Exploring the frontiers of therapeutic breadth of antifungal peptides: A new avenue in antifungal drugs.

The growing prevalence of fungal infections alongside rising resistance to antifungal drugs poses a significant challenge to public health safety. At the close of the 2000s, major pharmaceutical firms began to scale back on antimicrobial research due to repeated setbacks and diminished economic gains, leaving only smaller companies and research labs to pursue new antifungal solutions. Among various natural sources explored for novel antifungal compounds, antifungal peptides (AFPs) emerge as particularly promising. Despite their potential, AFPs receive less focus than their antibacterial counterparts. These peptides have been sourced extensively from nature, including plants, animals, insects, and especially bacteria and fungi. Furthermore, with advancements in recombinant biotechnology and computational biology, AFPs can also be synthesized in lab settings, facilitating peptide production. AFPs are noted for their wide-ranging efficacy, in vitro and in vivo safety, and ability to combat biofilms. They are distinguished by their high specificity, minimal toxicity to cells, and reduced likelihood of resistance development. This review aims to comprehensively cover AFPs, including their sources-both natural and synthetic-their antifungal and biofilm-fighting capabilities in laboratory and real-world settings, their action mechanisms, and the current status of AFP research. ONE-SENTENCE SUMMARY: This comprehensive review of AFPs will be helpful for further research in antifungal research.

A rare cause of malignant otitis externa and skull base osteomyelitis.

An elderly male with type 2 diabetes presented with a 2-month history of otalgia and severe headaches. He was diagnosed with malignant otitis externa (MOE) and was commenced on empirical treatment with oral ciprofloxacin. Pseudomonas is the most common cause of MOE. A baseline CT scan was undertaken that demonstrated skull base osteomyelitis (SBO) due to findings of bone erosion at the mastoid tip and an infiltrating soft tissue mass eroding the clivus. Eight weeks later, he returned with worsening and bilateral symptoms of otitis externa, hearing loss, temporomandibular pain and dysfunction. Worsening and now bilateral malignant otitis externa were confirmed with an MRI scan that also demonstrated a small fluid collection in his left temporal region. The collection was aspirated and grew scedosporium apiospermum. He was diagnosed with fungal SBO and was commenced on treatment with the antifungal voriconazole, with significant improvement in symptoms and radiological findings. Fungal osteomyelitis is more likely in immunosuppressed patients, particularly those with type 2 diabetes. Fungal aetiology should be suspected in patients with progressive symptoms, despite treatment. A microbiology diagnosis of fungal SBO or MOE can be challenging to obtain and can lead to diagnostic delay. A sampling of the external auditory canal can aid in diagnosing MOE; however, scedosporium may also be isolated as a commensal organism. Aspirations from accessible fluid collections, infratemporal fossa needle sample and bone biopsy can provide material for diagnosis. Scedosporium is a rare cause of disease in humans, however, fungal infections are increasing in humans, due to an increase in susceptible populations. Scedosporium apiospermum is a rare cause of SBO and should be considered in patients not responding to standard treatment.

[The preliminary application of mNGS in the diagnosis of invasive fungal sinusitis].

Objective: By conducting a retrospective analysis of the clinical data of 14 patients diagnosed with invasive fungal rhinosinusitis (IFRS) confirmed by metagenomics next generation sequencing (mNGS) technology, we aim to explore the rapid diagnosis value of mNGS in IFRS. Methods: The clinical data of 14 IFRS patients admitted to TianJin First Central Hospital were retrospectively analyzed from February 2021 to October 2023. The study cohort comprised 8 males and 6 females, with ages ranging from 14 to 77 years. All patients were diagnosed as IFRS by performing mNGS sequencing technology of nasal sinus lesion biopsy specimens. Clinical data such as laboratory examination, imaging examination, histopathological examination results, treatment plan and prognosis were summarized and analyzed. Results: All 14 patients were diagnosed as IFRS, with mNGS detecting pathogens such as Rhizopus (7 cases), Aspergillus (5 cases), Trichoderma (1 case), and Scedosporium apiospermum (1 case). Follow-up evaluations were conducted for a period ranging from 2 months to 2 years post-treatment. At the end of follow-up, 11 out of 14 IFRS patients achieved a complete cure with no signs of recurrence, while the symptoms of the remaining 3 patients significantly improved with comprehensive treatment. Conclusion: mNGS emerges as a highly effective diagnostic tool for IFRS, providing valuable microbiological evidence for clinical diagnosis and demonstrating promising clinical utility.

Clinical Approach to Dental Root Canal Filler-Induced Maxillary Sinus Fungal Mass Using Transnasal Endoscopy.

Accidentally extruded root canal filler within the sinuses may induce maxillary sinusitis with fungal mass. The authors describe 2 cases of gutta-percha-induced fungal masses in the left maxillary sinus of 2 women. The lesions were evaluated preoperatively using both computed tomography and magnetic resonance imaging, providing comprehensive insights into the condition. In one patient, the lesion was located such that it could be resected through the middle meatal antrostomy alone. However, the second patient presented with an anteroinferiorly situated lesion that necessitated not only a transnasal approach but also an endoscopic modified medial maxillectomy. Both patients recovered uneventfully after surgery. This case series is the first published report of 2 cases of gutta-percha-induced maxillary sinus fungal masses, with their imaging findings, successfully treated through different routes through transnasal endoscopic surgery. These reports highlight the need for a collaborative approach between dental practitioners and otolaryngologists. In addition to the patient's wishes, surgical interventions must consider the unique characteristics of each case and the potential for collaboration across different medical specialties.

Impact of lumacaftor/ivacaftor on the bacterial and fungal respiratory pathogens in cystic fibrosis: a prospective multicenter cohort study in Sweden.

BACKGROUND: A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden. OBJECTIVES: The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden. DESIGN: The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor. METHODS: Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed. RESULTS: Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive. CONCLUSION: The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.

Clinical performance of metagenomic next-generation sequencing for diagnosis of invasive fungal disease after hematopoietic cell transplant.

Background: Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. Methods: We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Results: Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. Conclusion: mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.

Devastating fungal endocarditis involving ascending aorta in a patient with a history of aortic valve replacement: a case report.

BACKGROUND: Fungal endocarditis is a rare but serious condition associated with high mortality rates. Various predisposing factors contribute to its occurrence, such as underlying cardiac abnormalities, cardiac surgeries, prosthetic cardiac devices, and central venous catheters. Diagnosing fungal endocarditis, particularly Aspergillus, poses challenges, often complicated by negative blood cultures. CASE PRESENTATION: This report details a case of extensive ascending aorta involvement in Aspergillus endocarditis (AE) in a 24-year-old man with a history of bioprosthesis aortic valve replacement (AVR). Three months post-AVR, he presented with pericardial effusion and aortic rupture, leading to a redo biological valved conduit aortic root replacement (Bentall surgery). Despite the intervention, the tubular graft exhibited extensive Aspergillus involvement, resulting in graft disruption and significant peri-aortic infection. A second redo procedure involving aortic homograft root replacement was performed. Unfortunately, the patient succumbed two days after the surgery. CONCLUSION: A combined approach of medical and surgical therapies is recommended to manage fungal endocarditis. Despite efforts, the mortality rate associated with Aspergillus endocarditis remains unacceptably high, with no significant difference observed between combination therapy and antifungal treatment alone. Further research is essential to explore novel therapeutic strategies and improve outcomes for patients with this challenging condition.

Effect of ozone gas on cultures of Candida albicans and Aspergillus fumigatus: evaluation of two ozonation devices.

INTRODUCTION: Candida albicans and Aspergillus fumigatus are two important agents of Healthcare-associated infections. This study aimed to evaluate the antifungal activity of ozone (O3) gas produced by two commercial devices against cultures of these two species. METHODOLOGY: Sterile plastic plates were inoculated with C. albicans and A. fumigatus and placed on a countertop at three distances (30 cm, 1 m, and 2 m) and three positions in relation to the wall (near, middle, and away), considering the source of O3. Plates were exposed to O3 for one hour and incubated. After incubation, the counting of colony-forming units was performed. As a control, an inoculated plate was incubated, without being exposed to O3. Tests were carried out with two different devices (namely, Mod.I and Mod.II), with the air conditioner on and off, in triplicate. RESULTS: Both devices showed antifungal activity. Mod. I presented better results, due to a higher flow rate. The best activity was on plates at 30 cm, middle position. Contrarily, on plates at 2m, near the wall, the inhibition activity was lower. The best results were obtained with the air conditioner off. Candida albicans was more sensitive to O3 than A. fumigatus. CONCLUSIONS: This method of decontamination by O3 gas shows potential due to its fast and easy execution. The establishment of new protocols for hygiene and hospital disinfection using this approach should be considered, which may reduce environmental contamination by fungi and, consequently, the burden of fungal infections.

An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection.

Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by Candida colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection. IMPORTANCE: In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.

Triazole antifungal drug interactions-practical considerations for excellent prescribing.

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.

Development and validation of machine learning-based models for predicting healthcare-associated bacterial/fungal infections among COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work. OBJECTIVE: We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection. METHODS: In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability. RESULTS: A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769. CONCLUSIONS: Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.

iAFPs-Mv-BiTCN: Predicting antifungal peptides using self-attention transformer embedding and transform evolutionary based multi-view features with bidirectional temporal convolutional networks.

Globally, fungal infections have become a major health concern in humans. Fungal diseases generally occur due to the invading fungus appearing on a specific portion of the body and becoming hard for the human immune system to resist. The recent emergence of COVID-19 has intensely increased different nosocomial fungal infections. The existing wet-laboratory-based medications are expensive, time-consuming, and may have adverse side effects on normal cells. In the last decade, peptide therapeutics have gained significant attention due to their high specificity in targeting affected cells without affecting healthy cells. Motivated by the significance of peptide-based therapies, we developed a highly discriminative prediction scheme called iAFPs-Mv-BiTCN to predict antifungal peptides correctly. The training peptides are encoded using word embedding methods such as skip-gram and attention mechanism-based bidirectional encoder representation using transformer. Additionally, transform-based evolutionary features are generated using the Pseduo position-specific scoring matrix using discrete wavelet transform (PsePSSM-DWT). The fused vector of word embedding and evolutionary descriptors is formed to compensate for the limitations of single encoding methods. A Shapley Additive exPlanations (SHAP) based global interpolation approach is applied to reduce training costs by choosing the optimal feature set. The selected feature set is trained using a bi-directional temporal convolutional network (BiTCN). The proposed iAFPs-Mv-BiTCN model achieved a predictive accuracy of 98.15 % and an AUC of 0.99 using training samples. In the case of the independent samples, our model obtained an accuracy of 94.11 % and an AUC of 0.98. Our iAFPs-Mv-BiTCN model outperformed existing models with a ~4 % and ~5 % higher accuracy using training and independent samples, respectively. The reliability and efficacy of the proposed iAFPs-Mv-BiTCN model make it a valuable tool for scientists and may perform a beneficial role in pharmaceutical design and research academia.

Infectious Diseases of the Brain and Spine: Fungal Diseases.

Advances in treatments of autoimmune diseases, acquired immunodeficiency syndrome, organ transplantation, and the use of long-term devices have increased the rates of atypical infections due to prolonged immune suppression. There is a significant overlap in imaging findings of various fungal infections affecting the central nervous system (CNS), often mimicking those seen in neoplastic and noninfectious inflammatory conditions. Nonetheless, there are imaging characteristics that can aid in distinguishing certain atypical infections. Hence, familiarity with a wide range of infectious agents is an important part of diagnostic neuroradiology. In this article, an in-depth review of fungal diseases of the CNS is provided.

Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.

BACKGROUND: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation. METHODS: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections. RESULTS: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex. CONCLUSIONS: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Epidemiology of fungal infection in COVID 19 in Spain during 2020 and 2021: a nationwide study.

We realize a nationwide population-based retrospective study to analyze the characteristics and risk factors of fungal co-infections in COVID-19 hospitalized patients as well as describe their causative agents in the Spanish population in 2020 and 2021. Data were obtained from records in the Minimum Basic Data Set of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health, and annually published with two years lag. The assessment of the risk associated with the development of healthcare-associated fungal co-infections was assessed using an adjusted logistic regression model. The incidence of fungal co-infection in COVID-19 hospitalized patients was 1.41%. The main risk factors associated were surgery, sepsis, age, male gender, obesity, and COPD. Co-infection was associated with worse outcomes including higher in-hospital and in ICU mortality, and higher length of stay. Candida spp. and Aspergillus spp. were the microorganisms more frequent. This is the first study analyzing fungal coinfection at a national level in hospitalized patients with COVID-19 in Spanish population and one of the few studies available that demonstrate that surgery was an independent risk factor of Aspergillosis coinfection in COVID-19 patients.

Estrogen contamination increases vulnerability of amphibians to the deadly chytrid fungus.

Aquatic contaminants and infectious diseases are among the major drivers of global amphibian declines. However, the interaction of these factors is poorly explored and could better explain the amphibian crisis. We exposed males and females of the Brazilian Cururu Toad, Rhinella icterica, to an environmentally relevant concentration of the estrogen 17-alpha-ethinylestradiol (an emerging contaminant) and to the chytrid infection (Batrachochytrium dendrobatidis), in their combined and isolated forms, and the ecotoxicity was determined by multiple biomarkers: cutaneous, hematological, cardiac, hepatic, and gonadal analysis. Our results showed that Cururu toads had many physiological alterations in response to the chytrid infection, including the appearance of cutaneous Langerhans's cells, increased blood leukocytes, increased heart contraction force and tachycardia, increased hepatic melanomacrophage cells, which in turn led to gonadal atrophy. The estrogen, in turn, increased the susceptibility of the toads to the chytrid infection (higher Bd loads) and maximized the deleterious effects of the pathogen: reducing leukocytes, decreasing the contraction force, and causing greater tachycardia, increasing hepatic melanomacrophage cells, and leading to greater gonadal atrophy, which were more extreme in females. The exposure to estrogen also revealed important toxicodynamic pathways of this toxicant, as shown by the immunosuppression of exposed animals, and the induction of the first stages of feminization in males, which corroborates that the synthetic estrogen acts as an endocrine disruptor. Such an intricate relationship is unprecedented and reinforces the importance of studying the serious consequences that multiple environmental stressors can cause to aquatic populations.

Sphenoid Sinus Mucosal Flap after Transsphenoidal Surgery-A Systematic Review.

Background and Objectives: Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and lateral shifting of sphenoid mucosa as sphenoid mucosal flap (SMF) during the transsphenoidal exposure of the sella may be important for later closure. This is the first systematic review to evaluate the utility of sphenoid mucosal flap for sellar reconstruction after transsphenoidal surgery. Materials and Methods: A systematic literature search was performed in January 2023: Cochrane, EMBASE, PubMed, Scopus, and Web of Science. The following keywords and their combinations were used: "sphenoid mucosa", "sphenoid sinus mucosa", "sphenoid mucosal flap", "sphenoid sinus mucosal flap". From a total number of 749 records, 10 articles involving 1671 patients were included in our systematic review. Results: Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a vascularized pedicled flap or as a free flap. Three different types of mucosal flaps, an intersinus septal flap, a superiorly based flap and an inferiorly based flap, were described in the literature. Total SMF covering compared to partial or no SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks (p = 0.008) and a shorter duration of the postoperative lumbar drain (p = 0.003), if applied. Total or partial SMF resulted in fewer local complications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation. Conclusions: SMF seems to be an effective technique for skull base reconstruction after transsphenoidal surgery, as it can reduce the usage of avascular grafts such as fat along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis and fungal infection, or it may improve the sinonasal quality of life by maintaining favorable wound healing through vascular flap and promote the normalization of the sphenoid sinus posterior wall. Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, particularly for higher-grade CSF leaks, are required.

Fungal infection mimicking soft tissue lesion: Role of on-site evaluation, special stain, and cellblock.

BACKGROUND: Fine-needle aspiration (FNA) cytology is a basic diagnostic method used for the investigation of superficial and deep lesions. The implementation of rapid on-site evaluation (ROSE) in cytological analysis can help in reducing the inadequacy rate and obtaining proper samples for further tests/analysis. CASE PRESENTATION: We report a case of 44-year-old male, who presented to our outpatient department with complaints of swelling in his right arm for the last 34 years. FNA with ROSE using 1% aq. toluidine blue helped identify the pathology (fungal lesion) in the patient with further confirmation by cellblock, periodic acid Schiff & Gomori methenamine silver stains. CONCLUSION: The role of FNA was significant in the above case, special stains prove their efficacy when sufficient sample is available. The differential diagnosis of fungal etiology should be considered in subcutaneous soft tissue lesions. There has been a major leap in diagnostic cytopathology with the advent of molecular testing. However, FNA still holds its charm.

Physio-molecular responses of tomato cultivars to biotic stress: Exploring the interplay between Alternaria alternata OP881811 infection and plant defence mechanisms.

Plant fungal diseases impose a formidable challenge for global agricultural productivity, a meticulous examination of host-pathogen interactions. In this intricate study, an exhaustive investigation was conducted on infected tomatoes obtained from Egyptian fields, leading to the precise molecular identification of the fungal isolate as Alternaria alternata (OP881811), and the isolate showed high identity with Chinese isolates (ON973896 and ON790502). Subsequently, fourteen diverse tomato cultivars; Cv Ferment, Cv 103, Cv Damber, Cv 186, Cv 4094, Cv Angham, Cv N 17, Cv Gesma, Cv 010, Cv branch, cv 2020, Cv 023, Cv Gana and Cv 380 were meticulously assessed to discern their susceptibility levels upon inoculation with Alternaria alternata. Thorough scrutiny of disease symptom manifestation and the extent of tomato leaf damage ensued, enabling a comprehensive evaluation of cultivar responses. Results unveiled a spectrum of plant susceptibility, with three cultivars exhibiting heightened vulnerability (Cv Ferment, Cv 103 and Cv Damber), five cultivars displaying moderate susceptibility (Cv 186, Cv 4094, Cv Angham, Cv N 17 and Cv Gesma), and six cultivars demonstrating remarkable resilience to the pathogen (Cv 010, Cv branch, cv, 2020; Cv 023, Cv Gana and Cv 380). In order to gain a thorough understanding of the underlying physiological patterns indicative of plant resistance against A. alternata, an in-depth exploration of polyphenols, flavonoids, and antioxidant enzymes ensued. These key indicators were closely examined, offering valuable insights into the interplay between plant physiology and pathogen response. Robust correlations emerged, with higher contents of these compounds correlating with heightened susceptibility, while lower levels were indicative of enhanced plant tolerance. In tandem with the physiological assessment, a thorough investigation of four pivotal defensive genes (PR5, PPO, PR3, and POX) was undertaken, employing cutting-edge Real-Time PCR technology. Gene expression profiles displayed intriguing variations across the evaluated tomato cultivars, ultimately facilitating the classification of cultivars into distinct groups based on their levels of resistance, moderate susceptibility, or heightened sensitivity. By unravelling the intricate dynamics of plant susceptibility, physiological responses, and patterns of gene expression, this comprehensive study paves the way for targeted strategies to combat plant fungal diseases. The findings contribute valuable insights into host-pathogen interactions and empower agricultural stakeholders with the knowledge required to fortify crop resilience and safeguard global food security.