Metal pollution in the topsoil of lands adjacent to Sahiwal Coal Fired Power Plant (SCFPP) in Sahiwal, Pakistan.

Coal fly ash from a coal fired power plant is a significant anthropogenic source of various heavy metals in surrounding soils. In this study, heavy metal contamination in topsoil around Sahiwal coal fired power plant (SCFPP) was investigated. Within distance of 0-10, 11-20, 21-30 and 31-40 km of SCFPP, total 56 soil samples were taken, 14 replicate from each distance along with a background subsurface soil sample beyond 60 km. Soil samples were subjected to heavy metals analysis including Fe, Cu and Pb by Atomic Absorption Spectrophotometer (AAS). Composite samples for each distance were analyzed for Al, As, Ba, Cd, Co, Cr, Mn, Mo, Ni, Se, Sr, Zn by Inductively Coupled Plasma (ICP). Pollution indices of exposed soil including Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation Index (Igeo), and Pollution Load Index (PLI) were calculated. Ecological risk index ([Formula: see text]) of individual metals and the Potential Ecological Risk Index (PERI) for all metals were determined. Soil samples within 40 km of SCFPP were significantly polluted with Pb (mean 2.81 ppm), Cu (mean 0.93 ppm), and Fe (mean 7.93 ppm) compared to their background values (Pb 0.45, Cu 0.3, and Fe 4.9 ppm). Some individual replicates were highly contaminated where Pb, Fe, and Cu values were as high as 6.10, 35.4 and 2.51 ppm respectively. PLI, Igeo, CF, and EF for metals classified the soil around CFPP as "moderate to high degree of pollution", "uncontaminated to moderately contaminated", "moderate to very high contamination", and "moderate to significant enrichment" respectively with average values for Cu as 2.75, 0.82, 3.09, 4.01; Pb 4.79, 1.56, 6.16, 7.76, and for Fe as 1.20, 0.40, 1.62, 3.35 respectively. Average Ecological Risk Index ([Formula: see text]) of each metal and Potential Ecological Risk Index (PERI) for all metals classified the soils as "low risk soils" in all distances. However, ([Formula: see text]) of Pb at a number of sites in all distances have shown "moderate risk". The linear correlation of physico-chemical parameter (EC, pH, Saturation %) and metals have recorded several differential correlations, however, their collective impact on Pb in 0-10 km, has recorded statistically significant correlation (p-value 0.01). This mix of correlations indicates complex interplay of many factors influencing metal concentrations at different sampling sites. The concentration of As, Cr, Co, Cd, and Zn was found within satisfactory limits and lower than in many parts of the world. Although the topsoil around SCFPP is largely recorded at low risk, for complete assessment of its ecological health, further research considering comprehensive environmental parameters, all important trace metals and variety of input pathways is suggested.

Mechanical ventilation in acute myocardial infarction: Outcomes from a prospective audit at a cardiovascular hospital in Pakistan.

BACKGROUND: This clinical audit aims to evaluate the clinical data regarding the management and outcomes of acute myocardial infarction (AMI) patients requiring mechanical ventilator (MV) support, along with identifying factors associated with prolonged MV support and 180-day mortality. MATERIALS AND METHODS: In this study, we audited clinical data regarding management, in-hospital and short-term outcomes of adult patients with AMI required MV support. Patients with prolonged MV duration (>24h) and/or 180-day mortality were compared with their counterparts, and associated factors were identified. The binary logistic and Cox regression analyses were performed to determine the predictors of prolonged MV duration and 180-day mortality. RESULTS: In a sample of 312 patients, 72.8% were male, and the mean age was 60.3±11.5 years. The median MV duration was 24 [24-48] hours, with 48.7% prolonged MV duration. The admission albumin level was found to be the independent predictor of prolonged MV duration with an adjusted OR of 0.42 [0.22-0.82]. Overall 7.4% were re-intubated, 6.7% needed renal replacement therapy, 17.6% required intra-aortic balloon pump (IABP) placement, and 16.7% required temporary pacemaker placement. The survival rate was 80.4% at the time of hospital discharge, 74.7% at 30-day, 71.2% at 90-day, and 68.6% at 180-day follow-up. Age, prolonged MV duration, and ejection fraction were found to be the independent predictors of cumulative 180-day mortality with adjusted HR of 1.04 [1.02-1.07], 1.02 [1.01-1.03], and 0.95 [0.92-0.98], respectively. CONCLUSIONS: Prolonged ventilator duration has significant prognostic implications; hence, tailored early recognition of high-risk patients needing more aggressive care can improve the outcomes.

Molecular identification and differential proteomics of drug resistant Salmonella Typhi.

This study aimed to elucidate differentially expressed proteins in drug resistant Salmonella Typhi. Among 100 samples, S. typhi were identified in 43 samples. In drug susceptibility profile, 95.3% (41/43), 80% (35/43) and 70% (30/43) resistances were observed against Nalidixic acid, Ampicillin, and Chloramphenicol respectively. No resistance was observed against Imipenum and Azithromycin while only 11% (5/43) isolates were found resistant to Ceftriaxone. Mass spectrometric differential analysis resulted in 23 up-regulated proteins in drug resistant isolates. Proteins found up-regulated are involved in virulence (vipB, galU, tufA, and lpp1), translation (rpsF, rpsG, rplJ, and rplR), antibiotic resistance (zwf, phoP, and ompX), cell metabolism (metK, ftsZ, pepD, and secB), stress response (ridA, rbfA, and dps), housekeeping (gapA and eno) and hypothetical proteins including ydfZ, t1802, and yajQ. These proteins are of diverse nature and functions but highly interconnected. Further characterization may be helpful for elucidation of new biomarker proteins and therapeutic drug targets.

Immunoaffinity-based mass spectrometric characterization of immunoreactive proteins of Salmonella Typhi.

Salmonella Typhi, a human-restricted Gram negative enterobacteriaceae, is the causative agent of typhoid fever in human being. The available serodiagnostic tools for the diagnosis of typhoid fever lack sensitivity and/or specificity. This study aimed to identify the immunoreactive proteins of S. Typhi that could help to develop improved diagnostic tools. Here, we performed immunoaffinity-based proteomic approach that uses charged columns to retrieve IgG and IgM antibodies from the plasma of typhoid patients followed by capture of S. Typhi proteins. These proteins were then characterized by mass spectrometry and bioinformatics tools. Using this approach, we identified 28 immunoreactive proteins of S. Typhi, in which 14 proteins were captured by IgG charged column and 4 proteins were captured by IgM column. We also identified 10 proteins (hlyE, rfbH, dapD, argI, glyA, pflB, trxB, groEL, tufA and pepD) captured by both columns. The prediction of antigenicity and immunogenicity resulted that 22 proteins were antigenic while 6 were non-antigenic on the scale of 0.4 threshold value of VaxiJen. These proteins successfully simulated the immune system in silico and in response higher amount of antibodies' titers were recorded in C-IMMSIM, confirming the immunogenic nature of these proteins. The identified proteins are of diverse nature and functions including those involved in virulence and pathogenesis, energy metabolism, cell development, biosynthesis of amino acids, regulatory functions and biosynthesis of cofactors. The findings of this study would be helpful in the development of improved vaccines and diagnostic tools for typhoid fever.

Non-Obstructive Coronaries In Patients Presenting With The Non St-Elevation Acute Coronary Syndrome.

BACKGROUND: Worldwide, cardiovascular diseases are the major cause of mortality and morbidity with acute coronary syndrome as the most common clinical manifestation. In a typical clinical setup, around 30% of the patients presented with "ST-segment elevation myocardial infarction (STEMI)" caused by the complete occlusion of the coronary artery and the remaining 70% with intermittent or partial occlusion of the coronary termed as non-ST elevation The aim of this study was to assess the prevalence and characteristics of non-obstructive coronary arteries among patients presenting with non ST-elevation acute coronary syndrome (NSTE-ACS) at a tertiary care cardiac center of Karachi, Pakistan. METHODS: This was a descriptive cross-sectional study, conducted at a tertiary care hospital in Karachi. Study inclusion criteria were patients of either gender admitted with NSTE-ACS and aged between 30-70 years. A routine coronary angiogram was performed in all the patients and the absence of ≥50% stenosis in any major epicardial vessel was taken in non-obstructive coronaries. RESULTS: A total of 174 patients (30-70 years) were included, of which 99 (56.9%) were male and the mean age was 59.43±11.24 years. In the distribution of socioeconomic status, 54 (31.0%) were lower class, middle class 81 (46.6%) while upper-class status were 39 (22.4%). Hypertension was observed in 76 (43.7%), chronic kidney disease in 20 (11.5%), and hyperlipidemia in 55 (31.6%). Non-obstructive coronary arteries were noted in 25 (14.4%) patients. CONCLUSIONS: It is to be concluded that non-obstructive coronary arteries are fairly prevalent in patients arriving in hospitals with NSTE-ACS in our population. Further research is needed to better understand the underlying pathophysiology and optimal management strategies for patients with NOCA in the setting of NSTEMI.

Timi Risk Index, A Simple Tool In Emergency Percutaneous Revascularization For The Prediction Of Contrast Induced Nephropathy.

BACKGROUND: Contrast induced nephropathy (CIN) is a common complication seen after primary percutaneous coronary intervention (PCI) which can contribute to increased morbidity and mortality in patients of acute ST elevation myocardial infarction (STEMI). Aim of this study was to validate the TIMI Risk Index (TRI) for the risk stratification of CIN in patients undergone primary PCI. METHODS: Consecutive patients of STEMI undergone primary PCI at a tertiary care cardiac center were included for this study. Patients in Killip class IV at presentation, patients with history of any PCI and chronic kidney diseases were excluded from this study. TRI was calculated using the formula " " and post-procedure serum creatinine level increase of either 25% or 0.5 mg/dL was taken as CIN. RESULTS: A total of 507 patients were included in this study out of which 82.2% were males and 17.8% were females. In total 8.7% (44) patients developed CIN. In the receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) for TRI was found to be 0.717, [0.649-0.758] for the prediction of CIN. Sensitive, specificity, positive predictive value and negative predictive value of TRI >22.8 to predict the development of CIN were 59.09%, 76.69%, 19.55% and 95.19% respectively. CONCLUSIONS: TIMI risk index is and easy to calculate and readily accessible score which has good predictive value to evaluate the risk of CIN in primary PCI setting.

The Road to Unconventional Detections: Paper-Based Microfluidic Chips.

Conventional detectors are mostly made up of complicated structures that are hard to use. A paper-based microfluidic chip, however, combines the advantages of being small, efficient, easy to process, and environmentally friendly. The paper-based microfluidic chips for biomedical applications focus on efficiency, accuracy, integration, and innovation. Therefore, continuous progress is observed in the transition from single-channel detection to multi-channel detection and in the shift from qualitative detection to quantitative detection. These developments improved the efficiency and accuracy of single-cell substance detection. Paper-based microfluidic chips can provide insight into a variety of fields, including biomedicine and other related fields. This review looks at how paper-based microfluidic chips are prepared, analyzed, and used to help with both biomedical development and functional integration, ideally at the same time.

Prospective Validation Of Heart Score For Suspected Acute Coronary Syndrome Patients.

BACKGROUND: The HEART score is reported to be a useful tool for the assessment of suspected acute coronary syndrome (ACS) patients, however, data regarding its validity in our population is scarce. Therefore, aim of this study was to evaluate the prognostic utility of the HEART score to predict major adverse cardiac events (MACE) within 6 weeks in patients presenting to emergency department with chest pain. METHODS: This prospective observational study included suspected ACS patients presented with chest pain to the emergency department of a tertiary care cardiac center. Inclusion criteria for the study were consecutive adult patients with suspected ACS, patients with definite diagnosis of ACS based on history, electrocardiography (ECG), and cardiac enzymes were excluded from the study. HEART score was calculated and patients with ≥7 score were also excluded. MACE over the 6-weeks after discharge were observed. RESULTS: Total of 281 patients were included in this analysis, 191 (68%) were male and mean age was 52.58±10.63 years. Mean HEART score was calculated to be 4.27±1.06 with 70.8% (199) in moderate risk [4-6]. Area under the curve of HEART score for the prediction of 6-weeks MACE was 0.874 [0.827-0.920] with MACE rate of 31.7% vs. 0% for low- and moderate-risk group respectively. CONCLUSIONS: HEART score showed good discriminating power for the prediction of 6-weeks MACE. Risk of MACE for the patients with HEART score of 0-3 is very low and such patients can be discharged from ER without extensive cardiac workup with proper follow-up planned.

Analysis of associated risk factors among recurrent cutaneous leishmaniasis patients: A cross-sectional study in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Leishmaniasis is the second and fourth highest cause of mortality and morbidity respectively among all tropical diseases. Recurrence in the onset of leishmaniasis is a major problem that needs to be addressed to reduce the case fatality rate and ensure timely clinical intervention. Here we are investigating the association of risk factors with recurrent cutaneous leishmaniasis to address this issue. MATERIAL AND METHODS: Patients received by Nasser Ullah Khan Babar Hospital in Peshawar, Pakistan from March 2019 to July 2020 were enrolled in this study. Those patients who developed symptoms after completion of treatment were included in Group-A while those who had atypical scars like leishmaniasis but were negative for cutaneous leishmaniasis were included in the comparison group tagged as Group B. All those individuals who had completed six weeks of treatment for CL but had normal complete blood counts (CBC) were included to avoid other underlying immunological pathologies, while we excluded those participants who had co-morbidities like diabetes, liver disease, cardiac disease, and pregnant and lactating women through their history Association was tested between Group-A and Group-B with other explanatory variables through chi-square test. The regression model was proposed to determine the predictors. RESULT: A total of 48 participants of both sexes were included in the study with a mean age of 32.2 ± 15.10. The data suggest that females are overrepresented among the patients with recurrent leishmaniasis [21(53.8 %,); p = 0.07]. Compared to patients; healthy participants had a higher proportion of adults (19-59 years) versus adolescents (13-18 years) [26(66.7 %) vs 07(17.9), p = 0.004]. Multivariate logistic regression analysis shows that females are 2.1 times more prone to infections among cases as compared to healthy individuals [unadjusted OR 2.20, 95 % confidence interval (CI) 1.5-10.6, p = 0.02; adjusted OR 2.1, 95 % CI 1.50-10.69, p = 0.02]. We propose that patients receiving intradermal were less likely to be infected as compared to those receiving intralesional injections [unadjusted OR 0.07.0, 95 % confidence interval (CI) 1.18-3.37, p = 0.03; adjusted OR 0.06, 95 % CI 1.18-3.38, p = 0.03]. CONCLUSION: Old age (adults) and sex (females) were the strongest predictors to be associated with recurrent leishmaniasis. Similarly, the choice of intradermal as compared to intralesional injection and the prolonged treatment duration were strongly associated with greater chances of recurrence.

The explorations of dynamic interactions of paxillin at the focal adhesions.

Paxillin is one of the most important adapters in integrin-mediated adhesions that performs numerous crucial functions relying on its dynamic interactions. Its structural behavior serves different purposes, providing a base for several activities. The various domains of paxillin display different functions in the whole process of cell movements and have a significant role in cell adhesion, migration, signal transmission, and protein-protein interactions. On the other hand, some paxillin-associated proteins provide a unique spatiotemporal mechanism for regulating its dynamic characteristics in the tissue homeostasis and make it a more complex and decisive protein at the focal adhesions. This review briefly describes the structural adaptations and molecular mechanisms of recruitment of paxillin into adhesions, explains paxillin's binding dynamics and impact on adhesion stability and turnover, and reveals a variety of paxillin-associated regulatory mechanisms and how paxillin is embedded into the signaling networks.

Epidemiological and hematological investigation of dengue virus infection.

Dengue is a mosquito-borne viral illness that infects humans. For the past few decades, it has been declared a global public health problem. The current study, conducted at the district headquarter hospital (DHQ) Bannu between June to September 2018, was based on the seroprevalence of antibodies against dengue virus serotypes and their hematological parameters among the patients. A total of 1738 individuals suspected of having dengue were diagnosed through NS1, IgG, and IgM antibodies and RT-PCR techniques. Of all the samples, 716 (41.19%) were found to be positive for dengue. A higher infection rate was found in males (65.92%) compared with females (34.07%). The most affected age group was 16-40 years, whereas the most affected tehsil was Bannu, where the DENV-3 serotype was prevalent. The rare serotype (DENV-4) was found in 1% of cases. Symptoms including fever (100%), myalgia (100%), headache (61.31%), vomiting (34.63%), and rashes were common among the dengue patients. However, the mild cases showed fewer clinical signs compared with the severely infected cases. The study also revealed a significant association (P < 0.05) between hematological parameters and dengue infection, showing a significant decrease in TC, eosinophils, neutrophils, and platelets and a significant increase in monocytes and lymphocytes. Based on the current report, it is concluded that patients with the above symptoms and hematological changes may have an increased probability of dengue and should be kept under observation to separate dengue-positive patients and to enhance the treatment process.

Synthesis of novel N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{[5-(un/substituted-phenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as potent antibacterial agents.

The synthetic methodology was initiated by reacting 1,4-benzodioxane-6-amine (1) with 2-bromoacetyl bromide (2) in aqueous alkaline media under dynamic pH control to get compound 2,3-dihydro-1,4-benzodioxin-6-yl-2-bromoacetamide (3). In the subsequent reactions, a variety of un/substituted-benzoic acids (4a-k), through a succession of three steps, was converted into respective oxadiazole nucleophiles, 7a-k. Finally, the targeted molecules, 8a-k, were obtained by reacting 7a-k with electrophile 3 in an aprotic polar solvent. These compounds were corroborated by spectral characterization like IR, EI-MS, 1H-NMR, and CHN analysis data. These molecules were screened for their antibacterial potential and most of them exhibited a potent activity. Moreover, their cytotoxicity was profiled through hemolytic activity and it was observed that majority of them was very modest in toxicity.

Synthesis and evaluation of novel 1, 2, 4-substituted triazoles for urease and anti-proliferative activity.

1,2,4-triazoles are a major group of heterocyclic compounds. In the current work, a concise library of such triazoles synthesized through a multistep protocol. The synthesis involved hydrazinolysis of ethyl-2-(p-Cl-phenoxy) acetate followed by reflux with phenyl isothiocyanate to yield the intermediate 2-[2-(p-Cl-phenoxy)acetyl)-N-phenyl-hydrazinecarbothioamide. This intermediate was then cyclized to form 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (the parent moiety) at alkaline pH. In parallel, 3-bromopropionyl bromide was reacted with a series of phenylamines to yield N-(substituted-phenyl)bromopropanamides. In the final step, N-substitution of 5-[p-(Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-thiol was carried out with N-(substituted-phenyl)bromopropanamides to give desired library of 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(substituted-phenyl) propan-amides (8a-l). The prepared moieties were identified via IR, NMR, & EIMS and evaluated for urease and anti-proliferative activities. 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(3-methyl-phenyl)propanamide 8k, was found to be most prominent hit as urease inhibitor (IC50= 42.57± 0.13 µM) using thiourea as standard (IC50= 21.25±0.15µM). The interaction of 8k with urease were studied using docking studies. Anti-proliferative activity results showed 8k as promising candidates and rest of the synthesized derivatives were found to be moderately anti-proliferative. Molecular docking results also displayed 8k, 8h, and 8c as potential hits for further study.

The raft cytoskeleton binding protein complexes personate functional regulators in cell behaviors.

Several cytoskeleton proteins interact with raft proteins to form raft-cytoskeleton binding protein complexes (RCPCs) that control cell migration and adhesion. The purpose of this paper is to review the latest research on the modes and mechanisms by which a RCPC controls different cellular functions. This paper discusses RCPC composition and its role in cytoskeleton reorganization, as well as the latest developments in molecular mechanisms that regulate cell adhesion and migration under normal conditions. In addition, the role of some external stimuli (such as stress and chemical signals) in this process is further debated, and meanwhile potential mechanisms for RCPC to regulate lipid raft fluidity is proposed. Thus, this review mainly contributes to the understanding of RCPC signal transduction in cells. Additionally, the targeted signal transduction of RCPC and its mechanism connection with cell behaviors will provide a logical basis for the development of unified interventions to combat metastasis related dysfunction and diseases.

A systematic review on active sites and functions of PIM-1 protein.

The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation, differentiation, migration, and other life activities. Many studies have related these functions to its molecular structure, subcellular localization and expression level. However, recognition of specific active sites and their effects on the activity of this constitutively active kinase is still a challenge. Based on the close relationship between its molecular structure and functional activity, this review covers the specific residues involved in the binding of ATP and different substrates in its catalytic domain. This review then elaborates on the relevant changes in protein conformation and cell functions after PIM-1 binds to different substrates. Therefore, this intensive study can improve the understanding of PIM-1-regulated signaling pathways by facilitating the discovery of its potential phosphorylation substrates.

Salmonella Typhi from Northwest Pakistan: Molecular Strain Typing and Drug Resistance Signature.

Objective: To determine the molecular strain typing and drug resistance pattern of Salmonella enterica serovar Typhi prevalent in Northwest Pakistan. Methodology: A total of 2,138 blood samples of suspected typhoid patients from Northwest Pakistan were collected followed by identification of Salmonella Typhi through biochemical, serological, and species-specific fliC-d gene amplification. These isolates were typed by variable-number tandem repeat (VNTR) profiling and investigated for drug resistance. Results: The overall prevalence of Salmonella Typhi was found to be 8.8% (n = 189). Thirty different VNTR strain types of Salmonella Typhi were detected and the most prevalent strain types were T1 and T4, whereas T27 was less prevalent strain. Among the 189 isolates 175 (92.5%) isolates were multidrug resistant, whereas 12 (5.8%) isolates were extensively drug resistant. Resistance to imipenem in Salmonella Typhi was not observed. Most of the isolates have genes encoding for resistance to fluoroquinolones, including gyrA (n = 164), gyrB (n = 160), parC (n = 164), parE (n = 160), ac(6')-ib-cr (n = 163), qnrS (n = 15), and qnrB (n = 3). Similarly, chloramphinicol (cat; n = 147), azithromycin (msrA; n = 3), and co-trimoxazole (dfrA7; n = 145) resistance genes were detected among Salmonella Typhi isolates. Conclusion: In this study, T1 and T4 type Salmonella Typhi strains were predominantly prevalent in Northwest Pakistan. Antibiotic resistance among Salmonella Typhi isolates were observed. Findings of the study would be helpful to devise an appropriate antibiotic policy to control the emergence of drug-resistant Salmonella Typhi in Pakistan.

Fluid Resuscitation In Cardiogenic Shock: An Assessment Of Responsiveness And Outcome.

BACKGROUND: Fluid replacement for resuscitation in cardiogenic shock (CS) patients remains a point of debate in clinical practice. The purpose of the study was to assess the frequency of fluid responsiveness and outcomes of patients with cardiogenic shock receiving fluid resuscitation at the critical care unit (ICU) of a tertiary care cardiac center. METHODS: In this descriptive case series, in which all mechanically ventilated CS patients were evaluated who were assessed for fluid responsiveness by a fluid challenge. It was conducted at the critical care unit of a tertiary care cardiac center in Karachi, Pakistan, from January 2020 to June 2020, by including 41 consecutive patients. Fluid challenge was given as either a 250 ml crystallized bolus or a passive leg raise (PLR) manoeuvre. An increase in the velocity time integral (ΔVTI) of ≥ 10% was considered fluid responsiveness. RESULTS: A total of 41 patients were evaluated: 25 (61%) were males, and the mean age was 61.9±17.0 years, and 36.6% (15) of the patients presented with non-ST elevation myocardial infarction (NSTEMI), followed by anterior wall ST elevation myocardial infarction (31.7% (13)). Fluid responsiveness was observed in 48.8% (20/41). Mean VTI change after the fluid challenge was 1.07±0.86. Survival rate was 33.3% (7/21) in fluid responders vs. 50.0% (10/20) in non-fluid responders; p=0.279. CONCLUSIONS: Almost half of patients presenting with CS from acute coronary syndrome are responsive to fluids. These findings support the routine evaluation by fluid challenge in these patients. Fluid challenge can be by either PLR or fluid bolus.

A SEIR model with memory effects for the propagation of Ebola-like infections and its dynamically consistent approximation.

BACKGROUND AND OBJECTIVE: We present and analyze a nonstandard numerical method to solve an epidemic model with memory that describes the propagation of Ebola-type diseases. The epidemiological system contemplates the presence of sub-populations of susceptible, exposed, infected and recovered individuals, along with nonlinear interactions between the members of those sub-populations. The system possesses disease-free and endemic equilibrium points, whose stability is studied rigorously. METHODS: To solve the epidemic model with memory, a nonstandard approach based on Grünwald-Letnikov differences is used to discretize the problem. The discretization is conveniently carried out in order to produce a fully explicit and non-singular scheme. The discrete problem is thus well defined for any set of non-negative initial conditions. RESULTS: The existence and uniqueness of the solutions of the discrete problem for non-negative initial data is thoroughly proved. Moreover, the positivity and the boundedness of the approximations is also theoretically elucidated. Some simulations confirm the validity of these theoretical results. Moreover, the simulations prove that the computational model is capable of preserving the equilibria of the system (both the disease-free and the endemic equilibria) as well as the stability of those points. CONCLUSIONS: Both theoretical and numerical results establish that the computational method proposed in this work is capable of preserving distinctive features of an epidemiological model with memory for the propagation of Ebola-type diseases. Among the main characteristics of the numerical integrator, the existence and the uniqueness of solutions, the preservation of both positivity and boundedness, the preservation of the equilibrium points and their stabilities as well as the easiness to implement it computationally are the most important features of the approach proposed in this manuscript.

Synthesis, characterization, antibacterial, hemolytic and thrombolytic activity evaluation of 5-(3-chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives.

A novel series of 5-(3-Chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives was efficiently synthesized and screened for antibacterial, hemolytic and thrombolytic activities. The molecule 7c remained the best inhibitor of all selected bacterial strains and furthermore possessed very low toxicity, 8.52±0.31. Compound 7a 7b and 7f showed very good thrombolytic activity relative to Streptokinase employed as reference drug. In addition to low toxicity and moderately good thrombolytic activity, the synthesized compounds possessed excellent to moderate antibacterial activity, relative to ciprofloxacin. All compounds especially 7b and 7f can be consider for further clinical studies and might be helpful in synthesis of new drugs for treatment of cardiovascular diseases.