Recent data suggests one fungus, Aspergillus fumigatus, causes more deaths annually than HIV or malaria combined. Coupled with rapid emergence of antifungal drug resistance, the limited range of effective treatments, and mortality rates of >50%, aspergillosis represents a major challenge in infectious diseases. Recent studies have identified long-noncoding RNAs (lncRNAs) involved in drug resistance and virulence in pathogenic yeasts such as Candida spp. However, there is very limited knowledge of lncRNAs in human pathogenic moulds, including A. fumigatus. Here we exploit transcriptomics data of A. fumigatus exposed to different environments to annotate transcripts mapping to 2388 genomic loci. After manual curation we generate a database of over 1000 lncRNAs. We observe that the lncRNAs display orchestrated transcriptional profiles upon drug treatment and many are proximal to genes involved in azole sensitivity. We knock out a set of intergenic lncRNAs and perform a large-scale phenotypic analysis to identify 60 lncRNA mutants displaying condition-dependent fitness changes with 35 mutants exhibiting a positive growth phenotype under azole stress. Overall, this study generates and experimentally validates an important resource that will enable the wider research community to increase understanding of the functional importance of lncRNAs in A. fumigatus, including their involvement in drug sensitivity.

Sleep disorders have emerged as a significant public health issue, adversely affecting quality of life and precipitating severe complications. The association between obstructive sleep apnea syndrome (OSAS) and otolaryngological manifestations appears to be underrecognized. This study posits that manifestations in the ear, nose and throat (ENT) among patients with OSAS and users of continuous positive airway pressure (CPAP) therapy are relatively common. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, this systematic review, registered at PROSPERO (No. CRD42023452473), involved a comprehensive search of the MEDLINE databases. We included studies published in English from 1979 to March 2021 that explored the linkages between OSAS, CPAP and otolaryngological manifestations. A total of 29 articles were reviewed, with findings indicating 12 studies on ear dysfunctions, 11 on nose dysfunctions and 6 on pharynx dysfunctions. Reported symptoms included hearing dysfunction, vestibular function disorders, cerebrospinal fluid leak, Eustachian tube (ET) dysfunction, rhinosinusitis, olfaction and taste disorders, dysphagia, dry mouth, and gastroesophageal reflux. The etiology of these ailments varies, yet an understanding of these symptoms can improve the diagnosis to confirm or rule out OSAS. Early identification of ENT symptoms related to OSAS may facilitate prompt diagnosis and mitigate serious complications.

BACKGROUND:The focus on health-related quality of life (HRQOL) in medical research is becoming more and more intensive, with attention being paid to the patient's subjective feelings and assessment of one's health status. Smell disorders can significantly impact human life. The Questionnaire of Olfactory Disorders (QOD) is a self-monitoring questionnaire that provides subjective information about olfactory disorders.OBJECTIVES:This study aimed to check the reliability and validation of the Polish version of QOD (QOD-PL) for use in patients with olfactory impairment in Poland.MATERIAL AND METHODS:A total of 158 patients (76 females, mean age (Mage) 45.97 ±16.37 years), suffering from chronic rhinosinusitis (CRS), whose olfactory function was measured using the Sniffin' Sticks test (SST), were studied. All patients completed 3 validated questionnaires: Importance of Olfaction (IO), Sino-Nasal Outcome Test-22 (SNOT-22) and QOD-PL.RESULTS:Internal consistency and test-retest reliability of the entire QOD-PL scale were good (Cronbach's α = 0.88). The convergent validity of the QOD-PL and its subscales correlated with IO and SNOT-22. The life quality statements in the QOD-PL (QOD-PL-LQ) score, its negative statements, and the mean score for VAS scales were significantly and positively correlated with all symptoms measured with SNOT-22 and none of the IO scales.CONCLUSIONS:The QOD-PL is a reliable, valid and important tool for assessing HRQOL in patients with olfactory disorders. However, it is important to note that not all of its subscales can be considered and interpreted separately.

ABSTRACT The pathogenic fungus Aspergillus fumigatus is a major etiological agent of fungal invasive and chronic diseases affecting tens of millions of individuals worldwide. A high-quality reference genome is a fundamental resource to study its biology, pathogenicity and virulence as well as to discover better and more effective treatments against diseases caused by this fungus. Here, we used PacBio Single Molecule Real-Time (SMRT) and Oxford Nanopore sequencing for de novo genome assembly of two laboratory reference strains of A. fumigatus, CEA10 and A1160. We generated full length chromosome assemblies and a comprehensive telomere to telomere coverage for these two strains including ribosomal repeats and the sequences of centromeres, which we discovered to be composed of long transposon elements.

Recent studies identified non-coding RNAs (ncRNAs) with unknown function that are responsible for major fitness changes in yeast. To understand ncRNA interplay and aid their functional assignment, the synthetic genetic array (SGA) methodology was employed to create >15,000 double mutants and to score their epistasis in different environments. Unlike the protein network, ncRNAs mostly displayed positive epistasis in rich medium. Interestingly, the negative interactions significantly increased under stressors, showing environmental-dependent functions for ncRNAs. No correlation was found between the network of ncRNAs and that of their neighbouring genes, suggesting functional independence. The U3 paralogs, SNR17A and SNR17B, share the majority of genetic interactions in rich medium as expected. For example, SUT480 interacted with both paralogs and its function was linked to 18S rRNA processing. However, under stressors, a large number of unique epistatic interactions were observed, supporting the notion that SNR17A and SNR17B have diverged and sub-functionalised after genome duplication.

Introduction The effect of SARS-CoV-2 on hearing has not been thoroughly examined. Factors limiting hearing tests in COVID-19 patients are hygiene requirements and the need to use specialized equipment. The objective of the study was to assess changes in hearing thresholds between diagnosis of COVID-19 and convalescence using a mobile app. Material and methods Patients with mild to moderate COVID-19 symptoms, who were isolating at home were enrolled in the study between 1 September 2020 and 31 January 2021. Subjects answered an online medical survey and self-assessed hearing thresholds using the Hearing TestTM mobile app (e-audiologia.pl). These procedures were done twice, once at the time of diagnosis and again 2 weeks after convalescence. Results A total of 67 subjects were found eligible for the study. At most frequencies the patients’ hearing did not differ between the first and second examinations; however, for 4 kHz, a statistically significant improvement in the hearing threshold was found (p = 0.05). Survey review revealed noticeable improvement (p = 0.001) over time in smell, taste, and nasal congestion. Conclusions It seems that SARS-CoV-2 infection caused a transient and selective (at 4 kHz) hearing impairment in patients who had had mild to moderate infection. The results suggest that as olfactory function returns after COVID-19, an improvement in hearing can be expected. Solutions based on mobile technology are useful for monitoring the hearing of patients in a pandemic.

It is now accepted that non-coding RNAs (ncRNAs) play important functional roles in the cell. Recent studies in Saccharomyces cerevisiae have identified a diverse catalogue of ncRNAs, where the majority of which a function has yet to be ascribed. Large scale phenotypic screening and transcriptional analysis using the yeast ncRNAs deletion collection have identified ncRNAs responsible for major fitness changes in rich and minimal media. Here, to understand the interplay between these non-coding RNAs, the synthetic genetic array (SGA) methodology was employed to shed light on the epistasis and plasticity of key ncRNAs in different environmental conditions. Thirty-eight ncRNA query strains were crossed with a library of 411 ncRNAs deletion mutant strains, encompassing CUTs, SUTs, snoRNAs and tRNAs. Over 1000 significant genetic interactions were observed. Unlike the protein SGA genetic interaction network, for which the majority of interactions are negative, the ncRNAs mostly displayed positive epistasis (~90.2%). Interestingly, in the presence of stressors, a significant increase in negative interactions was observed, suggesting that these ncRNAs may have environmentally dependent functions or may differentially regulate neighbouring genes in different conditions. The vast majority of ncRNA interactions (>90%) did not correlate with the epistasis of their neighbouring protein coding genes, suggesting that the ncRNA and protein interaction networks are mainly independent. The two U3 paralogues, SNR17A and SNR17B, responsible for 18S rRNA processing, share the majority of genetic interactions in rich medium as expected. However, a surprising large number of unique epistatic interactions were observed for these two snoRNAs when grown in stressful conditions, suggesting that SNR17A and SNR17B may have other roles in the cell under different environmental pressures and may have sub-functionalised after genome duplication, likely driven by environmental adaptation. Additionally, SUT480 was found to interact with SNR17A and its function was linked to the processing of 18S rRNA. ### Competing Interest Statement The authors have declared no competing interest.

The pathogenic fungus Aspergillus fumigatus is a major etiological agent of fungal invasive and chronic diseases affecting tens of millions of individuals worldwide. Draft genome sequences of two clinical isolates (Af293 and A1163) are commonly used as reference genomes for analyses of clinical and environmental strains. However, the reference sequences lack coverage of centromeres, an accurate sequence for ribosomal repeats, and a comprehensive annotation of chromosomal rearrangements such as translocations and inversions. Here, we used PacBio Single Molecule Real-Time (SMRT), Oxford Nanopore and Illumina HiSeq sequencing for de novo genome assembly and polishing of two laboratory reference strains of A. fumigatus, CEA10 (parental isolate of A1163) and its descendant A1160. We generated full length chromosome assemblies and a comprehensive telomere-to-telomere coverage for CEA10 and near complete assembly of A1160 including ribosomal repeats and the sequences of centromeres, which we discovered to be composed of long transposon elements. We envision these high-quality reference genomes will become fundamental resources to study A. fumigatus biology, pathogenicity and virulence, and to discover more effective treatments against diseases caused by this fungus.

Background. This review focuses on the frequency of symptoms in COVID-19 in comparison to SARS, influenza and common cold. Objectives. To evaluate and compa re the knowledge about the clinical features, symptoms and differences between patients with COVID-19, SARS, influenza, and common cold. The research can help ear, nose and throat specialists and other health practitioners manage patients during the COVID-19 pandemic. Material and methods. The biomedical databases used in the study included PubMed and MEDLINE. Statistical analysis using the Z-score test assessed which symptoms were more characteristic of COVID-19 than other viral diseases. Results. Among individuals with COVID-19, the most frequently reported symptoms were cough (70%), fever (45%), muscular pain (29%), and headache (21%), whereas sore throat (12%), and rhinorrhea (4%) were observed at lower rates. Fever was identified as most frequent in COVID-19 (74%), appearing at a higher rate in those cases than in influenza (68%) or the common cold (40%) (p < 0.05). In comparison to other viral diseases, sore throat was rarely reported in COVID-19 and SARS (12% and 18%, respectively) (p <0.05). In influenza and common cold, a cough was identified in 93% and 80% of cases (p < 0.05). Headache, rhinorrhea, muscular pain, and sore throat were more common in influenza (91%, 91%, 94%, and 84%, respectively) and common cold (89%, 81%, 94%, and 84%, respectively) than in COVID-19 (21%, 4%, 29%, and 12%, respectively) and SARS (45%, 12%, 55%, and 18%, respectively) (p < 0.05). Conclusions. The results of the analysis show that a greater number of general symptoms should lead to a diagnosis of influenza or common cold rather than COVID-19.

The compound Congo red (CR) has been historically used for coloring treatment and histological examination as well to inhibit the growth of yeast and filamentous fungi. It has been thought that CR binds to β-1,3-glucans in the fungal cell wall, disrupting the organization of the cell wall structure.

Malignant tumours of the larynx account for 50% of all head and neck neoplasms. Squamous cell carcinoma is the most common malignancy of the larynx and accounts for 95-98%. Leiomyosarcoma (LMS) originating in larynx is a very rare malignant tumour derived from the smooth muscle tissue. The authors present a case of a 75-year man with coexistent squamous cell carcinoma and leiomyosarcoma in the larynx 15 years after radiation therapy for promany laryngeal cancer. Two cases of the synchronous presence of these neoplasms have been reported so far in English literature. This paper presents the clinical picture, radiological and histopathological diagnoses, and treatment of this case.

The COVID-19 pandemic has forced the introduction of rigorous actions to prevent the spread of the human coronavirus (SARS-CoV-2). This respiratory illness is generally spread by droplets, though it can also be transmitted through contact with hands or surfaces of contaminated objects. Therefore, keeping all frequently touched household surfaces, such as phones, faucets, door knobs, and fridge handles, germ-free has come to the forefront of everyone's mind more than ever before. This situation raises the question of whether these recommendations should also apply to hearing aids (HAs) and the external part of cochlear implants (CIs) since these are a potential reservoir for microorganisms. Behind-the-ear HAs, speech processors, external coils, and magnets are devices with relatively large surfaces that often face the interlocutor; therefore their casings may be easily contaminated by airborne droplets from the nose or mouth. In addition, these devices are frequently in contact with the hands of the owner, parent, or caregiver. Children may pull off the device in defiance or frustration or misplace hearing devices, e.g., while sitting in a car seat. Their devices are usually taken off during daily naps as well.Credit/Freepik, coronavirus, sanitization, infection control.Little is known about microbial flora on the external parts of CIs and HAs. Only one small study has demonstrated polymicrobial colonization in 70 percent of cases on the outer surfaces of HAs, but no viruses were included.1 It is also known from published data that SARS-CoV-2 could live the longest (even three to seven days) on plastic surfaces—the basic material of HA and CI casings.2 So the question is: How can these devices be disinfected? Device manufacturers recommend following the instructions in the user manuals and wiping HAs or speech processors using just a soft, dry cloth—not wipes with any type of alcohol or chemicals. However, simple mechanical cleaning with a dry cloth seems to be insufficient with the coronavirus pandemic. Today's need to disinfect hearing devices goes beyond the manufacturers' instructions. How can this be accomplished without soap or household detergents? UNDERSTANDING ANTIBACTERIAL ACTIVITIES It is worth mentioning the results of studies that compared four different cleaning procedures for eyeglass frames, which are contaminated in up to 90 percent of cases.3,4 The authors found that dry cleaning with tissues and microfiber cloths reduces bacterial counts significantly less than cleaning with impregnated wipes. At the same time, the efficacy of alcohol wipes (99% –100% median reduction in bacteria) is slightly higher than that of alcohol-free ones.4 Alcohol formulas, in the correct concentration, display antimicrobial activity against not only vegetative bacteria, mycoplasmas, and fungi but also viruses, including SARS-CoV-2. Although non-alcoholic wet wipes, which contain detergents or antiseptics, have antibacterial properties, they have limited or even no antiviral activity. Generally, many antibacterial agents cannot significantly affect the structure of a virus. Even if they are effective against the animal strains of coronaviruses, no evidence has yet been found that they are active against the human coronavirus. Thus, popular disinfecting wipes containing chlorhexidine gluconate may to some extent destroy SARS-CoV-2, but those that are saturated with triclosan or benzalkonium chloride will not. Since COVID-19 has only been around for a few months, many existing disinfectants have not yet been tested against the new strain of the virus. The U.S. Environmental Protection Agency (EPA) has compiled a constantly updated online list of products that—while not specifically tested on SARS-CoV-2—have been proven effective on similar or harder-to-kill viruses, such as the rhinovirus.5 Of note, many disinfectants that have alcohol in concentrations over 70 percent or contain chlorine, sodium hypochlorite, phenol, and ammonium can cause serious skin reactions, as well as functional or cosmetic damage to the surface of an object. For example, a 0.1 percent to 0.5 percent sodium hypochlorite solution (available in the form of wet wipes) effectively reduces coronaviral titer within one minute. This could help in disinfecting smartphones or CI remote controls, but not in wiping a speech processor, which comes in contact with the delicate skin behind the auricle.6 BALANCING SAFETY & INFECTION CONTROL To maintain a balance between successful disinfection and user safety based on off-label experiences, it seems reasonable to extend daily care procedures by cleaning speech processors or HAs with hand wipes or hygienic pads saturated with household hydrogen peroxide (3%). Such disinfection will be effective if the surfaces remain moist for at least one to two minutes. Although hydrogen peroxide deactivates many hard-to-kill viruses, it gradually loses its properties 30 to 45 days after the container has been opened.7,8 Therefore, the application of ethanol or isopropyl alcohol, which also destroys SARS-CoV-2, would be even more justified if we leave it on a surface for at least 30 seconds. The concentrations of those two disinfectants are crucial—less than 70 percent will not effectively kill SARS-CoV-2. Regardless of the cleaning agent used, the surface of a speech processor should be dried with a soft, clean cloth. Each type of speech processor is sensitive to a given disinfectant in a different way. If discoloration occurs on the case during cleaning, it must be stopped and the processor should be dried. Microphones are another part that can easily be damaged if cleaned in the manner described; thus, this practice is discouraged. Based on the bacteriological examinations of surgeons' eyeglasses, it can be concluded that the above recommendations should certainly be considered by health care professionals using HAs and CIs. It has been shown that the glasses of such people can be a source of surgical infection, suggesting that contamination can be caused not only by a surgeon's fingers but can also be spread through the air.9 Even the best disinfection of a speech processor or HA will bring limited results in the case of a person without sufficient personal hygiene. The most common way to transmit coronavirus is by our hands, which is why cleaning and disinfecting our hands with alcohol are very important. Hopefully, the current pandemic will strengthen the practice of proper personal hygiene habits in society.

The frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited. We reasoned that clinically relevant antifungal resistance could derive from transcriptional rewiring, promoting drug resistance without concomitant reductions in pathogenicity. Here we report a genome-wide annotation of transcriptional regulators in A. fumigatus and construction of a library of 484 transcription factor null mutants. We identify 12 regulators that have a demonstrable role in itraconazole susceptibility and show that loss of the negative cofactor 2 complex leads to resistance, not only to the azoles but also the salvage therapeutics amphotericin B and terbinafine without significantly affecting pathogenicity.

Background: Fatigue is an important symptom that negatively affects the quality of life of patients with many chronic diseases. Although it is reported to be one of the most impactful symptoms, fatigue is often overlooked or ignored by clinicians. Aims: The purpose of this study was to estimate the prevalence of fatigue and to determine its correlations with socio-demographic and health-related issues in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Material and methods: 138 CRSwNP patients and 102 healthy control subjects filled out the Multidimensional Fatigue Inventory (MFI), the Sino-Nasal Outcome Test-22 (SNOT-22), the Beck Depression Inventory (BDI) and the International Physical Activity Questionnaire (IPAQ). All subjects underwent a full ENT examination. Results: Fatigue reportedly affected 53% of the patients with CRSwNP. A high percentage (37%) of patients with severe fatigue was noted. Among the three dimensions of fatigue which were assessed, physical fatigue was the most frequently reported. Patients with severe fatigue were significantly less physically active and had a greater symptom burden on the SNOT-22 ( p < 0.05), but they did not differ in regard to the advancement of sinus disease. The BDI and SNOT-22 scores were also significant predictors of fatigue in CRSwNP patients (p < 0.001). Conclusion: Fatigue is common in patients with CRSwNP, with a particularly high percentage suffering from severe fatigue. Special attention should be paid to CRSwNP patients with higher SNOT22 scores.

Aspergillus fumigatus is a human pathogen and the principal etiologic agent of invasive and chronic aspergillosis leading to several hundreds of thousands of deaths every year. Very few antifungals are available to treat infections caused by A. fumigatus, and resistance is developing to those we have. Our understanding of the molecular mechanisms that drive pathogenicity and drug resistance have been hampered by the lack of large mutant collections, which limits our ability to perform functional genomics analysis. Here we present a high-throughput gene knockout method that combines a highly reproducible fusion PCR method to enable generation of gene replacement cassettes with a multiwell format transformation procedure. This process can be used to generate 96 null mutants within 5 days by a single person at a cost of less than £18 ($24) per mutant and is being employed in our laboratory to generate a barcoded genome-wide knockout library in A. fumigatus. © 2019 The Authors.

Laryngeal schwannoma is a rare benign tumour of the larynx. Schwannomas derive from the Schwann cells. Magnetic resonance imaging (MRI) is the best imaging tool for suggesting the diagnosis. We report case of laryngeal schwannoma. The case was a 61-year-old man with a 1-year history of dysphonia and stridor. Laryngoscopy revealed a submucosal mass of the glottic area. A computed tomography scan of the larynx showed an 26(CC) x 18 (TR) x 24 (AP)mm expansile mass in the glottic area. Histopathological examination diagnosed a schwannoma of the larynx. External surgeries were successfully performed. Diagnosis and specific treatment are discussed.

A condylectomy of the mandibular condyle is considered to be the treatment of choice in most cases of condylar head hyperactivity. The aim of the procedure is to remove the growth center of the mandible which is responsible for the mandibular enlargement and asymmetry. This surgical procedure has an impact on the condyle shape and position, but the restoration of mandibular movement and a stable joint position (namely, the proper alignment of the newly shaped condylar head within the condyle fossa) should also be considered important surgical outcomes. In this article, the authors present their own experience in performing condylectomies with an arthroplasty procedure and a special forced suturing technique (FST) in terms of achieving early, accurate mandibular movement and maintaining a stable condyle position in early and late outcomes. Materials and Methods: A modified high condylectomy with arthroplasty and FST results had been studied in anatomical, radiological, and clinical model. Results: Early findings after FST are promising. A slight improvement in lateral jaw movement was noted after condylectomy with arthroplasty (P < 0.05) both in early and late follow-up. Incisal opening, mandibular protrusion, and lateral movement were sustained. A stable condyle position within the fossa was achieved in each case of condylectomy with arthroplasty (P< 0.05). Conclusions: The FST condylectomy and reattachment of the lateral pterygoid muscle in a new, wider position provided an improvement in lateral jaw movement as well as in incisal opening and mandibular protrusion in early follow-up examination compared to the presurgical values. It seems that the FST enabled a better new condylar head position in the glenoid fossa and improved early functional mandibular movement.