Evaluation of PD-1 Gene Expression Profile and Methylation of the Regulatory Regions in Patients with Ankylosing Spondylitis.

Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis. Objective: To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease. Methods: 30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR. Results: The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed. Conclusion: The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.

Identification of Novel Ribonucleotide Reductase Inhibitors for Therapeutic Application in Bile Tract Cancer: An Advanced Pharmacoinformatics Study.

Biliary tract cancer (BTC) is constituted by a heterogeneous group of malignant tumors that may develop in the biliary tract, and it is the second most common liver cancer. Human ribonucleotide reductase M1 (hRRM1) has already been proven to be a potential BTC target. In the current study, a de novo design approach was used to generate novel and effective chemical therapeutics for BTC. A set of comprehensive pharmacoinformatics approaches was implemented and, finally, seventeen potential molecules were found to be effective for the modulation of hRRM1 activity. Molecular docking, negative image-based ShaEP scoring, absolute binding free energy, in silico pharmacokinetics, and toxicity assessments corroborated the potentiality of the selected molecules. Almost all molecules showed higher affinity in comparison to gemcitabine and naphthyl salicylic acyl hydrazone (NSAH). On binding interaction analysis, a number of critical amino acids was found to hold the molecules at the active site cavity. The molecular dynamics (MD) simulation study also indicated the stability between protein and ligands. High negative MM-GBSA (molecular mechanics generalized Born and surface area) binding free energy indicated the potentiality of the molecules. Therefore, the proposed molecules might have the potential to be effective therapeutics for the management of BTC.

Outcomes Following Supracoronary Ascending Aortic Replacement with Aortic Valve Resuspension versus Modified Bentall's Operation for Acute Type A Aortic Dissection

Abstract Introduction: Type A acute aortic dissection (AAD) remains a challenging cardiac emergency despite the availability of various management strategies. This study compared the outcomes of supracoronary ascending aortic replacement (SCAAR) with aortic valve (AV) resuspension with those of modified Bentall's operation for type A AAD and the progression of aortic regurgitation (AR), long-term dilatation of aortic root and proximal arch, and long-term mortality in SCAAR patients. Methods: Sixty patients underwent surgery for type A AAD (January 2005 to December 2015). Forty-three patients underwent SCAAR with AV resuspension and 17 underwent modified Bentall's operation. All patients were followed up. Results: Upon follow-up of SCAAR patients (n=40), there was significant reduction in aortic root size (preoperative 39.3 mm [9.4] vs. postoperative 33.1 mm [9.1]; P<0.001). Three of these patients worsened to severe AR while others had similar or lesser degree of AR. On comparison between preoperative and postoperative dimensions of all patients (n=53), there was no significant difference in distal ascending aorta size (35.7 mm [8.1] vs. 34.4 mm [8.9]; P=0.52). However, an increase in descending thoracic aorta size (28.8 mm [7.8] vs. 33.7 mm [9.9]; P<0.001) was observed. In-hospital and late mortalities for SCAAR vs. modified Bentall's procedure were 11.7% (seven patients) (7% [3] vs. 23.5% [4]) and 28% (15 patients) (15% [6] vs. 69% [9]), respectively. Conclusion: SCAAR with AV resuspension is a safe surgical option for type A AAD. Preservation of AV is associated with better long-term outcomes and reduced mortality. Modified Bentall's operation may be associated with long-term mortality.

Clinical outcomes of del nido cardioplegia and st thomas blood cardioplegia in neonatal congenital heart surgery.

OBJECTIVES: Cardioplegia is essential for adequate myocardial protection. There continues to remain ambiguity regarding the ideal cardioplegia for adequate myocardial protection in congenital heart surgery. This study compares clinical outcomes using St Thomas II solution and Del Nido cardioplegia in neonates undergoing cardiac surgery. METHODS: All neonates (<30 days) from 2011 to 2017 who underwent surgery requiring cardioplegic arrest were analyzed retrospectively. We divided the cohort into two groups depending on cardioplegia received, as group A (Blood cardioplegia with St Thomas II solution, n = 56) and group B (Del Nido cardioplegia, n = 48). Various demographic, intraoperative, early postoperative, and discharge variables were analyzed. RESULTS: Two groups were similar in age, gender, pre-operative diagnosis, and risk category. Cardiopulmonary bypass (CPB) time (P = 0.002), aortic cross-clamp (ACC) time (P = 0.018), and the number of doses of cardioplegia (P < 0.001) were significantly lower with Del Nido group. Though vasoactive inotropic score (VIS) (P = 0.036) was high during the first 24 h in the immediate postoperative period in group A, there was no difference in early mortality among both groups (P = 0.749). Both groups did not show significant differences related to various postoperative and discharge variables. CONCLUSION: When compared to St. Thomas solution, the use of Del Nido cardioplegia solution in neonates is associated with a significant decrease in CPB and ACC times and VIS in the first 24 h after surgery. The choice of cardioplegia (St Thomas/Del Nido) in neonates does not affect early mortality and early postoperative clinical outcomes.

Outcomes Following Supracoronary Ascending Aortic Replacement with Aortic Valve Resuspension versus Modified Bentall's Operation for Acute Type A Aortic Dissection.

INTRODUCTION: Type A acute aortic dissection (AAD) remains a challenging cardiac emergency despite the availability of various management strategies. This study compared the outcomes of supracoronary ascending aortic replacement (SCAAR) with aortic valve (AV) resuspension with those of modified Bentall's operation for type A AAD and the progression of aortic regurgitation (AR), long-term dilatation of aortic root and proximal arch, and long-term mortality in SCAAR patients. METHODS: Sixty patients underwent surgery for type A AAD (January 2005 to December 2015). Forty-three patients underwent SCAAR with AV resuspension and 17 underwent modified Bentall's operation. All patients were followed up. RESULTS: Upon follow-up of SCAAR patients (n=40), there was significant reduction in aortic root size (preoperative 39.3 mm [9.4] vs. postoperative 33.1 mm [9.1]; P<0.001). Three of these patients worsened to severe AR while others had similar or lesser degree of AR. On comparison between preoperative and postoperative dimensions of all patients (n=53), there was no significant difference in distal ascending aorta size (35.7 mm [8.1] vs. 34.4 mm [8.9]; P=0.52). However, an increase in descending thoracic aorta size (28.8 mm [7.8] vs. 33.7 mm [9.9]; P<0.001) was observed. In-hospital and late mortalities for SCAAR vs. modified Bentall's procedure were 11.7% (seven patients) (7% [3] vs. 23.5% [4]) and 28% (15 patients) (15% [6] vs. 69% [9]), respectively. CONCLUSION: SCAAR with AV resuspension is a safe surgical option for type A AAD. Preservation of AV is associated with better long-term outcomes and reduced mortality. Modified Bentall's operation may be associated with long-term mortality.

Screening of ß1- and ß2-Adrenergic Receptor Modulators through Advanced Pharmacoinformatics and Machine Learning Approaches.

Cardiovascular diseases (CDs) are a major concern in the human race and one of the leading causes of death worldwide. ß-Adrenergic receptors (ß1-AR and ß2-AR) play a crucial role in the overall regulation of cardiac function. In the present study, structure-based virtual screening, machine learning (ML), and a ligand-based similarity search were conducted for the PubChem database against both ß1- and ß2-AR. Initially, all docked molecules were screened using the threshold binding energy value. Molecules with a better binding affinity were further used for segregation as active and inactive through ML. The pharmacokinetic assessment was carried out on molecules retained in the above step. Further, similarity searching of the ChEMBL and DrugBank databases was performed. From detailed analysis of the above data, four compounds for each of ß1- and ß2-AR were found to be promising in nature. A number of critical ligand-binding amino acids formed potential hydrogen bonds and hydrophobic interactions. Finally, a molecular dynamics (MD) simulation study of each molecule bound with the respective target was performed. A number of parameters obtained from the MD simulation trajectories were calculated and substantiated the stability between the protein-ligand complex. Hence, it can be postulated that the final molecules might be crucial for CDs subjected to experimental validation.

Public health workers' knowledge, attitude and practice regarding COVID-19: the impact of Field Epidemiology Training Program in the Eastern Mediterranean Region.

BACKGROUND: This study aimed to compare knowledge, attitude and practice (KAP) regarding COVID-19 between public health workers (PHWs) attended field epidemiology training program (FETP-trained) and those who did not attend FETP (non-FETP trained). METHODS: Multi-country cross-sectional survey was conducted among PHWs who participated in COVID-19 pandemic in 10 countries at EMR. Online questionnaire that included demographic information, KAP regarding COVID-19 pandemic was distributed among HCWs. Scoring system was used to quantify the answers, bivariate and Multivariate analysis performed to compare FETP-trained with non-FETP trained PHWs. RESULTS: Overall, 1337 PHWs participated, with 835 (62.4%) < 40 years of age, and 851 (63.6%) males. Of them, 423 (31.6%) had FETP, including that 189 (44.7%) had advanced level, 155 (36.6%) intermediate and 79 (18.7%) basic level training. Compared with non-FETP trained, FETP trained were older, having higher KAP scores. FETP participation was low in infection control, and PH laboratories. KAP mean scores for intermediate level attendees are comparable to advanced level. CONCLUSIONS: FETP-trained are having better KAP than non-FETP PHWs. Expanding the intermediate level, maintain the Rapid Response training and introduce the laboratory component are recommended to maximize the benefit from FETP. Infection control, antimicrobial resistance and coordination are areas where training should include.

Intracardiac relation of extrahepatic persistent right umbilical vein.

Persistent extrahepatic right umbilical vein without ductus venosus is a rare anomaly of systemic venous drainage and is reported to be associated with cardiac anomalies. We report the case of an 8-year-old boy diagnosed to have an ostium secundum atrial septal defect, in whom an abnormal vascular channel and its opening in the right atrium in close relationship to the inferior vena cava and coronary sinus opening was identified at operation. Post-operative evaluation of this vascular channel was diagnosed to be an extrahepatic persistent right umbilical vein.

Correction to: Midterm results of homografts in pulmonary position: a retrospective single-center study.

[This corrects the article DOI: 10.1007/s12055-020-01065-1.].

Evaluation of a novel fixed-space maintainer made of light-cured acrylic resin: an in vitro study.

To evaluate a fixed-space maintainer made of light-cure acrylic resin (LCAR) for its flexural and shear bond strength using different bonding systems to the enamel. 45 extracted primary teeth were selected. They were randomly divided into three equal groups (n = 15) along with the type of adhesive system (Tetric Flow, Transbond XT, and Fuji Ortho LC) used for bonding (LCAR) to the tooth surface. Surfaces were treated; LCAR was attached to the treated surfaces using a split Teflon mold. For flexural strength testing, ten bars of LCAR were made using another Teflon-split mold. Shear bond strength and mean flexural strength values were evaluated by a universal testing machine. The highest values of bond strength were recorded for Transbond XT, followed by Tetric Flow, while the lowest values were for Fuji Ortho LC. Various groups had a significant difference as investigated by ANOVA. ARI scores showed no significant difference in debond sites. Mean value and standard deviation of flexural strength for LCAR were 82.83 ± 5.2. LCAR has superior mechanical properties and could be an alternative to currently-in-use space maintainer though in vivo and in vitro trials are needed to progress the ultimate design of LCAR.

Analysis and modeling of realistic compound channels in transparent relay transmissions.

Analytical approaches for the characterisation of the compound channels in transparent multihop relay transmissions over independent fading channels are considered in this paper. Compound channels with homogeneous links are considered first. Using Mellin transform technique, exact expressions are derived for the moments of cascaded Weibull distributions. Subsequently, two performance metrics, namely, coefficient of variation and amount of fade, are derived using the computed moments. These metrics quantify the possible variations in the channel gain and signal to noise ratio from their respective average values and can be used to characterise the achievable receiver performance. This approach is suitable for analysing more realistic compound channel models for scattering density variations of the environment, experienced in multihop relay transmissions. The performance metrics for such heterogeneous compound channels having distinct distribution in each hop are computed and compared with those having identical constituent component distributions. The moments and the coefficient of variation computed are then used to develop computationally efficient estimators for the distribution parameters and the optimal hop count. The metrics and estimators proposed are complemented with numerical and simulation results to demonstrate the impact of the accuracy of the approaches.