Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Blockade of the protease ADAM17 ameliorates experimental pancreatitis.

Acute and chronic pancreatitis, the latter associated with fibrosis, are multifactorial inflammatory disorders and leading causes of gastrointestinal disease-related hospitalization. Despite the global health burden of pancreatitis, currently, there are no effective therapeutic agents. In this regard, the protease A Disintegrin And Metalloproteinase 17 (ADAM17) mediates inflammatory responses through shedding of bioactive inflammatory cytokines and mediators, including tumor necrosis factor α (TNFα) and the soluble interleukin (IL)-6 receptor (sIL-6R), the latter of which drives proinflammatory IL-6 trans-signaling. However, the role of ADAM17 in pancreatitis is unclear. To address this, Adam17ex/ex mice-which are homozygous for the hypomorphic Adam17ex allele resulting in marked reduction in ADAM17 expression-and their wild-type (WT) littermates were exposed to the cerulein-induced acute pancreatitis model, and acute (1-wk) and chronic (20-wk) pancreatitis models induced by the cigarette smoke carcinogen nicotine-derived nitrosamine ketone (NNK). Our data reveal that ADAM17 expression was up-regulated in pancreatic tissues of animal models of pancreatitis. Moreover, the genetic (Adam17ex/ex mice) and therapeutic (ADAM17 prodomain inhibitor [A17pro]) targeting of ADAM17 ameliorated experimental pancreatitis, which was associated with a reduction in the IL-6 trans-signaling/STAT3 axis. This led to reduced inflammatory cell infiltration, including T cells and neutrophils, as well as necrosis and fibrosis in the pancreas. Furthermore, up-regulation of the ADAM17/IL-6 trans-signaling/STAT3 axis was a feature of pancreatitis patients. Collectively, our findings indicate that the ADAM17 protease plays a pivotal role in the pathogenesis of pancreatitis, which could pave the way for devising novel therapeutic options to be deployed against this disease.

Cross-talk between IL-6 trans-signaling and AIM2 inflammasome/IL-1ß axes bridge innate immunity and epithelial apoptosis to promote emphysema.

Pulmonary emphysema is associated with dysregulated innate immune responses that promote chronic pulmonary inflammation and alveolar apoptosis, culminating in lung destruction. However, the molecular regulators of innate immunity that promote emphysema are ill-defined. Here, we investigated whether innate immune inflammasome complexes, comprising the adaptor ASC, Caspase-1 and specific pattern recognition receptors (PRRs), promote the pathogenesis of emphysema. In the lungs of emphysematous patients, as well as spontaneous gp130F/F and cigarette smoke (CS)-induced mouse models of emphysema, the expression (messenger RNA and protein) and activation of ASC, Caspase-1, and the inflammasome-associated PRR and DNA sensor AIM2 were up-regulated. AIM2 up-regulation in emphysema coincided with the biased production of the mature downstream inflammasome effector cytokine IL-1ß but not IL-18. These observations were supported by the genetic blockade of ASC, AIM2, and the IL-1 receptor and therapy with AIM2 antagonistic suppressor oligonucleotides, which ameliorated emphysema in gp130F/F mice by preventing elevated alveolar cell apoptosis. The functional requirement for AIM2 in driving apoptosis in the lung epithelium was independent of its expression in hematopoietic-derived immune cells and the recruitment of infiltrating immune cells in the lung. Genetic and inhibitor-based blockade of AIM2 also protected CS-exposed mice from pulmonary alveolar cell apoptosis. Intriguingly, IL-6 trans-signaling via the soluble IL-6 receptor, facilitated by elevated levels of IL-6, acted upstream of the AIM2 inflammasome to augment AIM2 expression in emphysema. Collectively, we reveal cross-talk between the AIM2 inflammasome/IL-1ß and IL-6 trans-signaling axes for potential exploitation as a therapeutic strategy for emphysema.

Cytosolic DNA sensor AIM2 promotes KRAS-driven lung cancer independent of inflammasomes.

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co-operators of oncogenic KRAS in the lung remains ill-defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent-in-melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS-addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine-derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome-associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK-induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D-driven LAC in both hematopoietic (immune) and non-hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2-deficient mice is associated with unaltered protein levels of mature Caspase-1 and IL-1ß inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D-driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase-1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor-promoting role, independent of inflammasomes, in mutant KRAS-addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

Exploring the Potential of Chemically Modified Graphyne Nanodots as an Efficient Adsorbent and Sensitive Detector of Environmental Contaminants: A First Principles Study.

In this study, we investigated the reactivity of γ-graphyne (Gp) and its derivatives, Gp-CH3, Gp-COOH, Gp-CN, Gp-NO2, and Gp-SOH, for the removal of toxic heavy metal ions (Hg+ 2, Pb+ 2, and Cd+ 2) from wastewater. From the analysis of the optimized structures, it was observed that all the compounds exhibited planar geometry. The dihedral angles (C9-C2-C1-C6 and C9-C2-C1-C6) were approximately 180.00°, indicating planarity in all molecular arrangements. To understand the electronic properties of the compounds, the HOMO (EH) and LUMO (EL) energies were calculated, and their energy gaps (Eg) were determined. The EH and EL values ranged between - 6.502 and - 8.192 eV and - 1.864 and - 3.773 eV, respectively, for all the compounds. Comparing the EH values, Gp-NO2 exhibited the most stable HOMO, while Gp-CH3 had the least stable structure. In terms of EL values, Gp-NO2 had the most stable LUMO, while Gp-CH3 was the least stable. The Eg values followed the order: Gp-NO2 < Gp-COOH < Gp-CN < Gp-SOH < Gp-CH3 < Gp, with Gp-NO2 (4.41 eV) having the smallest energy gap. The density of states (DOS) analysis showed that the shape and functional group modifications affected the energy levels. Functionalization with electron-withdrawing (CN, NO2, COOH, SOH) or electron-donating (CH3) groups reduced the energy gap. To specifically target the removal of heavy metal ions, the Gp-NO2 ligand was selected for its high binding energy. Complexes of Gp-NO2-Cd, Gp-NO2-Hg, and Gp-NO2-Pb were optimized, and their properties were analyzed. The complexes were found to be planar, with metal-ligand bond distances within the range of 2.092→3.442 Å. The Gp-NO2-Pb complex exhibited the shortest bond length, indicating a stronger interaction due to the smaller size of Pb+ 2. The computed adsorption energy values (Eads) indicated the stability of the complexes, with values ranging from - 0.035 to -4.199 eV. Non-covalent interaction (NCI) analysis was employed to investigate intermolecular interactions in Gp-NO2 complexes. The analysis revealed distinct patterns of attractive and repulsive interactions, providing valuable insights into the binding preferences and steric effects of heavy metals.

Virtual Care? Telepharmacy in Critical Care Settings for Patient-Centered Care and Multidisciplinary Collaboration: A Scoping Review of Activities, Benefits, Economic Impact, Challenges, and Knowledge Gaps.

Background: Very few studies have investigated telepharmacy (TP) in critical care. This scoping review undertook this task. Methods: We searched the following five electronic databases (PubMed, Embase, WoS, Scopus, CINAHL). Data were extracted from the articles and mapped out. Arksey and O'Malley's 6-step framework was used, and data synthesis identified activities, benefits, economic impact, challenges, and knowledge gaps of TP in critical care. Results: Out of 77 reports retrieved, 14 were included in the review as per inclusion criteria. Eight studies (57%) were published since 2020, and 9 (64%) were from the United States. Tele-ICU was in place before TP implementation in six studies (43%). TP used a range of synchronous/asynchronous communications. Studies reported wide assortment of reactive/scheduled TP activities. Patient outcomes were evaluated in one study of sedation-related TP interventions but they were not different despite improved compliance with sedation protocol. Most common clinical interventions/drugs included glycemic, electrolyte, and antimicrobial therapy management and antithrombotic agents among others. Acceptance of TP interventions was 75% or more in four studies and 51-55% in two studies. Benefits of TP included resolved drug-related problems, increased compliance with guidelines, maintained interactions with other health care providers, and patient safety among others. Three studies (21%) reported cost avoidance with TP interventions. Challenges included communication, intervention documentation, tracking implementation of recommendations, and monetary/financial and legislative/regulatory issues. Knowledge gaps comprised lack of frameworks for implementation/evaluation of TP in critical care, methodological aspects, lack of patient-specific outcomes, as well as institution/health-system aspects, and documentation systems, cost, legislative, and sustainability issues. Conclusions: TP in critical care is underpublished, and comprehensive frameworks for its implementation and evaluation remain lacking. Assessments are needed to evaluate the effect of TP in critical care on patient-specific outcomes, its economic and legal dimensions, methods to sustain it, as well as the role of documentation systems, collaboration models, and institutional characteristics.

Decision tree-based approach to extrapolate life cycle inventory data of manufacturing processes.

Life cycle assessment (LCA) plays a crucial role in green manufacturing to uncover the critical aspects for alleviating the environmental burdens due to manufacturing processes. However, the scarcity of life cycle inventory (LCI) data for the manufacturing processes is a considerable challenge. This paper proposes a novel approach to extrapolate LCI data of manufacturing processes. Taking advantage of LCI data in the Ecoinvent datasets, decision tree-based supervised machine learning models, namely decision tree, random forest, gradient boosting, and adaptive boosting, have been developed to extrapolate the data of GHG emissions, i.e., carbon dioxide, nitrous oxide, methane, and water vapor. Initially, a correlation analysis was conducted to derive the most influential factors on GHG quantities resulting from manufacturing activities. First, the collected data have been preprocessed and split into train and test sets (70% and 30%, respectively). Second, a five-fold cross-validation method was applied to tune the hyperparameters of the models. Then, the models were re-trained using the best hyperparameters and evaluated using the test set. The results reveal that the Gradient Boosting model has a superior predictive performance for extrapolating the GHG emission data, with average coefficients of determination (R2) on the test set <0.95. Moreover, the model predictions involve relatively low values of the average root mean squared error and an average mean percentage of error on the test set. The correlation and feature importance analyses emphasized that the workpiece material and manufacturing technology have a considerable effect on natural resource consumption, i.e., energy, material, and water inflows into the process. Meanwhile, energy consumption, water usage, and raw aluminum depletion were the most influential factors in GHG emissions. Eventually, a case study to extrapolate the inflows and the outflows for new manufacturing activities has been conducted using the validated models. The proposed GraBoost model provides a computational supplementary approach to estimate and extrapolate the GHG emissions for different manufacturing processes when LCI data are incomplete or don't exist within LCI databases.

The predictors of successful methotrexate treatment of tubal ectopic pregnancy.

BACKGROUND: The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy remain controversial. This study investigated the outcomes of ectopic pregnancy after one and two MTX doses and their independent predictors. METHODS: Retrospective cross-sectional study of women who consented to MTX treatment in 2017-2018 at our institution (N = 317). Of these, patients with Caesarean scar pregnancies were excluded because they require different treatment protocols (n = 25). All patients were treated according to our institution's protocol based on international guidelines and standardised across the three hospitals included in the current study. We retrieved patients' demographics, laboratory, ultrasonography, and clinical characteristics from our hospital database. Serum ß-human chorionic gonadotropin (ß-hCG) was measured using electrochemiluminescence immunoassay; ectopic pregnancy was diagnosed using ultrasonography (transvaginal probe). RESULTS: Two ninety-two patients were included in the current analysis. Age, pre-treatment ß-hCG levels, sonographic presence of yolk sac, presence of foetal cardiac activity, and pelvic pain were significantly different between patients with successful and unsuccessful outcomes. Younger age (adjusted odds ratio [aOR] 2.33, 95% confidence interval (CI) 1.16-4.66, p = .017), no pelvic pain (aOR 2.65, 95%CI 1.03-6.83, p = .043), lower initial ß-hCG level (aOR 1.32, 95%CI 1.08-1.59, p = .005), and absence of foetal cardiac activity (aOR 12.63; 95% CI 1.04-153.6; p = .047) were independently associated with success. Treatment failure odds were >2 folds higher for each 10-year age increase (p = .017), 32% higher for each 1000 IU/L increase in initial ß-hCG level (p = .005), and >2 folds higher in presence of pelvic pain (p = .043). CONCLUSIONS: MTX is effective in most patients, averting invasive surgery, which might affect fertility. Pre-treatment ß-hCG levels, age, pelvic pain, and foetal cardiac activity was independently associated with outcomes. Research should assess the relationship between the ectopic pregnancy size and treatment outcomes and refine ß-hCG titres where treatment would be ineffective.

Ectopic pregnancy is a pregnancy that occurs outside the uterus. It needs to be identified and treated quickly to prevent serious health complications. Ectopic pregnancies can be treated surgically or medically using a drug called methotrexate. Medical treatment of ectopic pregnancy is not always successful. Identifying the factors that predict the failure of medical treatment helps patients and doctors to choose more accurately between surgical and medical treatment options.A total of 292 women who received methotrexate for ectopic pregnancy and the factors that influence the outcomes of treatment were examined, 39 patients had treatment failure and required surgery. Older age, higher initial levels of ß-human chorionic gonadotropin (ß-hCG) hormone, the presence of pelvic pain, and foetal cardiac activity had increased risk of treatment failure. In the future, research could consider the relationship between the size of the ectopic pregnancy and the treatment outcomes and refine the ß-hCG level cut-off for better treatment effects.

Evaluation of acute flaccid paralysis surveillance system in the River Nile State - Northern Sudan, 2021.

BACKGROUND: One of the four main elements of the worldwide polio eradication strategy is acute flaccid paralysis surveillance (AFP). This system is based on (acute flaccid paralysis (AFP) cases reported and tested at World Health Organization (WHO) accredited laboratories. To measure and monitor performance, indicators were created. The current study aims to evaluate the system components, performance, and efficiency in River Nile State, Northern Sudan, and their compliance with World Health Organization (WHO) requirements for it to be adopted as a good system; its results can be used to certify whether a country is polio-free or not. MATERIAL AND METHODS: A facility-based retrospective descriptive study was conducted in the River Nile State, Northern Sudan, from Jan 2017 to Dec 2020. This study included all reporting sites/units, workers who reported acute flaccid paralysis (AFP) cases, and officers at the locality level. A total of 50 health institutions were visited for surveillance, and interviews with 59 health workers who were part of the AFP surveillance system were undertaken. The data were collected from participants using a pre-tested questionnaire designed and constructed by the World Health Organization (WHO) framework, and the data were analyzed using the SPSS version (22). RESULTS: The River Nile State's AFP surveillance system was of high quality in terms of the infrastructure that had been put in place and the effectiveness of the system's operations, as evidenced by the following statistics: from 2017 to 2020, the reported non-polio acute flaccid paralysis (AFP) cases were at a mean rate of 4.02 per 100,000 children under the age of 15; the majority of AFP reported cases were under 10 years; and males made up 73.3% of reported cases; The completeness of reports and surveillance documents exceeded 80%, and active surveillance was applied in 80% of reporting sites. CONCLUSION: Despite the fact that the surveillance system is capable of detecting cases, Sudan continues to report cases of imported polio from other countries, highlighting the need to strengthen surveillance systems and eradication efforts in these countries.

Exploring sex disparities in cardiovascular disease risk factors using principal component analysis and latent class analysis techniques.

BACKGROUND: This study used machine learning techniques to evaluate cardiovascular disease risk factors (CVD) and the relationship between sex and these risk factors. The objective was pursued in the context of CVD being a major global cause of death and the need for accurate identification of risk factors for timely diagnosis and improved patient outcomes. The researchers conducted a literature review to address previous studies' limitations in using machine learning to assess CVD risk factors. METHODS: This study analyzed data from 1024 patients to identify the significant CVD risk factors based on sex. The data comprising 13 features, such as demographic, lifestyle, and clinical factors, were obtained from the UCI repository and preprocessed to eliminate missing information. The analysis was performed using principal component analysis (PCA) and latent class analysis (LCA) to determine the major CVD risk factors and to identify any homogeneous subgroups between male and female patients. Data analysis was performed using XLSTAT Software. This software provides a comprehensive suite of tools for Data Analysis, Machine Learning, and Statistical Solutions for MS Excel. RESULTS: This study showed significant sex differences in CVD risk factors. 8 out of 13 risk factors affecting male and female patients found that males and females share 4 of the eight risk factors. Identified latent profiles of CVD patients, suggesting the presence of subgroups among CVD patients. These findings provide valuable insights into the impact of sex differences on CVD risk factors. Moreover, they have important implications for healthcare professionals, who can use this information to develop individualized prevention and treatment plans. The results highlight the need for further research to elucidate these disparities better and develop more effective CVD prevention measures. CONCLUSIONS: The study explored the sex differences in the CVD risk factors and the presence of subgroups among CVD patients using ML techniques. The results revealed sex-specific differences in risk factors and the existence of subgroups among CVD patients, thus providing essential insights for personalized prevention and treatment plans. Hence, further research is necessary to understand these disparities better and improve CVD prevention.

Concha-Type Microtia: New Surgical Incision.

BACKGROUND: Reconstruction of auricles for conchal-type microtia is challenging but rewarding. Many plastic surgeons consider autogenous rib cartilage as the standard material for framework fabrication. A healthy, scar-free skin envelope and a defined cartilaginous framework are also critical to successful ear reconstruction. OBJECTIVES: The aim of this study was to improve the outcome of the reconstruction and minimize complications by proposing a new surgical incision. METHODS: Thirty-three patients who underwent auricular reconstruction of concha-type microtia of various etiologies with the new skin flap incision between 2017 and 2022 were included in the study. Patients' clinical data, detailed surgical techniques, and postoperative care were recorded. RESULTS: Thirty-three patients (21 male, 12 female) were enrolled in the study. The mean age of the patients was 21.51 years at the time of reconstruction. The microtia was on the right side in 17 cases, on the left side in 12 cases, and 4 cases were bilateral; 12 cases were traumatic amputations of the helical component of the auricle, 11 cases were deformities after a burn, and 10 cases were congenital. The mean follow-up time was 17.43 months. A good initial projection without obvious scarring on the anterior surface of the auricle was achieved, with an overall complication rate of 5.42%. CONCLUSIONS: The surgical incision recommended in the study improves the final aesthetic result of the technique without any additional surgical risk.

The comparison of two different plumage-color lines of Japanese quail (Coturnix japonica) disclosed a significant effect in increasing abdominal fat contents with increasing age.

This study aimed to investigate the characteristic differences between the white and brown-feathered Japanese quails, by evaluating the carcass traits and egg fat content, blood parameters, and intestinal histopathological features. A total of 1200 1-day-old Japanese quail chicks of two varieties (brown and white-feathered) were used in this study. Live body weight and feed intake were reordered every week. At the 4th week of age, 80 birds from each variety were slaughtered and carcass quality measurements and histopathological changes were recorded. After 6 weeks of age, eggs were collected, and egg quality was assessed. The results revealed that white-feathered quails had significantly heavier body weights and higher growth rates. At 4 weeks of age, females of the white-feather quail had significantly heavier slaughter, after de-feathering, and carcass weights. Remarkable variations between the studied quail varieties, with significant dominance of females in both varieties, at the level of water holding capacity, pH, and meat tenderness ascertained an obvious superiority of white-feathered quails compared to brown ones and indicated the higher tendency of the white quails for meat production. These results were linked with significant changes in biochemical profiles including lipids biomarkers, total protein, and Ca and phosphorus levels along with variations in the intestinal morphometry. It can be concluded that white-feathered quails had, in general, higher values of productivity compared with the brown-feathered ones during growing and laying periods.

STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis.

OBJECTIVE: The absent in melanoma 2 (AIM2) cytosolic pattern recognition receptor and DNA sensor promotes the pathogenesis of autoimmune and chronic inflammatory diseases via caspase-1-containing inflammasome complexes. However, the role of AIM2 in cancer is ill-defined. DESIGN: The expression of AIM2 and its clinical significance was assessed in human gastric cancer (GC) patient cohorts. Genetic or therapeutic manipulation of AIM2 expression and activity was performed in the genetically engineered gp130 F/F spontaneous GC mouse model, as well as human GC cell line xenografts. The biological role and mechanism of action of AIM2 in gastric tumourigenesis, including its involvement in inflammasome activity and functional interaction with microtubule-associated end-binding protein 1 (EB1), was determined in vitro and in vivo. RESULTS: AIM2 expression is upregulated by interleukin-11 cytokine-mediated activation of the oncogenic latent transcription factor STAT3 in the tumour epithelium of GC mouse models and patients with GC. Genetic and therapeutic targeting of AIM2 in gp130 F/F mice suppressed tumourigenesis. Conversely, AIM2 overexpression augmented the tumour load of human GC cell line xenografts. The protumourigenic function of AIM2 was independent of inflammasome activity and inflammation. Rather, in vivo and in vitro AIM2 physically interacted with EB1 to promote epithelial cell migration and tumourigenesis. Furthermore, upregulated expression of AIM2 and EB1 in the tumour epithelium of patients with GC was independently associated with poor patient survival. CONCLUSION: AIM2 can play a driver role in epithelial carcinogenesis by linking cytokine-STAT3 signalling, innate immunity and epithelial cell migration, independent of inflammasome activation.

Soluble ACE2 and angiotensin II levels are modulated in hypertensive COVID-19 patients treated with different antihypertension drugs.

PURPOSE: This study examines the effect of antihypertensive drugs on ACE2 and Angiotensin II levels in hypertensive COVID-19 patients. INTRODUCTION: Hypertension is a common comorbidity among severe COVID-19 patients. ACE2 expression can be modulated by antihypertensive drugs such as ACEis and ARBs, which may affect COVID-19's prognosis. BB and CCB reduce mortality, according to some evidence. Their effect on circulating levels of ACE2 and angiotensin II, as well as the severity of COVID-19, is less well studied. MATERIALS AND METHODS: The clinical data were collected from 200 patients in four different antihypertensive medication classes (ACEi, ARB, BB, and CCB). Angiotensin II and ACE2 levels were determined using standard ELISA kits. ACE2, angiotensin II, and other clinical indices were evaluated by linear regression models. RESULTS: Patients on ACEi (n = 57), ARB (n = 68), BB (n = 15), or CCB (n = 30) in this study had mild (n = 76), moderate (n = 76), or severe (n = 52) COVID-19. ACE2 levels were higher in COVID-19 patients with severe disease (p = 0.04) than mild (p = 0.07) and moderate (p = 0.007). The length of hospital stay is correlated with ACE2 levels (r = 0.3, p = 0.003). Angiotensin II levels decreased with severity (p = 0.04). Higher ACE2 levels are associated with higher CRP and D-dimer levels. Elevated Angiotensin II was associated with low levels of CRP, D-dimer, and troponin. ACE2 levels increase with disease severity in patients taking an ARB (p = 0.01), patients taking ACEi, the degree of disease severity was associated with a decrease in angiotensin II. BB patients had the lowest disease severity. CONCLUSION: We found different levels of soluble ACE2, and angiotensin II are observed among COVID-19 patients taking different antihypertensive medications and exhibiting varying levels of disease severity. COVID-19 severity increases with elevated ACE2 levels and lower angiotensin II levels indicating that BB treatment reduces severity regardless of levels of ACE2 and angiotensin II.

Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, in vitro assays, and in silico studies.

Two new series of symmetric (1a-h) and asymmetric (2a-l) 1,4-DHP derivatives were designed, synthesised, and evaluated as anticancer agents. In vitro anticancer screening of target compounds via National cancer institute "NCI" revealed that analogues 1g, 2e, and 2l demonstrated antiproliferative action with mean growth inhibition percentage "GI%" = 41, 28, and 64, respectively. The reversal doxorubicin (DOX) effects of compounds 1g, 2e, and 2l were examined and illustrated better cytotoxic activity with IC50 =1.12, 3.64, and 3.57 µM, respectively. The most active anticancer analogues, 1g, 2e, and 2l, were inspected for their putative mechanism of action by estimating their epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), and Bruton's tyrosine kinase (BTK) inhibitory activities. Furthermore, the antimicrobial activity of target compounds was assessed against six different pathogens, followed by determining the minimum inhibitory concentration "MIC" values for the most active analogues. Molecular docking study was achieved to understand mode of interactions between selected inhibitors and different biological targets.

Critical care tele-pharmacy services during COVID-19 pandemic: A qualitative exploration of healthcare practitioners' perceptions.

WHAT IS KNOWN AND OBJECTIVE: The scope of clinical pharmacy services has changed during COVID-19 pandemic with the view to mitigating both exposure and spread of the virus. The performance of novel pandemic-driven services such as tele-pharmacy has remained unexplored, until now. The aim of this study is to investigate the perceptions of healthcare providers of the impact of tele-pharmacy services provided in critical care units during COVID-19. METHODS: A qualitative study of semi-structured interviews conducted with healthcare practitioners who worked in COVID-19 intensive care units and remotely interacted with clinical pharmacists at the Weill Cornell-affiliated Hamad Medical Corporation, Doha, Qatar. Random sampling technique was employed to recruit participants, with the resultant interview guide piloted before commencement of data collection process. RESULTS AND DISCUSSION: From a total 129 and 200 physicians and nurses, respectively, 20 interviews were conducted with physicians (n = 15), and nurses (n = 5). From these interactions, a number of major themes emerged including: satisfactory understanding across clinical environment and personnel (physician and nurses) about remote clinical pharmacists' roles; additional robust feedback on the perception of the remote clinical pharmacy service; an understanding by 'frontline' health personnel on the discernible differences between remote and in-person coverage of clinical pharmacists; a reflection by both physicians and nurses on the novel challenges involved in the implementation of such pandemic-driven service; and solutions to overcome these challenges. WHAT IS NEW AND CONCLUSION: In this novel qualitative study of pandemic-driven tele-pharmacy service, we found a positive perception amongst healthcare practitioners towards this service; with residual challenges that will need further evaluation by large sampled sized surveys or mixed methods research.

Assessment of plasmablast cells in immune thrombocytopenic purpura in children.

Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder with platelet destruction due to B- and T-cell dysregulation and antiplatelet autoantibodies production. Flow cytometry can be used to further characterize the B- and T-cell compartments involved in platelet destruction. This case-control study was to enumerate plasmablast cells in pediatric ITP patients and to correlate their levels with disease course. This study included 30 ITP patients and 10 controls. Identification and enumeration of Plasmablast were done by multicolor flow cytometry using specific antibody panels (CD19, CD27 & CD38) and sequential gating using FACSCanto flow cytometer and FlowJo software. We found that lymphocytes subpopulation in ITP patients and controls revealed increase in frequency of CD19 (B lymphocytes) in acute, persistent, and chronic ITP patients in comparison with controls (p < 0.001, 0.023, 0.001) respectively. Plasmablast cells could play a role in the pathogenesis of ITP and might guide therapy in ITP patients in the future.

"Post Bariatric Male Chest Re-shaping Using L-shaped Excision Technique".

BACKGROUND: Male chest deformity after massive weight loss is complex and challenging to treat because of differing grades of excessive parenchyma/fat ptosis, nipple malposition, over-stretched skin, ill-defined infra-mammary fold, and prominent axillary rolls. Patients are eager to restore balanced upper body dominance. Two fundamental techniques are used for large breasts with moderate to poor skin elasticity; (1) the inferior pedicle Wise skin pattern and (2) double incision with free nipple graft technique.The author presents his experience in treating such severe breast deformities, besides correcting the prominent axillary rolls using an L-shaped mastectomy excision. MATERIALS AND METHODS: Between March 2017 and December 2020, 55 consecutive patients were treated surgically for male chest re-contouring using the L-shaped mastectomy technique. Ages ranged from 20 to 57 years (median, 31 years). The average body mass index (BMI) was 29. The average follow-up period was 17 months (13-44 months). RESULTS: Fifty-one patients (92.8%) reported greater levels of postoperative satisfaction with their results owing to lack of any major complication and minimal minor complications (two cases of minor ischemia that healed spontaneously, two small hematomas, two small seromas, and four hypertrophic scars). CONCLUSION: The L-shaped excision is a useful procedure for severe grade gynecomastia with an atypical presentation in the form of complex chest deformity and prominent axillary roll after massive weight loss patients. The technique is associated with minor complications that are treated in an office setting. The technique preserves normal pigmentation and sensitivity of the nipple-alveolar complex. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Investigating the Safety of Multiple Body Contouring Procedures in Massive Weight Loss Patients.

INTRODUCTION: Deformities after massive weight loss are usually severe and affect many parts of the body, negatively impacting patients' social and intimate lives. A common request of patients after massive weight loss is to treat more than one anatomical area in one surgical procedure. Advantages include a single recovery period, lower surgical costs, and faster patient satisfaction. Disadvantages may include increased need for blood transfusions, longer hospital stay, and increased risk of common complications. OBJECTIVE: The main objective of the study is to compare operative risk, hospital length of stay, complication rate, and patient satisfaction in MWLP according to the number of surgical procedures performed in the same surgical setting. PATIENTS AND METHODS: This is a retrospective case-control study of 653 MWLP who underwent multiple contouring procedures simultaneously in a single surgical procedure. All patients underwent surgery between 2016 and 2020. The patients studied were divided into 4 groups according to the number of anatomical areas operated on. RESULTS: A total of 1254 body contouring procedures were included in the study. Follow-up time ranged from 13 to 41 months, with a mean of 17 months. The mean age in the study was 33 years old. Women accounted for 78% of the studied population and men accounted for 22%. The overall complication rate (major and minor) was 105 cases (16.07%) in all groups CONCLUSION: Patient satisfaction was highest in patients who underwent 2-3 procedures within the same surgical setting compared to patients who underwent +3 procedures. Nevertheless, this is clinically insignificant. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .