Detection of tongue edema caused by endotracheal intubation tube in ICU patients by ultrasonography: a prospective, observational, clinical study.

PURPOSE: We aimed to determine the tongue edema that may develop due to the pressure exerted by the endotracheal intubation (ETI) tube on the tongue during the follow-up period of mechanical ventilation in patients intubated in the intensive care unit (ICU) by submental ultrasonography (USG). Also, we aimed to investigate the effect of tongue edema on the oxygen saturation values (SpO2) measured two h after extubation. METHODS: One hundred patients aged 18-65 years, who were followed up with mechanical ventilation in the ICU from the 0th day of intubation, were included. Patients (n = 57) who were followed up on mechanical ventilation for four days or longer after ETI were included in the study group. Those who were followed up on mechanical ventilation for three days or less after endotracheal intubation and were extubated during this period were included in the control group (n = 43). The tongue cross-sectional areas (TSAs) of patients in both groups were measured twice with submental USG. The first measurement (TSA1) was performed on the 0th day of ETI in all patients in both groups. The second measurement (TSA2) was performed on the 4th day of ETI in the study group and just before extubation in the control group. The difference between TSA2 and TSA1 was defined as tongue edema. Also, the effect of tongue edema on the oxygen saturation levels measured at the 2nd h after extubation of the patients in the control group was investigated. RESULTS: The tongue edema was more prevalent in the study group (p < 0.01). A significant negative correlation was found between the SpO2 levels two hours after extubation and the increase in the mean TSA values indicating tongue edema (p < 0.01). The oxygen saturations of the patients with tongue edema were 4% lower than those without tongue edema. CONCLUSIONS: Tongue edema may develop due to the long-term application of pressure of the ETI tube on the tongue and may impair oxygenation after extubation. GOV IDENTIFIER: NCT05249738.

Animal models and mechanisms of tobacco smoke-induced chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and its global health burden is increasing. COPD is characterized by emphysema, mucus hypersecretion, and persistent lung inflammation, and clinically by chronic airflow obstruction and symptoms of dyspnea, cough, and fatigue in patients. A cluster of pathologies including chronic bronchitis, emphysema, asthma, and cardiovascular disease in the form of hypertension and atherosclerosis variably coexist in COPD patients. Underlying causes for COPD include primarily tobacco use but may also be driven by exposure to air pollutants, biomass burning, and workplace related fumes and chemicals. While no single animal model might mimic all features of human COPD, a wide variety of published models have collectively helped to improve our understanding of disease processes involved in the genesis and persistence of COPD. In this review, the pathogenesis and associated risk factors of COPD are examined in different mammalian models of the disease. Each animal model included in this review is exclusively created by tobacco smoke (TS) exposure. As animal models continue to aid in defining the pathobiological mechanisms of and possible novel therapeutic interventions for COPD, the advantages and disadvantages of each animal model are discussed.

Forthcoming complications in recovered COVID-19 patients with COPD and asthma; possible therapeutic opportunities.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been growing swiftly worldwide. Patients with background chronic pulmonary inflammations such as asthma or chronic obstructive pulmonary diseases (COPD) are likely to be infected with this virus. Of note, there is an argument that COVID-19 can remain with serious complications like fibrosis or other pathological changes in the pulmonary tissue of patients with chronic diseases. Along with conventional medications, regenerative medicine, and cell-based therapy could be alternative approaches to compensate for organ loss or restore injured sites using different stem cell types. Owing to unique differentiation capacity and paracrine activity, these cells can accelerate the healing procedure. In this review article, we have tried to scrutinize different reports related to the harmful effects of SARS-CoV-2 on patients with asthma and COPD, as well as the possible therapeutic effects of stem cells in the alleviation of post-COVID-19 complications. Video abstract.

Exhaled TGF-ß1 levels before and after an exercise challenge in asthmatic and healthy children, and during exacerbation.

BACKGROUND: There is conflicting data regarding the role of transforming growth factor-ß1 (TGF-ß1) in the pathogenesis of airway hyper-reactivity and asthma exacerbation. OBJECTIVE: To investigate the role of exhaled-TGF-ß1 in exercise-induced bronchospasm (EIB) in asthmatic and nonasthmatic healthy children, and in asthma exacerbation and asthma control. METHODS: The exhaled-TGF-ß1 levels of 56 stable asthmatic children and 15 nonasthmatic healthy children were evaluated before and 30 min after an exercise challenge. The exhaled-TGF-ß1 levels of 20 additional children with asthma exacerbation were evaluated. RESULTS: While no significant difference in the exhaled-TGF-ß1 levels was found at the baseline, exhaled-TGF-ß1 levels after the exercise challenge were significantly higher in the non-EIB (n = 31) asthmatics when compared to the asthmatic children with EIB (n = 25) (p = 0.04). Although there was a statistically significant increase in the concentration of the exhaled-TGF-ß1 after the exercise challenge in the non-EIB asthmatics (p = 0.008), the concentration of the TGF-ß1 was not increased after the exercise challenge in EIB + asthmatics. The exhaled-TGF-ß1 was significantly correlated with the ACT score (p = 0.01, r = 0.49) and the baseline FEV1 level (p = 0.02, r = 0.35). The exhaled-TGF-ß1 levels were significantly higher in the stable asthmatic children when compared to the nonasthmatic children (p < 0.0001). There was no significant difference in exhaled-TGF-ß1 levels after the exercise challenge in the nonasthmatics. The exhaled-TGF-ß1 levels were significantly lower in those children with asthma exacerbation when compared to the stable asthmatic children (p = 0.0003). CONCLUSION: Our results suggest that TGF-ß1 may play a role in suppressing airway reactivity and its deficiency is associated with asthma exacerbation.

The effects of desert dust storms, air pollution, and temperature on morbidity due to spontaneous abortions and toxemia of pregnancy: 5-year analysis.

Epidemiological studies have suggested an association between particulate air pollution, increased temperatures, and morbidity related to pregnancy outcomes. However, the roles of desert dust storms and climatological factors have not been fully addressed. The objectives of the present study were to investigate the association between desert dust storms, particulate matter with a diameter ≤10 µm (PM10), daily temperatures, and toxemia of pregnancy and spontaneous abortion in Gaziantep, South East Turkey. The study was conducted retrospectively at emergency department of two hospitals in Gaziantep city. Data from January 1, 2009, to March 31, 2014, were collected. Patients, who were diagnosed with toxemia of pregnancy and spontaneous abortion by radiological imaging modalities, were included in the study. Daily temperature ranges, mean temperature values, humidity, pressure, wind speed, daily PM10 levels, and records of dust storms were collected. A generalized additive regression model was designed to assess variable effects on toxemia of pregnancy and spontaneous abortion, while adjusting for possible confounding factors. Our findings demonstrated that presence of dust storms was positively associated with the toxemia of pregnancy both in outpatient admissions (OR=1.543 95% CI=1.186-2.009) and inpatient hospitalizations (OR=1.534; 95% CI=1.162-2.027). However, neither PM10 nor maximum temperature showed a marked association with spontaneous abortion or toxemia of pregnancy in our study population. Our findings suggest that desert dust storms may have an impact on the risk for adverse pregnancy outcomes such as toxemia of pregnancy. Health authorities should take necessary measures to protect pregnant women against detrimental effects of these storms.

CARM1 regulates senescence during airway epithelial cell injury in COPD pathogenesis.

Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease. Although cigarette smoke was considered the main cause of development, the heterogeneous nature of the disease leaves it unclear whether other factors contribute to the predisposition or impaired regeneration response observed. Recently, epigenetic modification has emerged to be a key player in the pathogenesis of COPD. The addition of methyl groups to arginine residues in both histone and nonhistone proteins by protein arginine methyltransferases (PRMTs) is an important posttranslational epigenetic modification event regulating cellular proliferation, differentiation, apoptosis, and senescence. Here, we hypothesize that coactivator-associated arginine methyltransferase-1 (CARM1) regulates airway epithelial cell injury in COPD pathogenesis by controlling cellular senescence. Using the naphthalene (NA)-induced mouse model of airway epithelial damage, we demonstrate that loss of CC10-positive club cells is accompanied by a reduction in CARM1-expressing cells of the airway epithelium. Furthermore, Carm1 haploinsuffficent mice showed perturbed club cell regeneration following NA treatment. In addition, CARM1 reduction led to decreased numbers of antisenescent sirtuin 1-expressing cells accompanied by higher p21, p16, and ß-galactosidase-positive senescent cells in the mouse airway following NA treatment. Importantly, CARM1-silenced human bronchial epithelial cells showed impaired wound healing and higher ß-galactosidase activity. These results demonstrate that CARM1 contributes to airway repair and regeneration by regulating airway epithelial cell senescence.

Asthma control and adherence in newly diagnosed young and elderly adult patients with asthma in Turkey.

OBJECTIVE: This study aimed to evaluate the factors that affect asthma control and adherence to treatment in newly diagnosed elderly asthmatics in Turkey compared with younger patients. METHODS: This real-life prospective observational cohort study was conducted at 136 centers. A web-based questionnaire was administered to the patients who were followed up for 12 months. RESULTS: Analysis included 1037 young adult asthma patients (age <65 years) and 79 elderly asthma patients (age ≥65 years). The percentage of patients with total control in the elderly and young groups were 33.9% and 37.1% at visit 1, 20.0% and 42.1% (p = 0.012) at visit 2, and 50.0% and 49.8% at visit 3, respectively. Adherence to treatment was similar for both groups. Visit compliance was better in the elderly group than in the young group at visit 1 (72.2% vs. 60.8%, p = 0.045), visit 2 (51.9% vs. 34.9%, p = 0.002), and visit 3 (32.9% vs. 19.4%, p = 0.004). Adherence to treatment increased with asthma control in both groups (both p < 0.001) but decreased with the presence of gastritis/ulcer, gastroesophageal reflux, and coronary artery disease in the elderly. CONCLUSIONS: Asthma control and adherence to treatment were similar for the elderly and young asthma patients, though the follow-up rate was lower in young patients. The presence of gastritis/ulcer, gastroesophageal reflux and coronary artery disease had negative impacts on the adherence to treatment in elderly adult patients.

A hereditary angioedema screening on an index case: Turkey.

BACKGROUND: Hereditary angioedema (HAE) is characterised by recurrent episodes of angioedema and can be fatal. OBJECTIVE: The present study aimed to screen HAE. METHODS: A total of 60 individuals were screened. The frequency and severity of symptoms were scored from 0 to 8. Measurements were taken of C4 and C1 esterase inhibitor protein (C1-INH) levels. Mutation in the C1 inhibitor gene was examined in 9 patients with HAE. RESULTS: A positive correlation between the C1 esterase inhibitor protein levels and C4 level was detected in the group as a whole (p < 0.001, r = 0.725, n = 60). Anegative correlation between the C1 esterase inhibitor protein level and severity score was observed in the whole group (p < 0.001, r = -0.486, n = 60). A negative correlation was also detected in the entire group between the C4 level and severity score (p = 0.002, r = -0.389, n = 60). In the patients with HAE, a positive correlation between the C1 esterase inhibitor protein level and C4 levels was detected (p = 0.034, r = 0.705, n = 9). A heterozygous c. 601A > T nonsense variant was identified at the C1 esterase inhibitor gene-SERPING1-in patients with Type 1 HAE. CONCLUSION: It is well known that there is a prolonged delay in the diagnosis of HAE. The present study demonstrates that it is very important and even life-saving to screen for HAE on the basis of an index case.

A hereditary angioedema screening in two villages, based on an index case, and identification of a novel mutation, "1033G>T", at the SERPING1 gene.

INTRODUCTION: Hereditary angioedema (HAE) may be fatal and diagnosis can be delayed up to 10 years. We aimed to screen HAE in two villages based on an index case of HAE and to investigate for the mutation of the C1 esterase inhibitor (C1-INH) gene. MATERIAL AND METHODS: A total of 124 people were screened in two villages. The frequency and severity of symptoms were scored. C4, C1-INH levels and C1-INH activity were measured. We investigated for mutations of the C1-INH gene. RESULTS: Thirty-five cases of type I HAE and 7 cases of type II HAE were determined. Thirty-one (73.8%) patients diagnosed with HAE were 18 years old or younger. There was a positive correlation between C4 levels, C1-INH levels (p < 0.0001, r = 0.81), and C1-INH activity levels (p < 0.0001, r = 0.631) and between the age at diagnosis and severity score (p < 0.0001, r = 0.651). A positive correlation was found between the age at first symptom onset and C4 levels (p = 0.002, r = 0.774), and C1-INH levels (p = 0.006, r = 0.714). A marginally significant negative correlation was found between C1-INH activity levels and severity scores (p = 0.1, r = -0.515). We identified a novel heterozygous 1033G>T missense variant of the C1-INH gene, SERPING1, in patients with type I HAE. CONCLUSIONS: There are long delay periods in the diagnosis of HAE and when the index case is present, family screening may be very important and even life-saving, in particular, in paediatric patients without symptoms. Furthermore, the present study provides evidence to link a novel mutation, c.1033G>T, to the development of HAE in a large HAE family from Turkey.

Real life profile of asthma and chronic obstructive pulmonary disease patients in Turkey.

INTRODUCTION: Despite the presentation of similar symptoms, the airway diseases have different underlying pathophysiological processes and must be distinguished to enable the administration of appropriate treatment. In several studies the clinician- and patient-related causes of poor compliance to treatment in asthma/chronic obstructive pulmonary disease (COPD) patients have been evaluated. This study aimed to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey. MATERIALS AND METHODS: This national, multicentre, prospective, observational study was conducted in 122 centres. A questionnaire including items related to demographic, clinical, laboratory parameters was applied. All patients were intended to be followed-up for 12 months. RESULT: 1892 adult patients (1116 asthma and 776 COPD) from 122 centres were enrolled. Overall 95%, 86% and 65% of intermittent, mild persistent and moderate persistent asthma patients were over-treated. Among COPD patients, the percentages of over-treated patients were 66%, 79% and 82% for those with GOLD stage A, B and C. Physicians' adherence to guidelines was appropriate in 93% of severe persistent asthma patients and 89% of GOLD stage D COPD patients. Among patients with high compliance to treatment, proportion of asthma patients with total control was 44% and that of COPD patients at GOLD stage A was 41%. In consecutive two visits, this figure increased to 52% and 63% in asthma patients and 54% and 50% in COPD patients. CONCLUSIONS: The main findings are: (a) patients are frequently over-treated and (b) patients do not adhere to visits as expected, in both asthma and COPD.

Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 µM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 µM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents.

The association between weather conditions and stroke admissions in Turkey.

Although several factors such as cigarette smoking, blood pressure, diabetes, obesity, hypercholesterolemia, physical inactivity and dietary factors have been well documented to increase the risk for stroke, there are conflicting data about the role of meteorological variables in the etiology of stroke. We conducted a retrospective study to investigate the association between weather patterns, including daily temperature, humidity, wind speed, and air pressure, and stroke admissions to the Emergency Department of Atatürk Training and Research Hospital in Ankara, Turkey, between January 2009 and April 2010. Generalized additive models with logistic link function were used to investigate the relationship between predictors and days with and without stroke admission at lags 0-4. A total of 373 stroke patients were admitted to the emergency department (ED) between January 2009 and April 2010. Of patients, 297 had ischemic stroke (IS), 34 hemorrhagic stroke (HS), and 42 subarachnoidal hemorrhage (SAH). Although we did not find any association between overall admissions due to stroke and meteorological parameters, univariable analysis indicated that there were significantly more SAH cases on days with lower daily mean temperatures of 8.79 ± 8.75 °C as compared to relatively mild days with higher temperatures (mean temperature = 11.89 ± 7.94 °C, p = 0.021). The multivariable analysis demonstrated that admissions due to SAH increased on days with lower daily mean temperatures for the same day (lag 0; odds ratio (OR) [95% confidence interval (95% CI)] = 0.93 [0.89-0.98], p = 0.004) and lag 1 (OR [95% CI] =0.76 [0.67-0.86], p = 0.001). Furthermore, the wind speed at both lag 1 (OR [95% CI] = 1.63 [1.27-2.09], p = 0.001) and lag 3 (OR [95% CI] = 1.43 [1.12-1.81], p = 0.004) increased admissions due to HS, respectively. In conclusion, our study demonstrated that there was an association between ED admissions due to SAH and HS and weather conditions suggesting that meteorological variables may, at least in part, play as risk factors for intracranial hemorrhages.

Impact of Earthquakes on Lung Health.

Earthquakes are catastrophic natural disasters that cause extensive damage to infrastructure and disrupt the lives of millions worldwide. Beyond the immediate physical and psychological damage caused by earthquakes, these events can significantly impact respiratory health. The inhalation of dust, smoke, particulates, toxic gases, and asbestos exposure can lead to various respiratory health pathologies. These include respiratory infections, exacerbations of pre-existing respiratory diseases, chest traumas, and pulmonary and venous thromboembolism. Longitudinal studies are necessary to assess the long-term respiratory health effects in affected populations. By addressing these knowledge gaps, future mitigation strategies and preparedness measures can be developed to minimize the respiratory health impacts of earthquakes and improve the well-being of affected communities. Robust building infrastructure and comprehensive earthquake preparedness are emerging as the most important determinants for not only mitigating building collapse but also significantly reducing the potential health impacts that follow. This comprehensive review aims to provide a systematic overview of the lung health impacts of earthquakes. It highlights the need for further research to identify specific pollutants, air contaminants, and environmental factors contributing to respiratory health issues following earthquakes.

Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms.

Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling.

HemN2 Regulates the Virulence of Pseudomonas donghuensis HYS through 7-Hydroxytropolone Synthesis and Oxidative Stress.

Compared to pathogens Pseudomonas aeruginosa and P. putida, P. donghuensis HYS has stronger virulence towards Caenorhabditis elegans. However, the underlying mechanisms haven't been fully understood. The heme synthesis system is essential for Pseudomonas virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and Pseudomonas virulence were barely pursued. In this study, we hypothesized that hemN2 deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four hemN genes in P. donghuensis HYS, and we reported for the first time that deletion of hemN2 significantly reduced the virulence of HYS towards C. elegans, whereas the reduction in virulence by the other three genes was not significant. Interestingly, hemN2 deletion significantly reduced colonization of P. donghuensis HYS in the gut of C. elegans. Further studies showed that HemN2 was regulated by GacS and participated in the virulence of P. donghuensis HYS towards C. elegans by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of P. donghuensis HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus Pseudomonas.

Medicinal Chemistry of Antisense Oligonucleotides for Therapeutic Use in SARS-CoV-2: Design Strategies and Challenges for Targeted Delivery.

BACKGROUND: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects. OBJECTIVE: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations. METHODS: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19. RESULTS: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics. CONCLUSION: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.