Search Results (1,545)

Age-related decline in immune system function is characterized by reduced numbers of naïve lymphocytes, the accumulation of senescent cells, impaired function of all immune cell types, and chronic low-grade inflammation (inflammaging). These alterations contribute to increased susceptibility to infections and malignancies, as well as to autoimmunity and other age-associated diseases. This article reviews current evidence on lifestyle interventions that may mitigate immune aging. Lifestyle-related strategies, including regular physical activity, nutritional interventions (e.g., different diets, caloric restriction, and other fasting-related approaches), stress reduction, and vaccination, are discussed as key modulators of immune function and systemic inflammation. Notably, vitamin D supplementation has been shown to reduce the incidence of autoimmune diseases by 22%. In comparison, caloric restriction has led to a decrease in CRP and TNF-α by 40% and 50%, respectively. Emerging complementary approaches, such as mind–body practices and controlled cold exposure, show promise, though current evidence remains limited and inconsistent. Therefore, integrated lifestyle strategies may slow aging-related immune decline and support healthy aging. However, longitudinal trials are required to define the optimal intervention parameters, population-specific thresholds, and the long-term durability of immune rejuvenation. Full article

Candida auris is a multidrug-resistant fungal pathogen associated with high mortality in healthcare settings. Although colonization is recognized as the harbinger of invasive infection, predicting which patients will develop bloodstream infection (BSI) and when this transition will occur remains a clinical challenge. In this study, patients aged ≥18 years with C. auris colonization identified at İzmir City Hospital between January 2023 and June 2025 were retrospectively analyzed. Colonization was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Of 71 colonized patients (median age 65 years; 69.0% male; 93.0% intensive care unit (ICU)-admitted), 31 (43.7%) developed bloodstream infection (BSI). In-hospital mortality was 62.0%, rising to 74.2% in the BSI group, though this difference did not reach statistical significance (p = 0.105). Competing risks analysis using the Aalen–Johansen method showed a cumulative BSI incidence of 38.2% (95% confidence interval (CI): 28–50%) by day 10 and 43.0% (95% CI: 32–54%) by day 30 following colonization detection. On multivariate logistic regression, diabetes mellitus was the sole variable independently associated with a lower risk of BSI development (adjusted odds ratio (OR): 0.19; 95% CI: 0.06–0.68; p = 0.010); this finding was directionally consistent but did not reach statistical significance in the multivariable Fine–Gray competing risks model (subdistribution hazard ratio (SHR): 0.334; 95% CI: 0.108–1.040; p = 0.057). All 40 tested isolates had high fluconazole minimum inhibitory concentration (MIC) values; micafungin susceptibility was 92.5%, while anidulafungin resistance was observed in 32.5% of isolates. Our findings demonstrate that nearly half of colonized patients developed BSI, with no identifiable safe window for intervention, underscoring the necessity of sustained infection control measures and susceptibility-guided antifungal therapy. Full article

Dental diseases have long been taught and treated as separate entities: cariology, operative dentistry, endodontics, and periodontology, each working within its own boundaries. However, increasing biological and clinical evidence suggests that this classified view does not fully reflect how disease progresses in the mouth. Instead, dental disease should be understood as a continuum within the interconnected tooth–pulp–periodontium complex. This review provides current evidence showing how dental caries can serve as the starting point of a process that can progress through pulpitis and apical periodontitis and eventually affect surrounding periodontal tissues. Caries is now widely known as a biofilm-driven and host-influenced condition shaped by ecological imbalance rather than specific pathogens alone. As lesions penetrate deeper into dentin, the structure becomes more permeable, permitting diffusion of microbial metabolites and signaling molecules toward the pulp. This initiates a multifaceted inflammatory reaction within the pulp tissue. At this stage, pulpitis becomes a critical turning point, where the outcome depends on microbial load, lesion activity, host response, and quality of clinical intervention. If the disease is not well controlled, it may lead to pulp necrosis, allowing infection to spread beyond the root canal and initiate periapical inflammation. Through anatomical pathways such as apical foramina and lateral canals, these processes can extend further, sometimes resembling or overlapping with periodontal disease. This overlap creates diagnostic challenges, as conventional tests may not always distinguish between conditions. A structured, pathway-based diagnostic approach is therefore essential. From a treatment perspective, this continuum model highlights early intervention, minimally invasive care, preservation of pulp vitality when possible, and maintenance of a strong coronal seal. Ultimately, stronger integration across dental disciplines can improve diagnosis, guide treatment decisions, support long-term tooth preservation, and promote unified dental education. This article presents a narrative review supported by a structured literature search and proposes a clinically actionable framework that extends established endodontic–periodontal concepts upstream to include caries initiation and restorative modulation. Full article

Phytopathogenic fungi pose a constant threat to worldwide agricultural production. Given the widespread development of fungicide resistance and increasing environmental and regulatory constraints, precision disease-control strategies are urgently needed to enhance selectivity, durability, and sustainability. This review critically examines recent advances in targeted fungicide discovery against phytopathogenic fungi. We categorize these strategies into three complementary groups: (1) targeting fungal biological processes that are essential or infection-associated; (2) disarming pathogen virulence by interfering with immune evasion and effector-mediated interactions; and (3) activating or redirecting host defence through host-directed or dual-action interventions. We compare these strategies with respect to mechanistic rationale, expected selectivity, resistance risk, and field-deployment challenges. Additionally, we discuss emerging enabling technologies—including compound repurposing, structural biology, and artificial intelligence-assisted fungicide design—that accelerate target identification and lead optimization. These strategies have begun to facilitate the discovery of compounds with improved specificity and disease-control potential. We believe that the integrated application of these approaches may support the development of more selective and potentially durable disease-control agents. Full article

Refractory thoracic infections require targeted antimicrobial combinations, repeated drainage interventions and often staged surgical procedures of varying complexity grades. In necrotizing pneumonia cases, successful treatment is complete removal of destroyed non-functional parenchyma, pleural cavity debridement, and complete pathogen eradication based on culture-based sensitivity-driven antimicrobials. The latter proves challenging in pan-resistant microbial strains where both medical and surgical treatments demonstrate limited effectiveness. We describe a case of persistent thoracic sepsis due to pan-resistant Pseudomonas receiving sequentially thoracoscopic decortication, thoracotomy for lobectomy, and open thoracostomy as the last treatment option to prevent fatal sepsis in view of non-available antibiotics. The immediate source-control effect raised the question of the ideal timing for selecting an aggressive thoracoplastic procedure despite its deforming nature over any other treatment approach. Full article

Residential buildings must now be designed and retrofitted as adaptive climate–health–work systems rather than as static housing units. This structured literature review synthesises peer-reviewed journal and conference evidence on residential taxonomy, ventilation, indoor environmental quality, overheating, airborne infection resilience, post-pandemic occupancy changes and future performance benchmarks. The review shows that single-family and multifamily buildings remain the most practical first-order categories because they differ in envelope exposure, ventilation pathways, system ownership, governance, retrofit feasibility and occupant control. Single-family dwellings generally provide greater household autonomy, roof-based renewable potential and room-level intervention flexibility, but can also carry higher envelope losses, lower density and stronger dependence on occupant operation. Multifamily buildings benefit from compactness and shared infrastructure, yet face additional risks from common services, vertical shafts, stack effects, corridor pressurisation, inter-zonal airflow and collective maintenance. Ventilation evidence indicates that natural, exhaust-only, supply, balanced heat-recovery, hybrid, demand-controlled and filtration-based strategies cannot be ranked universally; their effectiveness depends on climate, airtightness, pollutant source, occupancy, maintenance and governance. This review further shows that overheating, cooling-demand growth, airborne infection preparedness and remote work are shifting residential performance from winter-centric energy efficiency toward year-round thermal resilience, clean-air delivery and prolonged-occupancy functionality. A future taxonomy is therefore proposed around adaptive performance attributes, including thermal resilience, clean-air capacity, ventilation controllability, energy flexibility, remote-work readiness, vulnerability and retrofit potential. The core contribution is a hypothesis-generating, decision-support and benchmark-development framework for aligning residential design, retrofit and policy with health, indoor environmental quality, energy efficiency and carbon performance. Full article

Nosocomial pathogens persist on hospital surfaces contributing to healthcare-associated infections (HAIs), especially among vulnerable patients and in the presence of multidrug-resistant strains. Environmental surveillance is essential to prevent cross-contamination and support timely infection control interventions. However, conventional culture-based methods, although considered the gold standard, are labor-intensive and time-consuming, often delaying critical responses. This study evaluated loop-mediated isothermal amplification (LAMP) as a rapid screening tool for hospital environmental monitoring. A total of 100 surface samples were collected from different hospital wards and analyzed using both culture and LAMP assays targeting six major HAI-related pathogens: Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. LAMP showed excellent performance, with sensitivity of 1.00 for all targets and specificity ranging from 0.94 to 1.00. No statistically significant differences were observed between LAMP and culture results (p > 0.05). LAMP may represent a valuable complementary method for routine environmental surveillance. Full article

Background: The biological response of the periodontal ligament (PDL) following endodontic treatment remains insufficiently investigated. This systematic review aimed to evaluate the influence of endodontic treatment modalities on PDL-related healing outcomes and periapical tissue repair. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and the Cochrane Library were searched for randomized clinical trials published between 2015 and 2025. Studies evaluating the effects of endodontic interventions on clinical, radiographic, or biological outcomes associated with PDL healing. Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Ten randomized clinical trials involving approximately 710 participants were included. Endodontic treatment was generally associated with favorable healing outcomes, reflected by reductions in periapical lesion size, improvement of radiographic parameters, and resolution of clinical symptoms. Single-visit and multiple-visit treatments demonstrated comparable long-term healing outcomes, although single-visit protocols were associated with increased short-term postoperative discomfort. Activated irrigation techniques appeared to enhance healing compared with conventional irrigation methods. Most studies were judged as having some concerns regarding risk of bias. Conclusions: Current evidence suggests that endodontic treatment can promote favorable healing of the periodontal ligament–periapical complex through effective infection control and resolution of inflammation. However, the certainty of evidence remains moderate because of methodological heterogeneity and the limited availability of studies directly assessing biological PDL outcomes. Further well-designed randomized clinical trials with standardized outcome measures and longer follow-up periods are required. Full article

Small intestinal bacterial overgrowth (SIBO) refers to an abnormal increase in the number of bacteria in the small intestine and is observed in various diseases. SIBO can also develop after long-term use of proton pump inhibitors (drug-induced SIBO), bariatric surgery, gastrectomy, and other surgeries (postoperative SIBO). The aim of this narrative review is to summarize all of the published information on the treatment of SIBO in as much detail as possible and present it separately for each specific disease and intervention associated with SIBO. The most extensively studied drug for the treatment of SIBO is rifaximin. It eliminates SIBO in 63% of cases; however, most studies lack a control group. Small RCTs assessing the effects of this antibiotic on SIBO have reported conflicting results, and a meta-analysis showed no effect. A large RCT is required to verify the results of uncontrolled studies. Neomycin and norfloxacin showed efficacy in the treatment of SIBO in single RCTs, with elimination rates of 20 and 100%, respectively. Ciprofloxacin, rifamycin, metronidazole, and other antibiotics, as well as ursodeoxycholic acid, showed positive effects for the treatment of SIBO, but only in uncontrolled studies or in comparison with rifaximin or other drugs. The reported elimination rates were 54%, 67%, 79%, and 75%, respectively. Eradication therapy for Helicobacter pylori infection eliminated SIBO at a rate of approximately 70%. Probiotics have been tested for treatment of SIBO in various diseases. VSL#3 and Saccharomyces boulardii CNCM I-745 were effective in RCTs, with elimination rates of 58% and 80%, respectively. In conclusion, when selecting SIBO treatment regimens, those that have demonstrated the greatest efficacy for a specific concomitant disease should be preferred, despite the generally low level of evidence supporting these approaches in most cases. Full article

Background: Early management of adult burn injuries in resource-constrained environments—such as battlefields and primary care facilities—remains hindered by the absence of standardized, evidence-based protocols. This study aimed to systematically synthesize existing evidence and develop an integrated framework of actionable recommendations to optimize prehospital and early emergency care. Methods: A comprehensive evidence synthesis was conducted across 14 international and domestic bibliographic databases and authoritative repositories. Eligible sources included clinical practice guidelines, expert consensus statements, evidence summaries, and systematic reviews. Literature quality was appraised using validated instruments, and best-practice recommendations were extracted and thematically synthesized across the continuum of early burn care. Results: Fifty-nine high-quality studies yielded 77 recommendations across 13 domains, spanning from scene safety and burn process cessation through airway, breathing, and circulatory management to wound care, infection control, and transfer preparation. An integrated, context-adaptive framework was established to guide resource-calibrated interventions rather than rigid protocol adherence. Conclusions: These findings provide tiered guidance for frontline healthcare providers and inform the development of emergency care standards in resource-limited settings. Future research should prioritize field validation and contextual implementation to address barriers to evidence translation and enhance real-world applicability. Full article

Carbapenem-resistant Acinetobacter baumannii (CRAB) is considered a persistent clinical problem characterized by high mortality and restricted therapeutic options. The current antimicrobial regimen focuses on active bacteria without taking into account physiological states that influence the treatment response. Biofilm formation, metabolic changes, efflux activity, and membrane remodeling reduce antibiotic activity at infection sites and help bacteria survive despite in vitro susceptibility. Clinical performance is also compromised by inadequate tissue penetration, toxicity, and inconsistent pharmacokinetics, which reduce the ability to maintain effective antimicrobial activity at the target site. Therefore, a new strategy is needed that considers how bacteria behave during infection. Nanotherapeutic systems can optimize antimicrobial delivery by changing drug distribution and enabling sustained antimicrobial release within infected tissues. These properties can improve antimicrobial distribution within biofilms and structurally restricted infection sites. This review proposes a phenotype-guided approach linking dominant bacterial phenotypes with targeted nanotherapeutic intervention. Advances in nanoscale diagnostics and computational analysis allow earlier identification and more precise characterization of resistance features, so treatment decisions reflect the current state of infection. When integrated with nanotechnology, this information supports treatment approaches that adapt to changes in bacterial behavior over time. Extending this concept to host-directed and microbiome-informed interventions provides additional control by addressing factors that sustain infection beyond the pathogen. These elements create an integrated system that connects detection, analysis, and treatment, allowing therapy to match the biological conditions of infection for more precise CRAB management. Full article

East Coast Fever (ECF) causes approximately one million livestock deaths annually in sub-Saharan Africa, posing a significant threat to livestock. The wildlife–livestock interface complicates disease management, as wildlife serve as reservoirs. This study developed a Continuous Time Markov Chain (CTMC) model incorporating the wildlife–livestock interface to analyze ECF dynamics. Using the Galton–Watson approximation, we assessed the probability of disease extinction following the introduction of infected hosts or vectors. The probability of disease extinction calculated from the branching process is shown to be in good agreement with the probability approximated from numerical simulations. The disease dynamics of the deterministic model and the CTMC model are compared to ascertain the effect of demographic stochasticity on ECF dynamics. Differences in model predictions and asymptotic dynamics between stochastic and deterministic models were evident. The deterministic and stochastic formulations should therefore be viewed as complementary modeling frameworks, with the deterministic model characterizing average epidemic dynamics and the CTMC model capturing the probabilistic variability and extinction behavior inherent in real transmission processes. These differences are crucial for intervention strategies earmarked to prevent outbreaks. Our analysis revealed a high probability of ECF extinction if the disease emerges from recovered carrier cattle. Finite time to ECF disease extinction is estimated using 10,000 sample paths, and it is shown that the epidemic duration is shortest if the disease is introduced by infectious cattle. The epidemic duration is longest when the disease is introduced by infectious ticks. Additionally, we observed that host interactions at the wildlife–livestock interface play a critical role in shaping ECF transmission and informing control strategies. Full article

Background/Objectives: Hospital-Acquired Infections (HAI) represent one of the most frequent adverse events during care delivery, with the pediatric population (0–18 years) presenting unique vulnerabilities due to their developing immune systems, dependence on caregivers, and need for invasive devices. Despite the availability of general guidelines, existing high-level evidence is largely extrapolated from adult studies, and pediatric settings differ significantly in patient physiology and equipment size. This scoping review aims to map the key concepts, types of evidence, and research gaps related to strategies preventing HAI in pediatric patients. Methods: This scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The Population, Concept, and Context (PCC) framework will be utilized. We will include any strategy, intervention, or protocol aimed at preventing HAI. A comprehensive search will be conducted across ten major electronic databases and grey literature sources. Two independent reviewers will screen titles, abstracts, and full texts, followed by data extraction using a standardized tool to categorize the interventions and key findings. Results: The findings will synthesize diverse practices into a usable format for clinical decision-makers and identify gaps where primary pediatric research is lacking. This consolidated data aims to guide resource allocation and assist hospital infection control committees in updating pediatric safety protocols. Conclusions: This scoping review will establish a comprehensive baseline of pediatric-specific HAI prevention strategies. The findings will inform evidence-based practice, identify critical research gaps, and guide future investigations in the prevention of pediatric infections in healthcare settings. Full article

Although antiviral development against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been dominated by replication-directed strategies, structural and accessory proteins offer a complementary and increasingly important opportunity for small-molecule intervention. These proteins control key processes outside the core replication machinery, including viral entry, membrane remodelling, virion assembly, egress, and host immune modulation, thereby expanding the mechanistic scope of antiviral design. However, many of these targets are membrane-associated, oligomeric, conformationally dynamic, or function through protein–protein interactions, creating distinct challenges in target validation, assay design, and chemical optimisation. In this review, we comprehensively and critically evaluate the structural and accessory proteomes of SARS-CoV-2, with a strict focus on small-molecule tractability and translational relevance. We highlight the most credible direct-acting opportunities, focusing on the membrane (M), envelope (E), and nucleocapsid (N) structural proteins, together with the accessory protein open reading frame 3a (ORF3a), for which emerging chemical matter strengthens confidence in druggability. In contrast, Spike (S) and several host-interface accessory proteins, including ORF6, ORF8, ORF9b, and ORF10, are best viewed as more selective or earlier-stage opportunities that require stronger on-target chemical validation. Emphasis is placed on structural accessibility, mechanism-based assay systems, evidence quality, cellular and in vivo activity, and developability constraints relevant to exposure at the infection site. Rather than replacing replication-directed antivirals, these non-canonical targets are best considered adjunctive or complementary components of future combination strategies designed to broaden antiviral coverage, enhance robustness, and improve pandemic preparedness. Full article

Background/Objectives: Maintaining oral hygiene in infants in neonatal and pediatric intensive care is essential for preventing ventilator-associated pneumonia (VAP). Chlorhexidine (CHX) is widely used in adults but its safety and efficacy in infants remain uncertain, and it is not recommended for children under 6 years due to rinsing difficulties and mucosal irritation risk. Expressed breast milk (EBM), rich in immunological and antimicrobial components, has been explored as a biologically appropriate alternative. This review synthesizes evidence on EBM effectiveness and safety and contextualizes it against limited indirect evidence for CHX, as no head-to-head comparative trials were identified. Methods: A systematic search of PubMed, EMBASE, Cochrane Library, CINAHL, and Web of Science (January 2015–January 2026) identified randomized and non-randomized studies involving infants ≤ 12 months receiving EBM, colostrum, or CHX for oral care. Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for non-RCTs. Due to substantial clinical and methodological heterogeneity (differing populations, dosages, frequencies, delivery methods, and outcome definitions), a narrative synthesis was performed. Results: Seventeen studies met inclusion criteria (11 RCTs, n = 1185; 6 non-RCTs, n > 3000). EBM and oropharyngeal colostrum were associated with trends toward lower VAP incidence trends (0–4%), reduced bacterial colonization, improved oral health indices, shorter mechanical ventilation time, and reduced ICU/hospital stays, with no reported adverse events. Evidence for CHX in infants was limited to a single paediatric RCT and bundled interventions, showing no significant VAP reduction and associations with mucosal irritation. The risk of bias was generally low to moderate. Conclusions: Indirect evidence suggests EBM is a potentially beneficial option for infant oral hygiene, with favourable trends for infection-related outcomes and recovery parameters. However, all EBM–CHX comparisons are indirect, and CHX evidence in infants is limited by the risk of bias and heterogeneity. High-quality head-to-head randomized controlled trials are needed to determine optimal strategies and inform guidelines. Full article