Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and in trans effects on the protein regulatory network.

Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response to different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT053, SUT468) or rRNA processing (SUT075 and snR30). Overall, these data capture and integrate the regulatory and phenotypic network of ncRNAs and protein-coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.

Large-scale profiling of noncoding RNA function in yeast.

Noncoding RNAs (ncRNAs) are emerging as key regulators of cellular function. We have exploited the recently developed barcoded ncRNA gene deletion strain collections in the yeast Saccharomyces cerevisiae to investigate the numerous ncRNAs in yeast with no known function. The ncRNA deletion collection contains deletions of tRNAs, snoRNAs, snRNAs, stable unannotated transcripts (SUTs), cryptic unstable transcripts (CUTs) and other annotated ncRNAs encompassing 532 different individual ncRNA deletions. We have profiled the fitness of the diploid heterozygous ncRNA deletion strain collection in six conditions using batch and continuous liquid culture, as well as the haploid ncRNA deletion strain collections arrayed individually onto solid rich media. These analyses revealed many novel environmental-specific haplo-insufficient and haplo-proficient phenotypes providing key information on the importance of each specific ncRNA in every condition. Co-fitness analysis using fitness data from the heterozygous ncRNA deletion strain collection identified two ncRNA groups required for growth during heat stress and nutrient deprivation. The extensive fitness data for each ncRNA deletion strain has been compiled into an easy to navigate database called Yeast ncRNA Analysis (YNCA). By expanding the original ncRNA deletion strain collection we identified four novel essential ncRNAs; SUT527, SUT075, SUT367 and SUT259/691. We defined the effects of each new essential ncRNA on adjacent gene expression in the heterozygote background identifying both repression and induction of nearby genes. Additionally, we discovered a function for SUT527 in the expression, 3' end formation and localization of SEC4, an essential protein coding mRNA. Finally, using plasmid complementation we rescued the SUT075 lethal phenotype revealing that this ncRNA acts in trans. Overall, our findings provide important new insights into the function of ncRNAs.

Anatomical and Clinical Implications in Neocondyle Stability After a Condylectomy.

: 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.

A resource for functional profiling of noncoding RNA in the yeast Saccharomyces cerevisiae.

Eukaryotic genomes are extensively transcribed, generating many different RNAs with no known function. We have constructed 1502 molecular barcoded ncRNA gene deletion strains encompassing 443 ncRNAs in the yeast Saccharomyces cerevisiae as tools for ncRNA functional analysis. This resource includes deletions of small nuclear RNAs (snRNAs), transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and other annotated ncRNAs as well as the more recently identified stable unannotated transcripts (SUTs) and cryptic unstable transcripts (CUTs) whose functions are largely unknown. Specifically, deletions have been constructed for ncRNAs found in the intergenic regions, not overlapping genes or their promoters (i.e., at least 200 bp minimum distance from the closest gene start codon). The deletion strains carry molecular barcodes designed to be complementary with the protein gene deletion collection enabling parallel analysis experiments. These strains will be useful for the numerous genomic and molecular techniques that utilize deletion strains, including genome-wide phenotypic screens under different growth conditions, pooled chemogenomic screens with drugs or chemicals, synthetic genetic array analysis to uncover novel genetic interactions, and synthetic dosage lethality screens to analyze gene dosage. Overall, we created a valuable resource for the RNA community and for future ncRNA research.

Corticosteroid treatment is associated with increased filamentous fungal burden in allergic fungal disease.

BACKGROUND: Allergic diseases caused by fungi are common. The best understood conditions are allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Our knowledge of the fungal microbiome (mycobiome) is limited to a few studies involving healthy individuals, asthmatics, and smokers. No study has yet examined the mycobiome in fungal lung disease. OBJECTIVES: The main aim of this study was to determine the mycobiome in lungs of individuals with well-characterized fungal disease. A secondary objective was to determine possible effects of treatment on the mycobiome. METHODS: After bronchoscopy, ribosomal internal transcribed spacer region 1 DNA was amplified and sequenced and fungal load determined by real-time PCR. Clinical and treatment variables were correlated with the main species identified. Bronchopulmonary aspergillosis (n = 16), severe asthma with fungal sensitization (n = 16), severe asthma not sensitized to fungi (n = 9), mild asthma patients (n = 7), and 10 healthy control subjects were studied. RESULTS: The mycobiome was highly varied with severe asthmatics carrying higher loads of fungus. Healthy individuals had low fungal loads, mostly poorly characterized Malasezziales. The most common fungus in asthmatics was Aspergillus fumigatus complex and this taxon accounted for the increased burden of fungus in the high-level samples. Corticosteroid treatment was significantly associated with increased fungal load (P < .01). CONCLUSIONS: The mycobiome is highly variable. Highest loads of fungus are observed in severe asthmatics and the most common fungus is Aspergillus fumigatus complex. Individuals receiving steroid therapy had significantly higher levels of Aspergillus and total fungus in their bronchoalveolar lavage.

[A case of rare laryngeal neurogenic tumor].

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.

History of genome editing in yeast.

For thousands of years humans have used the budding yeast Saccharomyces cerevisiae for the production of bread and alcohol; however, in the last 30-40 years our understanding of the yeast biology has dramatically increased, enabling us to modify its genome. Although S. cerevisiae has been the main focus of many research groups, other non-conventional yeasts have also been studied and exploited for biotechnological purposes. Our experiments and knowledge have evolved from recombination to high-throughput PCR-based transformations to highly accurate CRISPR methods in order to alter yeast traits for either research or industrial purposes. Since the release of the genome sequence of S. cerevisiae in 1996, the precise and targeted genome editing has increased significantly. In this 'Budding topic' we discuss the significant developments of genome editing in yeast, mainly focusing on Cre-loxP mediated recombination, delitto perfetto and CRISPR/Cas.

Investigation of sinonasal anatomy via low-dose multidetector CT examination in chronic rhinosinusitis patients with higher risk for perioperative complications.

The aim of the study was to compare visualisation of the surgically relevant anatomical structures via low- and standard-dose multidetector CT protocol in patients with chronic rhinosinusitis (CRS) and higher risk for perioperative complications (i.e. presence of bronchial asthma, history of sinus surgery and advanced nasal polyposis). 135 adult CRS patients were divided randomly into standard-dose (120 kVp, 100 mAs) or low-dose CT groups (120 kVp, 45 mAs). The detectability of the vital anatomical structures (anterior ethmoid artery, optic nerve, cribriform plate and lamina papyracea) was scored using a five-point scale (from excellent to unacceptable) by a radiologist and sinus surgeon. Polyp sizes were quantified endoscopically according to the Lildholdt's scale (LS). Olfactory function was tested with the "Sniffin' Sticks" test. On the low-dose CT images, detectability ranged from 2.42 (better than poor) for cribriform plate among anosmic cases to 4.11 (better than good) for lamina papyracea in cases without nasal polyps. Identification of lamina papyracea on low-dose scans was significantly worse in each group and the same was the case with cribriform plates in patients with advanced polyposis and anosmia. Cribriform plates were the most poorly identified (between poor and average) among all the structures on low-dose images. Identification of anterior ethmoid artery (AEA) with reduced dose was insignificantly worse than with standard-dose examination. The AEA was scored as an average-defined structure and was the second weakest visualised. In conclusion, preoperatively, low-dose protocols may not sufficiently visualise the surgically relevant anatomical structures in patients with CRS and bronchial asthma, advanced nasal polyps (LS > 2) and history of sinus surgery. Low mAs value enables comparable detectability of sinonasal landmarks with standard-dose protocols in patients without analysed risk factors. In the context of planned surgery, the current preferences of the tube should be carefully evaluated for different patient constitutions to minimise the risk of complications.

Non-coding RNAs and disease: the classical ncRNAs make a comeback.

Many human diseases have been attributed to mutation in the protein coding regions of the human genome. The protein coding portion of the human genome, however, is very small compared with the non-coding portion of the genome. As such, there are a disproportionate number of diseases attributed to the coding compared with the non-coding portion of the genome. It is now clear that the non-coding portion of the genome produces many functional non-coding RNAs and these RNAs are slowly being linked to human diseases. Here we discuss examples where mutation in classical non-coding RNAs have been attributed to human disease and identify the future potential for the non-coding portion of the genome in disease biology.

The usefulness of free dicom viewers in rhinologic practice.

Indroduction: The planning of the course of surgery in patients with paranasal sinus disorders requires the meticulous evaluation of computed tomography (CT) scans. However, ENT doctors still often receive unsatisfactory DICOM images, which require multiplanar reconstruction (MPR). THE AIM: The objective of the present study was to evaluate and test DICOM viewers with MPR function currently available on the Internet for free. MATERIAL AND METHODS: Detailed Internet searches and analysis of databases were carried out to find the maximum number of browsers. Available software was downloaded to assess, qualitatively and quantitatively, the parameters and functions useful in rhinologic practice. Additionally, a questionnaire was developed in order to ascertain the expectations and habits of ENT doctors in relation to DICOM browsers and CT scan evaluation. RESULTS AND CONCLUSIONS: Among the hundreds of browsers, 17 programs were chosen to be included in the final comparison. The outcomes of the survey proved that many free DICOM tools are effective alternatives to commercially available programs. However, the results do not enable us to predict precisely which tool will meet the needs of each physician. The survey among ENT doctors highlighted their limited awareness of software with MPR functions, in particular those that scored best in the test.

The usefulness of free dicom viewers in rhinologic practice.

Indroduction: The planning of the course of surgery in patients with paranasal sinus disorders requires the meticulous evaluation of computed tomography (CT) scans. However, ENT doctors still often receive unsatisfactory DICOM images, which require multiplanar reconstruction (MPR). THE AIM: The objective of the present study was to evaluate and test DICOM viewers with MPR function currently available on the Internet for free. MATERIAL AND METHODS: Detailed Internet searches and analysis of databases were carried out to find the maximum number of browsers. Available software was downloaded to assess, qualitatively and quantitatively, the parameters and functions useful in rhinologic practice. Additionally, a questionnaire was developed in order to ascertain the expectations and habits of ENT doctors in relation to DICOM browsers and CT scan evaluation. RESULTS AND CONCLUSIONS: Among the hundreds of browsers, 17 programs were chosen to be included in the final comparison. The outcomes of the survey proved that many free DICOM tools are effective alternatives to commercially available programs. However, the results do not enable us to predict precisely which tool will meet the needs of each physician. The survey among ENT doctors highlighted their limited awareness of software with MPR functions, in particular those that scored best in the test.

IMPACT OF GENISTEIN AND PHYTIC ACID ON THE VIABILITY AND PROLIFERATION ACTIVITY OF NASAL POLYPS' CELLS IN AN IN VITRO MODEL.

In developed countries, chronic rhinosinusitis with nasal polyps is one of the diseases that diminish patients' quality of life most significantly. Treatment of that often incurable disease is based on the steroids and surgery in patients who had failed thorough conservative management. It appears that the introduction of new treatment agents suppressing inflammation process and inhibiting cells' proliferation would be a valuable therapeutic option. The aim of the present study was to evaluate the in vitro effect of genistein and phytic acid on the viability and growth rate of fibroblasts derived from nasal polyps. Cells were incubated with various concentrations of genistein (5-500 µM) and phytic acid (100-20,000 µM). After 72 h incubation, cells survivability and cells' growth rate were estimated by combination of WST-1 and LDH methods. QRT-PCR technique was used to determine the expression of histone H3, BCL-2, BAX and P53 genes. Caspase-8 and -9 expressions were evaluated by ELISA assay. Genistein and phytic acid significantly and in dose-specific manner decreased nasal polyps fibroblasts survivability and growth rate. Both agents in similar way decreased cell proliferation as measured by the expression of histone H3. They induce apoptotic machinery by modulating the expression of BCL-2, BAX and caspase-8 activity. Genistein and phytic acid have significant potential for a therapeutic role in the treatment of chronic rhinosinusitis.

ANTIPROLIFERATIVE AND CYTOTOXIC EFFECT OF SELECTED VITAMIN D ANALOGS ON NASAL POLYPS FIBROBLASTS AND OTHER CELLS WITH HIGHER PROLIFERATIVE POTENTIAL.

Besides well-known effect on bone and mineral metabolism vitamin D is involved in essential non-calcemic regulatory mechanisms, such as cellular proliferation, differentiation and apoptosis in various cell types. Major limitation for therapeutic use of calcitriol, a hormonally active form of vitamin D, is its calcemic and phosphatemic action. Recently, more selective vitamin D analogs which retain clinically useful activities with reduced toxicity have been designed. The aim of the present study was to evaluate the in vitro effect of vitamin D analogs on proliferation rate and survivability of cells with increased proliferative activity. The effect of calcitriol, PRI-2191, PRI-1890, PRI-1906 and PRI-2205 was examined. The experiments were performed on cultures derived from nasal polyps and cancer cells lines (SNB-19, C32 and SH-4). Cultures were incubated 72 h with tested compounds, each at the concentration of 0.025, 0.25, 2.5 and 25 µg/mL. The cytotoxic effect of vitamin D analogs and their influence on growth rate were determined using WST-1 assay. RT-QPCR technique was used to evaluate the expression of anti-apoptotic BCL-2 and pro-apoptotic BAX gene. Each of the tested compounds presented significant effect at the concentrations above 0.25 µg/mL. The strongest inhibition of the growth rate and decrease in cell survivability was observed after treatment with PRI-1890 and PRI-2191. Stimulation with calcitriol and other vitamin D analogs led to decrease BCL-2/BAX mRNA ratio in each cell lines. The apparent pro-apoptotic action revealed PRI-2191 followed by PRI-1890. It might be hypothesized that vitamin D analogs supplementation may provide therapeutic benefits not only in oncological patients but also in chronic rhinosinusitis.

[Bilateral squamous carcinoma of the external auditory canal--a case report]. / Obustronny rak plaskonablonkowy przewodu sluchowego zewnetrznego--opis przypadku.

Squamous cell carcinoma of the external auditory canal is a very rare and unusual malignancy, representing less than 0.2% of all head and neck cancers. The authors present a case of 78-year-old patient with bilateral squamous cell carcinoma of the external auditory canal-cT4N0M0 G2, pT4N2bM0, initially treated as a chronic otitis external. The patient was qualifies for the one-step removal of cancer of the earlobe and the external auditory canal. Because of complications during the operation, the plan of treatment was changed. The patient is under oncological control for 13 months.

Volume dependency for culture of fungi from respiratory secretions and increased sensitivity of Aspergillus quantitative PCR.

Diagnosis of aspergillosis is often difficult. We compared fungal yields from respiratory specimens using the Health Protection Agency standard culture method (BSOP57), a higher volume undiluted culture method Mycology Reference Centre Manchester (MRCM) and Aspergillus quantitative real time polymerase chain reaction (qPCR). Sputum, bronchial aspirate and bronchoalveolar lavage (BAL) samples (total 23) were collected from aspergillosis patients. One fraction of all samples was cultured using the MRCM method, one BSOP57 and one was used for qPCR. The recovery rate for fungi was significantly higher by MRCM (87%) than by BSOP57 (8.7%) from all 23 specimens. Sputum samples were 44% positive by MRCM compared to no fungi isolated (0%) by BSOP57. Bronchial aspirates were 75% positive by MRCM and 0% by BSOP57. BAL samples were positive in 20% by MRCM and 10% by BSOP57. qPCR was always more sensitive than culture (95.6%) from all samples. In general, over 100 mould colonies (81 Aspergillus fumigatus) were grown using the MRCM method compared with only one colony from BSOP57. This study provides a reference point for standardisation of respiratory sample processing in diagnostic laboratories. Culture from higher volume undiluted respiratory specimens has a much higher yield for Aspergillus than BSOP57. qPCR is much more sensitive than culture and the current UK method requires revision.

Olfaction-associated quality of life: Polish adaptation and validation of a Questionnaire of Olfactory Disorders (QOD-PL) in patients with chronic rhinosinusitis.

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.

The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus.

OBJECTIVES: Recent increases in triazole resistance in Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates in Manchester showed that >50% of resistant isolates had no mutation in cyp51A or its promoter. We investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51A mutations. METHODS: Twelve azole-resistant isolates, 10 of which were itraconazole resistant, were studied. Bioinformatic comparisons between Candida albicans efflux genes and A. fumigatus genome data identified 20 putative azole transporter genes. Basal and azole-induced expression of these genes and cyp51A was quantified using RT-PCR with comparison with clinical azole-susceptible isolates. Function of high basal or itraconazole-induced expression transporters was tested by gene knockout in azole-susceptible and azole-resistant isolates. RESULTS: All susceptible strains showed minimal basal expression of cdr1B compared with 8 of 10 azole-resistant strains with high basal expression of this gene (>5-fold), 3 of which showed >30-fold increased expression. Knockout of this gene resulted in a 4-fold reduction in itraconazole, posaconazole and voriconazole MICs for a susceptible clinical isolate and a 4-fold reduction in itraconazole susceptibility in a clinical resistant isolate. One strain showed a >500-fold induction of cyp51A. No increase in basal expression or expression after induction was seen for the 18 remaining putative transporters. CONCLUSIONS: The reasons behind the shift away from target site mutation in azole-resistant isolates from Manchester are unknown. The modest change in expression of cdr1B in azole-susceptible strains implies that only study of resistant isolates will lead to further understanding of resistance mechanisms in A. fumigatus.

Telomere-to-telomere genome sequence of the model mould pathogen Aspergillus fumigatus.

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.

High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease.

BACKGROUND: Oral triazole therapy is well established for the treatment of invasive (IPA), allergic (ABPA), and chronic pulmonary (CPA) aspergillosis, and is often long-term. Triazole resistance rates are rising internationally. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the frequency of triazole resistance. METHODS: Using an ultrasensitive real-time polymerase chain reaction (PCR) assay for Aspergillus spp., we assessed respiratory fungal load in bronchoalveolar lavage (BAL) and sputum specimens. In a subset of PCR-positive, culture negative samples, we further amplified the CYP51A gene to detect key single-nucleotide polymorphisms (SNPs) associated with triazole resistance. RESULTS: Aspergillus DNA was detected in BAL from normal volunteers (4/11, 36.4%) and patients with culture or microscopy confirmed IPA (21/22, 95%). Aspergillus DNA was detected in sputum in 15 of 19 (78.9%) and 30 of 42 (71.4%) patients with ABPA and CPA, compared with 0% and 16.7% by culture, respectively. In culture-negative, PCR-positive samples, we detected triazole-resistance mutations (L98H with tandem repeat [TR] and M220) within the drug target CYP51A in 55.1% of samples. Six of 8 (75%) of those with ABPA and 12 of 24 (50%) with CPA had resistance markers present, some without prior triazole treatment, and in most despite adequate plasma drug concentrations around the time of sampling. CONCLUSIONS: The very low organism burdens of fungi causing infection have previously prevented direct culture and detection of antifungal resistance in clinical samples. These findings have major implications for the sustainability of triazoles for human antifungal therapy.

Comparison of the clinical differences between COVID-19, SARS, influenza, and the common cold: A systematic literature review.

BACKGROUND: This review focuses on the frequency of symptoms in COVID-19 in comparison to SARS, influenza and common cold. OBJECTIVES: To evaluate and compare 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). CONCLUSION: 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.