Harnessing Intranasal Delivery Systems of Sumatriptan for the Treatment of Migraine

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.

Anatomical Evaluation of Root and Root Canal Configuration of Permanent Maxillary Dentition in the Population of the Kingdom of Saudi Arabia

Aim. This study is aimed at combining the sample sizes of all studies on permanent maxillary teeth conducted in different regions of the Kingdom of Saudi Arabia (KSA) to obtain a large sample size that represents the population of the KSA. The outcome of these combined studies is compared with international studies in terms of the number of roots, number of canals, and canal configurations on the basis of Vertucci’s classification. Methodology. The studies were systematically reviewed using the Preferred Reporting Items for Systematic Review and Meta-analysis chart. Studies were included in the analysis if they were conducted in the KSA, involved permanent human maxillary teeth, and had a sample of more than 10 teeth (power). By contrast, studies were excluded if they involved deciduous teeth in the sample size, investigated nonhuman teeth, were not conducted in the KSA, and were case reports, case series, review studies, and anomalies. Relevant literature was searched from PubMed, Scopus, Web of Science, Embase, Cochrane, and Direct Science by two calibrated teams, starting in August 2020, without time limits or language restrictions. Results. The database searches and cross-referencing identified a total of 19 relevant studies. All maxillary canines ( N = 1,018 ) had one root, whereas 98.4% had one canal and 98.3% had Vertucci type I. Moreover, 63.2% of the maxillary first premolars had two roots, and 91.4% had two canals. The most common Vertucci root canal configuration was type IV (64.6%). The maxillary second premolars mostly had one root (84.4%) and one canal (50.4%). The most common canal configuration was Vertucci type I (47.1%). The majority of maxillary first molars had three roots (98.9%), 48.7% of which had three canals, and 46.4% had four canals. The most prevalent feature of the canal morphology of mesiobuccal roots was Vertucci type II (35.3%). The investigated maxillary second molars had three roots, 88.0% of which had three canals. Conclusion. This systematic review represents the Saudi population since samples were combined from different studies from different regions of the country. Variations in findings were observed in the same group of teeth from different regions and the same region, while the overall combined samples results fell within the range of other international studies.

Genetic and Chemical Diversity of Edible Mushroom Pleurotus Species

The genus Pleurotus is one of the most widely cultivated and edible mushrooms with various cultivators. Three molecular characteristics were used to evaluate the genetic diversity of 132 tested samples. Phylogenetic analysis showed five clades for tested samples of the genus Pleurotus by the combined ITS and LSU sequences with strong bootstraps and Bayesian posterior probability supports. A total of 94 polymorphic fragments ranging from 10 to 100 bp were observed by using an intersimple sequence repeat (ISSR) marker. The DNA fragment pattern showed that P. ostreatus cultivator (strain P9) was clearly distinguished from wild strain based on their clear banding profiles produced. DNA GC content of the genus Pleurotus varied from 55.6 mol% to 43.3 mol%. Their chemical composition was also determined, including sugar, amino acid, polar lipid, mycolic acid, quinone, and fatty acid, which presented some high homogeneity. Most of the tested samples contained mycolic acid; glucose and arabinose as the main sugars; aspartic acid, arginine, lysine, tyrosine, and alanine as the main amino acids; and C16:0, C18:0, C18:2cis-9,12, anteiso-C14:0, and summed feature 8 as the main fatty acids. In addition, their polar lipid profiles were investigated for the first time, which significantly varied among Pleurotus species. The genus Pleurotus contained menaquinone-6 as the sole respiratory quinone, which showed a significant difference with that of its closely related genera. These results of this study demonstrated that the combined method above could efficiently differentiate each Pleurotus species and thus be considered an efficient tool for surveying the genetic diversity of the genus Pleurotus.

A U-Net Approach to Apical Lesion Segmentation on Panoramic Radiographs

The purpose of the paper was the assessment of the success of an artificial intelligence (AI) algorithm formed on a deep-convolutional neural network (D-CNN) model for the segmentation of apical lesions on dental panoramic radiographs. A total of 470 anonymized panoramic radiographs were used to progress the D-CNN AI model based on the U-Net algorithm (CranioCatch, Eskisehir, Turkey) for the segmentation of apical lesions. The radiographs were obtained from the Radiology Archive of the Department of Oral and Maxillofacial Radiology of the Faculty of Dentistry of Eskisehir Osmangazi University. A U-Net implemented with PyTorch model (version 1.4.0) was used for the segmentation of apical lesions. In the test data set, the AI model segmented 63 periapical lesions on 47 panoramic radiographs. The sensitivity, precision, and F1-score for segmentation of periapical lesions at 70% IoU values were 0.92, 0.84, and 0.88, respectively. AI systems have the potential to overcome clinical problems. AI may facilitate the assessment of periapical pathology based on panoramic radiographs.

Research Trends and Hotspots of Q Fever Research: A Bibliometric Analysis 1990-2019

Q fever is a worldwide distributed zoonosis caused by Coxiella burnetii, a Gram-negative bacterium. Despite existence of large amount of research data on the developments related to Q fever, no bibliometric analysis of this subject is available to our knowledge. Bibliometric studies are an essential resource to track scholarly trends and research output in a subject. This study is aimed at reporting a bibliometric analysis of publications related to Q fever (2,840 articles published in the period 1990-2019) retrieved from Science Citation Index Expanded, an online database of Clarivate Analytics Web of Science Core Collection. Data was retrieved using keywords “Q fever” or “Coxiella burnetii” in title, abstract, and author keywords to describe important research indicators such as the kind and language of articles, the most important publications, research journals and categories, authors, institutions, and the countries having the most significant contribution to this subject. Finally, the emerging areas in field of diagnosis, host range, and clinical presentation were identified. Word cluster analysis of research related to Q fever revealed that major focus of research has been on zoonosis, seroprevalence, laboratory diagnosis (mainly using ELISA and PCR), clinical manifestations (abortion and endocarditis), vectors (ticks), and hosts (sheep, goat, and cattle). This bibliometric study is intended to visualize the existing research landscape and future trends in Q fever to assist in future knowledge exchange and research collaborations.

Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus envelope and the host cell plasma membrane as a critical mechanism of infection. Metadichol®, a nanolipid emulsion of long-chain alcohols, has been demonstrated as a strong candidate that inhibits the proliferation of SARS-CoV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce viral infectivity, including that of coronaviruses (such as SARS-CoV-2) by modifying their lipid-dependent attachment mechanism to human host cells. The receptor ACE2 mediates the entry of SARS-CoV-2 into the host cells, whereas the serine protease TMPRSS2 primes the viral S protein. In this study, Metadichol® was found to be 270 times more potent an inhibitor of TMPRSS2 ( E C 50 = 96 ng / mL ) than camostat mesylate ( E C 50 = 26000 ng / mL ). Additionally, it inhibits ACE with an EC50 of 71 ng/mL, but it is a very weak inhibitor of ACE2 at an EC50 of 31 μg/mL. Furthermore, the live viral assay performed in Caco-2 cells revealed that Metadichol® inhibits SARS-CoV-2 replication at an EC90 of 0.16 μg/mL. Moreover, Metadichol® had an EC90 of 0.00037 μM, making it 2081 and 3371 times more potent than remdesivir ( E C 50 = 0.77 μ M ) and chloroquine ( E C 50 = 1.14 μ M ), respectively.

Mupirocin-Resistant Staphylococcus aureus in Iran: A Biofilm Production and Genetic Characteristics

The spread of mupirocin-resistant Staphylococcus aureus strains in hospitals and communities is a universal challenge. Limited data is available on the genetic features of high-level mupirocin resistant- (HLMUPR-) S. aureus isolates in Tehran. In the present research, we investigated 48 high-level mupirocin resistance S. aureus by antimicrobial activity, virulence analysis, biofilm formation, multilocus sequence typing (MLST), and staphylocoagulase (SC) typing. All the HLMUPR strains were positive for mupA gene. The frequency of multidrug resistance was 97.9%. Twenty-one (43.8%) were toxinogenic with 14 producing pvl (29.2%), 5 tst (10.4%), and two eta (4.2%). Among the HLMUPR isolates, biofilm production was detected in 45 (89.6%) isolates with complete dominance clfB, clfA genes, and a noticeably high frequency fnbA (95.8%), followed by fnbB (93.8%), eno and icaD (each 83.3%), sdrC (81.3%), ebps (79.2%), icaA (75%), sdrD (66.7%), fib (60.4%), sdrE (50%), cna (41.7%), and bap (4.2%). Coagulase typing distinguished isolates into four genotypic patterns including III (50%), II (27.1%), and type IVa (22.9%). A total of three clonal complexes (CCs) and 4 sequence types (STs) including CC/ST22 as the most prevalent (52.1%), CC8/ST239 (20.8%), CC/ST8 (16.7%), and CC/ST5 (10.4%) were identified in current work. According to our analysis, nonbiofilm producer isolates belonged to CC8/ST239 (6.3%) and CC/ST8 (4.2%). Fusidic acid-resistant isolates belonged to CC/ST45 ( n = 3 ) and CC8/ST239 ( n = 1 ). Observations highlighted the circulation of the CC/ST22 HLMUPR S. aureus strains with strong biofilm-production ability in our hospitals, indicating the possibility of transmission of this type between community and hospital.

Perfusion-Diffusion Ratio: A New IVIM Approach in Differentiating Solid Benign and Malignant Primary Lesions of the Liver

Introduction. In order to improve the efficacy of intravoxel incoherent motion (IVIM) parameters in characterising specific tissues, a new concept is introduced: the perfusion–diffusion ratio (PDR), which expresses the relationship between the signal S b decline rate as a result of IVIM and the rate of signal S b decline due to diffusion. The aim of this study was to investigate this novel approach in the differentiation of solid primary liver lesions. Material and Methods. Eighty-three patients referred for liver MRI between August 2017 and January 2020 with a suspected liver tumour were prospectively examined with the standard liver MRI protocol extended by DWI-IVIM sequence. Patients with no liver lesions, haemangiomas, or metastases were excluded. The final study population consisted of 34 patients with primary solid liver masses, 9 with FNH, 4 with regenerative nodules, 10 with HCC, and 11 with CCC. The PDR coefficient was introduced, defined as the ratio of the rate of signal S b decrease due to the IVIM effect to the rate of signal S b decrease due to the diffusion process, for b = 0 . Results. No significant differences were found between benign and malignant lesions in the case of IVIM parameters ( f , D , or D ∗ ) and ADC. Significant differences were observed only for PDR, with lower values for malignant lesions ( p = 0.03 ). The ROC analysis yielded an AUC value for PDR equal to 0.74, with a cut-off value of 5.06, sensitivity of 81%, specificity of 77%, and accuracy of 79%. Conclusion. PDR proved to be more effective than IVIM parameters and ADC in the differentiation of solid benign and malignant primary liver lesions.

Bioinformatic Analysis Identifies Biomarkers and Treatment Targets in Primary Sjögren’s Syndrome Patients with Fatigue

We aim to identify the common genes, biological pathways, and treatment targets for primary Sjögren’s syndrome patients with varying degrees of fatigue features. We select datasets about transcriptomic analyses of primary Sjögren’s syndrome (pSS) patients with different degrees of fatigue features and normal controls in peripheral blood. We identify common differentially expressed genes (DEGs) to find shared pathways and treatment targets for pSS patients with fatigue and design a protein-protein interaction (PPI) network by some practical bioinformatic tools. And hub genes are detected based on the PPI network. We perform biological pathway analysis of common genes by Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Lastly, potential treatment targets for pSS patients with fatigue are found by the Enrichr platform. We discovered that 27 DEGs are identified in pSS patients with fatigue features and the severe fatigued pSS-specific gene is RTP4. DEGs are mainly localized in the mitochondria, endosomes, endoplasmic reticulum, and cytoplasm and are involved in the biological process by which interferon acts on cells and cells defend themselves against viruses. Molecular functions mainly involve the process of RNA synthesis. The DEGs of pSS are involved in the signaling pathways of viruses such as hepatitis C, influenza A, measles, and EBV. Acetohexamide PC3 UP, suloctidil HL60 UP, prenylamine HL60 UP, and chlorophyllin CTD 00000324 are the four most polygenic drug molecules. PSS patients with fatigue features have specific gene regulation, and chlorophyllin may alleviate fatigue symptoms in pSS patients.

Qiguiyin Decoction Improves Multidrug-Resistant Pseudomonas aeruginosa Infection in Rats by Regulating Inflammatory Cytokines and the TLR4/MyD88/NF-κB Signaling Pathway

Pseudomonas aeruginosa (PA), a Gram-negative bacterium, has a high detection rate in hospital-acquired infections. Recently, the frequent appearance of multidrug-resistant (MDR) PA strain with high morbidity and mortality rates has aggravated the difficulty in treating infectious diseases. Due to its multiple resistance mechanisms, the commonly used antibiotics have gradually become less effective. Qiguiyin decoction (QGYD) is a clinically experienced prescription of Chinese herbal medicine, and its combined application with antibiotics has been confirmed to be effective in the clinical treatment of MDR PA infection, which could be a promising strategy for the treatment of drug-resistant bacterial infections. However, the mechanism of QGYD restoring antibiotics susceptibility to MDR PA remains unclear. In the present study, we investigated the effects of QGYD and levofloxacin (LEV) singly or in combination on MDR PA-induced pneumonia rat models. Further analysis was carried out in the serum differential expression profiles of inflammatory cytokines by cytokine antibody array. Besides, the lung TLR4/MyD88/NF-κB signaling pathway was detected by RT-qPCR. Our results showed that based on the treatment of MDR PA-infected rat model with LEV, the combination of QGYD improved the general state and immune organ index. Furthermore, it moderately increased the expressions of proinflammatory cytokines including IL-1β, IL-6, and TNF-α in the early stage of infection and decreased their release rapidly in the later stage, while regulated the same phase change of anti-inflammatory cytokine IL-10. In addition, the adhesion molecule ICAM-1 was significantly downregulated after QGYD combined with LEV treatment. Moreover, the mRNA expressions of TLR4, MyD88, NF-κB, and ICAM-1 were significantly downregulated. These results indicated that the mechanism of QGYD restoring LEV susceptibility to MDR PA was related to its regulation of inflammatory cytokines and the TLR4/MyD88/NF-κB signaling pathway, which provides theoretical support for the clinical application of QGYD combined with LEV therapy to MDR PA infection.