Evaluation of the mechanical properties and degradation behavior of chitosan-PVA-graphene oxide nanocomposite scaffolds in vitro.

Objectives: Chitosan (CTS) has been a popular option for scaffold fabrication because of its biocompatibility, biodegradability, antimicrobial and nonimmunogenic effects. However, it is of limited function, due to its low mechanical strength and its solubility in acidified media. These limitations could be overcome by its blending with PVA and incorporation with bioactive materials to improve its mechanical properties and tissue regeneration capability. Methods: Carbon based nanomaterials, such as graphene oxide (GO) incorporated with CTS/PVA blend to improve composite-scaffold stability. GO nanoparticles were chemically prepared and fully characterized. Different concentrations of both CTS and nano-GO were used for the fabrication of CTS/PVA/GO nanocomposite films through the solvent-casting method. The mechanical properties, thermal stability biodegradation, and swelling of the nanocomposite films were evaluated after characterization by XRD, FTIR and SEM, to detect the effect of GO incorporation in the scaffold to select the suitable dental application. Results: A better performance was observed in thermal stability, biodegradation, and water resistance after GO addition into CTS/PVA scaffolds. Regarding mechanical properties, groups were assessed by Kruskal Wallis test afterward Dunn's post hoc test. There was no significant difference in tensile strength between the nanocomposite films of CTS (2%) and CTS (3%). The tensile strength decreased after addition of nano-GO at different concentrations. The elastic modulus significantly increased when (1%) GO was added into the 1CTS (2%):1PVA. Conclusions: CTS/PVA/GO nanocomposite can be used in dental hard tissue engineering, as the incorporation of GO into the CTS/PVA polymer blend improves its properties which is regarded as the critical concentrations of CTS and GO.

Histopathological effects of the fruit extract of Citrullus colocynthis on the ovary of the tick Hyalomma dromedarii.

Hyalomma dromedarii is the predominant tick species parasitizing camels in Egypt which leads to mortalities in young animals that result in economic losses. It can transmit a lot of pathogens to animals and humans, such as the Crimean-Congo hemorrhagic fever virus, the Dhori virus, Kadam virus, Theileria annulata and spotted fever rickettsia. The continuous use of chemical acaricides has negative impact on the environment and almost led to acaricidal resistance, and hence the plant extracts represent alternative methods for controlling ticks. The present study was carried out to assess the histopathological effects on the ovary of fed female Hyalomma dromedarii following immersion in the ethanolic extract of fruits of Citrullus colocynthis (100 mg/mL). Light, scanning and transmission electron microscopy observations provided evidence that Citrullus colocynthis caused extensive damage to oocytes. Destruction of the internal organelles of oocytes, along with delay and/or inhibition of vitellogenesis were demonstrated. This is the first histological study that points to damage in H. dromedarii ovaries following treatment with the ethanolic extract of fruits of C. colocynthis. The data presented suggest that the plant extract affects the ovary either directly by entering the oocytes and/or indirectly by damaging the gut cells and digestion of blood that interfere with the development of oocytes, so it can be used as a promising agent for tick control.

Knowledge, Perceptions and Attitude of Researchers Towards Using ChatGPT in Research.

INTRODUCTION: ChatGPT, a recently released chatbot from OpenAI, has found applications in various aspects of life, including academic research. This study investigated the knowledge, perceptions, and attitudes of researchers towards using ChatGPT and other chatbots in academic research. METHODS: A pre-designed, self-administered survey using Google Forms was employed to conduct the study. The questionnaire assessed participants' knowledge of ChatGPT and other chatbots, their awareness of current chatbot and artificial intelligence (AI) applications, and their attitudes towards ChatGPT and its potential research uses. RESULTS: Two hundred researchers participated in the survey. A majority were female (57.5%), and over two-thirds belonged to the medical field (68%). While 67% had heard of ChatGPT, only 11.5% had employed it in their research, primarily for rephrasing paragraphs and finding references. Interestingly, over one-third supported the notion of listing ChatGPT as an author in scientific publications. Concerns emerged regarding AI's potential to automate researcher tasks, particularly in language editing, statistics, and data analysis. Additionally, roughly half expressed ethical concerns about using AI applications in scientific research. CONCLUSION: The increasing use of chatbots in academic research necessitates thoughtful regulation that balances potential benefits with inherent limitations and potential risks. Chatbots should not be considered authors of scientific publications but rather assistants to researchers during manuscript preparation and review. Researchers should be equipped with proper training to utilize chatbots and other AI tools effectively and ethically.

Association between interleukin-6-174G/C gene polymorphism and asthma severity: exploring the role of total serum IgE, blood eosinophils, and FeNO as markers of type 2 inflammation.

BACKGROUND: While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (- 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (- 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. METHODS: Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (- 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 - 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001). CONCLUSION: This study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (- 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

Gut microbiota and acute kidney injury: immunological crosstalk link.

The gut microbiota, often called the "forgotten organ," plays a crucial role in bidirectional communication with the host for optimal physiological function. This communication helps regulate the host's immunity and metabolism positively and negatively. Many factors influence microbiota homeostasis and subsequently lead to an immune system imbalance. The correlation between an unbalanced immune system and acute diseases such as acute kidney injury is not fully understood, and the role of gut microbiota in disease pathogenesis is still yet uncovered. This review summarizes our understanding of gut microbiota, focusing on the interactions between the host's immune system and the microbiome and their impact on acute kidney injury.

Even one dose of tocilizumab could hinder bad prognosis of cytokines storm in COVID-19 patients.

Severe COVID-19 pneumonia is a principal cause of death due to cascade of hyper inflammatory condition that leading to lung damage. Therefore, an effective therapy to countercurrent the surge of uncontrolled inflammation is mandatory to propose. Anti-interlukin-6 receptor antagonist monoclonal therapy, tocilizumab (TCZ) showed potential results in COVID-19 patients. This study aimed to emphasize the factors associated with mortality in COVID-19 patients that treated with tocilizumab and may influence the level of serum IL-6. A retrospective cohort study included all patients with clinical parameters that pointed to presence of cytokines storm and treated with one or more doses of TCZ beside the regular protocol of COVID-19 pneumonia. The factors that influence the mortality in addition to the level of serum IL-6 were analyzed. A total of 377 patients were included, 69.5 % of them received only one dose of TCZ which started mainly at the third day of admission. The mortality rate was 29.44 %. Regardless the time of starting TCZ, just one dose was fair enough to prevent bad consequence; OR = 0.04, P = 0.001.However, in spite of protective action of TCZ, older age and female sex were significant risk factors for mortality, P = 0.001 and 0.01 respectively, as well heart disease. Moreover, increasing the level of neutrophil, AST and IL-6 were associated with bad prognosis. In the same line, treatment with ivermectin, chloroquine and remdesivir inversely affect the level of IL-6. Early treatments of COVID-19 pneumonia with at least one dose of tocilizumab minimized the fatality rate.

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study.

BACKGROUND: A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. METHODS: A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. RESULTS: Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively. CONCLUSION: Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).

Interleukin-4 (C590T) Gene Polymorphism in Association with Asthma Severity.

Background: A significant link between T allele of the IL-4 (C590T) gene and developing asthma in some populations was reported. However, no study discussed the link between IL-4 (C590T) gene polymorphism and asthma severity groups (mild and severe). This study investigated the link between IL-4 gene variation and asthma severity. Methods: The study included 215 asthmatic patients, of which 102 had mild asthma, and 126 participants were healthy controls. A previously published polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify various IL-4 (C590T) gene polymorphism genotypes. Results: The T allele frequency was higher in mild asthma (p=0.002) but not in severe asthma (p=0.12) compared to controls. In mild asthma, the CT genotype and (CT+TT versus CC) increased the likelihood of asthma threefold (p<0.001, 0.001). However, no significant association with severe asthma was found in either genetic model. Stratification analysis showed that the C allele and CC genotype increased the risk of severe asthma (p=0.01). The recessive genetic model indicated a decrease in the risk of severe asthma (OR=0.5, p=0.01) in the non-adjusted regression analysis. Adjusting for age, sex, and other risk factors revealed that the IL-4 gene polymorphism did not influence the risk of severe asthma (OR=0.92, p=0.80); however, being an elderly female with a history of childhood-onset disease and associated nasal polyp (NP) increased the likelihood of severe asthma, OR=1.08, 2.01, 2.36, 8.42; p<0.001, 0.05, 0.05, <0.001, respectively. Conclusion: The T allele and CT genotype in the co-dominant genetic model and the (CT+TT) genotype in the recessive model were found to have a higher likelihood of developing mild asthma but not severe asthma; severe asthma was found to be higher in elderly females with a history of childhood-onset disease and associated nasal polyps.

Monocyte to eosinophil ratio as a diagnostic biomarker for overlap syndrome and predictor of disease exacerbation.

Objectives: Chronic Obstructive Pulmonary Disease (COPD) is one of the most common pulmonary diseases. The concomitant association of Obstructive Sleep Apnea (OSA) and COPD is known as the Overlap Syndrome (OS). This study aimed to identify markers for predicting OS, among routine laboratory tests, including differential blood counts.Methods: One hundred twenty-five patients with exacerbated COPD were enrolled in the study and screened for OSA using the Epworth Sleepiness Scale (ESS). Those with a positive ESS score underwent polysomnography (PSG) for confirmation. All patients were followed for 90 days to monitor for subsequent exacerbations.Results: Out of the 125 patients with exacerbated COPD, 25 were confirmed to have OSA. Those with OS had a significantly higher body mass index (BMI) (p < 0.001). The monocyte to eosinophil ratio (MER) was significantly higher in the OS group, while the neutrophil to monocyte (NMR) ratio and platelets to monocyte (PMR) ratio were significantly lower. Younger age, male sex, and higher body mass index (BMI) were all associated with OS. During the 90-day follow-up period after hospital discharge, 60% of patients with OS were re-admitted due to acute exacerbations. The hazard ratio for a second exacerbation increased by two-fold for every one-unit increase MER. The MER demonstrated excellent utility in predicting a second exacerbation, with an area under the curve (AUC) of 83% and a p-value of .005.Conclusion: The monocyte to eosinophil ratio (MER) was independent predictors of OS among exacerbated COPD patients and had a very good prognostic utility for predicting the next exacerbation episodes. Long term follow up is recommended to evaluate the severity of exacerbations and the effect of complications of OS on the morbidity and mortality of these patients.

Controlling Argas arboreus and A. persicus (Acari: Argasidae) by Adiantum capillus-veneris L. extracts with phytochemical analysis.

Argas species are parasites associated mostly with birds. Their infestations of the host may cause blood loss, resulting in anemia and finally death. Egypt loses millions of tons annually from birds because of these parasites. In addition, they can transmit pathogens to animals and humans. The acaricidal effects of the ethanolic and methanolic extracts of Adiantum capillus-veneris at different concentrations (1-4%) against semi-fed adults of Argas arboreus and A. persicus were investigated during 30 days after treatments. Mobility and mortality, acaricide efficacy, and the concentration that kills 50% of specimens (LC50) were estimated. The percentage of dead adults of both Argas species appeared during 6 days considerably until 30 days was significantly increased after treatment of either ethanol or methanol extracts of Adiantum at 1-4%, versus control groups. Ethanolic extracts (100% mortality) were more effective than methanolic ones (90% mortality) for both Argas species. Argas arboreus (80% efficacy and 5.9% LC50) was more resistant than A. persicus (100% efficacy and 4.1% LC50). Generally, males were more resistant than females. The chemical profile (by gas chromatography-mass spectrometry analysis) for the ethanolic extract of Ad. capillus-veneris at 4% (the most effective extract) was provided for the first time, which showed that the major group was sugars and sugar alcohols, and the main components were thymol-ß-d-glucopyranoside, D-(-)-Tagatofuranose, D-Arabinose, D-Galactose, D-(-)-Fructofuranose and Anthracene, 1-methyl. The efficiency of all these components was discussed. Based on the findings, bioactive compounds present in Ad. capillus-veneris have the potential to be applied as substitutes for synthetic acaricides and a biological control agent in the management of A. arboreus and A. persicus ticks.

Modified electrode decorated with silver as a novel non-enzymatic sensor for the determination of ammonium in water.

Ammonium is an essential component of the nitrogen cycle, which is essential for nitrogen cycling in ecosystems. On the other hand, ammonium pollution in water poses a great threat to the ecosystem and human health. Accurate and timely determination of ammonium content is of great importance for environmental management and ensuring the safety of water supply. Here we report a highly sensitive electrochemical sensor for ammonium in water samples. The modified electrode is based on the incorporation of silver nitrate (AgNO3) into a carbon paste embedded with 1-aminoanthraquinone and supported by multi-walled carbon nanotubes, which are commercially available. A potential of 0.75 V is applied to the modified electrode, followed by activation in hydrochloric acid. The modified electrode was used for square wave voltammetry of ammonium in water in the potential range of - 0.4-0.2 V. The performance of ammonium analysis was determined in terms of square wave frequency, square wave amplitude and concentration of electrolyte solution (sodium sulphate). The calculation of the surface area according to the Randles-Sevcik equation resulted in the largest surface area for the Ag/pAAQ/MWCNTs/CPE. The modified electrode exhibited a linear range of 5-100 µM NH4+ in 0.1 M Na2SO4 with a detection limit of 0.03 µM NH4+ (3σ). In addition, the modified electrode showed high precision with an RSD value of 9.93% for 10 repeated measurements. No interfering effect was observed at twofold and tenfold additive concentrations of foreign ions. Good recoveries were obtained in the analysis of tap and mineral water after spiking with a concentration of ammonium ions.

YKL-40 in serum: a promising biomarker of juvenile SLE and strongly correlated with disease duration.

BACKGROUND: The biological function of YKL-40 is not well determined in different inflammatory and autoimmune diseases; however, some data highlighted its possible connection with disease activity. AIM: We investigated the diagnostic utility of serum YKL-40 in patients with SLE and examined its correlation with disease activity. Additionally, we examined any differences in serum YKL-40 levels between juvenile and adult SLE patients. METHODS: We included 78 female patients with SLE and 42 controls. The level of YKL-40 in serum was measured by ELISA. RESULTS: The serum YKL-40 level in SLE patients was significantly higher compared to the control group (9 (3) ng/mL vs. 5.5 (0.1) ng/mL; p < 0.001). YKL-40 showed excellent diagnostic utility with an AUC of 1 (p < 0.001) and a cutoff point of 5.6, providing sensitivity and specificity of 100%. YKL-40 was higher in adolescents and those with a positive family history of SLE (p = 0.01 for both) and positively correlated with disease duration (r = 0.45, p < 0.001). YKL-40 level was significantly higher in patients with photosensitivity, fever, vasculitis, blood disorders, positive anti-dsDNA, and APL ab (p < 0.05 for all). Conversely, patients with skin manifestations had a significantly lower YKL-40 (p = 0.004). In juvenile SLE, the AUC was 0.65 and a p-value of 0.01, and at a cutoff value of (8.7) ng/mL, the sensitivity and specificity were 72% and 60%, respectively. CONCLUSION: YKL-40 in serum could be a promising biomarker in patients with SLE, especially in adolescent-onset cases. It is independently influenced by disease duration, anemia, thrombocytopenia, positive anti-dsDNA, and APL ab features.

Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response.

OBJECTIVE: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. SUBJECTS AND METHODS: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. RESULTS: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. CONCLUSION: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.

Right ventricular systolic function and mechanical dyssynchrony in ischemic or non-ischemic dilated cardiomyopathy: A speckle-tracking study.

AIM: This study assessed RV dyssynchrony (irrespective to QRS duration) and RV systolic function in non-ischemic dilated cardiomyopathy (NIDCM) versus ischemic dilated cardiomyopathy (IDCM) patients by using different echo-Doppler modalities. METHODS: Eighty-five cases (48 patients with DCM [whether ischemic or non-ischemic] and 37 age-matched healthy controls) were studied. Conventional echo-Doppler study, tissue Doppler (TDI), and speckle tracking (STE) were carried out to measure LV and RV systolic function. Time-to-peak negative longitudinal strain at the four RV sites were assessed by TDI derived strain and 2D speckle tracking. RESULTS: Patients with DCM (whether ischemic or non-ischemic) had significantly lower fractional area change, RV tricuspid annular systolic velocity (p < .001 for both), tricuspid annular plane systolic excursion (p = .01), RV-GLS whether TDI or 2D derived (p < .001). Twenty-nine patients (60%) showed right intraventricular delay (RV4SD > 60 ms). The RV-dyssynchrony index was negatively correlated to %FAC (r = -.362, p = .01), RV Sm (r = -.312, p = .04), and 2D-RV GLS (r = -.305, p = .05). Insignificant higher RV-dysynchrony index was detected in NIDCM compared to IDCM group; however, the basal septal segment was significantly delayed in dilated group. More impaired RV systolic function was detected in ischemic group. 2D STE and TDI showed a significant correlation in the assessment of the right-intraventricular delay (p = .001). CONCLUSION: Right-intraventricular dyssynchrony are detectable in patients with dilated cardiomyopathy (whether ischemic or non-ischemic) with a higher statistically insignificant value in non-ischemic group by using tissue Doppler imaging and 2D speckle tracking. More impairment of the RV systolic function was noticed in the ischemic group. Impaired RV systolic function was associated with right intraventricular delay.

Elevation of D-dimer levels are associated with early need for mechanical ventilation support in patients with COVID-19.

BACKGROUND: Severe COVID-19 disease is typically associated with an urgent need for supplemental oxygen therapy that may be successfully delivered through conventional methods or require invasive mechanical ventilation. Early prediction of the need for invasive mechanical ventilation could significantly improve outcomes of COVID-19 patients. Plasma levels of D-dimer and a number of inflammatory markers as well as values of complete blood counts, all measured in the first two days of hospital admission of COVID-19 patients, were evaluated for their significance as predictors of the eventual need for invasive mechanical ventilation support as well as their values as predictors of post-ventilation morbidly and mortality. METHODS: This retrospective cohort study was conducted at a single center and included data pertaining to 200 patients with previously confirmed moderate to severe COVID-19 disease in the period between May 2021 and the end of December 2022. Data were retrieved from medical records for further analysis. RESULTS: The mean (SD) age of patients stood at 59 (14) years of age, and with a majority of patients being male (77%). About 18% of cases, all of significantly older age, had been connected to invasive mechanical ventilation (IMV). Total leucocytic count (TLC), as well as levels of urea, creatinine, D-dimer, ferritin, and CRP in IMV patients were significantly higher than non-ventilated patients (p < 0.01 for all). In contrast, lymphocytic count, hemoglobin level, and platelet count were significantly lower in IMV patients (p < 0.001, 0.04, and 0.002, respectively). The mortality rate was significantly higher in IMV patients (p < 0.001). D-dimer independently predicted IMV demand (OR = 1, p = 0.001 in adjusted and unadjusted models). The utility of D-dimer was excellent; and the cutoff level of above 1415 µ/L showed sensitivity and specificity of about 92% and 76%, respectively. Also, the D-dimer level was very effective in predicting post-IMV survival; the AUC = 0.86, p = 0.02, and a cutoff value below 4558 µ/L was associated with 100% and 66% sensitivity and specificity, respectively. CONCLUSIONS: High D-dimer levels independently correlated with the need for invasive mechanical ventilation. Low levels of this marker could evidently predict post-IMV survival of mechanically ventilated COVID-19 patients. Measuring D-dimer levels during routine follow up of those patients would thus be useful in predicting patient outcomes.

Evaluation of tumour motion and internal/external correlation in lung SABR.

OBJECTIVE: This study aims to analyse lung tumour motion and to investigate the correlation between the internal tumour motion acquired from four-dimensional computed tomography (4DCT) and the motion of an external surrogate. METHODS: A data set of 363 4DCT images was analysed. Tumours were classified based on their anatomical lobes. The recorded gross tumour volume (GTV) information included the centroid GTV motion in the superior-inferior, anteroposterior and left-right directions, and in three-dimensions (3D). For the internal/external correlation, the RPM surrogate breathing signals of 260 patients were analysed via an in-house script. The external motion was correlated with the 3D centroid motion, and the maximum tumour motion via Spearman's correlation. The effect of tumour volume on the amount of motion was evaluated. RESULTS: The greatest 3D tumour amplitude was found for tumours located in the lower part of the lung, with a maximum of 26.7 mm. The Spearman's correlation of the internal 3D motion was weak in the upper (r = 0.21) and moderate in the middle (r = 0.51) and the lower (r = 0.52) lobes. There was no obvious difference in the correlation coefficients between the maximum tumour displacement and the centroid motion. No correlation was found between the tumour volume and the magnitude of motion. CONCLUSION: Our results suggest that tumour location can be a good predictor of its motion. However, tumour size is a poor predictor of the motion. ADVANCES IN KNOWLEDGE: This knowledge of the distribution of tumour motion throughout the thoracic regions will be valuable to research groups investigating the refinement of motion management strategies.

Comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: did dupilumab make a difference?

BACKGROUND: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT). METHODS: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score. RESULTS: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups. CONCLUSION: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.

Pro-apoptotic Bax mRNA expression: A novel predictor for systemic lupus erythematosus disease flare-up.

Objectives: In this study, we aimed to better understand the expression of pro-apoptotic Bad and Bax in the pathogenesis of systemic lupus erythematosus (SLE) and their relationship with the disease activity. Patients and methods: Between June 2019 and January 2021, a total of 60 female patients with SLE (median age 29 years; IQR, 25.0-32.0) and 60 age- and sex-matched healthy female controls (median age: 30 years; IQR, 24.0-32.0) were included. The Bax and Bad messenger ribonucleic acid (mRNA) expression was measured by real-time polymerase chain reaction. Results: The expression of Bax and Bad was significantly lower in SLE group than the control group. The median value of mRNA expression of Bax and Bad was 0.72 and 0.84, respectively versus 0.76 and 0.89 in the control group. The median value of (Bax*Bad)/ß-actin index was 17.8 in the SLE group and 19.64 in the control group. The expression of both Bax, Bad and (Bax*Bad)/ß-actin index had a good significant diagnostic utility (area under the curve [AUC]= 0.64, 0.70, and 0.65, respectively). The Bax mRNA expression showed a significant upregulation with disease flare-up. The efficacy of Bax mRNA expression in predicting SLE flare-up was good (AUC= 73%). In the regression model, the probability of flare-up reached 100%, with increasing Bax/ß-actin as well, and the likelihood of flare-up increased 10,314 times with every unit increase of Bax/ß-actin mRNA expression. Conclusion: Deregulation of the mRNA expression of Bax may have a role in the susceptibility to SLE and may be associated with disease flare. A better understanding of the expression of these pro-apoptotic molecules may carry a great potential for the development of specific effective therapies.

Association of genetic and epigenetic changes of insulin like growth factor binding protein-1 in Egyptian patients with type 2 diabetes mellitus.

BACKGROUND: Diabetes is one of the global health threat. Type 2 Diabetes mellitus (T2DM) is associated with life-threatening complications. This work, aimed to study the association between T2DM and IGFBP-1 gene methylation, gene polymorphism and serum levels of IGFBP-1. METHOD: We included 100 subjects with T2DM and 100 control. DNA methylation of IGFBP-1 was analyzed using pyrosequencing, IGFBP-1 gene polymorphism was analyzed using real time polymerase chain reaction and serum level of IGFBP-1 was measured by ELISA. RESULTS: There was DNA hyper methylation levels of IGFBP1 gene at each of the six CpG sites in T2DM patients than control (P < 0.001). IGFBP-1 gene polymorphism (rs 2854843) CC pattern was significantly associated with DM, P = 0.002. Also, there was decrease in serum IGFBP-1 in patients with T2DM than control group (P < 0.001). CONCLUSION: We concluded that DNA hyper methylation of IGFBP-1 gene and CC polymorphism (rs 2854843) of IGFBP-1 gene are associated with T2DM in Egyptian patients, also, decrease serum level of IGFBP-1. Further cohort study is recommended with large sample size to detect which one, epigenetic changes or polymorphism of IGFBP-1 gene, is the cause of T2DM or even both.

A comparison between the effectiveness of the fungi Beauveria bassiana and Metarhizium anisopliae for the control of Argas persicus with the emphasis of histopathological changes in the integument.

Argas persicus is an important ectoparasite of domestic fowl that causes heavy economic losses to the poultry industry. The present study was carried out to compare and assess the effects induced by spraying the fungi Beauveria bassiana and Metarhizium anisopliae separately, on the mobility and viability of semifed adult A. persicus, also to follow the histopathological effect induced by a selected concentration of 1010 conidia/ml of B. bassiana on the integument. Biological studies revealed a more or less similar pattern of response in adults treated with either of the two fungi (Increasing concentration resulting in more death along with examined period). As the estimated LC50 and LC95 of B. bassiana were recorded 5 × 109 and 4.6 × 1012 conidia/ml, respectively, and for M. anisopliae were 3 × 1011 and 2.7 × 1016 conidia/ml respectively, the fungus B. bassiana was more efficient than M. anisopliae when applied at the same concentrations. The study revealed that spraying of Beauveria at 1012 conidia/ml is sufficient to control A. persicus as it recorded 100% efficacy, so it might be selected to be the effective dose. Histological investigation of the integument treated with B. bassiana revealed the dispersal of the hyphal network on the after 11 days of treatment, accompanied by other changes. Results from our study verify the susceptibility of A. persicus to the pathogenic effect induced by spraying B. bassiana, which is sufficient for its control with the recording better results.