Molecular modelling on multiepitope-based vaccine against SARS-CoV-2 using immunoinformatics, molecular docking, and molecular dynamics simulation.

The pandemic of COVID-19 caused by SARS-CoV-2 has made a worldwide health emergency. Despite the fact that current vaccines are readily available, several SARSCoV-2 variants affecting the existing vaccine are to be less effective due to the mutations in the structural proteins. Furthermore, the appearance of the new variants cannot be easily predicted in the future. Therefore, the attempts to construct new vaccines or to modify the current vaccines are still pivotal works for preventing the spread of the virus. In the present investigation, the computational analysis through immunoinformatics, molecular docking, and molecular dynamics (MD) simulation is employed to construct an effective vaccine against SARS-CoV2. The structural proteins of SARS-CoV2 are utilized to create a multiepitope-based vaccine (MEV). According to our findings presented by systematic procedures in the current investigation, the MEV construct may be able to trigger a strong immunological response against the virus. Therefore, the designed MEV could be a potential vaccine candidate against SARS-CoV-2, and also it is expected to be effective for other variants.

The cut-off point of interleukin-6 level in acute coronary syndrome.

AIM: this study aimed to observe whether the interleukin-6 level in acute coronary syndrome (ACS) patients were higher than those in coronary heart disease (CHD) patients. In addition, we would like to observe the cut off point of interleukin-6 level in ACS. METHODS: this cross sectional study were conducted at Dr. Cipto Mangunkusumo General Hospital (RSUPN-CM), Persahabatan Hospital, MMC Hospital and Medistra Hospital, Jakarta. The study started from 1 May 2005 to 5 May 2006. RESULTS: in this observational study, as many as 62 CHD patients were collected and 84 ACS that met the study criteria. Demographic analysis showed that there was no difference in ages among the two groups (ACS and CHD). The risk factors of dyslipidemia, hypertension and lipid profile in the two groups did not differ significantly. Waist circumference and IMT, systolic and diastolic blood pressures in the two groups did not also differ significantly. Smoking was more prevalent in the groups of ACS than in the groups of CHD. In this study the IL-6 level in ACS (mean 40.85 pg/mL, SD 41.71, CI 95% 25.63-42.08 was higher than that in CHD (mean 4.58 pg/mL, SD 9.61, CI 95% 2.14-7.02). To identify the IL-6 level as the predictor for the occurrence of ACS, sensitivity and specificity were calculated at various cut-off points of IL-6 level. At cut-off point of IL-6 4.43 pg/mL the highest sensitivity (89.95%) and highest specificity (77.42%) were found with ROC of 0.87. CONCLUSION: it could be concluded that the IL-6 level in ACS were higher that those in CHD. The IL-6 level 4,43 pg/mL could differentiate the acute condition (ACS) and stable condition (non-ACS) with sensitivity of 89.95% and specificity of 77.42%, and ROC of 0.87.

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform.

OBJECTIVES: To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS: Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. RESULTS: During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. CONCLUSIONS: This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Efficacy and tolerability of amlodipine in the general practice treatment of essential hypertension in an asian multinational population.

OBJECTIVE: To evaluate the efficacy and tolerability of once-daily amlodipine (Pfizer Pharmaceuticals Inc.) alone or in combination with other antihypertensive drugs in an Asian population with essential hypertension. PATIENTS: An open study was undertaken in 165 male and 158 female patients with uncomplicated hypertension (diastolic blood pressure 95 to 115mm Hg). Patients were recruited from 41 general practices in seven Asian countries and received amlodipine 5mg daily for 4 weeks and then 10mg once daily for a further 4 weeks if the target diastolic blood pressure of /=10mm Hg had not been achieved. This one-step dose-adjustment period was followed by a 4-week maintenance period on a constant dose. Amlodipine was the sole medication in 284 patients and was added to other antihypertensive drugs in 39 patients uncontrolled on previous medication. RESULTS: 263 patients, including 131 males, were evaluated for efficacy at the final treatment visit. 166 (63%) patients achieved the target reduction in diastolic blood pressure with amlodipine 5mg once daily, while 84 patients achieved the target reduction with 10mg once daily. Systolic and diastolic blood pressure reductions were similar irrespective of gender or age, and there were no significant changes in resting heart rate in any subgroup. In 68 patients who underwent ambulatory monitoring, the systolic and diastolic blood pressures were reduced by once-daily amlodipine throughout the 24-hour period without change in the intrinsic circadian pattern. Amlodipine was well tolerated in all patient subgroups; adverse events accounted for less than 1% of treatment discontinuations, and there were no hospitalisations or deaths during the study. Investigators rated both the antihypertensive efficacy and tolerability of amlodipine as excellent or good in 93% of patients. CONCLUSION: In 263 Asian patients with uncomplicated essential hypertension treated in general practice, once-daily amlodipine in a dose of 5 or 10mg provided significant antihypertensive efficacy either as monotherapy or in combination with other antihypertensive drugs while maintaining a favourable tolerability profile regardless of gender or age.

The implementation of community participation in the control of malaria in rural Tanjung Pinang, Indonesia.

A study was undertaken to involve a hyperendemic community in Berakit village near Tanjung Pinang to participate actively in the control of malaria. Weekly chemoprophylaxis with chloroquine was given to all villagers of RK I with a population of about 700 for a period of one year. Nine cadres were selected from the community by the villagers for the distribution of the drug and coordinated by the head of the village. About 14-19 families were supervised by one cadre who was responsible for the weekly distribution of the drug to these families. The weekly dosage of the drug was adjusted according to age. The drug was taken in the presence of the cadres to assure the intake, and recorded by each cadre. The results showed that 93.7% of the villagers have taken the drug regularly. The remaining 6.3% of them showed refusal and irregular intake, or moved to another village during the period of prophylaxis. Although the drug has a bitter taste, most of the children were able to tolerate it. In general, mild side effects were reported and infrequently observed. Implementation of community participation to control malaria in this village showed good results which was reflected in the results of the malariometric surveys carried out before and after one year chemoprophylaxis. The spleen rate of about 600 villagers of RK I examined was 54.3% and the parasite rate 13.2% before the drug intervention. After one year chemoprophylaxis the spleen rate decreased to 21.7% and the parasite rate to 4.5% showing a significant difference.

Myocardial perfusion imaging in humans by contrast echocardiography using polygelin colloid solution.

This study evaluated the myocardial contrast effect and safety of polygelin colloid solution selectively injected into the coronary arteries in 25 patients during two-dimensional echocardiography. Six patients (group I) had selective intracoronary injections of nonagitated and 19 (group II) of hand-agitated polygelin colloid solution. Myocardial contrast was seen on two-dimensional echocardiographic cross sections in three patients of group I and in all patients of group II; in 16 patients it was also seen on M-mode echocardiograms. The contrast effect lasted for 15 to 60 seconds. The intensity of myocardial opacification was not significantly influenced by the amount of polygelin colloid solution injected, heart rate or cardiac size. The total number of contrast-enhanced segments after right and left coronary artery injections delineated the entire cross-sectional area in any given view. None of the patients developed symptoms during or immediately after the injections. One patient had transient second degree atrioventricular block after a right coronary wedge injection, one patient showed a QRS axis shift and two others had transient T wave changes. There were no aortic blood pressure changes and no significant serum enzyme (creatine kinase [CK], CK-MB fraction, glutamic oxaloacetic transaminase) elevation or alterations of left ventricular function assessed echocardiographically. It is concluded that hand-agitated polygelin colloid solution is a useful and safe intracoronary contrast agent for delineating myocardial perfusion areas on two-dimensional echocardiography in humans.

Assessment of right heart hemodynamics by contrast echocardiography.

We studied inferior vena cava contrast echocardiography after upper extremity injection in 70 subjects; 59 were patients and 11 were controls. Inferior vena cava contrast was seen in 35 patients and in 1 control. "A-wave synchronous pattern" of contrast appearance was observed in 13 patients and 1 normal subject. The pattern did not depend upon the height of right atrial a-wave pressure or the right ventricular (RV) end-diastolic pressure, but was related to the respiratory cycle. A "random pattern" of contrast appearance was seen in 3 patients with cardiac arrhythmia and normal right heart hemodynamics. One patient with ventricular premature beats showed both "a-wave synchronous" and "random" patterns. A "v-wave synchronous pattern" was found in 20 patients, of which 17 had tricuspid regurgitation. Persistence of inferior vena cava contrast correlated with the height of right atrial v-wave (r = 0.87, p less than 0.001) and the severity of tricuspid regurgitation estimated from RV cineangiography. The differences of RV systolic pressure and echocardiographic right ventricular dimension between the study patients with and without tricuspid regurgitation did not reach statistical significance. We conclude: the echocardiographic RV dimension and the degree of RV hypertension are not predictors for the presence of tricuspid regurgitation and its severity; inferior vena cava contrast echocardiography may be used to estimate the severity of tricuspid regurgitation.

Visualization and analysis of right heart blood flow patterns by contrast echocardiography.

UNLABELLED: The clinical utility of visualization of blood flow patterns across the tricuspid valve (TV) and pulmonary valve (PV) by M-mode contrast echocardiography was studied in 38 patients with documented valvular or congenital heart disease and in 15 controls. Diastolic turbulence was observed in the TV outflow side in three patients with tricuspid stenosis. Turbulent flow was also detected during systole in patients with septal defects (atrial septal defect in four patients and ventricular septal defect in one patient) in the right ventricular outflow tract and in three atrial septal defect patients also in the inflow tract, presumably because of increased volume of flow. Tricuspid regurgitation (11 patients) was characterized by retrograde laminar jet throughout systole, while in pulmonary regurgitation (six patients) retrograde flow was initially laminar although later on it might become turbulent. In pulmonary hypertension (29 patients) antegrade flow occurred approximately to mid-systole and then was interrupted by retrograde laminar flow which contributed to the mid-systolic closure of the pulmonary valve and pulmonary regurgitation in some cases. CONCLUSIONS: contrast echocardiography is a useful technique to analyse right heart blood flow patterns and may aid the diagnosis of various right heart abnormalities.

Contrast echocardiographic shunts may persist after atrial septal defect repair.

We performed contrast echocardiography on 19 subjects who were asymptomatic in the postoperative period after surgical repair of atrial septal defects. Eighteen of these subjects had adequate right heart echocardiographic contrast to assess the presence or absence of right-to-left shunting. Multiple M-mode and two-dimensional echocardiographic views were studied during several contrast injections with and without the Valsalva manoeuvre. Six patients had postoperative shunts and 12 patients had no postoperative shunts. The age of the six patients with postoperative shunts was 26 +/- 10 years (mean +/- s.d.) and that of the 12 patients without postoperative shunts was 39 +/- 14 years. Four out of six of the postoperative shunt group were males and of these three had patch repairs compared with two males out of 12 with patch repair in the no shunt group. There were no definite differences between the two groups in the following variables: type of atrial septal defect (primum v. secundum), preoperative shunt size, pre-operative peak right ventricular pressure, pre-operative New York Heart Association functional class, pre- or postoperative right ventricular or left ventricular dimensions, aortic and left atrial dimensions. Four of the six patients with postoperative contrast echo shunting underwent cardiac catheterization, showing no significant step-up in oxygen saturation in three, and a significant shunt in one patient who had patch dehiscence at re-operation. We conclude that right-to-left shunts as demonstrated by contrast echocardiography are common in the late postoperative period after atrial septal defect repair. They need not indicate unsuccessful repair or a haemodynamically important residual shunt.

Benefits from adding nifedipine to the treatment of unstable angina when beta-blockade and isosorbide dinitrate have proved inadequate.

Nifedipine (10 mg orally six times daily) was given to patients with unstable angina persisting despite adequate beta-blockade (group I, 35 patients) or despite the association of adequate beta-blockade and sublingual isosorbide dinitrate (group II, 47 patients). Stabilization of anginal symptoms was achieved in 31/35 patients of group I and in 39/47 patients of group II. Aorto-coronary bypass grafting was carried out in 19 patients because of persisting unstable angina (five patients) or because of the severity of residual angina (14 patients). Tolerance to these drug combinations was excellent, with side-effects consisting mainly of transient headache (eight patients) and noncardiac ankle edema (eight patients). Nifedipine was found to be valuable in stabilizing unstable angina persisting despite beta-blockade and nitrates.