搜索结果：Diseases (Basel, Switzerland)

Background: Epidemiological alerts about the possible spread of different pathogens have highlighted the risk of international travelers contracting infectious diseases when visiting endemic areas. The role of travelers in disease transmission underscores the importance of pre-travel consultations, which provide critical information on health risks, vaccinations, and preventive measures. Understanding travelers' risk perceptions and behaviors is essential for enhancing global health security in the post-pandemic era. Methods: A cross-sectional study (June 2023-January 2024) was conducted by administering an anonymous questionnaire at the Rome-Fiumicino Airport International Prophylaxis Clinic (USMAF-SASN). The questionnaire explored demographics, travel patterns, risk perceptions, vaccination behaviors, and sources of health information. Descriptive statistics and a multivariable logistic regression analysis were performed to identify low-risk perception predictors. Results: Among 217 participants, 89.8% were Italian, with a balanced representation of genders. The primary purpose of travel was tourism (61.6%), followed by work-related trip (23.1%). While 77.1% rated preventive measures as effective, 23.2% evaluated infection risk as low. Being male (aOR 3.63, 95% CI 1.37-9.61), and being a hotel user (aOR 6.27, 95% CI 2.43-16.15), was significantly associated with a lower risk perception. As expected, healthcare professionals and individuals using institutional healthcare sources showed a higher risk awareness. Vaccination uptake at the Airport Clinic was motivated by self-protection, vaccine confidence, and poor time flexibility to access local vaccination services, and last-minute plans, making the airport a more convenient option. Conclusions: Travelers' risk perception is influenced by gender, profession, accommodation type, and information sources. Public health strategies should enhance health literacy, promote pre-travel consultations, and improve access to preventive services. Strengthening collaborations between health authorities, educational institutions, and the travel sector is key to mitigating health risks and ensuring global health security. Future interventions should address structural vaccination barriers and improve outreach to under-informed travelers.

Background/Objectives: Metainflammation is a chronic low-grade inflammatory state driven by excessive nutrition and obesity. It is associated with adipocyte dysfunction, altered adipokine secretion, and the development of insulin resistance, which contributes to dysglycemia and hyperglycemia. Recent initiatives emphasize earlier recognition of pathological processes to enable timely detection and primary prevention of adverse cardiovascular outcomes. Metainflammation has traditionally been assessed using serum C-reactive protein (CRP) levels and several proposed indices, with inconsistent performance due to chronic inflammation-related changes in blood cell counts. This study aimed to evaluate a newly proposed MetaLGI score as a laboratory-based tool for identifying pronounced metainflammation in patients with metabolic syndrome. Methods: Patients with metabolic syndrome were assessed for metainflammation using the newly proposed MetaLGI score and compared with previously suggested indices and CRP-based definitions. The ability of these approaches to identify pronounced metainflammation and associated hematological and metabolic alterations was evaluated. Results: The MetaLGI score demonstrated superiority in recognizing pronounced metainflammation in patients with metabolic syndrome compared to previous indices. Additionally, the proposed laboratory definition of metainflammation showed better performance in identifying patients with increased platelet counts, highlighting its relevance for inflammation-related cardiovascular thrombosis. MetaLGI also outperformed earlier proposals in identifying patients with increased β-cell burden. Conclusions: The newly proposed MetaLGI score represents a superior and widely available laboratory-based method for detecting pronounced metainflammation in patients with metabolic syndrome. Its improved ability to identify increased platelet counts and β-cell burden suggests potential value for early risk stratification and primary prevention of cardiometabolic complications.

Background: Near-infrared spectroscopy (NIRS)-based wearable devices offer non-invasive, continuous monitoring of muscle oxygenation, providing direct microvascular and metabolic information that complements indirect indices of intensity such as heart rate and accelerometry. Their clinical applicability in chronic non-communicable diseases (NCDs) remains under active development. Methods: A structured narrative review was conducted in PubMed, Scopus, Web of Science, and IEEE Xplore (January 2010-January 2026) using pre-specified search strings combining NIRS, muscle oxygenation, SmO2, StO2, wearable, exercise intensity, ventilatory/lactate threshold, and individual chronic disease terms. Eligible studies addressed technical validation of wearable NIRS, NIRS-derived exercise intensity estimation, clinical applications in NCDs, or rehabilitation implementation. Evidence was synthesized thematically; quality of validation studies was appraised against AMSTAR-2-informed, COSMIN-informed, or Cochrane RoB-2 criteria. Results: Wearable continuous-wave NIRS shows acceptable concurrent validity with frequency-domain laboratory systems (r = 0.79; range 0.69-0.88; ±8% SmO2 agreement in 95% of measurements) and good test-retest reliability for moderate-to-severe domains (ICC 0.72-0.91). NIRS-derived breakpoints align more reliably with the second ventilatory/lactate threshold (ICC = 0.80) than with the first (ICC = 0.53), constraining its use for prescribing lower-intensity domains. In chronic obstructive pulmonary disease, peripheral arterial disease, chronic respiratory failure and selected cardiovascular conditions, wearable NIRS detects disease-specific patterns of muscle deoxygenation and post-exercise reoxygenation that track responses to rehabilitation. Conclusions: Current evidence supports wearable NIRS as a complementary, intensity-aware monitoring tool-particularly for delineating the heavy/severe-intensity boundary and detecting peripheral metabolic limitations-rather than as a stand-alone replacement for ventilatory or lactate thresholds. Because much of the evidence derives from small, single-sex or athlete-only cohorts, these findings should be regarded as a promising basis requiring further validation in broader NCD populations. Implementation in NCDs requires standardized placement and calibration protocols, sex- and body composition-stratified reference values, motion-artifact mitigation, and adequately powered longitudinal trials in clinical populations.

Invasive meningococcal disease (IMD) remains a rare but severe condition associated with high mortality and a significant risk of long-term sequelae. Despite global vaccination efforts, the epidemiology of Neisseria meningitidis continues to evolve, with serogroup B (MenB) representing the predominant cause of IMD in many high-income countries. This consensus document reviews current evidence on MenB epidemiology and the role of the multicomponent meningococcal serogroup B vaccine (4CMenB), with a focus on immunogenicity, strain coverage, real-world effectiveness, and remaining challenges. Protein-based MenB vaccines have overcome the limitations of polysaccharide approaches, demonstrating robust immunogenicity across age groups. Real-world data confirm substantial vaccine effectiveness, particularly in infant immunization programs and outbreak settings, with significant reductions in disease incidence. For example, in England in the 3 years after vaccine introduction, MenB IMD incidence declined by 75% in immunized infants compared to unvaccinated controls. Adjusted vaccine efficacy was 52.7% after the two-dose primary series and 59.1% following the booster dose, highlighting the contribution of the booster. However, protection is influenced by antigenic variability among circulating strains, resulting in incomplete and geographically variable coverage. In addition, antibody waning over time and the limited impact on nasopharyngeal carriage reduce the potential for long-term and indirect protection. These factors highlight the need to optimize vaccination strategies, including the timing of booster doses, particularly in adolescents, and the role of vaccination in different epidemiological contexts. In this regard, it is not precisely defined whether infants who were immunized in the first year of life need a booster dose in the preschool period, especially in countries with a high incidence of MenB disease. Moreover, it is not established whether and when adolescents who were vaccinated both in infancy and during the preschool period need a booster dose. Economic considerations and variability in national immunization policies further contribute to heterogeneity in vaccine implementation. Emerging evidence suggests possible cross-protection against other meningococcal serogroups and Neisseria gonorrhoeae, although findings remain inconsistent across different risk groups and do not allow us to recommend 4CMenB vaccine beyond MenB IBD prevention. 4CMenB is an effective tool for preventing MenB IMD, although further studies are needed. Future strategies should prioritize age-targeted boosting and enhanced genomic surveillance to maximize impact.

Cardiovascular diseases (CVDs) remain the leading global cause of morbidity and mortality, imposing an increasing clinical and socioeconomic burden. Despite significant therapeutic advances, optimal control of risk factors and long-term outcomes remain challenging, particularly in patients with complex comorbidities. This narrative review provides a comprehensive and up-to-date synthesis of pharmacological options across major cardiovascular domains, with a specific focus on hypertension, heart failure, arrhythmias, and hypertrophic cardiomyopathy, conditions in which hemodynamic, neurohormonal, and electrophysiological pathways play central roles. We summarize mechanisms of action, clinical evidence, safety profiles, and guideline-based indications of established therapies, highlighting their relevance to vascular tone regulation, neurohormonal modulation, endothelial signaling, and myocardial function, the mechanistic axes that intersect with pathways implicated in pulmonary vascular disease (PVD). In addition, we discuss emerging therapeutic targets and innovative agents such as renin-angiotensin-aldosterone system silencers, endothelin pathway modulators, SGLT2 inhibitors, soluble guanylate cyclase stimulators, myosin inhibitors, and other mechanism-based approaches. Current challenges and unmet clinical needs are examined in the context of translational relevance for PVD and the broader goal of advancing individualized pharmacotherapy. Continued therapeutic innovation targeting shared vascular, metabolic, and neurohormonal pathways holds promise for improving outcomes across both systemic and pulmonary vascular diseases.

The floodplains of the Paraná and Paraguay rivers form the Chaco wetland, one of the most species-rich plant ecosystems in Argentina. Because wild grasses can serve as reservoirs of fungal species that cause disease and mycotoxin contamination of cereal crops, we examined asymptomatic, wild grasses from the Chaco wetlands for the presence of the genus Fusarium, which includes multiple species that cause agriculturally important diseases and/or mycotoxin contamination of crops. We focused our efforts on the identification and characterization of the multispecies lineage known as the Fusarium fujikuroi species complex (FFSC). Using morphological traits and partial DNA sequences of the TEF1 gene, we determined that 58 isolates recovered from the grasses were members of FFSC. Fifty of the isolates were identified as one of six FFSC species, including the economically important plant pathogenic species F. proliferatum, F. subglutinans, and F. verticillioides. To our knowledge, two of the species, F. anthophilum and F. pseudocircinatum, have not been reported previously in Argentina. Our analyses also indicated that eight of the FFSC isolates were a novel species, herein described as Fusarium varsavskyanum. A polymerase chain reaction (PCR) assay and genome sequence data indicate that each isolate of F. varsavskyanum isolate had only one mating type idiomorph (MAT1-1 or MAT1-2), which suggests that the fungus is heterothallic. Genome sequence analysis indicated that F. varsavskyanum has the genetic potential to produce, (i) the emerging mycotoxins fusaric acid and beauvericin (or enniatins); (ii) the pigments bikaverin, carotenoids, and fusarubin; and (iii) the plant hormones auxins, cytokinins, and gibberellins. Thus, asymptomatic grasses from the Chaco wetland can harbor Fusarium species that in some agroecosystems can cause economically important diseases and/or mycotoxin contamination of crops. It remains to be determined whether the genotypes of Fusarium species that occur on the wetland grasses, including F. varsavskyanum genotypes, can negatively impact agriculture.

Vaccination remains one of the most effective strategies for preventing infectious diseases. Yet, the success of modern vaccines increasingly depends on the rational design of adjuvants that enhance and shape immune responses. In this review, we examine current and emerging adjuvant strategies for viral vaccines across the human lifespan. Traditional adjuvants, particularly aluminum salts, have long served as the foundation of vaccine formulations. Still, their limitations have driven the exploration of novel platforms, including emulsions, nucleic acid-based adjuvants, and advanced particulate delivery platforms with intrinsic immunostimulatory properties. These newer approaches act through diverse mechanisms, such as activating innate immune pathways via pattern recognition receptors (PRRs) and stimulating antigen-presenting cells (APCs), thereby improving both humoral and cellular immunity. Recent advances in molecular biology, nanotechnology, and systems vaccinology have deepened mechanistic understanding and enabled more precise modulation of immune responses. However, significant challenges remain, including incomplete knowledge of adjuvant mechanisms, limited diversity among licensed adjuvants, safety concerns, and inconsistent efficacy across age groups. In particular, immune immaturity in infants and immunosenescence in older adults highlight the need for age-specific adjuvant strategies. The review identifies critical gaps in comparative studies, long-term safety data, and the development of adjuvants capable of inducing broad and durable immunity. Further, this article integrates licensed and emerging viral vaccine adjuvants through a lifespan framework. Addressing these limitations through interdisciplinary research and precision-based approaches will be essential for advancing next-generation vaccines and improving global preparedness for emerging infectious diseases.

Neurodegenerative disorders, including Parkinson's and Alzheimer's diseases, are hallmarked by the progressive degeneration of neuronal networks. Given the lack of disease-modifying cures, current therapies are limited to symptomatic relief. Here, we investigated the neurotrophic potential of the skin secretion (SS) from Rhinella schneideri, its polar fraction (PF) and nonpolar (NPF) fraction, and respective subfractions on the morphology of neuron-like cells. Following initial H2O-CH2CL2 partitioning, PF and NPF subfractions were isolated via RP-HPLC. Chemical characterization using LC-MS-IT-TOF identified eight distinct molecules, notably bufotenine and marinobufagin. Cytotoxicity screening established safe working concentrations (100-250 ng/mL for SS/PF; 250-500 ng/mL for NPF and subfractions) for downstream morphological evaluations using High Content Screening (HCS). The subfraction polar 5 (SfP5) elicited a robust neurotrophic response, significantly enhancing all assessed morphometric parameters: total neurite outgrowth (+72%), branching points (+120%), maximum process length (+60%), and total number of processes (+35%). Our data show that Rhinella schneideri SS contains molecules that improve in vitro neuronal networks, serving as a promising source for preliminary screening of neuroprotective effects.

Hemolytic Uremic Syndrome (HUS) is a severe clinical manifestation primarily triggered by Shiga toxin-producing Escherichia coli (STEC). While Shiga toxins (Stx) are central to the development of systemic endothelial damage, current recombinant antibody developments have overwhelmingly focused on neutralizing the Stx2 subtype. However, numerous STEC isolates produce Stx1 either independently or alongside Stx2, revealing a critical need to diversify the antibody repertoire for comprehensive antitoxin therapies. To address this, we characterized two novel, fully human recombinant Fabs targeting Stx1 (FabB6:Stx1 and FabC8:Stx1) selected from a synthetic library via phage display. We evaluated their binding specificity and neutralizing activity in Vero and human proximal tubular epithelial (HK-2) cells, as well as in primary human glomerular endothelial cells (HGEC exposed to HUS-derived STEC supernatants. Both Fabs exhibited high specificity and nanomolar affinity for Stx1. Notably, they displayed cell-type-dependent neutralization profiles, with FabC8:Stx1 demonstrating superior and more consistent neutralization in HK-2 cells. Crucially, when evaluated alongside previously characterized anti-Stx2 antibodies (FabC11:Stx1/Stx2 and FabF8:Stx2), the Stx1-specific Fabs conferred complementary protection against clinical STEC isolates. These findings support the inclusion of Stx1-targeting recombinant antibodies into broader multi-toxin neutralization strategies, thereby expanding the therapeutic potential against STEC-associated diseases.

Uveitis is a heterogeneous group of intraocular inflammatory diseases and an important cause of visual impairment worldwide. Although current treatments mainly target inflammation, many patients develop chronic or recurrent disease, suggesting that inflammation control alone may not fully restore intraocular homeostasis. Increasing evidence highlights the blood-ocular barrier (BOB), including the blood-retinal barrier and blood-aqueous barrier, as a key regulator of the intraocular microenvironment. This review aims to summarize the bidirectional interaction between intraocular inflammation and blood-ocular barrier dysfunction in uveitis, and to highlight the clinical significance of barrier dysfunction in disease monitoring and management. In addition, this review discusses the potential value of incorporating barrier assessment into dynamic disease evaluation and relapse-aware management strategies. Recent studies suggest that inflammation and BOB dysfunction are bidirectionally linked. Inflammatory mediators disrupt barrier integrity, while barrier breakdown facilitates immune cell infiltration and further amplifies inflammation, forming a self-reinforcing cycle that may drive disease persistence. Importantly, BOB dysfunction also has clinical implications. Findings such as aqueous flare, macular edema on optical coherence tomography, and vascular leakage on fluorescein angiography reflect barrier status and can serve as dynamic indicators for disease monitoring. Persistent abnormalities despite reduced inflammatory cell activity may indicate incomplete barrier recovery or subclinical inflammation, helping to explain discordant clinical findings and the relapse-prone nature of uveitis. Rather than viewing BOB dysfunction solely as a pathological consequence of inflammation, this review highlights the potential clinical value in disease assessment and management. Barrier-related findings may provide additional information beyond conventional inflammatory evaluation, particularly in cases where inflammatory cell activity appears controlled, but underlying barrier alteration persists. Incorporating barrier assessment into monitoring may help interpret discordant clinical findings, improve evaluation of disease control, and support a more relapse-aware management strategy in uveitis. In addition, therapeutic approaches aimed at restoring barrier integrity may provide a more comprehensive strategy for achieving sustained remission and reducing recurrence risk.

Trichoderma longibrachiatum is a filamentous fungus that functions as a biocontrol agent against multiple plant diseases. However, the lack of a genetic transformation system has hindered studies on gene function and the underlying biocontrol mechanisms in this species. In this study, protoplast preparation conditions were optimized using single-factor experiments and response surface methodology, yielding 2.05 × 107 protoplasts/g. PEG-mediated transformation yielded a GFP-labeled strain (GFP-40418). This strain enhanced resistance against Meloidogyne incognita, with root galling decreased by 47.6%. Treatment with GFP-40418 enhanced the activities of antioxidant enzymes, including PAL, POX, SOD, PPO, APX, and CAT. Plants treated with GFP-40418 alone showed the highest expression value, with relative transcriptional levels of PR2, Pal1, LOX, MYC2, ETR1, and ACO1 that were 29.62, 5.76, 7.30, 3.64, 4.79, 9.99-fold higher in comparison with control plants, respectively. These findings provide a genetic platform for exploring the gene functions of T. longibrachiatum 40418 and validate its biocontrol prospect against root-knot nematodes.

Background: mRNA vaccines, first approved in December 2020, have been used globally to prevent infectious diseases, and those for treating cancers are being developed. Safety-related labelling changes of Comirnaty and Spikevax were made in June 2025; however, concerns remain. This study assessed the potential risks associated with mRNA vaccines on the indications previously approved, utilizing Real-World Data (RWD) of Adverse Events Following Immunization (AEFIs) derived from the Vaccine Adverse Event Reporting System (VAERS) and Academic Literature Databases (ALD). Methods: A Disproportionality Analysis (DPA) was performed using the Reporting Odds Ratio (ROR) and the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm on spontaneous case reports from VAERS. Statistical positive signals were cross-validated with literature case reports from ALD to provide more comprehensive medical descriptions and clearer causal assessments, and compared with safety information documented in clinical trials and on vaccine labelling. Time-to-onset, stratified, and immunization schedule analyses were conducted to characterize the safety profiles of mRNA vaccines. Results: In total, 5,040,725 spontaneous case reports and 4,387 literature case reports were analyzed. In both VAERS and ALD, new signals involving blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) and ear and labyrinth disorders (e.g., deafness) were detected from Comirnaty as Designated Medical Events (DMEs), while blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) from Spikevax in ALD only. No new signals were detected from other vaccines on the DMEs list. In VAERS, Serious Adverse Events (SAEs) were more common in females, while death risk was higher in males. In ALD, SAEs were more common in males for most mRNA vaccines, except Comirnaty. Medical history emerged as a key risk factor for SAEs, particularly among older adults. Conclusions: Statistically significant safety signals were detected across all mRNA vaccines based on five-year cumulative RWD, indicating the need of intensified monitoring of specific populations, including older adults and individuals with medical histories, alongside further optimization of vaccination strategies.

Background: Persistent high-risk human papillomavirus (hrHPV) infection causes over 99% of cervical precancers and cancers worldwide, with HPV genotype 16 (HPV16) responsible for 50% of the cases. Latvia ranks among the top EU countries for cervical cancer incidence and mortality. In the general Latvian population, 4.2% of women are hrHPV-infected, mostly with HPV16. However, information on the circulating HPV16 isolates is missing. Objectives: To study the genomic variability of the Latvian HPV16 isolates, compare them with HPV16 in Europe and across the globe, reveal features associated with the severity of cervical disease and uncover eventual sequence changes due to the national HPV vaccination. Methods: DNA was extracted from the formalin-fixed paraffin-embedded cervical tissues of women diagnosed with cervical intraepithelial neoplasia (CIN) stages I-III and squamous cell carcinoma (SCC) grades 1-3, collected between 2012 and 2024. Samples positive for HPV16 were subjected to whole genome sequencing (WGS) on the Illumina platform (n = 16) or Sanger sequencing of the E6/E7 coding region (n = 31). A consensus HPV16 sequence was generated, and single nucleotide polymorphisms (SNPs) and eventual amino acid substitutions (AAS) were analysed. Results: Complete genomes of 16 HPV16 variants were reconstructed, with 13 related to the European sublineage A1 and 3 to the sublineage A2 references. Sequences showed high conservation; still 93 non-redundant variants were identified. The highest variability was observed for the capsid protein L2, and the lowest, for oncoprotein E7. The prevalence of SNPs and AAS in the Latvian HPV16 variants, specifically in capsid protein L1, did not increase with time, showing no effect of HPV vaccination. Associations between HPV16 sequence features and severity of cervical disease were limited to AAS E6:L90V, which was significantly more common in SCC grade 2/3 than in CINII/III cases (p = 0.015). Conclusions: Highly conserved HPV16 genomes circulating in Latvia harbour a series of unique as well as common nonsynonymous SNPs with respective AAS, with one, AAS E6:L90V, associating with disease severity. No HPV vaccine escape variants were detected. Deciphering complete genomes of HPV16 from CIN and SCC cases in Latvia informs public authorities performing HPV vaccination and is useful for the management of HPV-associated cervical diseases.

Background: The 2025 EPI Managers' Meeting for West African countries in Guinea was a critical platform for EPI managers to make an in-depth analysis of immunization programmes. We present a structured analysis of immunization status in West Africa using a WHO Health System model to move beyond descriptive reporting toward systemic analysis for actionable solutions. Methods: The meeting convened EPI managers from 14 of the 17 West African countries and partners supporting the immunization program. Country and regional presentations, immunization and surveillance data and meeting discussions were analysed through a framework identifying (1) core problems, (2) systemic barriers using WHO health systems building blocks and (3) actionable recommendations or call for action. Results: Analysis revealed stagnating immunization coverage. Recovery from COVID-19 pandemic disruptions remained limited, with persistent outbreaks of vaccine-preventable diseases (VPD). Among the five Immunization Agenda 2030 objectives assessed, only Maternal and Neonatal Tetanus (MNT) elimination was on track. Four critical challenges emerged: (1) Routine immunization stagnation with DTP3 median coverage of 76%. This was associated with challenges related to poor data quality, weak implementation of innovative vaccination strategies and donor dependency, as 88.2% of countries financed less than 50% of routine vaccine costs domestically. (2) Sub-optimal progress in Big Catch-Up (BCU) implementation in some countries, revealing poor health system resilience. (3) Inability to sustain high coverage for new vaccine introductions despite significant progress, highlighting demand and service delivery gaps. (4) Persistent VPD outbreaks with geographical expansion and the resurgence of diphtheria epidemics since 2023. Conclusions: Persistent immunization challenges in West Africa appear to reflect interconnected systemic challenges, suggesting the need for a fundamental shift toward subnational strategies, integration of immunization services within primary health care (PHC) and improved data quality. Sustainable financing of the national EPI and acceleration of local vaccine manufacturing is essential to achieve immunization sovereignty in West Africa. Country Call for Action provides strategic guidance to reverse the trend toward the Immunization Agenda 2030 targets.

The dimorphic fungus Talaromyces marneffei causes talaromycosis, a life-threatening fungal disease with limited treatment options. Olorofim, a first-in-class orotomide antifungal that targets pyrimidine synthesis essential for fungal growth, has low minimum inhibitory concentration (MIC) against T. marneffei and clinical efficacy against other invasive fungal diseases. Here, we tested the hypothesis that olorofim synergistically enhances amphotericin B (AmB), a potent membrane-targeting antifungal, against T. marneffei in 55 clinical isolates using a validated colorimetric checkerboard assay. The MIC was defined as the lowest drug concentration inhibiting &#x2265; 95% of fungal growth. Drug interactions were assessed using the fractional inhibitory concentration index (FICI), which defines &#x2264;0.5 as synergy, 0.5 < FICI &#x2264; 4.0 as indifference, and FICI > 4 as antagonism. We found that interactions between AmB and olorofim were indifferent across all 55 isolates (0.5 < FICI &#x2264; 1.03). Time-kill assays showed an expected concentration-dependent fungicidal activity for AmB, but a concentration-independent fungistatic activity for olorofim against T. marneffei. Combinations of AmB and olorofim were also indifferent in time-kill experiments. Although synergy was not observed, and olorofim is unlikely to enhance AmB induction therapy, olorofim may have a role in the consolidation and maintenance therapy of talaromycosis.

Drug repurposing is often promoted as a faster, lower-risk alternative to de novo discovery, yet substantial barriers continue to limit successful implementation. We performed a scoping review of articles included in PubMed and ScienceDirect with the aim to identify and categorize challenges and analyze the intersections between them. Our review included 73 articles which revealed scientific, clinical, regulatory, economic, and implementation barriers, with the principal being the clinical translation of generated candidates. Scientific challenges include the necessity for new Phase II/III trials to validate efficacy, safety, and optimal dosing in new therapeutic contexts. Across disease areas, domain-specific barriers include subgroup-dependent responses in oncology, resistance and penetration challenges in anti-infectives, and data scarcity in rare diseases. Computational and AI-assisted approaches face fragmented data, model robustness, and insufficient validation. In addition, off-patent drugs face evidence requirements as rigorous as those for de novo entities, yet lack the market exclusivity incentives required to attract private investment. Additionally, an "institutional bottleneck" hinders academic researchers from bringing findings "on-label" due to a lack of regulatory infrastructure and collaborative frameworks. We conclude that drug repurposing requires a distinct translational paradigm involving multi-stakeholder collaboration and early regulatory engagement to bridge the gap between laboratory discovery and patient access.

This study aims to assess the acceptance of vaccinations among pregnant women, particularly against influenza, pertussis, COVID-19, and RSV, and to identify factors influencing their willingness to get vaccinated. It also seeks to evaluate the impact of the COVID-19 pandemic on maternal attitudes and behaviors regarding vaccination. The analysis involved a review of existing literature and studies to evaluate the level of vaccine acceptance among pregnant women before and after the COVID-19 pandemic. Factors contributing to vaccine hesitancy, including misinformation, lack of knowledge, and the influence of healthcare professionals, were examined. The findings indicated that, despite scientific evidence supporting the safety and efficacy of vaccines during pregnancy, public concerns remain about their impact on the developing fetus. The outbreak of the COVID-19 pandemic has increased awareness of the risk of infectious diseases, but at the same time, its impact on vaccination rates among pregnant women is ambiguous and geographically diverse. Misinformation and decreased access to healthcare during the pandemic negatively affected vaccine uptake. Trustworthy information provided by healthcare professionals emerged as a key factor in promoting vaccine acceptance. To improve vaccination rates among pregnant women, it is essential to provide clear, evidence-based information through healthcare professionals, particularly those directly caring for pregnant women. Educational campaigns should address concerns calmly and without judgment, emphasizing the safety and benefits of vaccinations. Enhanced access to healthcare and vaccinations, along with strategic information dissemination, can significantly improve vaccine acceptance during pregnancy. Lessons learned from past pandemics should be incorporated into the development of healthcare strategies aimed at implementing recommended vaccinations for pregnant women in the future.

Chronic respiratory diseases (CRDs) represent a significant global mortality burden, largely driven by viral-triggered exacerbations. In the elderly, susceptibility to viral pathogens is critically linked to the "interferon gap"-a kinetic delay in innate antiviral signaling resulting from immunosenescence and Th2-skewed inflammaging. While traditional vaccines provide pathogen-specific protection, their efficacy is often compromised by age-related immune hyporesponsiveness and antigenic drift. This perspective paper proposes a dual-phase, virus-agnostic immunomodulatory platform designed to restore mucosal immune competence and provide a rapid-response intervention for incipient exacerbations. Rather than acting as a pathogen-specific vaccine, the platform serves as a comprehensive host immune-rejuvenation engine and cellular adjuvant platform. The platform consists of two integrated stages: Allopriming and Alloantigen Inhalation Recall (AIR). Allopriming utilizes AlloStim&#xae; (activated, allogeneic Th1 cells) to leverage the evolutionarily conserved allo-rejection response, establishing a lung mucosal reservoir of allo-specific Th1 tissue-resident memory cells (Trm). Building on previously published Phase I/II data showing that Allopriming reverses biomarkers of immunosenescence and sustains durable heterologous antiviral responsiveness, the AIR strategy is introduced as a patient-administered rescue mechanism for frail CRD patients. AIR is designed to activate pre-positioned Trm cells at the earliest onset of symptoms, inducing a high-magnitude IFN-&#x3b3; surge in the lung mucosa. By bridging the senescent "interferon gap" with the rapid effector kinetics of Trm activation, this approach represents a novel paradigm toward reconstituting youthful-like antiviral mucosal immunity to both enhance vaccine efficacy in the elderly and protect against both seasonal pathogens and emerging viral triggers ("Disease X") of CRD. Future randomized studies in long-term care settings are planned to evaluate clinical outcomes in high-risk populations.

Skin injuries are common and can result from surgeries, burns, pressure sores, cuts, and diseases. Proper wound healing is crucial for maintaining homeostasis; wounds can be classified as acute or chronic. Acute wounds heal in four sequential phases: hemostasis, inflammation, proliferation, and remodeling. Chronic wounds arise when this process fails, often due to prolonged inflammation. Existing treatments for chronic wounds are limited, and antibiotic resistance complicates infection control, highlighting the urgent need for new therapies. Biomaterials, particularly gelatin, have gained attention for their biomimetic properties, biocompatibility, and ability to promote healing. Gelatin's ECM-like structure supports tissue metabolism, and it can be enriched with bioactive compounds to enhance tissue regeneration, collagen deposition, angiogenesis, and antimicrobial activity. This study evaluates the effectiveness of a 3D gelatin-based patch in vivo, using Hirudo verbana as a model. The patch, functionalized with chitosan and bioactive apatite nanoparticles, was implanted in injured leeches, with tissue samples collected at 72 h, 1 week, and 2 weeks. Scaffold integration, cell colonization, and healing effects were assessed through morphological, immunohistochemical, and ultrastructural analyses. The findings confirm H. verbana as a robust in vivo model for regenerative medicine and demonstrate the promising potential of gelatin-based patches.