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Introda significant: Onychomycosis is the most common nail disorder seen in clinical practice, and it may have significant impact on patient quality of life. Understanding risk factors for onychomycosis may help to devise screening and treatment guidelines for populations that are more susceptible to this infection. Using a national database, we aimed to explore associations between onychomycosis and age, sex, and underlying medical conditions, as well as to examine current onychomycosis treatment trends. Materials and Methods: We performed a nested, matched, case-control study of patients in the All of Us database aged ≥ 18 years (6 May 2018-1 January 2022). Onychomycosis cases were identified using International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine (SNOMED) diagnostic codes (ICD-9 110.1, ICD-10 B35.1, SNOMED 414941008). Demographic information (i.e., age, sex, and race), treatments, and co-diagnoses for onychomycosis patients and case-controls were recorded. Wald\'s test applied to multivariate logistic regression was used to calculate odds ratios and p-values between onychomycosis and co-diagnoses. Additionally, 95% confidence intervals were calculated with a proportion test. Results: We included 15,760 onychomycosis patients and 47,280 matched controls. The mean age of onychomycosis patients was 64.9 years, with 54.2% female, 52.8% Non-Hispanic White, 23.0% Black, 17.8% Hispanic, and 6.3% other, which was similar to controls. Patients with onychomycosis vs. controls were more likely to have a co-diagnosis of obesity (46.4%, OR 2.59 [2.49-2.69]), tinea pedis (21.5%, OR 10.9 [10.1-11.6]), peripheral vascular disease (PVD) (14.4%, OR 3.04 [2.86-3.24]), venous insufficiency (13.4%, OR 3.38 [3.15-3.59]), venous varices (5.6%, OR 2.71 [2.47-2.97]), diabetes mellitus (5.6%, OR 3.28 [2.98-3.61]), and human immunodeficiency virus (HIV) (3.5%, OR 1.8 [1.61-2.00]) (p < 0.05, all). The most frequently prescribed oral and topical medications were terbinafine (20.9%) and ciclopirox (12.4%), respectively. The most common therapeutic procedure performed was debridement (19.3%). Over the study period, ciclopirox prescriptions (Spearman correlation 0.182, p = 0.0361) and fluconazole prescriptions increased (Spearman correlation 0.665, p = 2.44 × 10-4), and griseofulvin (Spearman correlation -0.557, p = 0.0131) and itraconazole prescriptions decreased (Spearman correlation -0.681, p = 3.32 × 10-6). Conclusions: Our study demonstrated that age, obesity, tinea pedis, PVD, venous insufficiency, diabetes mellitus, and HIV were significant risk factors for onychomycosis. In addition, the most frequent oral and topical onychomycosis medications prescribed were terbinafine and ciclopirox, likely reflective of efficacy and cost considerations. Identifying and managing these risk factors is essential to preventing onychomycosis\' primary infections and recurrences and improving treatment efficacy.

Background Dermatophytosis is a public health concern in tropical countries. In India, a scalable number of dermatophytosis cases from multiple states are reported. In the eastern part of India, very few studies were published assessing the clinicomycological profiles of patients. Hence, we conducted this study to ascertain the clinicomycological profile of patients suffering from dermatophytosis with special reference to associated socio-environmental factors. Materials and methods This cross-sectional observational study was conducted in a tertiary care hospital situated in Bihar state of India from January 2021 to December 2021. We included a total of 330 patients of all age groups who were clinically diagnosed with superficial mycosis from the Department of Dermatology and sent for investigations to the Department of Microbiology. The collected specimens from the lesions were prepared with wet potassium hydroxide and examined under the microscope. Then, the specimens were inoculated and incubated at 25°C for up to four weeks. Fungal isolates were identified by gross appearance and microscopy if growth was observed. Results Among the 330 patients, 186 (56.4%) were males and 144 (43.6%) were females. The majority of the patients (54.5%) were from the low socioeconomic group and living in overcrowded places. Direct microscopy was positive in 198 (60%) patients, and culture was positive in 68 (20.61%) patients. The majority of the patients who were found positive in direct microscopy were from the age group of 21-30 years (39.9%), followed by 1-10 years (25.25%). A total of 92 (46.4%) cases were of tinea capitis, followed by 68 (34.3%) patients of tinea corporis. Trichophyton was the predominant fungus isolated, and Trichophyton mentagrophytes was the most common species (52.6%). Conclusion Tinea capitis was the most common provisionally diagnosed dermatophytosis in our tertiary care hospital in Bihar, an Indian state in its eastern zone. Low socioeconomic status and poor personal hygiene were the factors associated with the high prevalence of dermatophyte infections in this region of India. A detailed analysis of all these epidemiological factors is needed to limit the prevalence of dermatophytosis in tropical regions.

UNASSIGNED: The study aimed to determine the prevalence and pathogens of invasive fungal infection (IFI) among intensive care unit (ICU) patients. The next goal was to investigate the association between empirical antifungal treatment and mortality in ICU patients.
UNASSIGNED: Using microbiological events, we identified all ICU patients with IFI and then retrieved electronic clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The data were statistically analyzed using t-tests, chi-square tests, log-rank tests, and Cox regression.
UNASSIGNED: The most commonly reported fungi were Candida (72.64%) and Aspergillus (19.08%). The most frequently prescribed antifungal medication was fluconazole (37.57%), followed by micafungin (26.47%). In the survival study of ICU patients and patients with sepsis, survivors were more likely to receive empirical antifungal treatment. In contrast, non-empirical antifungal therapy was significantly associated with poor survival in patients with positive blood cultures. We found that the current predictive score makes an accurate prediction of patients with fungal infections challenging.
UNASSIGNED: Our study demonstrated that empirical antifungal treatment is associated with decreased mortality in ICU patients. To avoid treatment delays, novel diagnostic techniques should be implemented in the clinic. Until such tests are available, appropriate empirical antifungal therapy could be administered based on a model that predicts the optimal time to initiate antifungal therapy. Additional studies should be conducted to establish more accurate predictive models in the future.

The para-terphenyl derivative vialinin A (Vi-A), isolated from Thelephora fungi, has been characterized as a potent inhibitor of the ubiquitin-specific protease 4 (USP4). Blockade of USP4 contributes to the anti-inflammatory and anticancer properties of the natural product. We have investigated the interaction of Vi-A with USP4 by molecular modeling, to locate the binding site (around residue V98 within the domain in USP segment) and to identify the binding process and interaction contacts. From this model, a series of 32 p-terphenyl compounds were tested as potential USP4 binders, mainly in the vialinin, terrestrin and telephantin series. We identified 11 compounds presenting a satisfactory USP4 binding capacity, including two fungal products, vialinin B and aurantiotinin A, with a more favorable empirical energy of USP4 interaction (ΔE) than the reference product Vi-A. The rare p-terphenyl aurantiotinin A, isolated from the basidiomycete T. aurantiotincta, emerged as a remarkable USP4 binder. Structure-binding relationships have been identified and discussed, to guide the future design of USP4 inhibitors based on the p-terphenyl skeleton. The docking study should help the identification of other protease inhibitors from fungus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotic therapy. A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospitals were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in the respiratory tract and bloodstream were associated with a higher risk of death than that in the urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS.

Little is known about the relationship of COVID-19 outcomes with onychomycosis. We investigated the relationship of onychomycosis with COVID-19 outcomes. A retrospective cohort study was performed on SARS-CoV-2 positive adult outpatients or inpatients who had onychomycosis and other skin diseases. Overall, 430 adults were identified with SARS-CoV-2 and a skin disease, including 98 with diagnosed onychomycosis. In bivariable logistic regression models, onychomycosis was associated with increased hospitalization {odds ratio(OR) [95% confidence interval (CI)]: 3.56 [2.18-5.80]}, initial inpatient vs. outpatient visits (OR [95% CI]: 2.24 [1.35-3.74]), use of oxygen therapy (OR [95% CI]: 2.77 [1.60-4.79]), severe-critical vs. asymptomatic-mild severity (OR [95% CI]: 2.28 [1.32-3.94]), and death (OR [95% CI]: 7.48 [1.83-30.47]) from COVID-19, but not prolonged hospitalization (OR [95% CI]: 1.03 [0.47-2.25]). In multivariable models adjusting for socio-demographics, comorbidities, and immunosuppressant medication use, the associations with onychomycosis remained significant for hospitalization, inpatient visits, oxygen therapy, severe-critical COVID-19. Onychomycosis was a significant independent risk factor for COVID-19 severity, hospitalization, and receiving supplemental oxygen therapy.

Chitosan oligosaccharides (COS) are a derivative of low molecular weight chitosan and are potent natural antimicrobial agents. The antimicrobial activity of COS against Aspergillus flavus and Aspergillus fumigatus was evaluated by minimum inhibitory concentration (MIC) and inhibition of mycelial growth. The MICs of COS against these two fungi were 31.2 and 15.6 mg/mL, respectively. COS treatment rendered fungal mycelia wrinkled and deformed with a fractured appearance. COS also increased cellular permeability leading to a significant leakage of cellular components indicating membrane damage. This compound also dose-dependently reduced chitin production and enhanced chitinase activity while enhancing the accumulation of reactive oxygen species (ROS). These characteristics suggested that COS has inhibitory effects against food spoilage fungi and acts on the cell wall and membrane and alters cellular metabolism. COS shows promise for food industry applications since it is non-toxic to higher organisms.

Postoperative mediastinitis, a feared complication after cardiac surgery, is associated with high mortality, especially of critically ill patients. Candida species infections are rare and severe, with poorly known outcomes. We conducted a case-control study to describe the characteristics, management and outcomes of patients with postoperative Candida mediastinitis.
This French, monocentre, retrospective study included all patients with postoperative Candida mediastinitis (January 2003-February 2020) requiring intensive care unit admission. Candida mediastinitis patients (henceforth cases) were matched 1:1 with postoperative bacterial mediastinitis (henceforth control), based on 3 factors during mediastinitis management: age >40 years, cardiac transplantation and invasive circulatory device used. The primary end point was the probability of survival within 1 year after intensive care unit (ICU) admission.
Forty cases were matched to 40 controls. The global male/female ratio was 2.1, with mean age at admission 47.9 ± 13.8 years. Candida species were: 67.5% albicans, 17.5% glabrata, 15% parapsilosis, 5.0% tropicalis, 2.5% krusei and 2.5% lusitaniae. The median duration of mechanical ventilation was 23, 68.8% of patients received renal replacement therapy and 62.5% extracorporeal membrane oxygenation support. The probability of survival within the first year after ICU admission was 40 ± 5.5% and was significantly lower for cases than for controls (43 ± 8% vs 80 ± 6.3%, respectively; Log-rank test: P < 0.0001). The multivariable Cox proportional hazards model retained only renal replacement therapy [hazard ratio (HR) 3.7, 95% confidence interval (CI) 1.1-13.1; P = 0.04] and Candida mediastinitis (HR 2.4, 95% CI 1.1-5.6; P = 0.04) as independently associated with 1-year mortality.
Candida mediastinitis is a serious event after cardiac surgery and independently associated with 1-year mortality. Further studies are needed to determine whether deaths are directly attributable to Candida mediastinitis.

Postharvest fruit decay is caused by fungal pathogens and leads to major losses. In this study, specific mRNA sequences that are upregulated in the fungus Colletotrichum gloeosporioides during its quiescent stage in fruits, were identified using a CMOS sensor. The identification process was based on sandwich approach, where strands complementary to the C. gloeosporioides mRNA sequences (quiescent stage-specific) were immobilized on the CMOS surface, and exposed to the target complementary reporter strands. In the presence of a target sequence, the reporter strand (linked to the enzyme horseradish peroxidase (HRP)) was left in the system and a measurable light signal was produced. The complementary strands specifically anneal to the mRNA in the sample. The sensitivity of the technology was assessed by mRNA sequences isolated from C. gloeosporioides, and identified as 10 nM RNA. The effect of the pathogenicity state on the sensor performance was also evaluated. The CMOS sensor could detect quiescent fungi, which are barely detectable by other means. The unique capability of the proposed system to detect and recognize the fungus during both pathogenic and quiescent stages, will allow the development of new sensors that can monitor the amount of undetectable quiescent fungi in harvested fruit, enabling improved food management.