Adaptive Sampling Methods for Molecular Dynamics in the Era of Machine Learning.

Molecular dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively long time scales of these processes. Many enhanced sampling approaches have emerged to tackle this problem, including biased sampling and path-sampling methods. In this Perspective, we focus on adaptive sampling algorithms. These techniques differ from other approaches because the thermodynamic ensemble is preserved and the sampling is enhanced solely by restarting MD trajectories at particularly chosen seeds rather than introducing biasing forces. We begin our treatment with an overview of theoretically transparent methods, where we discuss principles and guidelines for adaptive sampling. Then, we present a brief summary of select methods that have been applied to realistic systems in the past. Finally, we discuss recent advances in adaptive sampling methodology powered by deep learning techniques, as well as their shortcomings.

Development and Validation of a Novel Risk Stratification Model for Slow-Flow/No-Reflow During Primary Percutaneous Coronary Intervention (the RK-SF/NR Score).

In this study, we developed and validated a novel risk stratification model to predict slow-flow/no-reflow (SF/NR) during the primary percutaneous coronary intervention (PCI), namely the RK-SF/NR score. A total of 1,711 consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergone primary PCI. A novel risk stratification model was developed in the development dataset and tested in the validation dataset. The overall incidence rate of SF/NR during the procedure was 28.8% (493/1,711). The final solution consisted of 9 variables: female gender (points = 2), total ischemic time ≥8 hours (points = 1), cardiac arrest at presentation (points = 2), left ventricular end-diastolic pressure ≥24 mm Hg (points = 3), left ventricular ejection fraction ≤30% (points = 2), culprit proximal left anterior descending artery (points = 3), thrombus grade ≥4 (points = 6), preprocedure thrombolysis in myocardial infarction (TIMI) 0 flow (points = 2), and lesion length ≥35 mm (points = 3). In the validation set, the area under the curve the RK-SF/NR score was 0.775 (0.722 to 0.829) and a score ≥10 has sensitivity of 77.9% (68.2% to 85.8%), negative predictive value of 87.3% (82.3% to 91.0%), specificity of 62.6% (56.0% to 68.9%), and positive predictive value of 46.3% (41.4% to 51.2%). In conclusion, RK-SF/NR score had shown good discriminating power for predicting SF/NR during primary PCI with good sensitivity and negative predictive value. Hence, the proposed model can have good clinical utility for screening patients at high risk of developing SF/NR during primary PCI.

A strategy for mitigating avian colibacillosis disease using plant growth promoting rhizobacteria and green synthesized zinc oxide nanoparticles.

Avian colibacillosis caused by the zoonotic pathogen Escherichia coli is a common bacterial infection that causes major losses in the poultry sector. Extracts of different medicinal plants and antibiotics have been used against poultry bacterial pathogens. However, overuse of antibiotics and extracts against pathogenic strains leads to the proliferation of multi-drug resistant bacteria. Due to their environmentally friendly nature, nanotechnology and beneficial bacterial strains can be used as effective strategies against poultry infections. Green synthesis of zinc oxide nanoparticles (ZnO-NPs) from Eucalyptus globulus leaves was carried out in this study. Their characterization was done by UV-vis spectroscopy, X-ray diffraction (XRD), and Fourier transmission infrared spectroscopy (FT-IR) which confirmed their synthesis, structure, and size. In vitro, antimicrobial activities of plant leaf extract, ZnO-NPs, and plant growth-promoting rhizobacteria (PGPR) were checked against E. coli using well diffusion as well as disc diffusion method. Results proved that the antimicrobial activity of ZnO-NPs and PGPR strains was more enhanced when compared to eucalyptus leaf extract at 36 h. The maximum relative inhibition shown by ZnO-NPs, PGPR strains and eucalyptus leaf extracts was 88%, 67% and 58%, respectively. The effectiveness of ZnO-NPs was also increased with an increase in particle dose and treatment time. The 90 mg/ml of ZnO-NPs was more effective. PGPR strains from all over the tested strains, Pseudomonas sp. (HY8N) exhibited a strong antagonism against the E. coli strain as compared to other PGPR strains used in this study. However, combined application of PGPR (Pseudomonas sp. (HY8N)) and ZnO-NPs augment antagonistic effects and showed maximum 69% antagonism. The study intends to investigate the binding affinity of ZnO-NPs with the suitable receptor of the bacterial pathogen by in silico methods. The binding site conformations showed that the ligand ZnO binds with conserved binding site of penicillin-binding protein 6 (PBP 6) receptor. According to the interactions, ZnO-NPs form the same interaction pattern with respect to other reported ligands, hence it can play a significant role in the inhibition of PBP 6. This research also found that combining ZnO-NPs with Pseudomonas sp. (HY8N) was a novel and effective technique for treating pathogenic bacteria, including multidrug-resistant bacteria.

Comparative assessment of clinical profile and outcomes after primary percutaneous coronary intervention in young patients with single vs multivessel disease.

BACKGROUND: Even though percutaneous coronary intervention (PCI) improved the survival of patients with acute myocardial infarction, still multivessel coronary artery disease remains an important factor burdening prognosis and it is being associated with a worse prognosis compared to single-vessel disease (SVD). AIM: To compare the clinical profile and outcomes after the primary PCI in young patients with SVD vs multivessel disease (MVD). METHODS: The retrospective cohort of patients were divided into two groups: SVD and MVD group. The study population consisted of both male and female young (≤ 45 years) patients presented with ST-elevation myocardial infarction (STEMI) at the National Institute of Cardiovascular Disease, Karachi, Pakistan and undergone primary PCI from 1st July 2017 to 31st March 2018. Pre and post-procedure management of the patients was as per the guidelines and institutional protocols. RESULTS: A total of 571 patients with STEMI, ≤ 45 years were stratified into two groups by the number of vessels involved, 342 (59.9%) with SVD and 229 (40.1%) with MVD. The average age of these patients was 39.04 ± 4.86 years. A lower prevalence of hypertension and diabetes was observed in SVD as compare to MVD group (25.1% vs 38%, P < 0.01; 11.7% vs 27.5%, P < 0.001) respectively. While, smoking was more prevalent among the SVD group as compare to MVD group (36.3% vs 28.4%, P = 0.05). The high-C Lesion was observed in a significantly higher number of younger patients with MVD as compared to SVD group (48.8% vs 39.2%, P = 0.021). Post-procedure thrombolysis in myocardial infarction flow grade was found to be not associated with the number of diseased vessels with a P value of 0.426 and thrombolysis in myocardial infarction flow grade III was observed in 98% vs 96.5% of the patients is SVD vs MVD group. CONCLUSION: The MVD comprised of around 40% of the young patients presented with STEMI. Also, this study shows that diabetes and hypertension have a certain role in the pathogenesis of multivessel diseases, therefore, preventive measures for diabetes and hypertension can be effective strategies in reducing the burden of premature STEMI.

Clinical and procedural predictors and short-term survival of the patients with no reflow phenomenon after primary percutaneous coronary intervention.

OBJECTIVES: In the present study, we analysed the incidence of no-reflow phenomenon, its clinical and procedural predictors, and associated in-hospital outcomes for the patients undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: No-reflow phenomenon after primary PCI is a procedural complication associated with adverse post-procedure outcomes. METHODS: Data for this study were extracted from global registry, NCDR®, the site of National Institute of Cardiovascular Disease (NICVD), Karachi from July 2017 to March 2018. The demographic, clinical, and procedural characteristics, and in-hospital outcomes were analysed for the patients with and without no-reflow after primary PCI. RESULTS: Of total of 3255 patients, no-reflow phenomenon was found in 132 (4.1%) patients and it was associated with significantly higher in-hospitality mortality (6.8% vs. 2.9%; p = 0.01), cerebrovascular accident (1.5% vs. 0%; p < 0.001), post procedure bleeding (2.3% vs. 0.5%; p = 0.009), and cardiogenic shock (3.8% vs. 1.2%; p = 0.011). The multivariate analysis showed advanced age [odds ratio = 1.63, 95% confidence interval 1.09-2.44, p = 0.018], diabetes [1.66, 1.14-2.42, p = 0.009], prior history of CABG [8.70, 1.45-52.04, p = 0.018], low pre-procedure TIMI flow grade [2.04, 1.3-3.21, p = 0.002], longer length of target lesion [1.51, 1.06-2.16, p = 0.023], and 10 fold raised troponin I [1.55, 1.08-2.23, p = 0.018] were the independent predictors of no-reflow. CONCLUSIONS: In this selected group of patients, the no-reflow phenomenon after primary percutaneous coronary intervention is not that uncommon. It is associated with an increased risk of adverse post-procedure hospital course including mortality. Pathophysiology of the no-reflow phenomenon is complex and opaque, however, it can be predicted based on certain clinical and procedural characteristics.

Procedural determinants of fluoroscopy time in patients undergoing cardiac catheterization.

BACKGROUND & OBJECTIVE: Due to increase in number of cardiac catheterization procedures safety concerns is an issue nowadays. Multiple diagnostic modalities use radiations, which also put a patient at higher cumulative radiation exposure. Therefore steps should be taken to minimize radiation exposure during cardiac catheterization. Hence determination of factors which prolong FT will result in better understanding of problem. This retrospective study was undertaken to determine factors responsible for prolong fluoroscopy time in patients undergoing coronary artery catheterization. METHODS: This retrospective study was conducted at catheterization Laboratory National Institute of Cardiovascular Diseases, Karachi from June 2014 to June 2015. Patients of either gender, aged between 18 to 90 years undergoing cardiac catheterization procedures were included. Radiation exposure time was measured in terms of fluoroscopy time. RESULTS: A total of 957 patients were included in this study out of which 731 were of diagnostic Coronary Angiograms (CA) and 226 were of Percutaneous Coronary Intervention (PCI). The mean age of the study participants was 54.12±10.89 years and majority 734(76.6%) were male. Mean fluoroscopy time (FT) in the patients subjected to PCI was 9.61±6.07 minutes while in cases for CA 4.17±4.13 minutes. FT for CA was observed significantly dependent on procedural access, operator's experience, and LV angiogram. While FT for PCI was found dependent on number of stents deployed during the procedure. CONCLUSION: For invasive coronary angiographic procedures radial route increased fluoroscopy time. For percutaneous coronary intervention femoral and radial route fluoroscopy time were not significantly different.

Managed successfully: Iatrogenic aortic dissection during primary percutaneous coronary intervention.

Iatrogenic aortic dissection caused by primary percutaneous coronary intervention (PCI) is a rare but potentially fatal complication; therefore prompt recognition of this life-threatening condition is crucial. We present herein a case of a 70-year-old lady who underwent primary PCI for transmural myocardial infarction of left anterior descending artery territory. Manipulation of the extra backup (EBU) guiding catheter during an attempt to cannulate the left system resulted in an aortic dissection. The patient was managed conservatively with strict monitoring in the coronary care unit (CCU), and underwent serial evaluation with non-invasive imaging studies including a computed tomography angiography (CTA). On the 3rd post-procedure day, she developed cerebrovascular accident from which she recovered completely. Repeat CT angiogram showed complete resolution of the ascending aortic dissection. Initial follow-up was conducted at 2 weeks and the patient was doing well.

Regression of right ventricular systolic pressure after successful percutaneous mitral commissurotomy in patients with isolated severe mitral stenosis.

OBJECTIVE: To know the regression of right ventricular pressure after successful percutaneous transluminalmitral commissurotomy (PTMC) in patients with severe isolated mitral stenosis. METHODS: This descriptive study was performed in inpatient and outpatient department of National Institute of Cardiovascular Disease from 1st February 2016 to 31st August 2016. Echocardiography of all patients with successful PTMC were recorded 24 hours and 06 months following PTMC to see for Regression of right ventricular pressure along with other baseline echocardiographic parameters. RESULTS: A total of 99 patients with severe isolated mitral stenosis who had undergone successful PTMC were studied. Females were 65(65.7%) and males 34(34.3%). Mean age was 27.44±6.26 years. TTE performed before and after PTMC showed significant difference in mean mitral valve area (0.89cm ±0.089cm2 vs. 1.68±0.128 cm2, p valve <0.001) and mean left atrial diameter (4.66± .82cm vs. 4.46± 0.65cm). Mean mitral valve gradient pre PTMC was significantly higher (16.38±2.51 mm of Hg) than that of post PTMC 24 hours (4.75±1.31 mm of Hg) and Post PTMC 06 months (5.22±1.21 mm of Hg), p valve <0.001. Mean right ventricular systolic pressure (RVSP) pre PTMC was significantly higher 62.3±10.91 mm of Hg than that of post PTMC 24 hour's 57.51±9.67 mm of Hg and post PTMC 06 moths 46.49±7.8mm of Hg, p value 0.001. Mean LVEF 50.14± 5.82. CONCLUSION: There was a significant regression of right ventricular pressure following successful PTMC in mid-term (06 months) follow up of severe isolated mitral stenosis patients.

Angiocardiographic findings in patients with biphasic T-wave inversion in precordial leads.

OBJECTIVE: To determine the angiocardiographic findings in patients with unstable angina showing biphasic inversion of T-waves in precordial leads on electrocardiogram, commonly referred to as the Wellen's syndrome. METHODS: The descriptive, cross-sectional study was carried out at the National Institute of Cardiovascular Diseases, Karachi, between February and November, 2010. Using convenience sampling, the first 100 consecutive patients showing the characteristic electrocardiogram pattern with a history of chest pain indicative of unstable angina and undergoing coronary angiography were included. Data was collected with the aid of a questionnaire to assess the coronary risk factors, and angiographic findings were recorded during cardiac catherisation of the patients. All the data collected was sorted and analysed on SPSS version 16 for statistical analysis. RESULTS: Biphasic T-wave inversion was seen most commonly in leads v2-v3 in 26 (26%) patients, and in leads v2-v4 in 25 (25%) patients. Angiographic findings revealed that 50 (50%) patients had coronary artery stenosis in the proximal part of the left anterior descending artery, while 22 (22%) showed the occlusion in the middle segment. Right coronary artery established the dominance of heart in 75 (75%) of the patients and the two-vessel disease was most commonly observed during cardiac catherisation. CONCLUSION: The classical pattern of biphasic T-wave inversion on electrocardiogram was seen associated with stenosis in the proximal as well as middle part of the left anterior descending coronary artery. This electrocardiogram pattern may not be well defined during the symptomatic phase of acute ischaemia and, hence, maybe overlooked. Prompt recognition and early intervention may significantly reduce morbidity and mortality in such patients.

Detection and sequencing of plasmid encoded tetracycline resistance determinants (tetA and tetB) from food-borne Bacillus cereus isolates

OBJECTIVE@#To investigate the detection and sequencing of plasmid encoded tetracycline resistance genes (tetA and tetB) from food-borne and standard strains of Bacillus cereus (B. cereus).@*METHODS@#A PCR was carried out to detect the tetracycline resistance genes (tetA and tetB) in food-borne B. cereus strains and the amplified products were sequenced.@*RESULTS@#The phenotypic resistance against tetracycline was observed in 39 of the 118 food-borne isolates and two reference strains (MTCC 430 and MTCC 1307) of B. cereus. Among the phenotypically resistant isolates, tetA was detected in 36 food-borne isolates and two reference strains (MTCC 430 and MTCC 1307), whereas, tetB was detected in 12 food-borne isolates and MTCC 1307 strain.@*CONCLUSIONS@#A close association was therefore found between phenotypic resistance against tetracycline and presence of tetracycline resistance genes. The tetA and tetB gene fragments were amplified, purified and sequenced. The gene sequences of the isolates studied herein were found similar to tetA and tetB gene sequences of other bacteria available in NCBI. The occurrence of tetA and tetB genes in B. cereus indicate the horizontal transfer of antibiotic resistance determinants from other bacteria into B. cereus. The transfer of these resistant determinants to other potentially pathogenic bacteria may be a matter of great concern.

Aspiration of thrombus in ST segment elevation myocardial infarction.

OBJECTIVE: To evaluate the impact of Export Aspiration Catheter with restoration of ECG changes, arterial flow and myocardial perfusion in patients with ST segment elevation Myocardial Infarction undergoing Percutaneous Coronary Intervention (PCI). METHODS: A total of 40 consecutive patients with ST Segment Elevation Myocardial Infarction (STEMI) were selected. They underwent treatment according to the surgeon's discretion to either standard PCI or PCI with thrombus aspiration Catheter. Primary end points of the study were ST Segment resolution (STR) > 70% and myocardial blush grade (MBG) > 2. RESULTS: The base line clinical and procedural characteristics were same for both the groups. In the post intervention comparison the thrombus aspiration group was found to have significantly better outcomes as compared to the standard PCI group with regards to TIMI flow grade (p = 0.009) and myocardial blush grade (p = 0.001). Considering the criteria for MBG and STR together, the thrombus aspiration was found to have significantly better outcome than the standard PCI group (p = 0.017). CONCLUSION: This non-randomized study shows that Export Aspiration Catheter group with STEMI undergoing primary PCI is feasible and results in better angiographic ECG and myocardial perfusion rates compared with standard PCI. Role of export catheter in rescue PCI and thrombus Sapheneous Venous Graft (SVG) as primary PCI is questionable and needs larger randomized studies to prove its efficacy.

Greek technique for type 4a coronary artery bifurcation lesions.

In routine coronary angiography, bifurcation lesion is not uncommon. Current practice of dealing with type 4a coronary bifurcation lesions (lesions of main branch without significant lesions of the side branch) may lead to true bifurcation lesions after stenting due to axial plaque redistribution. This series describes an experience with Greek technique for treatment of type 4a bifurcation lesions in 18 patients for primary stenting of main vessel with simultaneous kissing balloon of side branch in an effort to avoid snow plough effect.