HBO1/KAT7/MYST2 HAT complex regulates human adenovirus replicative cycle.

Human adenoviruses (HAdV) belong to a small DNA tumor virus family that continues as valuable models in understanding the viral strategies of usurping cell growth regulation. A number of HAdV type 2/5 early viral gene products interact with a variety of cellular proteins to build a conducive environment that promotes viral replication. Here we show that HBO1 (Histone Acetyltransferase Binding to ORC1), a member of the MYST histone acetyltransferase (HAT) complex (also known as KAT7 and MYST2) that acetylates most of the histone H3 lysine 14, is essential for HAdV5 growth. HBO1/MYST2/KAT7 HAT complexes are critical for a variety of cellular processes including control of cell proliferation. In HBO1 downregulated human cells, HAdV5 infection results in reduced expression of E1A and other viral early genes, virus growth is also reduced significantly. Importantly, HBO1 downregulation reduced H3 lysine 14 acetylation at viral promoters during productive infection, likely driving reduced viral gene expression. HBO1 was also associated with viral promoters during infection and co-localized with viral replication centers in the nuclei of infected cells. In transiently transfected cells, overexpression of E1A along with HBO1 stimulated histone acetyltransferase activity of HBO1. E1A also co-immunoprecipitated with HBO1 in transiently transfected cells. In summary, our results demonstrate that HAdV recruits the HBO1 HAT complex to aid in viral replication.

Evaluation of transpalatal distraction in cleft palate patients.

PURPOSE: The aim of this study was to evaluate the effect of combining a bone-borne palatal expander (distractor) with a maxillary osteotomy in the treatment of narrowed maxillae in treated cleft palate patients. Few articles in the literature isolated the effects of transpalatal distraction in cleft patients and most either excluded cleft patients or grouped them with non-cleft patients. The hypothesis is that the use of a bone-borne palatal expander in conjunction with a maxillary osteotomy would improve the amount of maxillary expansion at the anterior segment with less tipping of the segments and provide a harmonious arch form. METHODS: We studied four patients above 14 years of age with repaired cleft palate and progressive anterior constriction of the arch. All patients received a bone-borne distractor (UNI-Smile Distractor, Titamed, Belgium) combined with a LeFort I level osteotomy without pterygomaxillary disjunction. Dental models and CBCT measurements were used to analyze the skeletal and dental effects of the intervention. RESULT: All the patients who completed the trial had satisfactory expansion and normalization of the maxillary arch form. The average increase in the intercanine distance was 12.9 mm while the average increase in the intermolar distance was 7.2 mm. No significant change in molar inclination or buccal bone thickness was observed. CONCLUSION: The use of bone-borne palatal expanders aided by a maxillary osteotomy (transpalatal distraction) in treated cleft palate patients can provide a harmonious arch form in adolescent and adult patients. This trial was registered in the clinical trials registry with the ID NCT03837652 on February 12, 2019.

Gender differences in two-dimensional and three-dimensional speckle tracking echocardiography left ventricular measurements among healthy preschool pediatric population.

BACKGROUND: Speckle-tracking echocardiography (STE) is an upcoming echocardiographic modality to measure global as well as segmental left ventricular systolic function expressed numerically as strain values independent of angle and ventricular geometry. We conducted this prospective study on 200 healthy preschool children with structurally normal hearts, to determine gender-based differences in two-dimensional (2D) global longitudinal strain (GLS) and three-dimensional (3D) GLS. RESULTS: Age-matched 104 males and 96 females were included, 2D GLS results for the males showed longitudinal strain ranging from - 18.1 to - 29.8 with a mean of - 21.7202 ± 5.094322, while for females 2D GLS ranged from - 18.1 to - 30.7 with a mean of - 22.0646 ± 2.167802, also 3D GLS values were measured and compared based on gender, where 3D GLS in males ranged from - 18 to - 24 with a mean value of 20.49 ± 1.28, while for females ranged from - 17 to - 30 with a mean value of 20.47 ± 1.755. The gender-based difference for both 2D GLS and 3D GLS showed non-significant P values. CONCLUSION: In healthy subjects below 6 years, 2D STE and 3D STE values showed no difference between males and females, unlike the adult population, to the best of our knowledge, this is one of the few studies in the literature that aims at comparing these measurements in the healthy pediatric group. In routine clinical practice, these values may be used to assess myocardial function or the early signs of malfunction.

Assessment of left ventricular systolic function using two- and three-dimensional speckle tracking echocardiography among healthy preschool-age pediatric children.

BACKGROUND: Accurate measurements of left ventricular (LV) volumes and function are important in the management of patients with various cardiac abnormalities. Two-dimensional (2D) speckle tracking echocardiography (STE) is shown to be accurate in detecting subclinical myocardial dysfunction when most of the conventional echocardiography parameters were normal. Three-dimensional (3D) echocardiography is a new noninvasive imaging technique that has been shown to be accurate in determining cardiac volume and performance. Establishment of normal range values of 3D STE over a different range of ages is crucial before applying this recent technology in clinical applications. This study aimed to assess feasibility of 3D LV STE and establish normal values for the LV systolic function among healthy Egyptian preschool-age pediatric population using 2D and 3D STE. RESULTS: A total of 200 subjects (95%) met the criteria for 2DSTE analysis, 10 were excluded from the 2D analysis and 180 subjects (85%) met the criteria for 3D STE analysis. Regarding the 2D STE GLS, the mean was -22.1345 ± 2.166%, GCS was f -19.02 ± 1.23%, and GRS was 42.25 ± 2.35%. There was a strongly positive significant correlation between age and 2D values of GLS (P = 0.001). The GCS showed a weakly positive nonsignificant correlation with age (P = 0.28), while GRS showed a strongly negative significant correlation with age (P = 0.001). Regarding the 3D STE data, GLS mean was -20.48 ± 1.526%, GCS mean was -13.90 ± 2.05%, while GRS mean was 47.21 ± 2.382%. 3D GLS values had a strongly positive significant correlation with age (P = 0.001). While GCS showed a weakly positive nonsignificant correlation (P = 0.955), GRS showed a strongly negative significant correlation (P = 0.001). Linear correlation analysis of 2D and 3D values of strain showed that GLS had a strongly positive significant correlation (P = 0.001), while GCS showed a weakly positive nonsignificant correlation (P = 0.161) and GRS showed a strongly positive significant correlation (P = 0.001). Conclusions 3D global strain analysis using the 3D STE is feasible in the preschool-age pediatric population. Results were almost concordant with previous observations in most of the values except for GCS, especially 3D values which could be attributed to different vendor system used and different ethnicity. Further studies are required to reinforce these data using the GE vendor machine.

Safety and efficacy of percutaneous patent ductus arteriosus closure: a multicenter Egyptian experience.

BACKGROUND: Transcatheter closure of patent ductus arteriosus (PDA) has gained acceptance over the last two decades, replacing the surgery in more than 90% of the cases, so the safety and efficacy of transcather closure of PDA have been evaluated by studying different experiences from different centers in developing countries. The aim is to report our experience with PDA transcather closure, with focus on the adverse events and complications faced during the procedure. RESULTS: Outcome data on PDA transcatheter closure were collected from two different tertiary centers in a multicenter registry. During the period from June 2017 till January 2021, 308 PDA closure were recorded, using device in 197 (64%) and coils in 111 (36%) patients, most of the patients were in pediatric age group from 6 months to 6 years and only 10 patients (3.2%) were adults. Most patients had isolated PDA of 92%, and 9 (2.9%) patients had residual PDAs either post-surgical or transcatheter closure. Median minimum PDA diameter was 2.8 mm (range 1-7.6 mm; IQR 1.8-3.8 mm). The procedure was successful in 293 patients (95%). Complications occurred in 15/308 patients (5%), and only 6 (2%) of them were major complications, but none was life threating. Frequent complications were device embolization (2%), hemolysis (1%), arrhythmia (1%). Younger age, low body weight and longer procedure time were associated with a high complication rate (p < 0.005). Device-related complications were more common than coil-related complications (2.5% versus 0.5%). CONCLUSIONS: Although transcatheter closure of PDA is considered to be effective procedure with low complications rate, however, complications should be anticipated and managed properly.

Pulmonary Embolism and Cardiac Tamponade in Critical Care Patients with COVID-19; Telemedicine's Role in Developing Countries: Case Reports and Literature Review.

INTRODUCTION: In this study, two cases that demonstrate the importance of bedside echocardiography and hands-off telemedicine technology for diagnosis and intervention in patients with coronavirus disease 2019 (COVID-19) are discussed. CASE PRESENTATION: We report two cases of cardiac emergency associated with COVID-19. Case 1 is a 50-year-old female patient with chronic hypertension and chronic renal failure. Case 2 is a 64-year-old female with atrial fibrillation and recent stroke. Both were admitted to an isolation intensive care unit that was designated specifically to patients with COVID-19. CONCLUSIONS: During admission, both patients had sudden deterioration characterized by oxygen desaturation and hypotension necessitating inotropic support. As a result, for both patients, bedside echocardiography was performed by the attending intensivist. Echocardiographic findings showed cardiac tamponade and acute pulmonary embolism, respectively, which were confirmed by a cardiologist through telemedicine technology. Proper emergency management was initiated, and both patients recovered well. Limited bedside transthoracic echocardiography had a front-line impact on the treatment and outcome of the two patients with COVID-19. By implementing telemedicine technology, the lives of two patients were saved, demonstrating the significance of telemedicine in isolation intensive care units in the developing countries during the COVID-19 pandemic.

Telemedicine Improves the Short-Term Medical Care of Acute ST-Segment Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention.

Objectives: Telemedicine appears to be a promising tool for healthcare professionals to deliver remote care to patients with cardiovascular diseases especially during the COVID-19 pandemic. We aimed in this study to evaluate the value of telemedicine added to the short-term medical care of acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). Methods: Two hundred acute STEMI patients after primary PCI were randomly divided into two groups. One hundred patients in group A (study group) received a monthly videoconferencing teleconsultation using a smartphone application for 3 months starting 1 week after discharge and at least a single face-to-face (F2F) clinic visit. We reviewed in each virtual visit the symptoms of patients, adherence to healthy lifestyle measures, medications, smoking cessation, and cardiac rehabilitation. Group B (control group) included 100 patients who received at least a single F2F clinic visit in the first 3 months after discharge. Both groups were interviewed after 4 months from discharge for major adverse cardiac events (MACE), adherence to medications, smoking cessation, and cardiac rehabilitation. A survey was done to measure the satisfaction of patients with telemedicine. Results: There was no significant difference between both groups in MACE and their adherence to aspirin, P2Y12 inhibitor, and beta-blockers. However, group A patients had better adherence to statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, smoking cessation, and cardiac rehabilitation. Sixty-one percent of patients stated that these videoconferencing teleconsultations were as good as the clinic visits, while 87% of patients were satisfied with telemedicine. Conclusions: Telemedicine may provide additional benefit to the short-term regular care after primary PCI to STEMI patients through videoconferencing teleconsultations by increasing their adherence to medications and healthy lifestyle measures without a significant difference in the short-term MACE. These virtual visits gained a high level of satisfaction among the patients.

The relation between ACKR4 and CCR7 genes expression and breast cancer metastasis.

AIMS: Breast cancer is the most severe malignant tumor in women. Chemokines and their receptors appear to be implicated in tumorigenesis and metastatic pattern. Also the scavenger atypical chemokine receptors are emerging as crucial regulators for the availability of chemokines. Therefore the aim of the present study is to evaluate the expression of CCR7, ACKR4 and their ligand; CCL21 in human breast cancer. MAIN METHODS: In this study, RT-PCR was done to detect the expression of CCR7 and ACKR4 in 50 non-metastatic and 30 metastatic breast cancer tissue. Also CCL21 level in the serum of study group was detected by ELISA. The expression of all markers is compared to 80 control healthy individual. KEY FINDINGS: Our results revealed the increase in expression of CCR7 and CCL21 level in metastatic group compared to non-metastatic and control groups while ACKR4 expression is significantly increased in breast tissues of non-metastatic patients compared to both control and metastatic groups. Also there was significant positive correlation between CCR7 expression and CCL21 level in cancer patients and significant negative correlation between ACKR4 and both CCR-7 and CCL21 in both non-metastatic and metastatic cancer groups. SIGNIFICANCE: Thus, it might be elucidating that ACKR4 and CCR7 could be a novel target for tumor therapy as targeting the chemokine-receptors axis might represent a powerful tool to prevent infiltration and metastasis and consequently improve cancer prognosis and treatment.

First trimester fetal echocardiography limitations and its expected clinical values.

BACKGROUND: Fetal cardiac activity could be observed between 6th and 7th gestational weeks, early performance of fetal echocardiography could be implemented to screen for fetal heart disease. The effectiveness of early first trimester fetal echocardiography has not been adequately investigated, especially with modern sonographic technological advances. The purpose of the study is to evaluate the capability to visualize fetal cardiac structures within the first trimester as early as 10th gestational weeks and to elucidate the value of using color Doppler in visualization of cardiac structures within early gestation. A prospective clinical trial conducted on 150 study subjects, 44 of them were twin gestations. Cases were fully assessed by fetal echocardiographic examination from 10th gestational week to 13 gestational weeks in a sequential manner weekly. The research study was conducted at cardiology department fetal unit in one of the tertiary hospitals. RESULTS: Four chamber view was mostly visualized from 12 gestational weeks, whereas cardiac axis was fully visualized in all cases from 12 gestational weeks; on the other hand, IVC assessment by 2D was satisfactorily visualized in 78.26% of cases and by color Doppler in 82.61% of cases at 13 gestational weeks, pulmonary veins were visualized in 21.74% of cases by 2D and 43.5% of cases by color Doppler at 13 gestational weeks, and interestingly, ventricular inflows were satisfactorily visualized in almost all cases from 10th gestational weeks. CONCLUSIONS: First trimester fetal echo is an outstanding enhancement in management pathways of cases susceptible to have fetal cardiac abnormalities permitting early detection of structural cardiac anomalies triggering a cascade of scanning for extra cardiac anomalies to aid in evaluation and assessment of the best management course for those affected cases.

Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation.

AIM OF THE STUDY: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. MATERIALS AND METHODS: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-ß1 (TGF-ß1), and EZH2 expression were measured. RESULTS: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-ß1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. CONCLUSION: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions.