Search Results (6,714)

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies. Full article

Measuring antimicrobial use (AMU) in animal production can provide useful data for monitoring AMU over time, which will promote antimicrobial resistance (AMR) reduction. This study involved the daily collation and validation of active primary drug sales and prescription data from veterinary outlets and clinics of the Kaduna metropolis. In total, 83.7% of the identified antimicrobials were in the form of oral medication, and most were registered antibiotics (52.8%). Parenteral and topical forms were also identified, with 94% also being antibiotics. The estimated AMU was 282 mg/kg population correction unit (PCU). Poultry represented the most significant population, constituting 99% (31,502,004) of the study population. The class-specific AMU was antibiotics, with 274 mg/kg PCU. The antiprotozoal AMU was 418 mg/kg PCU. The anthelminthic AMU was the highest at 576 mg/kg PCU. This study has provided useful and practical information on the trends in antimicrobial use in animals, with poultry being the most important animal population involved in AMU and oxytetracycline being the most abused antibiotic in animal production. Antimicrobial stewardship (AMS) should be targeted at poultry populations, with an emphasis on reducing antibiotic use/consumption. Full article

Background/Objectives: Pica, the compulsive ingestion of non-nutritive substances, has long been observed in patients with iron deficiency anemia (IDA). This behavior is particularly noted in adults, including pregnant women, and poses both diagnostic and management challenges. We conducted a review of studies from the past decade to evaluate the epidemiology and nature of pica in adult IDA patients and the outcome of various treatment strategies on anemia and pica behaviors. Methods: We searched PubMed, Scopus, and Cochrane Library for peer-reviewed articles (including observational studies, clinical trials, and reviews) published in English between 2015 and 2025. Inclusion criteria targeted studies of adult populations with IDA that reported on pica prevalence, characteristics, or treatment outcomes. We also reviewed clinical guidelines and meta-analyses on IDA treatment in adults for recommended management approaches. Results: Pica was found to be a prevalent symptom among individuals with IDA, but was readily treatable with appropriate iron deficiency treatment. Among treatment options, both oral and parenteral iron supplementation were found to be effective in resolving iron deficiency and pica. Choice of treatment depends on tolerance to oral iron, speed of resolution required, and comorbid conditions. Conclusions: Pica is closely intertwined with IDA; our review highlighted the prevalence of pica among individuals with IDA, which serves as both a clinical clue to underlying anemia and a potential source of complications. Crucially, the treatment of IDA is also effective for pica. We recommend oral iron therapy on alternate-day dosing as first-line therapy to minimize side effects, alongside dietary optimization. If IDA and pica are resistant to oral iron supplementation or oral iron cannot be tolerated, parenteral iron therapy can be considered. Full article

This study examines whether regional infrastructure can predict economic resilience in European regions, focusing on resistance, recovery, and reorientation during the COVID-19 crisis. While infrastructure is widely recognized as a key factor influencing regional resilience, its explicit role has been underexplored in the European context. Using a comprehensive literature review and spatial econometric models applied to NUTS-2 level data from 2017 to 2024, we investigate the direct and spatial spillover effects of various infrastructure types—transportation, healthcare, tourism, education, and digital access—on regional resilience outcomes. We apply OLS and four spatial models (SEM, SLX, SDEM, SDM) under 29 spatial weighting matrices to account for spatial autocorrelation. Results show that motorway density, early school leaving, and healthcare infrastructure in neighbouring regions significantly affect resistance. For recovery, railway density and GDP per capita emerge as key predictors, with notable spatial spillovers. Reorientation is shaped by population structure, railway density, and tourism infrastructure, with both positive and negative spatial dynamics observed. The findings underscore the importance of infrastructure not only in isolation but also within regional systems, revealing complex interdependencies. We conclude that policymakers must consider spatial externalities and coordinate infrastructure investments to enhance regional economic resilience across interconnected Europe. Full article

This study sought to quantify and characterize diverse rootstock scion interactions in cacao around graft compatibility, disease resistance, nutrient use efficiency, vigor traits, and translocation of nonstructural carbohydrates. In total, 106 grafts were performed with three scion cultivars (Matina 1/6, Criollo 22, Pound 7) and nine diverse open-pollinated seedling populations (BYNC, EQX 3348, GNV 360, IMC 14, PA 107, SCA 6, T 294, T 384, T 484). We found evidence for both local and translocated graft incompatibility. Cross sections and Micro-XCT imaging revealed anatomical anomalies, including necrosis and cavitation at the junction and accumulation of starch in the rootstock directly below the graft junction. Scion genetics were a significant factor in explaining differences in graft take, and graft take varied from 47% (Criollo 22) to 72% (Pound 7). Rootstock and scion identity both accounted for differences in survival over the course of the 30-month greenhouse study, with a low of 28.5% survival of Criollo 22 scions and a high of 72% for Pound 7 scions. Survival by rootstocks varied from 14.3% on GNV 360 to 100% survival on T 294 rootstock. A positive correlation of 0.34 (p = 0.098) was found between the graft success of different rootstock–scion combinations and their kinship coefficient, suggesting that relatedness of stock and scion could be a driver of incompatibility. Significant rootstock–scion effects were also observed for nutrient use efficiency, plant vigor, and resistance to Phytophthora palmivora. These findings, while preliminary in nature, highlight the potential of rootstock breeding to improve plant nutrition, resilience, and disease resistance in cacao. Full article

Streptococcus iniae (S. iniae) is a globally significant aquatic pathogen responsible for severe economic losses in aquaculture. While the S. iniae infection often exhibits distinct seasonal patterns strongly correlated with water temperature, there is limited knowledge regarding the temperature-dependent immune evasion strategies of S. iniae. Our results demonstrated a striking temperature-dependent virulence phenotype, with significantly higher A. latus mortality rates observed at high temperature (HT, 33 °C) compared to low temperature (LT, 23 °C). Proteomic analysis revealed temperature-dependent upregulation of key virulence factors, including streptolysin S-related proteins (SagG, SagH), antioxidant-related proteins (SodA), and multiple capsular polysaccharide (cps) synthesis proteins (cpsD, cpsH, cpsL, cpsY). Flow cytometry analysis showed that HT infection significantly reduced the percentage of lymphocyte and myeloid cell populations in the head kidney leukocytes of A. latus, which was associated with elevated caspase-3/7 expression and increased apoptosis. In addition, HT infection significantly inhibited the release of reactive oxygen species (ROS) but not nitric oxide (NO) production. Using S. iniae cps-deficient mutant, Δcps, we demonstrated that the cps is essential for temperature-dependent phagocytosis resistance in S. iniae, as phagocytic activity against Δcps remained unchanged across temperatures, while NS-1 showed significantly reduced uptake at HT. These findings provide new insights into the immune evasion of S. iniae under thermal regulation, deepening our understanding of the thermal adaptation of aquatic bacterial pathogens. Full article

The use of chemical pesticides in agriculture has led to the development of resistant pest populations, posing a challenge to long-term pest management. This review aims to evaluate the scientific literature on the individual and combined use of baculoviruses with conventional chemical and biological insecticides to combat Plutella xylostella, Spodoptera exigua, and Spodoptera frugiperda in broccoli, tomato, and maize crops. Notable findings include that both individual Plutella xylostella nucleopolyhedrovirus (PxNPV) and the combination of Plutella xylostella granulovirus (PxGV) and azadirachtin at a low dose effectively control Plutella xylostella; both combinations of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) with emamectin benzoate and chlorfenapyr reduced resistance in Spodoptera exigua and increased the efficacy of the insecticides; and the combination of Spodoptera frugiperda nucleopolyhedrovirus (SfMNPV) and spinetoram is effective against Spodoptera frugiperda. Integrating baculoviruses into pest management strategies offers a promising approach to mitigate the adverse effects of chemical pesticides, such as resistance development, health risks, and environmental damage. However, there remains a broad spectrum of research opportunities regarding the use of baculoviruses in agriculture. Full article

Background: Obesity and its complications have increased in both adults and children, with pediatric populations developing metabolic disorders at earlier ages. Long non-coding RNAs, particularly MEG3, are involved in obesity through regulation of lipogenic genes including ATF4, FTO, SREBP1, FASN, and ACACA. However, data on MEG3 expression in pediatric obesity are limited. This study evaluated MEG3, FTO, and ATF4 expression in PBMCs from children with obesity and their associations with added sugar intake and lipid metabolism genes. Methods: In this cross-sectional study 71 children within the age range of 6 to 12 years were included (28 normal weight and 43 with obesity). Anthropometrical and clinical parameters and dietary added sugar consumption were analyzed. Real-time PCR was performed to assess MEG3, FTO, ATF4, SREBP1, FASN, and ACACA gene expression in peripheral blood mononuclear cells. Results: The expression of MEG3, ATF4, FTO, SREBP1, FASN, and ACACA was decreased in children with obesity. MEG3 and FTO showed sex-dependent expression in children without obesity, while additional sex-related differences were observed for SREBP1, FASN, ACACA, FTO, and MEG3 in children with obesity. MEG3 was associated with the expression of SREBP1, FASN, ACACA, FTO, and ATF4. In insulin-resistant (IR) children, MEG3, ATF4, FTO, ACACA, and SREBP1 were reduced, while FASN was increased. Added sugar intake negatively correlated with FTO, SREBP1, and ACACA. Conclusions: The MEG3, FTO, and ATF4 expression was altered in children with obesity, showing sex- and IR-related differences. Added sugar intake correlated negatively with lipogenic gene expression. Full article

Cancer remains a significant global health challenge, with China being particularly affected because of its large population. Regulated cell death (RCD) mechanisms, including autophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis, play complex roles in cancer development and progression. This review explores the dual roles of autophagy and apoptosis in cancer, highlighting their tumor-suppressive and tumor-promoting functions. Autophagy can maintain genomic stability, induce apoptosis, and suppress protumor inflammation, but it may also support tumor cell survival and drug resistance. Apoptosis, while primarily tumor-suppressive, can paradoxically promote cancer progression in certain contexts. Other RCD mechanisms, such as necroptosis, pyroptosis, and ferroptosis, also exhibit dual roles in cancer, influencing tumor growth, metastasis, and immune responses. Understanding these mechanisms is crucial for developing targeted cancer therapies. This review provides insights into the intricate interplay between RCD mechanisms and cancer, emphasizing the need for context-dependent therapeutic strategies. Full article

Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity of invasive species and environmental temperature variations. We assessed and interpreted the epigenetic mechanisms of invasive and indigenous species’ differential tolerance to thermal stress through the invasive species Bemisia tabaci Mediterranean (MED) and the indigenous species Bemisia tabaci AsiaII3. We examine their thermal tolerance following exposure to heat and cold stress. We found that MED exhibits higher thermal resistance than AsiaII3 under heat stress. The fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) results proved that the increased thermal tolerance in MED is closely related to DNA methylation changes, other than genetic variation. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of DNA methyltransferases (Dnmts) suggested that increased expression of Dnmt3 regulates the higher thermal tolerance of female MED adults. A mechanism is revealed whereby DNA methylation enhances thermal tolerance in invasive species. Our results show that the Dnmt-mediated regulation mechanism is particularly significant for understanding invasive species’ successful invasion and rapid adaptation under global warming, providing new potential targets for controlling invasive species worldwide. Full article

This study applies Computational Fluid Dynamics (CFD) and mathematical modeling to examine uterine and umbilical arterial blood flow during pregnancy, providing a more detailed understanding of hemodynamic changes across gestation. Statistical analysis of Doppler ultrasound data from a large cohort of more than 200 pregnant women (in the second and third trimesters) reveals significant increases in the umbilical arterial peak systolic velocity ($PSV$) between the 22nd and 30th weeks, while uterine artery velocities remain relatively stable, suggesting adaptations in vascular resistance during pregnancy. By combining the Navier–Stokes equations with Doppler ultrasound-derived inlet velocity profiles, we quantify several key fluid dynamics parameters, including time-averaged wall shear stress ($TAWSS$), oscillatory shear index ($OSI$), relative residence time ($RRT$), Reynolds number ($Re$), and Dean number ($De$), evaluating laminar flow stability in the uterine artery and secondary flow patterns in the umbilical artery. Since blood exhibits shear-dependent viscosity and complex rheological behavior, modeling it as a non-Newtonian fluid is essential to accurately capture pulsatile flow dynamics and wall shear stresses in these vessels. Unlike conventional imaging techniques, CFD offers enhanced visualization of blood flow characteristics such as streamlines, velocity distributions, and instantaneous particle motion, providing insights that are not easily captured by Doppler ultrasound alone. Specifically, CFD reveals secondary flow patterns in the umbilical artery, which interact with the primary flow, a phenomenon that is challenging to observe with ultrasound. These findings refine existing hemodynamic models, provide population-specific reference values for clinical assessments, and improve our understanding of the relationship between umbilical arterial flow dynamics and fetal growth restriction, with important implications for maternal and fetal health monitoring. Full article

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article