropy (FA) and mean diffusivity (MD) obtained from diffusion tensor imaging. Retinal imaging was evaluated centrally for 4 retinal signs: (1) central retinal arteriolar equivalent-lowest (worst) quartile vs top 3 quartiles; (2) arteriovenous nicking (present vs absent); (3) focal arteriolar narrowing (present vs absent); (4) retinopathy (mild, moderate, severe vs none). We used multivariable-adjusted Poisson regression with robust SEs for lacunes and cerebral microbleeds and linear regression for other MRI measures. Models were adjusted for age, sex, race-center, education, APOE ε4 allele, smoking, drinking, body mass index, hypertension, diabetes, and low-density lipoprotein cholesterol. We also adjusted for intracranial volume when WMHs and brain volumes were analyzed.

Among 1,809 participants (mean visit 3 age = 59 years, mean visit 5 age = 77 years, 60% female, 27% Black), comparing participants with focal arteriolar narrowing present vs absent, worse white matter integrity (FA: difference = -0.006, 95% CI -0.010 to -0.001; MD: difference = 0.141 × 10^-4 mm²/s, 95% CI 0.047-0.235) and higher WMH burden (difference = 5.119 cm³, 95% CI 1.352-8.885) were found, after adjusting for demographic and cardiovascular factors. Retinopathy was associated with cerebral microbleeds (prevalence ratio = 1.597, 95% CI 1.052-2.426). We did not find other significant associations between retinal microvascular signs and brain MRI measures.

Midlife retinal microvascular abnormalities may be a valuable risk indicator of late-life CSVD neuroimaging markers. Retinal fundus photography might be a promising tool for early identification of CSVD.

Spasticity is a persistent and debilitating consequence of stroke and effective rehabilitation is a healthcare priority. Botulinum neurotoxin A (BoNT-A) with supportive therapy has increasingly been embedded within clinical practice for treatment of post-stroke spasticity. But the evidence for this approach has hitherto been limited to the findings of a limited number of small trials. The InTENSE trial was undertaken specifically to provide high-quality clinical trial evidence focusing on the effect of BoNT-A and adjunctive therapy on upper limb spasticity. While the clinical trial did not detect a significant impact upon clinical outcomes, there remains a need to evaluate any impact on the broader use of healthcare resources and overall cost-effectiveness. A detailed cost-utility analysis of the InTENSE trial was undertaken. The costs over the 12-month follow-up period were compared with quality-adjusted life years (QALY) gained using utilities generated from the EQ-5D three level (EQ-5D-3L) instrument. There were no significant differences in QALY gained between the intervention and control groups identified, or in the majority of health and community care costs. The Incremental Cost-Effectiveness Ratio per QALY gained was estimated at AU $63,947.11 (Australian dollars), which is well above accepted thresholds for cost-effectiveness in Australia. The study was unable to identify evidence for the cost-effectiveness of treatment approaches combining BoNT-A with adjunctive therapy.

Extracranial arteriovenous malformations (AVMs) are rare congenital vascular anomalies that often require endovascular treatment due to symptoms such as pain, bleeding, or functional impairment. Endovascular strategies include arterial, venous, or combined embolization approaches; however, recurrence remains a major challenge. We retrospectively evaluate the technical success, safety, and clinical outcomes of arterial-only versus combined arterial and venous embolization for the treatment of extracranial AVMs.

This single-center retrospective study included 14 patients (mean age 31.8 ± 21.7 years; 64% female) with symptomatic extracranial AVMs (Schobinger stage II) treated between 2017 and 2023. AVMs were classified angiographically (Yakes classification) and treated with embolization via arterial or combined access routes. The primary endpoint was technical success (defined as angiographic nidus occlusion), while secondary endpoints included clinical recurrence and procedure-related complications. Follow-up included clinical and Doppler ultrasound assessments.

Nine patients (64%) underwent arterial embolization alone; five (36%) received combined arterial and venous embolization, including Lauromacrogol injection via direct puncture. Technical success was achieved in all cases (100%). Clinical recurrence occurred in two patients (14%), both from the arterial-only group. One major complication (tongue ischemia) occurred in a single patient (7%). No complications or recurrences were observed in the combined treatment group. Statistical analysis showed no significant difference in recurrence or complication rates between groups.

A growing body of evidence is amassing in the literature suggesting a correlation between Alzheimer's disease (AD) and thrombotic vascular complications, which led to the suggestive hypothesis that thrombosis may contribute to AD onset and progression by damaging the neurovasculature and reducing the cerebral blood flow. In turn, low cerebral blood flow is likely to contribute to neurodegeneration by reducing nutrient and oxygen supply and impairing toxic metabolite removal from the brain tissue.

We searched the literature for studies in animal models of AD or patients diagnosed with the disease that reported circulating markers of platelet hyperactivity or hypercoagulation, or histological evidence of brain vascular thrombosis.

Platelet hyperactivity and hypercoagulability have been described in multiple animal models of AD, and histological evidence of neurovascular thrombosis has also been reported. Similarly, clinical studies on patients with AD showed circulating markers of platelet hyperactivity and hypercoagulation, or histological evidence of neurovascular thrombosis collected from post-mortem brain tissue samples.

Taken together, a convincing picture is emerging that suggests a strong correlation between systemic or neurovascular thrombosis and AD. Nonetheless, a mechanistic role for haemostasis dysregulation and neurovascular damage in the onset or the progression of AD remains to be proven. Future research should focus on this important question in order to clarify the mechanisms underlying AD and identify a treatment for this disease.