Impact of microbial-based biopreparations on soil quality, plant health, and fruit chemistry in raspberry cultivation.

Application of microbial-based biopreparations as a pre-harvest strategy offers a method to obtain sustainable agricultural practices and could be an important approach for advancing food science, promoting sustainability, and meeting global food market demands. The impact of a bacterial-fungal biopreparation mixture on soil-plant-microbe interactions, fruit chemical composition and yield of 7 raspberry clones was investigated by examining the structural and functional profiles of microbial communities within leaves, fruits, and soil. Biopreparation addition caused the enhancement of the microbiological utilization of specific compounds, such as d-mannitol, relevant in plant-pathogen interactions and overall plant health. The biopreparation treatment positively affected the nitrogen availability in soil (9-160%). The analysis of plant stress marker enzymes combined with the evaluation of fruit quality and chemical properties highlight changes inducted by the pre-harvest biopreparation application. Chemical analyses highlight biopreparations' role in soil and fruit quality improvement, promoting sustainable agriculture. This effect was dependent on tested clones, showing increase of soluble solid content in fruits, concentration of polyphenols or the sensory quality of the fruits. The results of the next-generation sequencing indicated increase in the effective number of bacterial species after biopreparation treatment. The network analysis showed stimulating effect of biopreparation on microbial communities by enhancing microbial interactions (increasing the number of network edges up to 260%) of and affecting the proportions of mutual relationships between both bacteria and fungi. These findings show the potential of microbial-based biopreparation in enhancing raspberry production whilst promoting sustainable practices and maintaining environmental homeostasis and giving inshght in holistic understanding of microbial-based approaches for advancing food science monitoring.

Metabolic homeostasis in fungal infections from the perspective of pathogens, immune cells, and whole-body systems.

SUMMARYThe ability to overcome metabolic stress is a major determinant of outcomes during infections. Pathogens face nutrient and oxygen deprivation in host niches and during their encounter with immune cells. Immune cells require metabolic adaptations for producing antimicrobial compounds and mounting antifungal inflammation. Infection also triggers systemic changes in organ metabolism and energy expenditure that range from an enhanced metabolism to produce energy for a robust immune response to reduced metabolism as infection progresses, which coincides with immune and organ dysfunction. Competition for energy and nutrients between hosts and pathogens means that successful survival and recovery from an infection require a balance between elimination of the pathogen by the immune systems (resistance), and doing so with minimal damage to host tissues and organs (tolerance). Here, we discuss our current knowledge of pathogen, immune cell and systemic metabolism in fungal infections, and the impact of metabolic disorders, such as obesity and diabetes. We put forward the idea that, while our knowledge of the use of metabolic regulation for fungal proliferation and antifungal immune responses (i.e., resistance) has been growing over the years, we also need to study the metabolic mechanisms that control tolerance of fungal pathogens. A comprehensive understanding of how to balance resistance and tolerance by metabolic interventions may provide insights into therapeutic strategies that could be used adjunctly with antifungal drugs to improve patient outcomes.

Development of a clinical risk score for the prediction of Pneumocystis jirovecii pneumonia in hospitalised patients.

BACKGROUND: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-ß-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. METHODS: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve. RESULTS: Participants had a median age of 60 years (interquartile range [IQR] 49-68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71-0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. CONCLUSION: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

Optimizing fungal extracellular vesicle proteomic profiling through combined analysis of in-solution and in-gel digestion.

Proteomics offers a powerful tool to identify proteins within diverse microbial organisms, environments, and organelles, including extracellular vesicles (EVs). Fungal EVs are of particular interest due to their roles in cellular development and communication. While several methods exist to isolate EVs from cells, a universally accepted approach for EV protein characterization is lacking. This study investigated in-solution digestion (SD) and in-gel digestion (GD), for characterizing proteins from Neurospora crassa EVs, followed by LC-MS/MS analysis. GD identified three to four-times more proteins than SD while using the same number of unique peptides. Although GD requires a higher amount of starting sample, it offers a more comprehensive protein identification for fungal EVs, potentially preventing the omission of crucial data.

Structure and assembly process of skin fungal communities among bat species in northern China.

Background: The skin fungal communities of animals play a crucial role in maintaining host health and defending against pathogens. Because fungal infections can affect the skin microbiota of bats, gaining a comprehensive understanding of the characteristics of healthy bat skin fungal communities and the ecological processes driving them provides valuable insights into the interactions between pathogens and fungi. Methods: We used Kruskal-Wallis tests and Permutational Multivariate Analysis of Variance (PERMANOVA) to clarify differences in skin fungal community structure among bat species. A Generalized Linear Model (GLM) based on a quasi-Poisson distribution and partial distance-based redundancy analysis (db-RDA) was performed to assess the influence of variables on skin fungal communities. Using community construction models to explore the ecological processes driving fungal community changes, t-tests and Wilcoxon tests were used to compare the alpha diversity and species abundance differences between the fungal structure on bat species' skin and the environmental fungal pool. Results: We found significant differences in the composition and diversity of skin fungal communities among bat species influenced by temperature, sampling site, and body mass index. Trophic modes and skin fungal community complexity also varied among bat species. Null model and neutral model analysis demonstrated that deterministic processes dominated the assembly of skin fungal communities, with homogeneous selection as the predominant process. Skin fungal communities on bat species were impacted by the environmental fungal reservoir, and actively selected certain amplicon sequence variants (ASVs) from the environmental reservoir to adhere to the skin. Conclusion: In this study, we revealed the structure and the ecological process driving the skin fungal community across bat species in northern China. Overall, these results broaden our knowledge of skin fungal communities among bat species, which may be beneficial to potential strategies for the protection of bats in China.

Voriconazole in the treatment of invasive aspergillosis of orbit.

Background: The aim of the study was to evaluate the outcomes of voriconazole in terms of functional recovery and response on imaging in the management of invasive aspergillosis of orbit. Methods: This was a prospective non-comparative interventional study. Diagnosed cases of invasive orbital aspergillosis were studied in a tertiary care hospital. Intravenous voriconazole followed by oral treatment was given. Sinus debridement was done, where needed. The response to treatment was assessed clinically and on radiology. Results: A total of 10 diagnosed cases of invasive orbital aspergillosis were studied. Nine cases (90%) occurred in immunocompetent patients. Predisposing sinus infection was seen in 8 patients (80%). The most common presenting complaint was the protrusion of eye. On voriconazole treatment, there was a statistically significant improvement in vision and extraocular movements from first week onwards (p = 0.01 and p = 0.02, respectively) and reduction in proptosis from second week onwards (p = 0.003). Imaging was done at three months follow-up which revealed a good response to treatment in 90% of patients. All patients tolerated the drug well except one who had transient hepatic dysfunction. The mean follow-up was 5.8 months (range: 3-12 months). There was no recurrence of disease till the last follow-up. Conclusion: Invasive orbital aspergillosis commonly presents as sino-orbital disease, mostly in immunocompetent adult patients. Voriconazole is a safe and effective drug with good short-term clinical outcome.

Association between the pre-transplantation serum ferritin level and outcomes of hematopoietic stem cell transplantation: A systematic review and meta-analysis.

Background: Iron overload, as indicated by evaluated serum ferritin (SF) level, occurs commonly in patients with hematological diseases. To evaluate the association between pre-transplant SF level and outcomes of hematopoietic stem cell transplantation (HSCT), we performed this systematic review and meta-analysis. Methods: PubMed, Embase, Web of Science and the Cochrane Library electronic database were searched from inception to August 2023, and 56 studies with 14149 patients were found to be eligible. Results: An elevated pre-transplantation SF level was associated with inferior overall survival (hazard ratio [HR],1.77; 95 % confidence interval [CI],1.61-1.96) and disease-free survival (HR, 1.86; 95 % CI, 1.58-2.19), and increased risk of non-relapse mortality (HR, 1.73; 95 % CI, 1.49-2.02), and relapse (HR, 1.46; 95 % CI, 1.29-1.65). However, no meaningful association was observed between SF levels and acute graft-versus-host disease (GVHD) (risk ratio [RR], 1.09; 95 % CI, 0.96-1.24), or chronic GVHD (RR, 0.95; 95 % CI, 0.79-1.16). Furthermore, an elevated pre-transplantation SF level was associated with a higher risk of fungal infection (RR, 1.56; 95 % CI, 1.16-2.10), but not with bacterial infection (RR, 1.09; 95 % CI, 0.80-1.50). Moreover, an elevated pre-transplantation SF level was related to a higher risk of death due to relapse/disease progression (RR, 1.72; 95 % CI, 1.33-2.23) and infection (RR, 2.21; 95 % CI, 1.55-3.15), but not death due to GVHD (RR, 1.18; 95 % CI, 0.79-1.77). Conclusions: A higher pre-transplantation SF level was significantly associated with a higher risk of relapse/disease progression and infections, which contributed to worse survival in patients undergoing HSCT. In particular, a higher SF level was related to a higher risk of fungal infection, indicating that patients with a higher pre-transplantation SF level require more attention regarding the risk of fungal infection after HSCT.

Use of microalgal-fungal pellets for hydroponics effluent recycling and high-value biomass production.

Hydroponic effluent (HE), enriched with inorganic nutrients, presents a viable, low-cost cultivation medium for microalgal biomass production and subsequent resource recovery. However, downstream processing, particularly biomass harvesting, remains a critical challenge for microalgal biorefineries. Therefore, the present study explored the potential of microalgal-fungal pellets (MAFP) in HE recycling for the production of biochemical-rich biomass. The optimized fungi-to-microalgae ratio (F:A) of 1:3 resulted in 100 % microalgal pelletization within 6 h. Surface characteristics suggested that metabolically active fungi with opposite charges facilitate microalgal pelletization. Further, MAFP exhibited a packed porous structure that was resilient to shear forces and had a high capacity for nutrient uptake. MAFP cultivation in HE demonstrated complete removal of ammonia-nitrogen (NH3-N), phosphate (PO4³â»), and nitrate-nitrogen (NO3⁻-N) within 7-9 days. The produced biomass was rich in biomolecules, including lipids (18.36 ± 0.12 % TS), protein (52.06 ± 2.1 % TS), and carbohydrates (28.95 ± 0.05 % TS). Besides, the high methane potential of MAFP (SMP ≈ 502.74 ± 19.1 mL CH4 g-1 VS, and TMP ≈ 817.68 ± 12.5 mL CH4 g-1 VS) indicated its suitability for biogas production. In essence, MAFP offers efficient HE recycling and biochemically rich biomass production, advancing towards a green and circular bioeconomy.

Demographic and Microbiological Profile of Corneal Ulcers in Eastern India.

PURPOSE: To evaluate the microbiological profile of corneal ulcers presenting at a tertiary care eye hospital in eastern Uttar Pradesh (UP), India. METHODS: This retrospective, observational study included patients with corneal ulcers who underwent corneal scraping and microbiological examination of the sample from May 2014 to October 2023. The demographic details, predisposing factors, and clinical examination data of the patients were noted. Microbiology report of staining and culture (blood agar and Sabaraud's dextrose agar) of corneal scraping sample was analyzed in percentage. Reports of antimicrobial susceptibility testing were also noted and analyzed. RESULTS: A total of 695 corneal scraping samples were examined during the study period. The mean age of the patients was 45.95 years. Among the patients, 412 (59.28%) were males and 283 (40.72%) were females. Among the patients, 402 (57.84%) belonged to an agricultural background. Trauma was the most common predisposing factor associated with 350 (50.36%) cases. The corneal scraping samples were stain-positive in 455 (65.47%) cases, of which, 130 (28.57%) were gram-positive and 325 (71.43%) were positive on potassium hydroxide (KOH) mount. Culture was positive in 306 (44.03%) cases, of which, bacterial isolates were found in 78 (25.49%), and fungal isolates were found in 228 (74.51%). Fusarium was the most common fungal isolate in 72 (31.58%) cases followed by Aspergillus in 60 (26.32%) cases. Among the bacterial isolates, Staphylococcus aureus was the most common in 20 (25.64%) cases followed by Pseudomonas and Streptococcus. The antimicrobial susceptibility testing showed that 47 (60.26%) of the bacterial isolates were sensitive to fluoroquinolones while the rest 31 (39.74%) were resistant. All the Staphylococcus aureus strains (including four cases of methicillin-resistant Staphylococcus aureus) were susceptible to vancomycin and linezolid, while 7 (35%) were resistant to moxifloxacin. None of the Pseudomonas strains were multidrug resistant. Among the fungal isolates, 220 (96.49%) were susceptible to voriconazole and 189 (82.89%) were sensitive to amphotericin B. CONCLUSION: Fungal corneal ulcers are more common compared to bacterial ulcers in eastern India, particularly eastern UP and Bihar. This article highlights the importance of microbial testing and provides insight into the prevalent organisms and their antimicrobial susceptibility pattern in this geographic location, the knowledge of which will help clinicians in the appropriate management of these cases.

Myco-nanotechnological approach to synthesize gold nanoparticles using a fungal endophyte, Penicillium oxalicum and unravelling their antibacterial activity and anti-breast cancer role via metabolic reprogramming.

The present study has been designed to fabricate fungal endophyte assisted gold nanoparticles and elucidate their anti-breast cancer potential. The aqueous extract of fungal endophyte, Penicillium oxalicum, associated with the medicinal plant Amoora rohituka has been used for the fabrication of gold nanoparticles (POAuNPs). The physicochemical characterization using UV-Vis spectroscopy, FTIR, XRD, DLS, Zeta potential, TEM and FESEM analysis revealed stable, uniform distribution, spherical-shape and crystalline nature of POAuNPs with size range of 3-46 nm. Further, POAuNPs potentially inhibited the growth of pathogenic bacterial strains, E. coli and S. aureus. The synthesized POAuNPs has shown potential antioxidant effects against DPPH, superoxide and nitric oxide radical scavenging assay with an EC50 value of 8.875±0.082, 52.593±2.506 and 43.717±1.449 µg/mL, respectively. Moreover, the value of EC50 for total antioxidant capacity of POAuNPs was found to be 23.667±1.361 µg/mL. The cell viability of human breast cancer cells, MDA-MB-231 and MCF-7 was found to be reduced after treatment with POAuNPs and IC50 values were found to be 19.753±0.640 and 35.035±0.439 µg/mL respectively. Further, in vitro biochemical assays revealed POAuNPs induced metabolic reprogramming in terms of reduced glucose uptake and increased LDH release and, disruption of oxidative balance through depletion of GSH level, increased nitric oxide level and lipid peroxidation as a possible pathway to suppress the human breast cancer cell proliferation. Apoptosis-specific nuclear modulations induced by POAuNPs in human breast cancer cells were validated through DAPI nuclear staining. The present investigation thus attempted to show first ever fabrication of gold nanoparticles using aqueous extract of P. oxalicum associated with A. rohituka. The results revealed unique physico-chemical characteristics of myogenic gold nanoparticles and screening their effect against breast cancer via metabolic reprogramming and induction of apoptosis thus adds great significance against cancer therapeutics, suggesting further exploration to develop nanotherapeutic drugs.

Role of Posaconazole Drug in the Treatment of Invasive Fungal Disease: A Review.

Posaconazole is an antifungal medication used primarily to treat invasive fungal in-fections caused by various organisms, such as Aspergillus, Candida, and certain molds. It be-longs to the class of drugs known as triazole antifungals. Clinical studies have reported posaconazole to be effective in treating various invasive fungal infections, especially in patients who are immunocompromised, such as those with weakened immune systems due to conditions like HIV/AIDS, undergoing chemotherapy, or having received an organ transplant. It has ef-fectively treated invasive candidiasis, aspergillosis, zygomycosis, and other serious fungal in-fections. The effectiveness of the drug varies based on factors, such as the type of infection, the patient's immune status, and the site of infection. This review describes the types of infection, the drug's safety profile, the development of resistance to posaconazole, and strategies to man-age or prevent resistance.

Erratum: The growth-promoting and disease-suppressing mechanisms of Trichoderma inoculation on peanut seedlings.

[This corrects the article DOI: 10.3389/fpls.2024.1414193.].

Responses of soil fungal community composition and function to wetland degradation in the Songnen Plain, northeastern China.

Introduction: Wetlands are ecosystems that have a significant impact on ecological services and are essential for the environment. With the impacts of rapid population growth, wetland reclamation, urbanization, and land use change, wetlands have undergo severe degradation or loss. However, the response of soil fungal communities to wetland degradation remains unknown. It is crucial to comprehend how the diversity and population dynamics of soil fungi respond to varying levels of degradation and ecological progression in the wetlands of the Songnen Plain. Methods: In this study, high- throughput sequencing technology to analyze the variety and abundance of soil fungi in the undegraded (UD), light degraded (LD), moderate degraded (MD), and severe degraded (SD) conditions in the Halahai Nature Reserve of Songnen Plain. This study also explored how these fungi are related to the soil's physicochemical properties in wetlands at various degradation levels. Results: The findings indicated that Basidiomycota and Ascomycota were the primary phyla in the Songnen Plain, with Ascomycota increasing and Basidiomycota decreasing as wetland degradation progressed. Significant differences were observed in soil organic carbon (SOC), total nitrogen (TN),and soil total potassium (TK) among the succession degradation stages. With the deterioration of the wetland, there was a pattern of the Shannon and Chao1 indices increasing and then decreasing. Non-metric Multidimensional Scaling (NMDS) analysis indicated that the fungal community structures of UD and LD were quite similar, whereas MD and SD exhibited more distinct differences in their fungal community compositions. Redundancy analysis (RDA) results indicated that Soil Water content (SWC) and total nitrogen (TN) were the primary environmental factors influencing the dominant fungal phylum. According to the FUNGuild prediction, Ectomycorrhizal and plant pathogens gradually declining with wetland degradation. Discussion: In general, our findings can offer theoretical support develop effective solutions for the preservation and rehabilitation of damaged wetlands.

Antigenic peptide-tobacco mosaic virus conjugates as a fungal vaccine candidate.

Fungal infections are becoming an increasingly serious challenge in clinic due to the increase in drug resistance and the lack of anti-fungal drugs. Vaccination is a useful approach to prevent fungal infections. However, the balance between effectiveness and side effects presents a challenge in vaccine development. In this work, we designed a plant virus-based conjugate vaccine. The non-infectiveness and innate immunogenicity of plant viruses make this vaccine both safe and effective. By conjugating a fungal antigenic peptide to the tobacco mosaic virus (TMV), the resultant vaccine improved the uptake efficiency of antigenic peptides by antigen-presenting cells and enhanced the ability to target lymph nodes. The results of in vivo vaccination in mice showed a significant increase of antigen-specific IgG antibody levels induced by the TMV conjugate vaccine. This work suggests that TMV conjugate vaccines may become a potential vaccine candidate for preventing fungal infections.

Characterization of Bipolaris bicolor germination: effects of a physical factor on fungal adaptability.

Studies on physiological responses to stimuli from physical factors are essential for understanding the dynamics of the microorganisms and higly important for the management of plant diseases. Besides, the development of an epidemiological model for pathogen populations requires studying their physiological responses to physical stimuli. The objective of this study was to evaluate the germination dynamics of spores from six isolates of Bipolaris bicolor under effects of light at 25 °C. Suspensions of 1.6 × 105 conidia mL- 1 from the B. bicolor isolates were inoculated onto Petri dishes containing agar-water culture medium and incubated in a BOD chamber under two physical conditions: (a) constant darkness and (b) constant light for five hours. The study was conducted in a completely randomized design, with a 6 × 2 factorial arrangement (six B. bicolor isolates and two physical conditions) and five replications. The length of the germ tube was measured hourly. The constant darkness resulted in higher mean germ tube growth for the pathogen; however, differences in the final germination percentage were found among the isolates. The isolate F-24-02 exhibited the highest germination adaptability to constant darkness, presenting the longest germ tube length.

The Zoonotic Potential of Fungal Pathogens: Another Dimension of the One Health Approach.

Zoonotic diseases are caused by viruses, bacteria, fungi and parasites and they comprise about 75% of all emerging infectious diseases. These can be transmitted via the direct (scratches on skin or animal bites) or indirect mode (through environmental shedding of infectious agent by the infected animal) of transmission. Environmental changes, whether in the form of urbanization, industrialization or destruction of wildlife habitats, lead to more human invasion in wildlife areas, subsequently leading to an increased passage of animals towards human dwellings and more exposure to animals, making humans susceptible to these infections. Climate change is another major factor. Global warming and the evolving thermotolerance of fungi, adapting more to human body temperature than their saprophytic nature, is leading to the emergence of humans as new hosts for fungi. The domestication of animals, rising populations, enhanced tourism, migratory populations, intrusions into wildlife, etc., are other known factors. Zoonotic fungal infections have long been neglected and are now gaining due attention. In this review, we briefly discuss the various aspects currently known for zoonotic fungal infections and bring forth the importance of this particular issue to be addressed in a timely manner.

Fundamentals of Edible Coatings and Combination with Biocontrol Agents: A Strategy to Improve Postharvest Fruit Preservation.

Challenges in global food supply chains include preserving postharvest quality and extending the shelf life of fruits and vegetables. The utilization of edible coatings (ECs) combined with biocontrol agents (BCAs) represents a promising strategy to enhance the postharvest quality and shelf life of these commodities. This review analyzes the most recent developments in EC technologies and their combination with BCAs, highlighting their synergistic effects on postharvest pathogen control and quality maintenance. Various types of ECs, including polysaccharides, proteins, and lipids, are discussed alongside coating fundamentals and the mechanisms through which BCAs contribute to pathogen suppression. The review also highlights the efficacy of these combined approaches in maintaining the physicochemical properties, sensory attributes, and nutritional value of fruits. Key challenges such as regulatory requirements, consumer acceptance, and the scalability of these technologies are addressed. Future research directions are proposed to optimize formulations, improve application techniques, and enhance the overall efficacy of these biocomposite coatings and multifunctional coatings. By synthesizing current knowledge and identifying gaps, this review provides a comprehensive understanding of the potential and limitations of using ECs and BCAs for sustainable postharvest management.

Evolution of Laboratory Diagnostics for Cryptococcosis and Missing Links to Optimize Diagnosis and Outcomes in Resource-Constrained Settings.

Cryptococcal meningitis is one of the leading causes of death in sub-Saharan Africa among patients with advanced HIV disease. Early diagnosis is crucial in improving treatment outcomes. Despite advances and the availability of modern and point-of-care diagnostics for cryptococcosis, gaps still exist in resource-constrained settings, leading to unfavorable treatment outcomes. Here, we review the current outstanding issues or missing links that need to be filled to optimize the diagnosis of cryptococcosis in resource-constrained settings to improve treatment outcomes. We highlight the evolution of cryptococcosis diagnostics; the roles of early fungicidal activity, cryptococcal antigen titers, antifungal susceptibility testing, and therapeutic drug monitoring; and the missing links to optimize diagnosis and outcomes, including practical recommendations.

Management and outcomes of histoplasmosis in youth with inflammatory bowel disease in an endemic area.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) prescribed immunosuppressive therapies including antitumor necrosis factor (aTNF) therapies are at increased risk of histoplasmosis. We aim to evaluate the presentation, management, and outcomes of youth with IBD and concurrent histoplasmosis. METHODS: Single center, retrospective review of youth with IBD diagnosed with histoplasmosis from January 12, 2007 to January 1, 2022. Management and outcomes were followed for up to 2 years after diagnosis. RESULTS: Nineteen patients (10 male, median age 16 years, range 8-22) with IBD were diagnosed with histoplasmosis: disseminated (N = 15/19; 79%), pulmonary (N = 3/19; 16%), lymph node (N = 1/19; 5%). At the time of histoplasmosis diagnosis, patients were predominantly receiving aTNF therapy (N = 17/19; 89%, median duration 21.9 months (interquartile range 8.5-52.0). Thirteen (13/19, 68%) patients required hospitalization and 2/19 (11%) required intensive care. All achieved antigen clearance with no recurrences. At the time of histoplasmosis diagnosis, aTNF was stopped in 15/17 (88%) patients and the following IBD therapies were initiated: 5-aminosalicylates (N = 4/19; 21%), 6-mercaptopurine (N = 3/19; 16%), enteral therapy (N = 2/19; 11%), and vedolizumab (N = 2/19; 11%); 6 of 19 (32%) received no IBD therapy and 2 of 19 (11%) patients continued aTNF. During follow-up, 6 of 19 (32%) patients had an emergency department (ED) visit and/or hospitalization for symptoms attributed to active IBD, all of whom had discontinued aTNF; one patient required colectomy. CONCLUSIONS: Severe histoplasmosis infection in youth with IBD was rare. IBD treatment was modified by reducing immunosuppression. Histoplasmosis outcomes were favorable, but multiple patients required hospitalization or ED visits for IBD symptoms. The optimal approach to managing IBD during histoplasmosis treatment is challenging and requires further study.

Advances in Dendritic-Cell-Based Vaccines against Respiratory Fungal Infections.

Ever since the discovery of dendritic cells by Ralph Steinman and Zanvil Cohn in 1973, it is increasingly evident that dendritic cells are integral for adaptive immune responses, and there is an undeniable focus on them for vaccines development. Fungal infections, often thought to be innocuous, are becoming significant threats due to an increased immunocompromised or immune-suppressed population and climate change. Further, the recent COVID-19 pandemic unraveled the wrath of fungal infections and devastating outcomes. Invasive fungal infections cause significant case fatality rates ranging from 20% to 90%. Regrettably, no licensed fungal vaccines exist, and there is an urgent need for preventive and therapeutic purposes. In this review, we discuss the ontogeny, subsets, tissue distribution, and functions of lung dendritic cells. In the latter part, we summarize and discuss the studies on the DC-based vaccines against pulmonary fungal infections. Finally, we highlight some emerging potential avenues that can be incorporated for DC-based vaccines against fungal infections.