Susceptibility-Weighted MRI for Predicting NF-2 Mutations and S100 Protein Expression in Meningiomas.

S100 protein expression levels and neurofibromatosis type 2 (NF-2) mutations result in different disease courses in meningiomas. This study aimed to investigate non-invasive biomarkers of NF-2 copy number loss and S100 protein expression in meningiomas using morphological, radiomics, and deep learning-based features of susceptibility-weighted MRI (SWI). This retrospective study included 99 patients with S100 protein expression data and 92 patients with NF-2 copy number loss information. Preoperative cranial MRI was conducted using a 3T clinical MR scanner. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and subsequent registration of FLAIR to high-resolution SWI was performed. First-order textural features of SWI were extracted and assessed using Pyradiomics. Morphological features, including the tumor growth pattern, peritumoral edema, sinus invasion, hyperostosis, bone destruction, and intratumoral calcification, were semi-quantitatively assessed. Mann-Whitney U tests were utilized to assess the differences in the SWI features of meningiomas with and without S100 protein expression or NF-2 copy number loss. A logistic regression analysis was used to examine the relationship between these features and the respective subgroups. Additionally, a convolutional neural network (CNN) was used to extract hierarchical features of SWI, which were subsequently employed in a light gradient boosting machine classifier to predict the NF-2 copy number loss and S100 protein expression. NF-2 copy number loss was associated with a higher risk of developing high-grade tumors. Additionally, elevated signal intensity and a decrease in entropy within the tumoral region on SWI were observed in meningiomas with S100 protein expression. On the other hand, NF-2 copy number loss was associated with lower SWI signal intensity, a growth pattern described as "en plaque", and the presence of calcification within the tumor. The logistic regression model achieved an accuracy of 0.59 for predicting NF-2 copy number loss and an accuracy of 0.70 for identifying S100 protein expression. Deep learning features demonstrated a strong predictive capability for S100 protein expression (AUC = 0.85 ± 0.06) and had reasonable success in identifying NF-2 copy number loss (AUC = 0.74 ± 0.05). In conclusion, SWI showed promise in identifying NF-2 copy number loss and S100 protein expression by revealing neovascularization and microcalcification characteristics in meningiomas.

The Efficiency of Focused Assessment with Sonography for Trauma in Pediatric Patients with Blunt Torso Trauma.

Introduction: Focused Assessment with Sonography for Trauma (FAST) has attracted attention for its use in the detection of intra-abdominal pathology for pediatric patients. However, computed tomography (CT) remains the gold standard for the assessment of blunt torso trauma. The study examines the effectiveness of FAST both in the detection of intra-abdominal pathology in pediatric patients (<19 years) with blunt torso trauma and in the determination of the need for CT for further examination. Methods: The study was designed as a retrospective observational investigation of diagnostic value. The pediatric patients who were admitted to the Emergency Department with blunt torso trauma between January 2013 and October 2016 were included in the study. The sample of the study comprised 255 patients who met the inclusion criteria. The primary outcome was the effectiveness of FAST in the detection of intra-abdominal pathology and the determination of the need for CT. The secondary outcome was to identify the agreement between CT and FAST for intra-abdominal injuries. The Chi-square test and Fisher's exact test were used for comparisons. A logistic regression model was developed to determine the variables that independently affect the agreement between FAST and CT. Results: FAST was determined to have low sensitivity (20.3%) despite its high specificity (87%). However; FAST had a good negative likelihood ratio. There was a poor agreement between CT and FAST in terms of the presence of both intra-abdominal and intrathoracic injuries in pediatric patients with blunt trunk trauma. The error rate of FAST increased by five-fold, especially in the presence of concomitant thorax trauma. However, FAST had a good negative likelihood ratio. Conclusion: FAST should not be regarded as an equivalent tool to CT for pediatric patients with blunt torso trauma. It is, instead, a noteworthy complementary tool that is a negative predictor.

Impact of the empirical therapy timing on the clinical progress of septic shock patients.

AIM: To evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock. MATERIALS AND METHOD: We included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis. RESULTS: Antibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality. CONCLUSION: Training programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation.

Association between vitamin D receptor gene FokI polymorphism and mortality in patients with sepsis.

BACKGROUND: Sepsis is life-threatening organ dysfunction as a result of the host's dysregulated immune response to infection. The vitamin D receptor (VDR) gene FokI polymorphism influences immune cell behavior. In the present study, we aimed to investigate the association between VDR FokI polymorphism and mortality in sepsis and non-sepsis patients in the intensive care unit (ICU). METHODS AND RESULTS: This is a prospective observational study involving 96 sepsis and 96 non-sepsis patients admitted to the Ege University ICU. VDR FokI polymorphisms were investigated, as well as the relationship between the identified polymorphisms and mortality.  In-hospital mortality was 27.1% in the sepsis group and 8.33% in the non-sepsis group (p = 0.001). The frequencies of VDR FokI TT, TC, and CC genotypes were 8 (8.33%), 48 (50.0%), and 40 (41.7%) in the sepsis group, and 11 (11.5%), 42 (43.8%), and 43 (44.8%) in the non-sepsis group, respectively (p = 0.612). In the sepsis group, the frequencies of Fokl TT, TC, and CC genotypes did not differ significantly between survivors and non-survivors. However, homozygous C allele carriers had lower overall mortality (p = 0.047). CONCLUSION: The VDR FokI polymorphism, particularly the CC genotype, appears to be associated with lower mortality in ICU patients.

Development and pharmaceutical investigation of novel cervical cancer-targeting and redox-responsive melittin conjugates.

Cervical cancer has recently become one of the most prevalent cancers among women throughout the world. Traditional cancer therapies generate side effects due to off-target toxicity. Thus, novel cancer medications coupled with suitable drug delivery systems are required to improve cancer therapies. Melittin peptide has a high affinity to disrupt cancer cells. In this study, we designed targeted and redox-responsive Melittin conjugates for cervical cancer and then tested them in vitro. Folic acid and squamous cell carcinoma-specific peptide (CKQNLAEG) were used as targeting agents to design various conjugates. Our findings indicate that both anticancer conjugates were effective against different cancer cell lines, including MCF-7, C33A, and HeLa. Moreover, these conjugates were found to have antioxidant and antibacterial effects as well as reduced hemolytic activity. The CM-Target (N-terminus cysteine modified-Melittin-targeting peptide-functionalized conjugate) has become more stable and acted specifically against squamous cell carcinoma, whereas folic acid (FA)-containing conjugates acted efficiently against all cancer types studied, especially for breast cancer. According to our results, these anticancer conjugates may be possible anticancer drug candidates that have fewer adverse effects.

In vitro efficacy of different PEGylation designs on cathelicidin-like peptide with high antibacterial and antifungal activity.

Recent reports on antibiotic resistance have highlighted the need to reduce the impact of this global health issue through urgent prevention and control. The World Health Organization currently considers antibiotic resistance as one of the most dangerous threats to global health. Therefore, Antimicrobial peptides (AMPs) are promising for the development of novel antibiotic molecules due to their high antimicrobial effects, non-inducing antimicrobial resistance (AMR) properties, and broad spectrum. Hence, in this study, we developed novel antimicrobial peptide/polymer conjugates to reduce the adverse effects of TN6 (RLLRLLLRLLR) peptide. We demonstrate how our constructs function in vitro in terms of antimicrobial activity, hemolytic activity, cytotoxicity, and protease resistance. Our findings show that our molecules are effective against different types of microorganisms such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant S. aureus, vancomycin-resistant Enteroccus faecium, and Candida albicans, which are known to be pathogenic and antibiotic-resistant. Our constructs generally showed low cytotoxicity relative to the peptide in HaCaT and 3T3 cells. Especially these structures are very successful in terms of hemotoxicity. In the bacteremia model with S. aureus, the naked peptide (TN6) was hemotoxic even at 1 µg/mL, while the hemotoxicity of the conjugates was considerably lower than the peptide. Remarkably in this model, the hemolytic activity of PepC-PEG-pepC conjugate decreased 15-fold from 2.36 to 31.12 µg/mL compared to the bacteria-free 60-min treatment. This is proof that in the case of bacteremia and sepsis, the conjugates specifically direct to bacterial cell membranes rather than red blood cells. In addition, the PepC-PEG-pepC conjugate is resistant to plasma proteases. Moreover, morphological and intracellular damage of the peptide/conjugates to Escherichia coli are demonstrated in SEM and TEM images. These results suggest our molecules can be considered potential next-generation broad-spectrum antibiotic molecule/drug candidates that might be used in clinical cases such as bacteremia and sepsis.

Bioinspired Multi-Layer Biopolymer-Based Dental Implant Coating for Enhanced Osseointegration.

The major drawbacks of metal-based implants are weak osseointegration and post-operational infections. These limitations restrict the long-term use of implants that may cause severe tissue damage and replacement of the implant. Recent strategies to enhance the osseointegration process require an elaborate fabrication process and suffer from post-operative complications. To address the current challenges taking inspiration from the extracellular matrix (ECM), the current study is designed to establish enhanced osseointegration with lowered risk of infection. Natural biopolymer pectin, peptide amphiphiles, and enzyme-mimicking fullerene moieties are governed to present an ECM-like environment around the implant surfaces. This multifunctional approach promotes osseointegration via inducing biomineralization and osteoblast differentiation. Application of the biopolymer-based composite to the metal surfaces significantly enhances cellular attachment, supports the mineral deposition, and upregulates osteoblast-specific gene expression. In addition to the osteoinductive properties of the constructed layers, the inherent antimicrobial properties of multilayer coating are also used to prevent infection possibility. The reported biopolymer-artificial enzyme composite demonstrates antimicrobial activity against Escherichia coli and Bacillus subtilis as a multifunctional surface coating.

A Novel Peptide-Based Detection of SARS-CoV-2 Antibodies.

The need for rapidly developed diagnostic tests has gained significant attention after the recent pandemic. Production of neutralizing antibodies for vaccine development or antibodies to be used in diagnostic tests usually require the usage of recombinant proteins representing the infectious agent. However, peptides that can mimic these recombinant proteins may be rapidly utilized, especially in emergencies such as the recent outbreak. Here, we report two peptides that mimic the receptor binding domain of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigate their binding behavior against the corresponding human immunoglobulin G and immunoglobulin M (IgG and IgM) antibodies in a clinical sample using a quartz crystal microbalance (QCM) sensor. These peptides were immobilized on a QCM sensor surface, and their binding behavior was studied against a clinical serum sample that was previously determined to be IgG and IgM-positive. It was determined that designed peptides bind to SARS-CoV-2 antibodies in a clinical sample. These peptides might be useful for the detection of SARS-CoV-2 antibodies using different methods such as enzyme-linked immunosorbent assay (ELISA) or lateral flow assays. A similar platform might prove to be useful for the detection and development of antibodies in other infections.

Comparison of a novel antigen detection test with reverse transcription polymerase chain reaction assay for laboratory diagnosis of SARS-CoV-2 infection.

Molecular diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction (RT-PCR) in respiratory specimens is considered the gold standard method. This method is highly sensitive and specific but it has some limitations such as being expensive and requiring special laboratory equipment and skilled personnel. RapidFor™ Antigen Rapid Test Kit is a commercially available Ag-RDT which is produced in Turkey and designed to detect the nucleocapsid antigen of SARS-CoV-2 in nasopharyngeal swab samples. The aim of this study was to evaluate the performance of this novel SARS-CoV-2 antigen detection considering the RT-PCR method as the gold standard. Four hundred forty-four nasopharyngeal swab samples which were collected from the patients who met clinical criteria of COVID-19 from ten centers in Turkey between September 2020 and February 2021 were included in the study. All the nasopharyngeal swab samples were tested for SARS-CoV-2 RNA using commercial RT-PCR kits (Bioeksen and A1 Lifesciences, Istanbul, Turkey) according to the manufacturer's instructions. Viral loads were assessed according to the cycle threshold (Ct) values. RapidFor™ SARS-CoV-2 antigen test (Vitrosens Biotechnology, Istanbul, Turkey) was used to investigate the presence of SARS-CoV-2 antigen in all samples following the manufacturer's instructions. Out of 444 nasopharyngeal swab samples tested, 346 (77.9%) were positive and 98 (22.1%) were negative for SARS-CoV-2 RNA by RTPCR. Overall sensitivity of the RapidFor™. Antigen Rapid Test Kit was 80.3% whereas specificity was found to be 87.8%. Positivity rate of rapid antigen test in samples with Ct values over 25 and below 30 was 82.7%, while it increased to 95.7% in samples 20 ≤ Ct < 25 and reached 100% in samples with Ct values below 20. RapidFor™ SARS-CoV-2 Ag test might be a good choice in the screening of symptomatic and asymptomatic patients and their contacts for taking isolation measures early, with advantages over RT-PCR as being rapid, easy and being applicable in every laboratory and even at point of care.

Comparison of Lower and Upper Limb Remote Ischemic Preconditioning to Prevent Contrast-Induced Nephropathy: A Randomized Pilot Study with a Control Group / Comparación del preacondicionamiento isquémico remoto de la extremidad inferior y superior para evitar la nefropatía inducida por el contraste: Un estudio piloto aleatorizado con un grupo de control

ABSTRACT Background: The role of remote ischemic preconditioning (RIPC) in preventing the development of contrast-induced nephropathy (CIN) and whether there is a difference between the results of applications of RIPC to the upper or lower extremities has not been adequately demonstrated. Methods: We included the patients who underwent coronary angiography due to stable angina pectoris in this single center, randomized, pilot study. We randomly enrolled a total of 168 patients in one of three groups (60 patients in the upper limb RIPC group, 58 patients in the lower limb RIPC group, and 50 patients in the control group). Results: According to the Acute Kidney Injury Network (AKIN), CIN did not develop in any RIPC patients and developed in 6% of controls (OR: 3.511, 95% CI: 2.757-4.471, p=0.025). According to the European Society of Urogenital Radiology (ESUR) guidelines, CIN developed in 1.7% of RIPC patients and 8% of controls (p=0.065). It was found that creatinine levels increased in the control group and decreased in the RIPC groups (baseline: 0.81±0.19mg/dL and 0.86±0.25mg/dL and control: 0.76±0.17mg/dL and 0.91±0.36mg/ dL, p <0.001). When the upper and lower limb RIPC results were compared, there was no statistically significant difference in the incidence of CIN. In multivariate analyses we found out that baseline eGFR, baseline mean blood pressure, contrast agent volume, and RIPC were independently associated with the development of CIN. Conclusions: RIPC is a practically useful method in preventing CIN in patients undergoing coronary angiography. Upper or lower-limb RIPC applications seem to have a similar effect.

RESUMEN No se ha demostrado adecuadamente el papel del preacondicionamiento isquémico remoto (RIPC) en la prevención del desarrollo de nefropatía inducida por contraste (NIC) y si existe una diferencia entre los resultados de las aplicaciones de RIPC en las extremidades superiores o inferiores. Se incluyó a los pacientes sometidos a coronariografía por angina de pecho estable en este estudio piloto, aleatorizado, unicéntrico. Inscribimos al azar a un total de 168 pacientes en uno de los tres grupos (60 pacientes en el grupo de RIPC de miembros superiores, 58 pacientes en el grupo de RIPC de miembros inferiores, 50 pacientes en el grupo de control). De acuerdo con la Acute Kidney Injury Network (AKIN), NIC no se desarrolló en ningún paciente con RIPC y se desarrolló en el 6% de los controles (OR: 3,511, IC del 95%: 2,757-4,471, p = 0,025). Según las directrices de la Sociedad Europea de Radiología Urogenital (ESUR), la NIC se desarrolló en el 1,7% de los pacientes con RIPC y en el 8% de los controles (p = 0,065). Se encontró que los niveles de creatinina aumentaron en el grupo de control y disminuyeron en los grupos de RIPC (línea de base: 0,81 ± 0,19 mg / dL y 0,86 ± 0,25 mg / dL y control: 0,76 ± 0,17 mg / dL y 0,91 ± 0,36 mg / dL, p <0,001). Cuando se compararon los resultados de RIPC de miembros superiores e inferiores, no hubo diferencias estadísticamente significativas en la incidencia de NIC. En análisis multivariado descubrimos que la TFGe basal, la presión arterial media basal, el volumen del agente de contraste y la RIPC se asociaron de forma independiente con el desarrollo de NIC. La RIPC es un método prácticamente útil en la prevención de NIC en pacientes sometidos a coronariografía. Las aplicaciones de RIPC de miembros superiores o inferiores parecen tener un efecto similar.

Melatonin in preservation solutions prevents ischemic injury in rat kidneys.

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.

Surface microbiota and associated staphylococci of houseflies (Musca domestica) collected from different environmental sources.

Houseflies (Musca domestica) are important mechanical vectors for the transmission of pathogenic microorganisms. In this study, 129 houseflies (69 males and 60 females) were collected from 10 different environmental sources and a laboratory population was used. The surface microbiota of houseflies was identified by Next-Generation Sequencing. Staphylococci from the surfaces of houseflies were selectively isolated and their virulence genes, antibiotic susceptibilities, biofilm formation, and clonal relatedness were determined. Metagenomic analysis results demonstrated that Staphylococcus, Bacillus, and Enterococcus were mostly present on the surface of houseflies at the genus level. Additionally, the isolated 32 staphylococcal strains were identified as Staphylococcus sciuri (n = 11), S. saprophyticus (n = 9), S. arlettae (n = 6), S. xylosus (n = 4), S. epidermidis (n = 1) and S. gallinarum (n = 1). tetK, tetM, tetL, ermC, msrAB, and aad6 genes were found to carry by some of the staphylococcal strains. The strains were mostly resistant to oxacillin, penicillin, and erythromycin and three strains were multi-drug resistant. There was a statistical difference between housefly collection places and antibiotic resistance of isolated staphylococci to penicillin G, gentamicin, and erythromycin (p < 0.05). Biofilm test showed that 17 strains were strong biofilm formers, and it plays important role in the transmission of these bacteria on the surface of houseflies. Staphylococcal strains showed extracellular proteolytic and lipolytic activity in 31 and 12 strains, respectively. Closely related species were found in PFGE analysis from different environmental sources. By this study, surface microbiota and carriage of pathogenic staphylococci on the surfaces of houseflies and their virulence properties were elucidated.

Diagnostic Accuracy of Early Systolic Notching in Pulmonary Embolism.

OBJECTIVE: Recently, a cardiac sonography finding, early systolic notching (ESN), was reported with high sensitivity and specificity for the diagnosis of pulmonary embolism (PE) in a limited population. The aim of this study was to determine the diagnostic accuracy of ESN finding for PE in emergency department (ED) patients. METHOD: This prospective multicenter study was conducted in 4 academic EDs. All patients who underwent computed tomography angiography for suspected PE were included in the study. After inclusion, cardiac ultrasound including the right ventricular outflow tract Doppler signal was performed. The diagnostic tests of ESN finding were used for PE and its subgroups. RESULTS: In the study, 183 of 201 patients met the study criteria. Of all patients, 52.5% had PE (n = 96), and 19.7% (n = 36) had ESN finding. In all ED patients, the sensitivity of ESN for PE was 34% (95% CI 25-45), and the specificity was 97% (95% CI 90-99). In the subgroup analysis, the sensitivity of ESN for PE with high or intermediate-high risk was 69% (95% CI 49-85), and the specificity was 90% (95% CI 84-94). Inter-rater reliability for ESN finding between the cardiologist and emergency physician was strong with a kappa statistic of 0.87. CONCLUSION: The pulmonary Doppler flow of ESN was moderate to high specific but low sensitive for PE in all ED patients. In the subgroup analysis, this finding was moderate specific and low sensitive.

Comparison of Standard Technique, Ultrasonography, and Near-Infrared Light in Difficult Peripheral Vascular Access: A Randomized Controlled Trial.

OBJECTIVES: Successful placement of a peripheral intravenous catheter (PIVC) on the first attempt is an important outcome for difficult vascular access (DVA) patients. This study compared standard technique, ultrasonography (USG), and near-infrared light (NIR) in terms of success in the first attempt in patients with DVA. METHODS: This was a prospective, randomized controlled study. The study was conducted in a tertiary care hospital. Emergency department patients who describe DVA history, have no visible or palpable veins, and were assessed by the nurse to have a difficult PIVC were included to study. The PIVC procedure was performed on patients by standard, USG, or NIR device techniques. For all approaches, the success of the first attempt was the primary aim. Total procedure time, the total number of attempts, and the need for rescue intervention were secondary aims. RESULTS: This study evaluated 270 patients. The first attempt success rates for USG, standard, and NIR methods were 78.9%, 62.2%, and 58.9%, respectively. The rate of first attempt success was higher in patients who underwent USG (USG versus standard, P = .014; USG versus NIR, P = .004; standard versus NIR, P = .648). The total median (IQR) procedure time for USG, standard, and NIR methods was 107 (69-228), 72 (47-134), and 82 (61-163) seconds, respectively. The total procedure time was longer in patients undergoing USG (standard versus USG, P <.001; NIR versus USG, P = .035; standard versus NIR, P = .055). The total median (IQR) number of attempts of USG, standard, and NIR methods were 1 (1-1), 1 (1-2), and 1 (1-2), respectively. A difference was found among the groups regarding the total number of attempts (USG versus NIR, P = .015; USG versus standard P = .108; standard versus NIR, P = .307). No difference was found among groups in terms of the need for rescue methods. CONCLUSION: It was found that USG increases the success of the first attempt compared with the standard method and NIR in patients with DVA.

Simple concentration method enables the use of gargle and mouthwash instead of nasopharyngeal swab sampling for the diagnosis of COVID-19 by PCR.

Since its emergence in December 2019, SARS-CoV-2 is causing one of the most devastating pandemics in human history. Currently, the most important method for definitive diagnosis of COVID-19 is identification of SARS-CoV-2 RNA in nasopharyngeal swab samples by RT-PCR. Nasopharyngeal swab sampling is a discomforting procedure sometimes with adverse effects, which also poses a risk for infection for the personnel performing the sampling. We have developed a new method for concentrating biological samples, which enabled us to use gargle and mouthwash samples to be used in RT-PCR, for the diagnosis of COVID-19, as an alternative to nasopharyngeal swab samples. We have analyzed nasopharyngeal and gargle and mouthwash samples, before and after concentration, of 363 patients by RT-PCR for the presence of SARS-CoV-2. Among 114 patients in which SARS-CoV-2 was identified in at least one of their samples, the virus was identified in 76 (66.7%), 67 (58.8%), and 101 (88.6%) of nasopharyngeal swab, gargle, and mouthwash samples before and after concentration, respectively. When concentrated by our new method, gargle and mouthwash samples can be used instead of nasopharyngeal samples in identification of SARS-CoV-2 by RT-PCR, with the same or better sensitivity. Eliminating the need for nasopharyngeal sampling will save the patients from an invasive and painful procedure and will lower the risk of infection for the healthcare personnel taking the sample. This easy sampling procedure may decrease the workload of hospitals, shorten the turnaround time of obtaining test results, and thus enable rapid isolation of infected patients.

Comparison of intravenous ibuprofen and paracetamol in the treatment of fever: A randomized double-blind study.

OBJECTIVE: Fever is one of the frequent reasons for admission to the emergency department. Studies comparing oral forms of non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol with intravenous (IV) forms for fever are common in the literature. Our study is the first emergency department study comparing IV forms of ibuprofen and paracetamol in the treatment of febrile patients. METHODS: A randomized, double-blind study was conducted in a tertiary university emergency department for a six-month period. Patients aged 18-65 years who had a fever of ≥38.0 °C were included. Patients were administered 400 mg of IV ibuprofen and 1000 mg of IV paracetamol. The primary aim of the study was to determine whether there was a difference in the effect of the two drugs on fever. The secondary aim was to investigate whether there was a difference in terms of numeric rating scale (NRS) measurements and the need for additional antipyretic therapy. RESULTS: A total of 200 people, 100 of whom were female, were included in the study. The mean age was 30.77 ± 10.61 years. The mean initial temperature for ibuprofen and paracetamol was 38.79 ± 0.470 °C and 38.70 ± 0.520 °C, respectively, with no difference noted between the groups (p = 0.380). It was found that both drugs significantly provided fever control in the first 30 min (p < 0.001), with no difference between them in terms of fever reduction (p = 0.980). Both drugs significantly improved in accompanying symptoms, although both drugs did not show superiority to each other (p = 0.0226). When evaluated in terms of a need for rescue medication, no significant difference was found between the two drugs (p = 0.404). No side effects were encountered during the study. CONCLUSION: In adult age group patients admitted to the emergency department with high fever, the IV forms of 1000 mg paracetamol and 400 mg ibuprofen effectively and equally reduce complaints, such as fever and accompanying pain. They can be effectively used as each other's rescue medicine and as an alternative to each other in patients with comorbid diseases.

Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma.

BACKGROUND: In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings. METHODS: The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses. Using the workflow, 58 WES analyses from matched blood and tumor samples of 52 patients were analyzed: 47 primary and 11 recurrent diffuse gliomas. RESULTS: The median mean read depths were 199.88 for tumor and 110.955 for normal samples. For germline variants, a median of 22 (14-33) variants per patient was reported. There was a median of 6 (0-590) reported somatic short variants per tumor. A median of 19 (0-94) broad SCNAs and a median of 6 (0-12) gene-level SCNAs were reported per tumor. The gene with the most frequent somatic short variants was TP53 (41.38%). The most frequent chromosome-/arm-level SCNA events were chr7 amplification, chr22q loss, and chr10 loss. TMB in primary gliomas were significantly lower than in recurrent tumors (p = 0.002). MSI incidence was low (6.9%). CONCLUSIONS: We demonstrate that WES can be practically and efficiently utilized for clinical analysis of individual brain tumors. The results display that NOTATES produces clinically relevant results in a concise but exhaustive manner.

Glycoengineering of Mammalian Expression Systems on a Cellular Level.

Mammalian expression systems such as Chinese hamster ovary (CHO), mouse myeloma (NS0), and human embryonic kidney (HEK) cells serve a critical role in the biotechnology industry as the production host of choice for recombinant protein therapeutics. Most of the recombinant biologics are glycoproteins that contain complex oligosaccharide or glycan attachments representing a principal component of product quality. Both N-glycans and O-glycans are present in these mammalian cells, but the engineering of N-linked glycosylation is of critical interest in industry and many efforts have been directed to improve this pathway. This is because altering the N-glycan composition can change the product quality of recombinant biotherapeutics in mammalian hosts. In addition, sialylation and fucosylation represent components of the glycosylation pathway that affect circulatory half-life and antibody-dependent cellular cytotoxicity, respectively. In this chapter, we first offer an overview of the glycosylation, sialylation, and fucosylation networks in mammalian cells, specifically CHO cells, which are extensively used in antibody production. Next, genetic engineering technologies used in CHO cells to modulate glycosylation pathways are described. We provide examples of their use in CHO cell engineering approaches to highlight these technologies further. Specifically, we describe efforts to overexpress glycosyltransferases and sialyltransfereases, and efforts to decrease sialidase cleavage and fucosylation. Finally, this chapter covers new strategies and future directions of CHO cell glycoengineering, such as the application of glycoproteomics, glycomics, and the integration of 'omics' approaches to identify, quantify, and characterize the glycosylated proteins in CHO cells. Graphical Abstract.

Mutations and Copy Number Alterations in IDH Wild-Type Glioblastomas Are Shaped by Different Oncogenic Mechanisms.

Little is known about the mutational processes that shape the genetic landscape of gliomas. Numerous mutational processes leave marks on the genome in the form of mutations, copy number alterations, rearrangements or their combinations. To explore gliomagenesis, we hypothesized that gliomas with different underlying oncogenic mechanisms would have differences in the burden of various forms of these genomic alterations. This was an analysis on adult diffuse gliomas, but IDH-mutant gliomas as well as diffuse midline gliomas H3-K27M were excluded to search for the possible presence of new entities among the very heterogenous group of IDH-WT glioblastomas. The cohort was divided into two molecular subsets: (1) Molecularly-defined GBM (mGBM) as those that carried molecular features of glioblastomas (including TERT promoter mutations, 7/10 pattern, or EGFR-amplification), and (2) those who did not (others). Whole exome sequencing was performed for 37 primary tumors and matched blood samples as well as 8 recurrences. Single nucleotide variations (SNV), short insertion or deletions (indels) and copy number alterations (CNA) were quantified using 5 quantitative metrics (SNV burden, indel burden, copy number alteration frequency-wGII, chromosomal arm event ratio-CAER, copy number amplitude) as well as 4 parameters that explored underlying oncogenic mechanisms (chromothripsis, double minutes, microsatellite instability and mutational signatures). Findings were validated in the TCGA pan-glioma cohort. mGBM and "Others" differed significantly in their SNV (only in the TCGA cohort) and CNA metrics but not indel burden. SNV burden increased with increasing age at diagnosis and at recurrences and was driven by mismatch repair deficiency. On the contrary, indel and CNA metrics remained stable over increasing age at diagnosis and with recurrences. Copy number alteration frequency (wGII) correlated significantly with chromothripsis while CAER and CN amplitude correlated significantly with the presence of double minutes, suggesting separate underlying mechanisms for different forms of CNA.