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Sodium‐glucose cotransporter 2 (SGLT2) inhibitors, originally designed to manage blood sugar levels in individuals with type 2 diabetes (T2D), have emerged as a crucial class of drugs for managing cardio‐renal diseases. These drugs work by targeting the SGLT2 protein in the kidneys, promoting the excretion of glucose and influencing metabolic pathways beyond glucose control. The relationship between cardio‐renal diseases and SGLT2 inhibitors has been explored through landmark trials and real‐world evidence (RWE) studies, demonstrating significant reductions in cardio‐renal complications. This review discusses the importance of RWE studies alongside randomized controlled trials in understanding the real‐world effectiveness and safety of SGLT2 inhibitors. It outlines the advantages and disadvantages of RWE compared to RCTs, highlighting their complementary roles in providing comprehensive insights into treatment outcomes. By examining a range of RWE studies, the review underscores the cardio‐renal benefits of SGLT2 inhibitors across various patient populations. Safety assessments indicate that SGLT2 inhibitors are generally well tolerated, with severe adverse events being rare. Common issues, such as genital mycotic infections and urinary tract infections, are acknowledged, alongside less frequent but significant adverse events including diabetic ketoacidosis, lower‐limb amputations, and bone fractures. In summary, SGLT2 inhibitors show promising cardio‐renal protective effects in real‐world scenarios across diverse populations in T2D, indicating their potential as early intervention measures. Continued research is essential for gaining a thorough understanding of their long‐term effects and safety profiles. [ABSTRACT FROM AUTHOR]

Microbial infections are the most significant threats to human health, and there has been a recent increase in the number of deaths exclusively attributed to bacterial and fungal infections. The development of biofilms by bacterial and fungal pathogens has been identified as a key adaptive antimicrobial resistance (AMR) mechanism, in addition to intrinsic and extrinsic AMR. Various bioactive molecules have been isolated from marine organisms for use in biofilm therapies. These compounds are structurally complex, biocompatible, and economically viable. Studies have demonstrated that bioactive chemicals obtained from marine sources, marine-bioinspired nanomaterials, and marine polymer-antibiotic conjugates can control the biofilms and virulence factors of microbial pathogens. Microbial infections are major human health issues, and, recently, the mortality rate owing to bacterial and fungal infections has been increasing. In addition to intrinsic and extrinsic antimicrobial resistance mechanisms, biofilm formation is a key adaptive resistance mechanism. Several bioactive compounds from marine organisms have been identified for use in biofilm therapy owing to their structural complexity, biocompatibility, and economic viability. In this review, we discuss recent trends in the application of marine natural compounds, marine-bioinspired nanomaterials, and marine polymer conjugates as possible therapeutic agents for controlling biofilms and virulence factors. We also comprehensively discuss the mechanisms underlying biofilm formation and inhibition of virulence factors by marine-derived materials and propose possible applications of novel and effective antibiofilm and antivirulence agents. [ABSTRACT FROM AUTHOR]

Invasive fungal diseases affect more than two million people worldwide. The increasing incidence of invasive fungal infections is the result of many factors, including an increase in the resistance to current drugs. As such, there is an urgent need to obtain new drugs that are efficient, selective, and able to overcome existing resistance mechanisms. Candida yeasts are responsible for more than 70% of all nosocomial invasive fungal diseases. In this work, we describe the synthesis of nickel (II)(NHC) complexes based on xanthines, by direct metalation of xanthinium salts with nickelocene NiCp2to yield [NiCpI(NHC)] complexes. For methyl caffeine, a biscarbene complex [NiCp(NHC)2]+is also formed, resulting from carbene dissociation from the corresponding monocarbene. [NiCpI(NHC)] complexes are active as antifungals for Candida yeasts and show toxicity for human cells (HeLa) that is dependent on the substitution of N7 of the xanthine moiety. The biscarbene complex 5[NiCp(NHC)2]+is highly selective for Candida glabrata and shows very low toxicity for human cells, being a promising candidate for selective treatment of C. glabrata infections. [ABSTRACT FROM AUTHOR]

Background: The utility of two disease-severity indices, namely bronchiectasis severity index (BSI) and FACED score in allergic bronchopulmonary aspergillosis (ABPA) remains unknown. Objective: To correlate the BSI and FACED scores with immunological parameters (serum IgE [total and A. fumigatus-specific], A. fumigatus-specific IgG, blood eosinophil count), and high-attenuation mucus on chest computed tomography in ABPA. The secondary objectives were to evaluate the correlation between BSI and FACED scores and correlate the BSI/FACED scores with the bronchiectasis health questionnaire (BHQ) and Saint George's Respiratory Questionnaire (SGRQ). Methods: We included treatment-naïve ABPA subjects with bronchiectasis in a prospective observational study. We computed the BSI and FACED scores for each subject before initiating treatment. The subjects also completed two quality-of-life questionnaires (BHQ and SGRQ). Results: We included 91 subjects. The mean (standard deviation) BSI and FACED scores were 3.43 (3.39) and 1.43 (1.27). We found no correlation between BSI or FACED with any immunological parameter or high-attenuation mucus. There was a strong correlation between BSI and FACED scores (r = 0.76, p < 0.001). We found a weak correlation between BSI and BHQ/SGRQ and FACED and SGRQ. Conclusion: We found no correlation between BSI and FACED with immunological parameters in ABPA. However, we found a significant correlation between BSI and FACED and a weak correlation between SGRQ and BHQ. ABPA likely requires a separate disease-severity scoring system. [ABSTRACT FROM AUTHOR]

Background: Suppurative perichondritis of the auricle is a common disease that can easily cause malformations if it develops into an uncontrolled infection. In nearly half of the cases, otolaryngologists cannot identify the pathogens involved. Case presentation: In the present work, we described two cases of pyogenic perichondritis, with negative on conventional culture. However, using metagenomic next-generation sequencing (mNGS), we detected fungal infections in the patients and after the patients were given anti-fungal treatment, the patients achieved a good prognosis. Conclusions: These cases highlighted the possibility that fungi might be the involved pathogens in patients who have had multiple negative bacterial cultures, and mNGS should be applied in these cases. mNGS could be used as a supplement to traditional culture methods. [ABSTRACT FROM AUTHOR]

There has been concern over whether to use sodium-glucose-cotransporter-2 (SGLT-2) inhibitors in patients that use catheters due to the concern for increased urinary tract infections (UTIs). The concern is that patients who use catheters are already at an increased risk for UTIs and that SGLT-2-inhibitors may promote bacterial growth due their mechanism of action, ie. increasing glycosuria. The objective of this study was to evaluate whether using empagliflozin, a SGLT-2-inhibitor, in patients who also use catheters, increases their risks for UTIs. A retrospective chart review of electronic health records at a single-center was completed of all Veterans who received an empagliflozin prescription and were also using catheters between October 1, 2015 and September 30, 2022. Veterans were included if they were using catheters for at least 2 months prior to starting empagliflozin and were on both therapies for at least 2 months concurrently. The primary outcome for this study is the number of UTIs occurring prior to and after beginning empagliflozin treatment. Additional secondary outcomes included change in A1c, change in body mass index (BMI), UTI-hospitalizations, and fungal infections. Of the 91 patients with concurrent empagliflozin and catheter-use, only 25 Veterans were included. There was an occurrence of.09 UTIs/month pre-empagliflozin compared to.07 post-empagliflozin (P =.61). There was an observed trend in Veterans with Type 2 Diabetes having an increased rate of UTIs. There was no statistically significant difference found in UTI rates when comparing catheters alone to concurrent catheter and empagliflozin-use. [ABSTRACT FROM AUTHOR]

Mucormycosis is a serious fungal infection caused by fungi in the order of Mucorales. Orbital mucormycosis occurs more frequently in rhino-orbital, sino-orbital, and rhino-orbito-cerebral forms of the disease, while isolated orbital mucormycosis is much less common. Herein, we present four cases of immunocompetent children who developed primary cutaneous mucormycosis, which subsequently invaded and progressed to orbital mucormycosis following direct traumatic injury caused by pecking from Acridotheres tristis (Common Myna). Given the low prevalence of orbital mucormycosis in healthy children, an unknown source of infection and delayed diagnosis followed by late therapeutic interventions could result in life-threatening conditions and serious sequelae. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics. To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis. Systematic review and meta-analysis. MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023. Prospective and retrospective studies with 1-group and 2-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis. Adult and/or paediatric patients with CNS aspergillosis. Galactomannan testing on CSF specimens. European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent. QUADAS-2 assessment in duplicate. Bivariate restricted maximum likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver operating characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none). We included eight studies (n = 342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI, 57.2–78.7%) and 94.4% (95% CI, 82.8–98.3%), respectively. Using meta-regression, galactomannan cut-off (p = 0.38), EORTC/MSGERC criteria version (p = 0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p = 0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analysing the EORTC/MSGERC criteria reference standard used (e.g. 2002 vs. 2008 definitions) or whether paediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and 1-group design studies. CSF galactomannan is a highly specific but insensitive test for use as a component of CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations. [ABSTRACT FROM AUTHOR]

Objective To study the etiological and anatomical factors in pathophysiology of invasive fungal rhinosinusitis affecting the skull base. Design Retrospective clinical study over 5 years. Setting Single-center tertiary referral hospital. Materials and Methods All cases of invasive fungal rhinosinusitis with clinicoradiological and/or operative evidence of anterior and central skull base, orbit, and orbital apex involvement with or without intracranial disease were included in the study. Patients with a sinonasal-palatal disease without the involvement of the skull base or orbit were excluded from the study. In addition, we assessed the risk factors such as coronavirus disease 2019 (COVID-19) infection, diabetes mellitus (DM), and other immunocompromised conditions. Results There were 79 patients, of which 65.8% had skull base rhino-oribitocerebral mucormycosis (ROCM), and 34.2% had Aspergillus infection. The mean duration from onset of the symptom to presentation of ROCM was 36.75 ± 20.97 days, while for the Aspergillus group was 21 weeks. The majority of patients (66%) with ROCM presented after 30 days of symptom onset. Among ROCM patients, 88.7% had a history of COVID-19 infection, and 96% had DM. In 40.8% of patients with Aspergillus infection, the tissue diagnosis was unavailable, and galactomannan assay and clinicoradiological assessment were used for diagnosis. The most common area of the skull base involved was the pterygopalatine fossa (88.5%), followed by the infratemporal fossa (73.1%). The most common neurovascular structure (75%) involved was the pterygopalatine ganglion and the infraorbital nerve. Conclusion With the increasing incidence of invasive fungal infections worldwide, particularly after the COVID-19 pandemic, it is crucial to understand the evolving nature of this disease. ROCM, documented in the literature to cause fulminant disease, became a chronic illness, possibly due to the improvement of the patient's immunity during the disease course. [ABSTRACT FROM AUTHOR]

Understanding the role of the toll-like receptor (TLR) genes in responses to fungal (Fusarium solani) infections is essential to avoid disease outbreaks in the aquaculture industry. This study evaluated the response of eleven TLR genes including protein toll-like receptor-1 (PTL-1), Toll-like receptor 13 × isoform (TLR-13x), Toll-like receptor Tollo-1 (TLR-TO-1), Toll-like receptor Tollo-2 (TLR-TO2), Toll-like receptor Tollo-3 (TLR-TO3), Toll-like receptor Tollo-4 (TLR-TO4), Toll-like receptor 13 (TLR-13), Toll-like receptor 3 (TLR-3), Toll-like receptor 4 (TLR-4), Toll-like receptor 6 (TLR-6), and protein toll-like receptor-2 (PTL-2) to a fungal infection. This study also predicted the transcription factors (TFs) that control their expression in Litopenaeus vannamei. After F. solani infection, the 11 TLR genes were expressed variably in hemocytes, the hepatopancreas, and the gills at various times post-infection. The TLR downstream genes MyD88, IL1, and TNF-alpha were also upregulated after fungal infection. The promoter's region of eleven TLR genes exhibited 320 TFs. Ten transcription factors (WT-1, C/EBP, GATA, Oct, TBP, Sox, RAP1, SRF, NF-1, and Sp1) were the most abundant among the eleven TLR genes analyzed. Our study provided the first information on the involvement of TLR genes in responding to fungal infection and suggested that they play significant roles in the L. vannamei immune response. Such outcomes would promote the growth and consolidation of the aquaculture industry. [ABSTRACT FROM AUTHOR]

Botryomycosis is a rare granulomatous response to chronic bacterial infection most frequently associated with Staphylococcus aureus. This disease, which predominantly affects immunocompromised patients, may present with cutaneous, visceral, or soft tissue manifestations. Soft tissue involvement typically has an aggressive mass-like appearance on imaging which can be concerning for malignancy. In immunocompromised patients, botryomycosis can resemble fungal infection both clinically and histologically; therefore, definitive diagnosis requires tissue sampling along with histological and microbiological analysis. Presented here is a 25-year-old man with an enlarging intramuscular soft tissue mass of the right forearm as his first presentation of undiagnosed acquired immunodeficiency syndrome (AIDS). MR imaging showed a mildly T2 hyperintense and enhancing mass with infiltrative margins extending through tissue planes. Biopsy of the mass revealed Staphylococcus aureus–associated botryomycosis, which improved with nonsurgical treatment employing antibiotics. Unfortunately, the patient subsequently expired from other manifestations of his new AIDS diagnosis. This case describes the MR and PET-CT appearance of botryomycosis and also underscores that infection can mimic sarcoma, particularly in the setting of immunodeficiency. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a major health threat with high morbidity and mortality, highlighting the urgent need for rapid diagnostic tools to detect antifungal resistance. Traditional culture-based antifungal susceptibility testing (AFST) methods often fall short due to their lengthy process. In our previous research, we developed a whole-slide imaging (WSI) technique for the high-throughput assessment of bacterial antibiotic resistance. Building on this foundation, this study expands the application of WSI by adapting it for rapid AFST through high-throughput monitoring of the growth of hundreds of individual fungi. Due to the distinct "budding" growth patterns of fungi, we developed a unique approach that utilizes specific cell number change to determine fungi replication, instead of cell area change used for bacteria in our previous study, to accurately determine the growth rates of individual fungal cells. This method not only accelerates the determination of antifungal resistance by directly observing individual fungal cell growth, but also yields accurate results. Employing Candida albicans as a representative model organism, reliable minimum inhibitory concentration (MIC) of fluconazole inhibiting 100% cells of Candida albicans (denoted as MIC100) was obtained within 3h using the developed method, while the modified broth dilution method required 72h for the similar reliable result. In addition, our approach was effectively utilized to test blood culture samples directly, eliminating the need to separate the fungi from whole blood samples spiked with Candida albicans. These features indicate the developed method holds great potential serving as a general tool in rapid antifungal susceptibility testing and MIC determination. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis (PCM) is an endemic fungal disease that occurs in Latin America and primarily affects humans. The disease has been rarely documented in non-human primates. This report details a disseminated and fatal case of PCM caused by Paracoccidioides brasiliensis in a western black-handed tamarin (Saguinus niger) under human care. Histopathological examination revealed extensive pyogranulomatous inflammation in the lungs, spleen, liver, lymph nodes, kidneys, epididymis, right testicle, heart, adrenal gland and intestines, associated with characteristic yeast forms consistent with Paracoccidioides spp and confirmed by immunohistochemistry. Molecular analysis indicated a high nucleotide similarity with P. brasiliensis sequences for both the 18S rRNA and gp43 genes. This naturally occurring infection highlights the susceptibility of these animals to PCM and their role in ecoepidemiology warrants further investigation. [ABSTRACT FROM AUTHOR]

Chytridiomycosis is a fungal disease responsible for massive amphibian die-offs worldwide, caused by the fungus Batrachochytrium dendrobatidis (Bd). Potential symbiotic relationships between frogs and the bacteria residing on their skin—referred to as skin-bacteria—may inhibit Bd growth, aiding in resistance to this lethal disease. This research had three main objectives: (1) to detect the presence of Bd in native populations of Atelopus balios, A. bomolochos, and A. nanay in the central Andes and coastal southern regions of Ecuador; (2) to identify the culturable skin-bacteria; and (3) to analyze differences among the bacterial communities in the three Atelopus species studied. Skin swabs were collected from two populations of A. balios (107–203 m a.s.l.) and one population each of A. bomolochos and A. nanay (3,064–3,800 m a.s.l.). These swabs served two purposes: first, to detect Bd using conventional PCR; and second, to isolate culturable bacteria, which were characterized through DNA sequencing, molecular phylogeny, and community composition similarity analysis (Jaccard index). Results showed that Bd was present in all species, with positive Bd PCR amplification found in 11 of the 12 sampled amphibians. The culturable skin-bacteria were classified into 10 genera: Pseudomonas (31.4%), Stenotrophomonas (14.3%), Acinetobacter (11.4%), Serratia (11.4%), Aeromonas (5.7%), Brucella (5.7%), Klebsiella (5.7%), Microbacterium (5.7%), Rhodococcus (5.7%), and Lelliottia (2.9%). The Jaccard index revealed that bacterial genera were least similar in A. bomolochos and A. balios (J = 0.10), while the highest similarity at the genus level was between A. bomolochos and A. nanay (J = 0.33). At the clade-species level, only A. bomolochos and A. nanay show common bacteria (J = 0.13). Culturable bacterial communities of specimens diagnosed as Bd positive (n = 10) or Bd negative (n = 1) share a J value of 0.1 at genus and 0.04 at species-clade level. The prevalence of Bd and the composition of cutaneous bacteria could be influenced by Bd reservoirs, Atelopus biology, and intrinsic environmental conditions. This research contributes to understanding the relationship between endangered Andean species and Bd, and explores the potential use of native skin-bacteria as biocontrol agents against Bd. [ABSTRACT FROM AUTHOR]

Background: Fungi are common opportunistic pathogens that pose a significant threat to immunocompromised patients, particularly when late detection occurs. Methods: In this study a multiplex real-time PCR has been developed for simultaneous detection of common fungal pathogens associated with invasive mycoses in a diagnostic setting. Results: The specificity of the assay was rigorously tested on 40 types of organisms (n = 65), demonstrating 100% specificity. The limit of detection was determined to be 100 pg/μl (106 copies/μl), achievable within a rapid 3-h timeframe. The PCR assay efficiency exhibited a range between 89.77% and 104.30% for each target organism, with linearity falling between 0.9780 and 0.9983. Conclusion: This multiplex real-time PCR assay holds promise for enhancing the timely and accurate diagnosis of invasive mycoses, particularly in immunocompromised patient populations. [ABSTRACT FROM AUTHOR]

Background and Aims: Superficial fungal infections are common dermatological reasons to visit a doctor in primary care in Finland. However, their variable clinical picture and minor symptoms may lead to delayed diagnosis. We aimed to investigate the epidemiology and patient profile of fungal infections treated in secondary care over a decade. Methods: This is a retrospective study including adult patients with a fungal infection in the scalp, nails, or superficial skin diagnosed at the Oulu University Hospital, Finland between the years 2010 and 2021. Results: There were 573 patients with male predominance (57.6%). All studied fungal infections were more common in the oldest age group (>61 years). The number of fungal infections increased from the year 2017 onward. Only one‐third (37.7%) of the patients were referred to the dermatology clinic because of a suspected dermatophyte infection, and in 46.0% of cases, the diagnostic delay exceeded 6 months. The most common fungal infection was tinea pedis (n = 295, 51.5%) followed by tinea unguium (n = 275, 48.0%); as concomitant infection, they were present in 108 (18.8%) of all patients. The most common pathogen causing a fungal infection was Trichophyton rubrum. Conclusion: During the study period, the incidence of diagnosed superficial fungal skin infections increased. There was a remarkable diagnostic delay from the onset of symptoms to diagnosis in these most common dermatological conditions. Key points: Superficial fungal infections are highly prevalent and they cause burden and decrease the quality of life.We found that the incidence of superficial fungal infections treated in secondary care was increasing.Fungal infections affect both genders, but more often males and especially those who are older.There was a remarkable diagnostic delay in these diseases. [ABSTRACT FROM AUTHOR]

Fungal trunk disease (FTD) poses a significant threat to hazelnut (Corylus avellana L.) production worldwide. In Chile, the fungus Diplodia mutila, from the Botryosphaeriaceae family, has been frequently identified causing this disease in the Maule and Ñuble Regions. However, control measures for D. mutila remain limited. This research aimed to evaluate the effectiveness of chemical and biological fungicides against D. mutila under in vitro, controlled pot experiment, and field conditions. An in vitro screening of 30 fungicides was conducted. The effectiveness was assessed by measuring the length of vascular lesions in hazelnut branches inoculated with D. mutila mycelium disks under controlled and field conditions. Field trials were conducted in a hazelnut orchard in Ñiquén, Ñuble Region, Chile. The results showed that three biological and five chemical fungicides were selected in vitro with >31% inhibition after 14 days. In pot experiments, all fungicides reduced necrotic lesions on branches by 32% to 61%. In field experiments, the most effective systemic fungicides were fluopyram/tebuconazole, fluxapyroxad/pyraclostrobin, and tebuconazole, while the effectiveness of antagonists Pseudomonas protegens ChC7 and Bacillus subtilis QST713 varied with seasonal temperatures. Effective conventional and biological fungicides against D. mutila could be integrated into disease management programs to protect hazelnut wounds from infections. [ABSTRACT FROM AUTHOR]

Background: Our study discusses the probable etiologies and characteristics of pulmonary cavities in post-COVID-19 patients. A pulmonary cavity is a late complication of the disease, yet it has led to multiple referrals to our tertiary hospital in Tehran, Iran. Methods: We conducted a retrospective case-series study on 20 patients who were admitted to our center between April 2020 and September 2021. They were all diagnosed with COVID-19 and concomitantly developed pulmonary cavities. We assessed their electronic medical records in 2021 and compared their characteristics with other studies based on the available literature. Result: Of the 20 patients with cavities, 12 (60%) had been diagnosed with prior COVID-19, and 9 (45%) had type 2 diabetes mellitus. 9 patients (54%) had bacterial superinfections while 4 (44%) had fungal infections. All patients received corticosteroids, but only 4 (20%) were additionally administered Tocilizumab. Conclusion: COVID-19 patients can develop pulmonary cavities during recovery; however, this infrequent radiologic finding depends on specific risk factors. [ABSTRACT FROM AUTHOR]

Mucormycosis, a lethal fungal infection caused by Rhizopus oryzae, has gained significant attention due to its association with the COVID-19 pandemic. The causal relationship between COVID-19 and mucormycosis is not yet fully understood. This narrative review focuses on the pathophysiology of mucormycosis, particularly in the context of COVID-19. Mucormycosis primarily affects immunocompromised individuals and is commonly observed in diabetic patients with COVID-19 who receive high doses of corticosteroids. The most common presentation of mucormycosis in COVID-19 is rhino-orbital-cerebral mucormycosis. Early diagnosis and prompt initiation of treatment, including extensive surgical intervention and appropriate antifungal therapy, are crucial in preventing fatal complications. The global prevalence of mucormycosis varies widely, with a higher incidence in developing countries such as India. Diabetes mellitus remains the leading risk factor globally, while COVID-19 and corticosteroid therapy also predispose immunocompromised patients to mucormycosis. The impaired phagocytic activity in immunosuppressed individuals and the ability of Mucorales to acquire iron from the host play significant roles in the pathogenesis of mucormycosis. Endothelial damage and thrombosis, along with hyperglycemia, acidosis, and increased serum iron levels observed in COVID-19, contribute to the aggressive nature of mucormycosis in these patients. The review emphasizes the need for further research to establish a causal association between COVID-19, corticosteroid therapy, and mucormycosis, and highlights the importance of understanding the underlying mechanisms to improve the management and outcomes of patients with this devastating fungal infection. [ABSTRACT FROM AUTHOR]

Background: The most common superficial fungal infections are tinea corporis, tinea cruris, tinea capitis, tinea pedis, tinea unguium, and tinea facie and cutaneous Candida albicans infections such as oral thrush, oropharyngeal candidiasis, vaginal candidiasis, and onychomycosis. Aims and Objectives: (i) Analysis of prescription pattern of antifungal drugs and (ii) to study common adverse effects. Materials and Methods: A retrospective, observational study conducted in B. K. L. Walawalkar Hospital, Sawarde, Ratnagiri. A total of 993 case papers were analyzed after getting approval from the institutional ethics committee and permission from dermatology department. The frequency with percentage was used for the analysis of data. Results: In 993 patients with superficial fungal infections, 523 (52.7%) were males and 470 (47.3%) were females. Majority of patients were belonged to 21-40-year age group, i.e., 439 (44.2%) followed by 41-60 years, i.e., 244 (24.6%). Our study shows that the most common superficial fungal infections with single lesion were tinea corporis (22.3%), tinea cruris (14.6%), and pityriasis versicolor (13.9%). In Candida albicans, the most common infection was onychomycosis 14 (1.4%). The most common antifungal prescribed was luliconazole (20.84%) followed by itraconazole (20.58%). The most common route was topical route (68.26%). Combination of drugs was not prescribed. Different prescription indicators were that the average number of drugs prescribed per encounter was 3.4 and average number of drugs prescribed per encounter was 2.7. Conclusion: Most commonly prescribed newer antifungal was luliconazole. Next most commonly prescribed by oral route was itraconazole. In our study prescription pattern were rational approach in two points, they are no use of combination of drugs and many drugs were selected from essential medicinal list. [ABSTRACT FROM AUTHOR]

Mucormycosis is an angioinvasive disease caused by fungi of the order Mucorales. In this article, three case reports of rhinocerebral mucormycosis developing after COVID-19 infection in a diabetic patient are presented. Early diagnosis and treatment of those high morbidity conditions are vital to better outcomes. [ABSTRACT FROM AUTHOR]

Introduction The SARS-CoV-2 virus primarily affects the lungs causing a heightened immune response due to viral and host cell interaction, which prompts the release of proinflammatory cytokines and reduces the defense mechanisms of the immune system, making the patient vulnerable to secondary infections. The study aims to identify the incidence and risk factors for secondary infections developing after COVID-19. Methods and Materials A retrospective study was conducted on 669 patients who were readmitted after COVID-19 to a tertiary care hospital. The development of secondary infections in these populations was identified. The data were collected from the medical records department. Statistical Analysis Incidence was calculated by the ratio of the total number of patients who developed secondary infections among readmitted patients divided by the total number of readmitted patients during the study period. Univariate analysis was performed to identify the statistically significant variables that were used in logistic regression for identifying the risk factors for secondary infection. Statistical analysis was performed in SPSS version 28.0. Results and Discussion In this study, 85 patients were found to have developed secondary infections with an incidence of 12.7%. Among the reported six infections, mucormycosis showed the highest incidence (34.1%), followed by sepsis and urinary tract infection. Nine patients developed tuberculosis as a post-COVID-19 secondary infection. General risk factors for secondary infections include male gender, presence of comorbidities such as diabetes mellitus and chronic kidney disease (CKD), intensive care unit (ICU) admission, elevated levels of interleukin-6 (IL-6) and D-dimer, and administration of steroids particularly medium-dose steroids. Conclusion Secondary infections can occur within 43 days of COVID-19 infection for every 12.7 per 100 patients in whom there is bacterial or fungal infections. Of these secondary infections, incidence of mucormycosis and sepsis was found to be higher in our study. COVID-19-infected patients who have either of these factors such as elevated inflammatory markers (Il-6 and D-dimer), the presence of comorbidities such as diabetes mellitus and CKD, ICU admission, and the use of steroids are at risk of developing secondary infections. Through proper screening, we can prevent patients who are at risk of developing secondary infections. [ABSTRACT FROM AUTHOR]

Summary: Background and Objectives: Knowledge about the current spectrum of dermatomycoses is important for diagnosis and therapy. Patients and Methods: A retrospective, monocentric analysis of mucocutaneous fungal infections diagnosed at a large European academic dermatology department in Munich was conducted; 87,229 samples from 48,916 patients from January 1, 2011, to August 30, 2020, were included. Results: Fungi were detected in 11,513 samples from 48,916 (23.54%), and 36 different species were identified. Candida (C.) albicans was the most common pathogen (5,055 detections; 43.91% of all positive samples), followed by Trichophyton (T.) rubrum (3,076 detections; 26.72% of all positive samples) and Candida parapsilosis (923 detections; 8.02% of all positive samples). Rare pathogens such as Trichophyton raubitschekii were also detected. Coinfections with multiple species were detected in 44 cases. Conclusions: Even though C. albicans, T. rubrum, and C. parapsilosis were confirmed as the most common pathogens, rare pathogens should also be considered in clinical practice. The predominant spectrum of fungi differed from that reported in other countries. Furthermore, a difference in the pathogen spectrum could be observed depending on the age group and body site. [ABSTRACT FROM AUTHOR]

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Finding safe and reliable alternatives to fungicides is currently one of the biggest challenges in agriculture. In this regard, this experiment investigated the effectiveness of different elicitors, botanical extracts and essential oils to control grey mold (Botrytis cinerea) and powdery mildew (Podosphaera aphanis) on strawberry plants. This trial was conducted in field conditions under a plastic tunnel with strawberry plants 'Elsanta'. A first group of strawberry plants was treated before flowering with elicitors [acibenzolar-S-Methyl–(BTH), chitosan], botanical extracts (seaweed extract, alfalfa hydrolysate) and essential oils (thyme and juniper), and grey mold incidence on flowers was evaluated (Experiment 1). Furthermore, a second group of plants was treated before (Experiment 2) and after (Experiment 3) controlled inoculation with P. aphanis. The results indicated that the incidence of flower infected by B. cinerea was reduced by approximately 50% with thyme and juniper essential oils' applications compared to the untreated control, with no significant difference observed compared to the commercial fungicide penconazole (positive control). As a consequence, the final yield of essential-oil-treated plants was +27% higher than that of non-treated plants. No significant differences emerged for other tested products against grey mold. However, gene expression analysis showed an up-regulation (>2 ÷ 5 folds as compared to control 4 days after application) of FaEDS1, FaLOX and PR gene expression (FaPR1, FaPR5, FaPR10) in leaves treated with BTH. The other natural substances tested also induced defense-related genes, albeit at a lower level than BTH. In Experiment 2, all treatments applied prior to inoculation significantly reduced the incidence and severity of powdery mildew as compared to control. At 28 days after inoculation, chitosan and thyme essential oil applications performed similarly to their positive controls (BTH and penconazole, respectively), showing a significant reduction in disease incidence (by −84 and −92%) as compared to control. Post-inoculum application of essential oils (Experiment 3) showed an efficacy similar to that of penconazole against powdery mildew. These results indicated that the tested substances could be used as alternatives to fungicides for the control of grey mold and powdery mildew in strawberry, therefore representing a valuable tool for the control of these fungal diseases under the framework of sustainable agriculture. [ABSTRACT FROM AUTHOR]

Fungal infections pose a significant challenge in numerous developing nations and worldwide, necessitating urgent solutions. Oral administration of antifungal medications often leads to severe adverse reactions. Hence, employing topical delivery systems is preferred to ensure efficient dermal delivery of antifungal agents while minimizing side effects. Furthermore, the incorporation of penetration enhancers into nanocarriers loaded with antifungal agents has demonstrated enhanced efficacy in combating mycotic infections. Consequently, ultra-deformable penetration enhancer-containing vesicles (PEVs) were developed to explore this promising approach. In this study, Labrasol® and Transcutol® were used as penetration enhancers in formulating ultra-deformable PEVs containing the antifungal agent Fluconazole (FCZ). The PEVs underwent comprehensive characterization, including measurements of particle size (PS), charge, and entrapment efficiency (EE%). The results revealed that the size of tested PEVs ranged from 100 to 762 nm. All particles exhibited a negative charge, with a minimum zeta potential (ZP) of −38.26 mV, and an intermediate entrapment efficiency (EE%) that reached approximately 40%w/w. Ex-vivo studies demonstrated the ability of PEVs to deliver FCZ to the dermis while minimizing transdermal delivery. The selected formula was tested in-vivo using candidiasis-induced rat model and showed a superiority in its antifungal effect against Candida Albicans compared to the drug control. Stability studies were executed for the selected formula, and revealed good stability shown by the insignificant change in the PS, ZP& EE% over a six-month period. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections represent a concerning healthcare issue, with Candida spp. reported as the main aetiological agent. Candida spp. bloodstream infections show high mortality rates, indicating increasing antifungal-resistance episodes as a contributing feature. Despite the global prevalence of C. albicans, non-albicans species emerged as significant in the last decades. Methods: The present manuscript reports a five-year evaluation on Candida spp. bloodstream isolates and their antifungal susceptibility profiles, aiming to enrich the literature and epidemiological data. Results: According to the gathered data, antifungal-resistance cases remained uncommon. However, the study revealed rare resistance phenotypes such as a single case of pan-echinocandin resistance C. albicans. Conclusions: Finally, a comprehensive review of Candida spp. antifungal resistance integrates the data, emphasizing the extreme species-specific variability and the consequent importance of always providing species identification. [ABSTRACT FROM AUTHOR]

Calcineurin–nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor–treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus , in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2 , CCL3 , and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils. [ABSTRACT FROM AUTHOR]

Fungal infections present significant clinical challenges due to their diverse types and the increasing incidence of drug-resistant strains. Traditional antifungal treatments often encounter issues with penetration, efficacy and patient compliance. The study involves a comprehensive review of the structure and mechanism of transfersomes, their advantages over conventional and other nano carriers, and the integration of herbal extracts. Key aspects include improved skin penetration, enhanced bioavailability of herbal actives, and targeted delivery to infected areas. Transfersomes demonstrate significant benefits in antifungal therapy, including higher efficacy, faster symptom relief, reduced side effects and improved patient compliance. The enhanced penetration and stability of transfersomes facilitate a more effective delivery of herbal actives, making them a superior choice for topical treatments. The study also identifies areas for future research, such as optimizing formulation processes and exploring combination therapies to maximize therapeutic outcomes. Transfersomes represent a transformative advancement in the field of topical drug delivery. Their integration with herbal medicines offers a promising approach to addressing fungal infections more effectively. Future research should focus on clinical validation and further refinement of transfersome-based formulations to fully realize their potential in enhancing the management of fungal infections and other dermatological conditions. [ABSTRACT FROM AUTHOR]

There are several benefits to use topical treatments for fungal infections, such as being able to target the infection directly and lowering the risk of widespread side effects. Antifungal drugs must get through the top layer of skin, when they are applied to the skin in order to work at their best. An antifungal drug called chlorphenesin was used to help it spread more quickly and stop the fungal growth. By using the above mentioned drug the cream formulation was prepared and optimised. The all of prepared formulation batches were analysed, and all of them were passed as per the requirements. The results of all tests showed that the cream can be used on the face to protect against fungal diseases. The study's results clearly shows that the prepared formulations having the antifungal activity on the various fungi studied in this study. [ABSTRACT FROM AUTHOR]

The purpose of this study was to ascertain the changes in the main biochemical composition of the aromatic plants, such as Curcuma longa and Allium cepa, which are infected with their corresponding pathogenic fungus and the medicinal plants, which include Tinospora cordifolia, Ocimum tenuiflorum, and Alloe vera. Fungal infections' effects on total protein, MDA, H2O2, total phenols, total flavonoids and total tannins. Additionally, we assessed the activity of antioxidant enzymes in each of the five plants that were tested after they were infected with fungi. When comparing several plants afflicted with fungal infections to controls, a notable difference was seen in all metrics. Despite being medicinal plants, the aforementioned five plants experience a significant reduction in output as a result of numerous fungal diseases. Furthermore, the detrimental impact of pathogens during the course of infection on plant leaves was closely linked to variations in the concentration of its primary biochemical groups. Controlling fungal diseases through the implementation of suitable management measures is therefore crucial to safeguarding the plant with significant commercial value. [ABSTRACT FROM AUTHOR]

Background: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. Methods: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. Results: The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57–73% response rate). Conclusions: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections. [ABSTRACT FROM AUTHOR]

Dermatophytosis in cattle is most often caused by infection with Trichophyton verrucosum (T. verrucosum), but also with Trichophyton rubrum (T. rubrum), Trichophyton mentagrophytes (T. mentagrophytes) and others, regardless of the geographical zone. The infection is transmitted through direct contact between animals as well as infected environmental elements. The human-to-human transmission of fungal infection is also possible.. This retrospective study was conducted based on a detailed analysis of the results of the mycological examination and medical documentation of 40 patients from Greater Poland, diagnosed with cattle-to-human dermatophytoses from March 2017 to November 2023. T. verrucosum accounted for 97.5% of infections and T. mentagrophytes for 2.5%; no other species of dermatophytes from cattle were found. Superficial skin mycosis in humans associated with cattle was more often diagnosed in small children and men directly engaged in cattle breeding. The dominant etiological factor of the superficial fungal skin infection was T. verrucosum, which mainly affected the scalp in children and upper limbs in adult men. In relation to the cattle population in Greater Poland, the number of cases of superficial skin mycoses among cattle breeders and their family members over the period of more than six and a half years of observation does not seem to be high. [ABSTRACT FROM AUTHOR]

Fungal infections have become an important public health problem. Currently, there are only three available classes of antifungals for the treatment of invasive infections. Two of them, azoles and polyenes, target the synthesis of ergosterol or bind to sterols. A promising strategy to improve current therapies is the use of natural compounds in combinational therapies with the existing antifungals. In this work, we analyzed the changes in the susceptibility of the mutant strain of Nakaseomyces glabratus (Candida glabrata) lacking the ERG6 gene (encoding the sterol C-24 methyltransferase in ergosterol biosynthesis) in the presence of catechin and antifungal azoles. The reduced content of ergosterol in the Cgerg6Δ mutant resulted in the increased tolerance of the mutant cells to both azoles and polyenes. The combination of catechin with fluconazole or miconazole led to the growth inhibition of the azole-resistant Cgerg6Δ mutant strain. In the presence of catechin and miconazole, the Cgerg6Δ mutant fails to properly activate the expression of genes encoding the transcription factors CgYap1p and CgMsn4p, as well as the gene expression of CgCTA1, which are involved in oxidative stress response and lead to the intracellular accumulation of ROS. Finally, we show that catechin administration reduces mortality in a Galleria mellonella model infected with C. glabrata. Our work thus supports the use of catechin in combination therapies for fungal infections and shows that the CgERG6 gene could be a potential new drug target. [ABSTRACT FROM AUTHOR]

This review investigates the different zoonotic infections transmitted from fish to humans, focusing on microorganisms such as bacteria, parasites, viruses, and fungi. The study aims to elucidate the pathways through which these infections occur, the severity of the diseases in humans, and the clinical manifestations in fish and humans. The primary transmission methods include ingesting undercooked fish, contact with contaminated water, and exposure through open wounds. Notably, zoonotic bacteria, such as Vibrio, Mycobacterium, Streptococcus, and Aeromonas, present significant health risks and economic impacts on aquaculture. Parasitic infections, such as those caused by Anisakis and liver flukes, often result from consuming raw or undercooked fish, leading to gastrointestinal and systemic diseases. Viral pathogens like noroviruses and hepatitis A virus are primarily transmitted via contaminated seafood. Though less common, fungal infections can occur through direct contact with infected fish or the environment. This review emphasizes the importance of molecular diagnostic techniques for detecting zoonotic agents and highlights preventive measures to mitigate the risks. Effective management strategies include educating those in fish handling, ensuring proper cooking and handling practices, and implementing robust monitoring and quality control systems within aquaculture settings. [ABSTRACT FROM AUTHOR]

The interplay between the insect immune system and entomopathogenic fungi during cuticle penetration is not yet fully understood. Here, we show that a secretory protein COA1 (coat of appressorium 1) from Metarhizium robertsii, an entomopathogenic fungus causing diseases in a wide range of insects, is required to avoid host immune recognition during cuticle penetration. COA1 is highly expressed on the cuticle and translocated to the cell surface, where it directly binds with and masks carbohydrates of the fungal cell wall to avoid provoking the host's intense immune response. Deletion of Coa1 results in a robust immune response, leading to a reduction in bacterial load in both the gut and hemocoel and ultimately attenuating fungal virulence. Our work reveals a novel cell surface protein indispensable for fungal pathogenicity via masking cell wall carbohydrates to avert a hypersensitive response from the host. The insect pathogenic fungus Metarhizium robertsii secretes a small protein, COA1, to mask the antigenic structural components of the cell wall, thereby evading insect immune recognition during the penetration of the insect cuticle. [ABSTRACT FROM AUTHOR]

Anther smuts are fungal diseases that have detrimental effects on the biology of their host plants. We investigated the transmission of Anther smut Antherospora vindobonensis to its host, Scilla vindobonensis under natural and laboratory conditions. Plants flowering early in spring were less vulnerable to disease (∼ 20–30% of plants which appeared early in the season were diseased) than flowers that bloom at the end of the season (∼ 60% of plants which appeared late in the season were diseased) which contradicts the patterns observed for other anther smuts species. Diseased plants showed thicker stems, lower nectar production and smaller flower radius than healthy plants. The disease prevalence in S. vindobonensis was not influenced by plant density. The production of spores in diseased flowers was 125 times higher than the production of pollen in healthy flowers. The number of pollen grains attached to pollinator bodies from healthy plants under controlled conditions was similar to the number of spores attached from diseased plants. Experienced honeybees in the field showed almost identical preferences for healthy plants (65%) over diseased ones, as did naïve bumblebees under controlled laboratory conditions (69%). eDNA metabarcoding revealed that healthy flowers attracted a significantly higher number of arthropod species (M = 6.23, SE = 1.48) than diseased flowers (M = 2.32, SE = 0.31). Strong seasonal differences in the risk of infection suggest that S. vindobonensis solves the trade-off between low pollinator availability and low risk of infection at the beginning of the season and high risk of infection and high pollinator availability at the end of season. By reproducing early in the season, plants can reduce the risk of disease. [ABSTRACT FROM AUTHOR]

Mucormycosis is a concerning invasive fungal infection with difficult diagnosis, high mortality rates, and limited treatment options. Iron availability is crucial for fungal growth that causes this disease. This study aimed to computationally target iron uptake proteins in Rhizopus arrhizus, Lichtheimia corymbifera, and Mucor circinelloides to identify inhibitors, thereby halting fungal growth and intervening in mucormycosis pathogenesis. Seven important iron uptake proteins were identified, modeled, and validated using Ramachandran plots. An in-house antifungal library of ~ 15,401 compounds was screened in molecular docking studies with these proteins. The best small molecule-protein complexes were simulated at 100 ns using Maestro, Schrodinger. Toxicity predictions suggested all six molecules, identified as the best binding compounds to seven proteins, belonged to lower toxicity levels per GHS classification. A molecular mechanics GBSA study for all seven complexes indicated low standard deviations after calculating free binding energies every 10 ns of the 100 ns trajectory. Density functional theory via quantum mechanics approaches highlighted the HOMO, LUMO, and other properties of the six best-bound molecules, revealing their binding capabilities and behaviour. This study sheds light on the molecular mechanisms and protein–ligand interactions, providing a multi-dimensional view towards the use of FDBD01920, FDBD01923, and FDBD01848 as stable antifungal ligands. [ABSTRACT FROM AUTHOR]

We conducted a retrospective, observational study among acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis or talaromycosis to assess AmB formulations-related adverse events (AEs). Total 205 eligible patients were enrolled. Of them, 139 received AmB therapy, 51 received liposomal AmB (L-AmB) therapy, and 15 received AmB cholesteryl sulfate complex (ABCD) therapy. The incidences of total AEs between the AmB, L-AmB and ABCD group had no significant differences. The ABCD group had significantly higher incidences of hepatotoxicity and hematological toxicity than the AmB and L-AmB groups. The incidence of grade 3–4 hematological toxicity in the ABCD group was significantly higher than that in the AmB and L-AmB groups. Multinomial logistic regression models showed that compared with AmB, ABCD had a higher risk for the occurrence of grade 3–4 hematological toxicity (aOR = 43.924, 95%CI 6.296-306.418; p < 0.001). We demonstrated that ABCD was more prone to hepatotoxicity and hematological toxicity than AmB and L-AmB among AIDS patients, which is worth noting. [ABSTRACT FROM AUTHOR]

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-β-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. [ABSTRACT FROM AUTHOR]

Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our pathophysiological understanding of these infections, particularly the role of fungal cell walls in growth and immune response, remains limited. Here we conducted multidimensional solid-state NMR analysis to examine cell walls in five Mucorales species, including key mucormycosis causative agents like Rhizopus and Mucor species. We show that the rigid core of the cell wall primarily comprises highly polymorphic chitin and chitosan, with minimal quantities of β-glucans linked to a specific chitin subtype. Chitosan emerges as a pivotal molecule preserving hydration and dynamics. Some proteins are entrapped within this semi-crystalline chitin/chitosan layer, stabilized by the sidechains of hydrophobic amino acid residues, and situated distantly from β-glucans. The mobile domain contains galactan- and mannan-based polysaccharides, along with polymeric α-fucoses. Treatment with the chitin synthase inhibitor nikkomycin removes the β-glucan-chitin/chitosan complex, leaving the other chitin and chitosan allomorphs untouched while simultaneously thickening and rigidifying the cell wall. These findings shed light on the organization of Mucorales cell walls and emphasize the necessity for a deeper understanding of the diverse families of chitin synthases and deacetylases as potential targets for novel antifungal therapies. Pathogenic Mucorales fungi are common in immunocompromised. Here, Cheng et al. determine the molecular architecture of their chitin/chitosan-rich cell walls and the restructuring that occurs in response to the chitin inhibitor nikkomycin. [ABSTRACT FROM AUTHOR]

Fall armyworm (FAW), Spodoptera frugiperda is a generalist pest known to feed on more than 300 plant species, including major staple crops such as rice, maize and sorghum. Biological control of FAW using a combination of a major indigenous egg parasitoid Telenomus remus and entomopathogenic fungi was explored in this study. Metarhizium anisopliae strains (ICIPE 7, ICIPE 41, and ICIPE 78) and Beauveria bassiana ICIPE 621 which demonstrated effectiveness to combat the pest, were evaluated through direct and indirect fungal infection to assess their pathogenicity and virulence against T. remus adults, S. frugiperda eggs and their effects on T. remus parasitism rates. Metarhizium anisopliae ICIPE 7 and ICIPE 78 exhibited the highest virulence against T. remus adults with LT50 values >2 days. ICIPE 7 induced the highest T. remus mortality rate (81.40 ± 4.17%) following direct infection with dry conidia. Direct fungal infection also had a significant impact on parasitoid emergence, with the highest emergence rate recorded in the M. anisopliae ICIPE 7 treatment (42.50 ± 5.55%), compared to the control ± (83.25 ± 5.94%). In the indirect infection, the highest concentration of 1 x 109 conidia ml-1 of ICIPE 78 induced the highest mortality (100 ± 0.00%) of T. remus adults, and the highest mortality (51.25%) of FAW eggs, whereas the least FAW egg mortality (15.25%) was recorded in the lowest concentration 1 x 105 conidia ml-1 of ICIPE 41. The number of parasitoids that emerged and their sex ratios were not affected by the different fungal strain concentrations except in ICIPE 7 at high dose. This study showed that potential combination of both M. anisopliae and B. bassiana with T. remus parasitoid can effectively suppress FAW populations. [ABSTRACT FROM AUTHOR]

Fungi are ubiquitous in the environment and play a key role in the decomposition and recycling of nutrients. On the one hand, their special properties are a great asset for the agricultural and industrial sector, as they are used as source of nutrients, producers of enzymes, pigments, flavorings, and biocontrol agents, and in food processing, bio-remediation and plant growth promotion. On the other hand, they pose a serious challenge to our lives and the environment, as they are responsible for fungal infections in plants, animals and humans. Although host immunity opposes invading pathogens, certain factors favor the manifestation of fungal diseases. The prevalence of fungal infections is on the rise, and there is an alarming increase in the resistance of fungal pathogens to approved drugs. The limited number of antimycotics, the obstacles encountered in the development of new drugs due to the poor tolerability of antifungal agents in patients, the limited number of unique antifungal targets, and the low species specificity contribute to the gradual depletion of the antifungal pipeline and newly discovered antifungal drugs are rare. Promising candidates as nextgeneration therapeutics are antimicrobial proteins and peptides (AMPs) produced by numerous prokaryotic and eukaryotic organisms belonging to all kingdom classes. Importantly, filamentous fungi from the order Eurotiales have been shown to be a rich source of AMPs with specific antifungal activity. A growing number of published studies reflects the efforts made in the search for new antifungal proteins and peptides (AFPs), their efficacy, species specificity and applicability. In this review, we discuss important aspects related to fungi, their impact on our life and issues involved in treating fungal infections in plants, animals and humans. We specifically highlight the potential of AFPs from Eurotiales as promising alternative antifungal therapeutics. This article provides insight into the structural features, mode of action, and progress made toward their potential application in a clinical and agricultural setting. It also identifies the challenges that must be overcome in order to develop AFPs into therapeutics. [ABSTRACT FROM AUTHOR]

Background: No comprehensive meta‐analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta‐analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD −0.62%, 95% CI [−0.80, −0.44], p < 0.00001, I2 = 91%) and 15 mg (MD −0.69%, 95% CI [−0.91, −0.47], p < 0.00001, I2 = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Invasive aspergillosis (IA) can lead to life‐threatening respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) support. However, data on ECMO experience in the management of IA patients are scarce.The purpose of this systematic review was to evaluate the potential benefits and risks of ECMO as a supportive intervention for critically ill patients with IA.We conducted a systematic review of the literature using the search terms ECMO, extracorporeal membrane oxygenation, Aspergillus and Aspergillosis in two databases (Medline and Scopus). Clinical data were extracted by two independent investigators. Clinical parameters, such as mode of ECMO support, duration of treatment and clinical outcomes, were assessed.Overall, 32 patients were included in the analysis. The age ranged from 5 to 69 years, 59% were male, and 38% were female. The majority of patients suffered from ARDS (82%). 82% received VV‐ECMO, and 18% received VA‐ECMO. Aspergillus fumigatus was the most frequent cause of IA, coinfections were frequently observed (51%). The overall mortality was 78%. Complications during ECMO support were observed in 21 of the 39 cases (53.8%).IA poses significant management challenges for critically ill ICU patients, even with ECMO support. Although ECMO appears to improve survival of patients at high risk of AI, potential risks such as bacterial superinfection and altered pharmacokinetics of antifungal drugs must be carefully considered. [ABSTRACT FROM AUTHOR]

Wheat stripe rust (WSR), a fungal disease capable of inflicting severe crop loss, threatens most of global wheat production. Breeding for genetic resistance is the primary defense against stripe rust infection. Further development of rustresistant wheat varieties depends on the ability to accurately and rapidly quantify rust resilience. In this study we demonstrate the ability of visible through shortwave infrared reflectance spectroscopy to effectively provide high-throughput classification of wheat stripe rust severity and identify important spectral regions for classification accuracy. Random forest models were developed using both leaf-level and canopy-level hyperspectral reflectance observations collected across a breeding population that was scored for WSR severity using 10 and 5 severity classes, respectively. The models were able to accurately diagnose scored disease severity class across these fine scoring scales between 45-52% of the time, which improved to 79-96% accuracy when allowing scores to be off-by-one. The canopy-level model demonstrated higher accuracy and distinct spectral characteristics relative to the leaf-level models, pointing to the use of this technology for field-scale monitoring. Leaf-level model performance was strong despite clear variation in scoring conducted between wheat growth stages. Two approaches to reduce predictor and model complexity, principal component dimensionality reduction and backward feature elimination, were applied here. Both approaches demonstrated that model classification skill could remain high while simplifying high-dimensional hyperspectral reflectance predictors, with parsimonious models having approximately 10 unique components or wavebands. Through the use of a high-resolution infection severity scoring methodology this study provides one of the most rigorous tests of the use of hyperspectral reflectance observations for WSR classification. We demonstrate that machine learning in combination with a few carefully-selected wavebands can be leveraged for precision remote monitoring and management of WSR to limit crop damage and to aid in the selection of resilient germplasm in breeding programs. [ABSTRACT FROM AUTHOR]

Background: Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods: This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden's index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results: Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG's area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer's 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p < 0.001), other invasive fungal infections (OR 4.46; 95% CI 2.10–9.49, p < 0.001) and gram-negative bacteremia (OR 29.02; 95% CI 9.03–93.23, p < 0.001). The application of optimal BDG cut-off values determined by Youden's index (252 pg/ml, 390 pg/ml, and 202 pg/ml) specific for all patients and subgroups with or without confounders improved the specificity (79%, 74%, and 88%) and corresponding PPV (75%, 65%, and 85%), while maintaining reasonable sensitivity and NPV. Conclusions: Tailoring serum BDG cutoff specific to PJP and incorporating consideration of confounders could enhance serum BDG's diagnostic performance in the ICU settings. [ABSTRACT FROM AUTHOR]

Dermatomycoses are the most widespread fungal skin infections worldwide and directly affect patients' quality of life. They are challenging to manage because of the need for prolonged treatment and the development of resistance to antifungal agents. This article studies the antifungal activity of trifluoromethylthiolated cinnamate derivatives on Candida species and dermatophytes as well as possible mechanisms of action, irritability, and cytotoxicity tests. These molecules show activity against dermatophyte fungi with minimum inhibitory concentrations (MIC) as low as 0.39 μg mL−1. In particular, chloroaromatic derivatives demonstrated the best inhibition profile (1.56–6.25 μg mL−1). Importantly, our series of molecules were not active against Candida spp., being selective for dermatophytes. A study of the mechanism of action suggests that our SCF3 cinnamates do not bind directly to ergosterol or the cell wall. The physicochemical parameters and the absence of irritability resulting from the HET‐CAM test demonstrate that compound 8 can be considered a future candidate for the therapy of dermatophytosis. [ABSTRACT FROM AUTHOR]